WO2018035416A1 - Reagents and methods for glycosylation - Google Patents

Abstract

The invention provides methods and regents for the glycosylation of organic molecules. In one aspect, the invention provides a method for glycosylating a hydroxyl-containing organic compound (i.e., a glycosyl acceptor) comprising contacting a glycosyl donor with the hydroxyl-containing organic compound, in the presence of an oxidant, to yield a glycosylated organic compound. In certain embodiments, the methods provided herein provide glycosylation products with high anomeric selectivity. The methods can be applied to the synthesis of disaccharides, trisaccharides, polysaccharides, glycans, etc. Also provided herein are compounds (e.g., glycosyl donors and acceptors) which are useful building blocks in the provided reactions.

Description

REAGENTS AND METHODS FOR GLYCOSYLATION RELATED APPLICATIONS

[0001] The present application claims priority under 35 U.S.C. § 119(e) to U.S. provisional patent application, U.S.S.N.62/377,271, filed August 19, 2016, the entire contents of which is incorporated herein by reference. BACKGROUND OF THE INVENTION

[0002] The development of new chemistry to address problems in the preparation of important biomolecules has helped to greatly advance our understanding of biology and has significantly impacted our ability to treat human disease. While these advances have been applied to nucleosides and nucleotides (components of DNA and RNA) and peptides and proteins, an extremely important class of molecules, carbohydrates, has not seen the same advancements. The chemistry of carbohydrates, also known as saccharides, sugars, and glycans, has lagged far behind. The reasons for this are multifaceted, but have nothing to do with the importance of these molecules. All living cells have attached glycans, and these molecules modulate cell signaling, recognition, immunity, and inflammation with far reaching implications in the understanding and treatment of a large variety of health problems. Instead, the reasons are due to synthetic and analytical difficulties related to their stereochemically rich structures, but also to the technical difficulties in their preparation which involves multistep syntheses for each unit, instability of active glycosyl transfer reagents, and the need to use difficult reagents to handle combined with aqueous sensitivity hampered by challenging physical properties of the reagents. These issues have hindered the availability of ready-to-use building blocks that has contributed to limited work by the synthetic community and generally relegated the area to a group of highly specialized scientists. These issues are summarized in the National Research Council’s report, “Transforming Glycoscience, A Roadmap for the Future” (2012, National Academy Press, Washington). SUMMARY OF THE INVENTION

[0003] The present invention provides systems, methods, and regents for the glycosylation of organic molecules and/or the synthesis of more complex carbohydrates. In one aspect, the invention provides methods for glycosylating a hydroxyl-containing organic compound (i.e., a glycosyl acceptor) comprising contacting a glycosyl donor with the hydroxyl-containing organic compound (i.e., the glycosyl acceptor), in the presence of an oxidant, to yield a glycosylated organic compound.

[0004] In certain embodiments, the glycosyl donor is a compound of one of the following formulae:

or a salt thereof.

[0005] In certain embodiments, the glycosyl donor is:

or a salt thereof.

[0006] Glycosyl acceptors useful in the methods provided herein are any compounds comprising a free hydroxyl group (i.e.,–OH group). The compound comprising a free hydroxyl group may be a small molecule, large molecule, natural product, pharmaceutical drug, etc. The compound containing a free hydroxyl group may also be a carbohydrate (e.g., monosaccharide, disaccharide, trisaccharide, polysaccharide). For example, sugars comprising free hydroxyl groups can be glycosyl acceptors, such as (but not limited to) compounds of the following formulae:

and salts thereof, wherein:

R¹ is optionally substituted alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted carbocyclyl, or optionally substituted acyl.

[0007] For example, in certain embodiments, the glycosyl acceptor is the following:

or a salt thereof.

[0008] Scheme 1 shows a general outline of a certain embodiment of the methods provided herein. The reaction of reagents such as 9 (a glycosyl donor; stereochemistry arbitrarily drawn as glucose as an example) and 10 (glycosyl acceptor; stereochemistry arbitrarily drawn as glucose as an example), provide the disaccharide 11, now containing a“latent glycosyl donor” moiety. In Scheme 1, Pg is any hydroxyl protecting group, defined herein. The method can further comprise a step of deprotecting the latent glycosyl donor moiety to unveil an active glycosyl donor, which can be used in a subsequent glycosylation step. For example, deprotection of the phenolic ester in 11 (Scheme 1) can be accomplished to reveal 13, and repeating the steps with a glycosyl acceptor such as 10, or other building blocks, would build up the saccharide. The methods described herein offer the ability to grow the carbohydrate in multiple directions as needed. The ability to form linear or branched substrates relies on tactical protecting group strategies (described herein). Additionally, protecting group choices can allow for predictable substrate control of anomeric selectivity, which is important in carbohydrate synthesis.

[0009] Additionally, the present invention provides compounds (e.g., glycosyl donors and glycosyl acceptors), and salts thereof, which are useful in glycosylation reactions and in carbohydrate preparation. In another aspect, the present invention provides kits comprising one or more of the compounds provided herein. [0010] The details of certain embodiments of the invention are set forth in the Detailed Description of Certain Embodiments, as described below. Other features, objects, and advantages of the invention will be apparent from the Definitions, Examples, and Claims. DEFINITIONS

[0011] Definitions of specific functional groups and chemical terms are described in more detail below. The chemical elements are identified in accordance with the Periodic Table of the Elements, CAS version, Handbook of Chemistry and Physics, 75^th Ed., inside cover, and specific functional groups are generally defined as described therein. Additionally, general principles of organic chemistry, as well as specific functional moieties and reactivity, are described in Organic Chemistry, Thomas Sorrell, University Science Books, Sausalito, 1999; Smith and March, March’s Advanced Organic Chemistry, 5^th Edition, John Wiley & Sons, Inc., New York, 2001; Larock, Comprehensive Organic Transformations, VCH Publishers, Inc., New York, 1989; and Carruthers, Some Modern Methods of Organic Synthesis, 3^rd Edition, Cambridge University Press, Cambridge, 1987.

[0012] Compounds described herein can comprise one or more asymmetric centers, and thus can exist in various stereoisomeric forms, e.g., enantiomers and/or diastereomers. For example, the compounds described herein can be in the form of an individual enantiomer, diastereomer or geometric isomer, or can be in the form of a mixture of stereoisomers, including racemic mixtures and mixtures enriched in one or more stereoisomer. Isomers can be isolated from mixtures by methods known to those skilled in the art, including chiral high pressure liquid chromatography (HPLC) and the formation and crystallization of chiral salts; or preferred isomers can be prepared by asymmetric syntheses. See, for example, Jacques et al., Enantiomers, Racemates and Resolutions (Wiley Interscience, New York, 1981); Wilen et al., Tetrahedron 33:2725 (1977); Eliel, E.L. Stereochemistry of Carbon Compounds (McGraw-Hill, NY, 1962); and Wilen, S.H., Tables of Resolving Agents and Optical Resolutions p.268 (E.L. Eliel, Ed., Univ. of Notre Dame Press, Notre Dame, IN 1972). The invention additionally encompasses compounds as individual isomers substantially free of other isomers, and alternatively, as mixtures of various isomers.

[0013] In a formula, is a single bond where the stereochemistry of the moieties immediately attached thereto is not specified, is absent or a single bond, and or is a single or double bond. When an atom or formula is drawn with no stereochemistry specified, it is to be understood that the formula is meant to encompass all possible stereoisomers (e.g., enantiomers, diastereomers, epimers) of the compounds. [0014] Unless otherwise stated, structures depicted herein are also meant to include compounds that differ only in the presence of one or more isotopically enriched atoms. For example, compounds having the present structures except for the replacement of hydrogen by deuterium or tritium, replacement of ¹⁹F with ¹⁸F, or the replacement of ¹²C with ¹³C or ¹⁴C are within the scope of the disclosure. Such compounds are useful, for example, as analytical tools or probes in biological assays.

[0015] When a range of values is listed, it is intended to encompass each value and sub-range within the range. For example“C_1-6 alkyl” is intended to encompass, C₁, C₂, C₃, C₄, C₅, C₆, C_1-6, C_1-5, C_1-4, C_1-3, C_1-2, C_2-6, C_2-5, C_2-4, C_2-3, C_3-6, C_3-5, C_3-4, C_4-6, C_4-5, and C_5-6 alkyl.

[0016] The term“aliphatic” refers to alkyl, alkenyl, alkynyl, and carbocyclic groups.

Likewise, the term“heteroaliphatic” refers to heteroalkyl, heteroalkenyl, heteroalkynyl, and heterocyclic groups.

[0017] The term“alkyl” refers to a radical of a straight-chain or branched saturated hydrocarbon group having from 1 to 10 carbon atoms (“C_1-10 alkyl”). In some embodiments, an alkyl group has 1 to 9 carbon atoms (“C_1-9 alkyl”). In some embodiments, an alkyl group has 1 to 8 carbon atoms (“C_1-8 alkyl”). In some embodiments, an alkyl group has 1 to 7 carbon atoms (“C_1-7 alkyl”). In some embodiments, an alkyl group has 1 to 6 carbon atoms (“C_1-6 alkyl”). In some embodiments, an alkyl group has 1 to 5 carbon atoms (“C_1-5 alkyl”). In some embodiments, an alkyl group has 1 to 4 carbon atoms (“C_1-4 alkyl”). In some embodiments, an alkyl group has 1 to 3 carbon atoms (“C_1-3 alkyl”). In some embodiments, an alkyl group has 1 to 2 carbon atoms (“C_1-2 alkyl”). In some embodiments, an alkyl group has 1 carbon atom (“C₁ alkyl”). In some embodiments, an alkyl group has 2 to 6 carbon atoms (“C_2-6 alkyl”). Examples of C_1-6 alkyl groups include methyl (C₁), ethyl (C₂), propyl (C₃) (e.g., n-propyl, isopropyl), butyl (C₄) (e.g., n-butyl, tert-butyl, sec-butyl, iso-butyl), pentyl (C₅) (e.g., n-pentyl, 3-pentanyl, amyl, neopentyl, 3-methyl-2-butanyl, tertiary amyl), and hexyl (C₆) (e.g., n-hexyl). Additional examples of alkyl groups include n-heptyl (C₇), n- octyl (C₈), and the like. Unless otherwise specified, each instance of an alkyl group is independently unsubstituted (an“unsubstituted alkyl”) or substituted (a“substituted alkyl”) with one or more substituents (e.g., halogen, such as F). In certain embodiments, the alkyl group is an unsubstituted C_1-10 alkyl (such as unsubstituted C_1-6 alkyl, e.g.,−CH₃ (Me), unsubstituted ethyl (Et), unsubstituted propyl (Pr, e.g., unsubstituted n-propyl (n-Pr), unsubstituted isopropyl (i-Pr)), unsubstituted butyl (Bu, e.g., unsubstituted n-butyl (n-Bu), unsubstituted tert-butyl (tert-Bu or t-Bu), unsubstituted sec-butyl (sec-Bu), unsubstituted isobutyl (i-Bu)). In certain embodiments, the alkyl group is a substituted C_1-10 alkyl (such as substituted C_1-6 alkyl, e.g.,−CF₃, Bn).

[0018] The term“heteroalkyl” refers to an alkyl group, which further includes at least one heteroatom (e.g., 1, 2, 3, or 4 heteroatoms) selected from oxygen, nitrogen, or sulfur within (i.e., inserted between adjacent carbon atoms of) and/or placed at one or more terminal position(s) of the parent chain. In certain embodiments, a heteroalkyl group refers to a saturated group having from 1 to 10 carbon atoms and 1 or more heteroatoms within the parent chain (“heteroC_1-10 alkyl”). In some embodiments, a heteroalkyl group is a saturated group having 1 to 9 carbon atoms and 1 or more heteroatoms within the parent chain

(“heteroC_1-9 alkyl”). In some embodiments, a heteroalkyl group is a saturated group having 1 to 8 carbon atoms and 1 or more heteroatoms within the parent chain (“heteroC_1-8 alkyl”). In some embodiments, a heteroalkyl group is a saturated group having 1 to 7 carbon atoms and 1 or more heteroatoms within the parent chain (“heteroC_1-7 alkyl”). In some embodiments, a heteroalkyl group is a saturated group having 1 to 6 carbon atoms and 1 or more heteroatoms within the parent chain (“heteroC_1-6 alkyl”). In some embodiments, a heteroalkyl group is a saturated group having 1 to 5 carbon atoms and 1 or 2 heteroatoms within the parent chain (“heteroC_1-5 alkyl”). In some embodiments, a heteroalkyl group is a saturated group having 1 to 4 carbon atoms and 1 or 2 heteroatoms within the parent chain (“heteroC_1-4 alkyl”). In some embodiments, a heteroalkyl group is a saturated group having 1 to 3 carbon atoms and 1 heteroatom within the parent chain (“heteroC_1-3 alkyl”). In some embodiments, a heteroalkyl group is a saturated group having 1 to 2 carbon atoms and 1 heteroatom within the parent chain (“heteroC_1-2 alkyl”). In some embodiments, a heteroalkyl group is a saturated group having 1 carbon atom and 1 heteroatom (“heteroC₁ alkyl”). In some embodiments, a heteroalkyl group is a saturated group having 2 to 6 carbon atoms and 1 or 2 heteroatoms within the parent chain (“heteroC_2-6 alkyl”). Unless otherwise specified, each instance of a heteroalkyl group is independently unsubstituted (an“unsubstituted heteroalkyl”) or substituted (a“substituted heteroalkyl”) with one or more substituents. In certain

embodiments, the heteroalkyl group is an unsubstituted heteroC_1-10 alkyl. In certain embodiments, the heteroalkyl group is a substituted heteroC_1-10 alkyl.

[0019] The term“alkenyl” refers to a radical of a straight-chain or branched hydrocarbon group having from 2 to 10 carbon atoms and one or more carbon-carbon double bonds (e.g., 1, 2, 3, or 4 double bonds). In some embodiments, an alkenyl group has 2 to 9 carbon atoms (“C_2-9 alkenyl”). In some embodiments, an alkenyl group has 2 to 8 carbon atoms (“C_2-8 alkenyl”). In some embodiments, an alkenyl group has 2 to 7 carbon atoms (“C_2-7 alkenyl”). In some embodiments, an alkenyl group has 2 to 6 carbon atoms (“C_2-6 alkenyl”). In some embodiments, an alkenyl group has 2 to 5 carbon atoms (“C_2-5 alkenyl”). In some

embodiments, an alkenyl group has 2 to 4 carbon atoms (“C_2-4 alkenyl”). In some

embodiments, an alkenyl group has 2 to 3 carbon atoms (“C_2-3 alkenyl”). In some

embodiments, an alkenyl group has 2 carbon atoms (“C₂ alkenyl”). The one or more carbon- carbon double bonds can be internal (such as in 2-butenyl) or terminal (such as in 1-butenyl). Examples of C_2-4 alkenyl groups include ethenyl (C₂), 1-propenyl (C₃), 2-propenyl (C₃), 1- butenyl (C₄), 2-butenyl (C₄), butadienyl (C₄), and the like. Examples of C_2-6 alkenyl groups include the aforementioned C_2-4 alkenyl groups as well as pentenyl (C₅), pentadienyl (C₅), hexenyl (C₆), and the like. Additional examples of alkenyl include heptenyl (C₇), octenyl (C₈), octatrienyl (C₈), and the like. Unless otherwise specified, each instance of an alkenyl group is independently unsubstituted (an“unsubstituted alkenyl”) or substituted (a “substituted alkenyl”) with one or more substituents. In certain embodiments, the alkenyl group is an unsubstituted C_2-10 alkenyl. In certain embodiments, the alkenyl group is a substituted C_2-10 alkenyl. In an alkenyl group, a C=C double bond for which the stereochemistry is not specified (e.g.,−CH=CHCH₃ or ) may be an (E)- or (Z)- double bond.

[0020] The term“heteroalkenyl” refers to an alkenyl group, which further includes at least one heteroatom (e.g., 1, 2, 3, or 4 heteroatoms) selected from oxygen, nitrogen, or sulfur within (i.e., inserted between adjacent carbon atoms of) and/or placed at one or more terminal position(s) of the parent chain. In certain embodiments, a heteroalkenyl group refers to a group having from 2 to 10 carbon atoms, at least one double bond, and 1 or more heteroatoms within the parent chain (“heteroC_2-10 alkenyl”). In some embodiments, a heteroalkenyl group has 2 to 9 carbon atoms at least one double bond, and 1 or more heteroatoms within the parent chain (“heteroC_2-9 alkenyl”). In some embodiments, a heteroalkenyl group has 2 to 8 carbon atoms, at least one double bond, and 1 or more heteroatoms within the parent chain (“heteroC_2-8 alkenyl”). In some embodiments, a heteroalkenyl group has 2 to 7 carbon atoms, at least one double bond, and 1 or more heteroatoms within the parent chain (“heteroC_2-7 alkenyl”). In some embodiments, a heteroalkenyl group has 2 to 6 carbon atoms, at least one double bond, and 1 or more heteroatoms within the parent chain (“heteroC_2-6 alkenyl”). In some embodiments, a heteroalkenyl group has 2 to 5 carbon atoms, at least one double bond, and 1 or 2 heteroatoms within the parent chain (“heteroC_2-5 alkenyl”). In some embodiments, a heteroalkenyl group has 2 to 4 carbon atoms, at least one double bond, and 1 or 2 heteroatoms within the parent chain (“heteroC_2-4 alkenyl”). In some embodiments, a heteroalkenyl group has 2 to 3 carbon atoms, at least one double bond, and 1 heteroatom within the parent chain (“heteroC_2-3 alkenyl”). In some embodiments, a heteroalkenyl group has 2 to 6 carbon atoms, at least one double bond, and 1 or 2 heteroatoms within the parent chain (“heteroC_2-6 alkenyl”). Unless otherwise specified, each instance of a heteroalkenyl group is independently unsubstituted (an“unsubstituted heteroalkenyl”) or substituted (a “substituted heteroalkenyl”) with one or more substituents. In certain embodiments, the heteroalkenyl group is an unsubstituted heteroC_2-10 alkenyl. In certain embodiments, the heteroalkenyl group is a substituted heteroC_2-10 alkenyl.

[0021] The term“alkynyl” refers to a radical of a straight-chain or branched hydrocarbon group having from 2 to 10 carbon atoms and one or more carbon-carbon triple bonds (e.g., 1, 2, 3, or 4 triple bonds) (“C_2-10 alkynyl”). In some embodiments, an alkynyl group has 2 to 9 carbon atoms (“C_2-9 alkynyl”). In some embodiments, an alkynyl group has 2 to 8 carbon atoms (“C_2-8 alkynyl”). In some embodiments, an alkynyl group has 2 to 7 carbon atoms (“C_{2- 7} alkynyl”). In some embodiments, an alkynyl group has 2 to 6 carbon atoms (“C_2-6 alkynyl”). In some embodiments, an alkynyl group has 2 to 5 carbon atoms (“C_2-5 alkynyl”). In some embodiments, an alkynyl group has 2 to 4 carbon atoms (“C_2-4 alkynyl”). In some

embodiments, an alkynyl group has 2 to 3 carbon atoms (“C_2-3 alkynyl”). In some

embodiments, an alkynyl group has 2 carbon atoms (“C₂ alkynyl”). The one or more carbon- carbon triple bonds can be internal (such as in 2-butynyl) or terminal (such as in 1-butynyl). Examples of C_2-4 alkynyl groups include, without limitation, ethynyl (C₂), 1-propynyl (C₃), 2- propynyl (C₃), 1-butynyl (C₄), 2-butynyl (C₄), and the like. Examples of C_2-6 alkenyl groups include the aforementioned C_2-4 alkynyl groups as well as pentynyl (C₅), hexynyl (C₆), and the like. Additional examples of alkynyl include heptynyl (C₇), octynyl (C₈), and the like. Unless otherwise specified, each instance of an alkynyl group is independently unsubstituted (an“unsubstituted alkynyl”) or substituted (a“substituted alkynyl”) with one or more substituents. In certain embodiments, the alkynyl group is an unsubstituted C_2-10 alkynyl. In certain embodiments, the alkynyl group is a substituted C_2-10 alkynyl.

[0022] The term“heteroalkynyl” refers to an alkynyl group, which further includes at least one heteroatom (e.g., 1, 2, 3, or 4 heteroatoms) selected from oxygen, nitrogen, or sulfur within (i.e., inserted between adjacent carbon atoms of) and/or placed at one or more terminal position(s) of the parent chain. In certain embodiments, a heteroalkynyl group refers to a group having from 2 to 10 carbon atoms, at least one triple bond, and 1 or more heteroatoms within the parent chain (“heteroC_2-10 alkynyl”). In some embodiments, a heteroalkynyl group has 2 to 9 carbon atoms, at least one triple bond, and 1 or more heteroatoms within the parent chain (“heteroC_2-9 alkynyl”). In some embodiments, a heteroalkynyl group has 2 to 8 carbon atoms, at least one triple bond, and 1 or more heteroatoms within the parent chain (“heteroC_{2- 8} alkynyl”). In some embodiments, a heteroalkynyl group has 2 to 7 carbon atoms, at least one triple bond, and 1 or more heteroatoms within the parent chain (“heteroC_2-7 alkynyl”). In some embodiments, a heteroalkynyl group has 2 to 6 carbon atoms, at least one triple bond, and 1 or more heteroatoms within the parent chain (“heteroC_2-6 alkynyl”). In some

embodiments, a heteroalkynyl group has 2 to 5 carbon atoms, at least one triple bond, and 1 or 2 heteroatoms within the parent chain (“heteroC_2-5 alkynyl”). In some embodiments, a heteroalkynyl group has 2 to 4 carbon atoms, at least one triple bond, and 1or 2 heteroatoms within the parent chain (“heteroC_2-4 alkynyl”). In some embodiments, a heteroalkynyl group has 2 to 3 carbon atoms, at least one triple bond, and 1 heteroatom within the parent chain (“heteroC_2-3 alkynyl”). In some embodiments, a heteroalkynyl group has 2 to 6 carbon atoms, at least one triple bond, and 1 or 2 heteroatoms within the parent chain (“heteroC_2-6 alkynyl”). Unless otherwise specified, each instance of a heteroalkynyl group is independently unsubstituted (an“unsubstituted heteroalkynyl”) or substituted (a“substituted

heteroalkynyl”) with one or more substituents. In certain embodiments, the heteroalkynyl group is an unsubstituted heteroC_2-10 alkynyl. In certain embodiments, the heteroalkynyl group is a substituted heteroC_2-10 alkynyl.

[0023] The term“carbocyclyl” or“carbocyclic” refers to a radical of a non-aromatic cyclic hydrocarbon group having from 3 to 14 ring carbon atoms (“C_3-14 carbocyclyl”) and zero heteroatoms in the non-aromatic ring system. In some embodiments, a carbocyclyl group has 3 to 10 ring carbon atoms (“C_3-10 carbocyclyl”). In some embodiments, a carbocyclyl group has 3 to 8 ring carbon atoms (“C_3-8 carbocyclyl”). In some embodiments, a carbocyclyl group has 3 to 7 ring carbon atoms (“C_3-7 carbocyclyl”). In some embodiments, a carbocyclyl group has 3 to 6 ring carbon atoms (“C_3-6 carbocyclyl”). In some embodiments, a carbocyclyl group has 4 to 6 ring carbon atoms (“C_4-6 carbocyclyl”). In some embodiments, a carbocyclyl group has 5 to 6 ring carbon atoms (“C_5-6 carbocyclyl”). In some embodiments, a carbocyclyl group has 5 to 10 ring carbon atoms (“C_5-10 carbocyclyl”). Exemplary C_3-6 carbocyclyl groups include, without limitation, cyclopropyl (C₃), cyclopropenyl (C₃), cyclobutyl (C₄), cyclobutenyl (C₄), cyclopentyl (C₅), cyclopentenyl (C₅), cyclohexyl (C₆), cyclohexenyl (C₆), cyclohexadienyl (C₆), and the like. Exemplary C_3-8 carbocyclyl groups include, without limitation, the aforementioned C_3-6 carbocyclyl groups as well as cycloheptyl (C₇), cycloheptenyl (C₇), cycloheptadienyl (C₇), cycloheptatrienyl (C₇), cyclooctyl (C₈), cyclooctenyl (C₈), bicyclo[2.2.1]heptanyl (C₇), bicyclo[2.2.2]octanyl (C₈), and the like.

Exemplary C_3-10 carbocyclyl groups include, without limitation, the aforementioned C_3-8 carbocyclyl groups as well as cyclononyl (C₉), cyclononenyl (C₉), cyclodecyl (C₁₀), cyclodecenyl (C₁₀), octahydro-1H-indenyl (C₉), decahydronaphthalenyl (C₁₀),

spiro[4.5]decanyl (C₁₀), and the like. As the foregoing examples illustrate, in certain embodiments, the carbocyclyl group is either monocyclic (“monocyclic carbocyclyl”) or polycyclic (e.g., containing a fused, bridged or spiro ring system such as a bicyclic system (“bicyclic carbocyclyl”) or tricyclic system (“tricyclic carbocyclyl”)) and can be saturated or can contain one or more carbon-carbon double or triple bonds.“Carbocyclyl” also includes ring systems wherein the carbocyclyl ring, as defined above, is fused with one or more aryl or heteroaryl groups wherein the point of attachment is on the carbocyclyl ring, and in such instances, the number of carbons continue to designate the number of carbons in the carbocyclic ring system. Unless otherwise specified, each instance of a carbocyclyl group is independently unsubstituted (an“unsubstituted carbocyclyl”) or substituted (a“substituted carbocyclyl”) with one or more substituents. In certain embodiments, the carbocyclyl group is an unsubstituted C_3-14 carbocyclyl. In certain embodiments, the carbocyclyl group is a substituted C_3-14 carbocyclyl.

[0024] In some embodiments,“carbocyclyl” is a monocyclic, saturated carbocyclyl group having from 3 to 14 ring carbon atoms (“C_3-14 cycloalkyl”). In some embodiments, a cycloalkyl group has 3 to 10 ring carbon atoms (“C_3-10 cycloalkyl”). In some embodiments, a cycloalkyl group has 3 to 8 ring carbon atoms (“C_3-8 cycloalkyl”). In some embodiments, a cycloalkyl group has 3 to 6 ring carbon atoms (“C_3-6 cycloalkyl”). In some embodiments, a cycloalkyl group has 4 to 6 ring carbon atoms (“C_4-6 cycloalkyl”). In some embodiments, a cycloalkyl group has 5 to 6 ring carbon atoms (“C_5-6 cycloalkyl”). In some embodiments, a cycloalkyl group has 5 to 10 ring carbon atoms (“C_5-10 cycloalkyl”). Examples of C_5-6 cycloalkyl groups include cyclopentyl (C₅) and cyclohexyl (C₅). Examples of C_3-6 cycloalkyl groups include the aforementioned C_5-6 cycloalkyl groups as well as cyclopropyl (C₃) and cyclobutyl (C₄). Examples of C_3-8 cycloalkyl groups include the aforementioned C_3-6 cycloalkyl groups as well as cycloheptyl (C₇) and cyclooctyl (C₈). Unless otherwise specified, each instance of a cycloalkyl group is independently unsubstituted (an“unsubstituted cycloalkyl”) or substituted (a“substituted cycloalkyl”) with one or more substituents. In certain embodiments, the cycloalkyl group is an unsubstituted C_3-14 cycloalkyl. In certain embodiments, the cycloalkyl group is a substituted C_3-14 cycloalkyl. [0025] The term“heterocyclyl” or“heterocyclic” refers to a radical of a 3- to 14-membered non-aromatic ring system having ring carbon atoms and 1 to 4 ring heteroatoms, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur (“3-14 membered heterocyclyl”). In heterocyclyl groups that contain one or more nitrogen atoms, the point of attachment can be a carbon or nitrogen atom, as valency permits. A heterocyclyl group can either be monocyclic (“monocyclic heterocyclyl”) or polycyclic (e.g., a fused, bridged or spiro ring system such as a bicyclic system (“bicyclic heterocyclyl”) or tricyclic system (“tricyclic heterocyclyl”)), and can be saturated or can contain one or more carbon- carbon double or triple bonds. Heterocyclyl polycyclic ring systems can include one or more heteroatoms in one or both rings.“Heterocyclyl” also includes ring systems wherein the heterocyclyl ring, as defined above, is fused with one or more carbocyclyl groups wherein the point of attachment is either on the carbocyclyl or heterocyclyl ring, or ring systems wherein the heterocyclyl ring, as defined above, is fused with one or more aryl or heteroaryl groups, wherein the point of attachment is on the heterocyclyl ring, and in such instances, the number of ring members continue to designate the number of ring members in the heterocyclyl ring system. Unless otherwise specified, each instance of heterocyclyl is independently unsubstituted (an“unsubstituted heterocyclyl”) or substituted (a“substituted heterocyclyl”) with one or more substituents. In certain embodiments, the heterocyclyl group is an unsubstituted 3-14 membered heterocyclyl. In certain embodiments, the heterocyclyl group is a substituted 3-14 membered heterocyclyl.

[0026] In some embodiments, a heterocyclyl group is a 5-10 membered non-aromatic ring system having ring carbon atoms and 1-4 ring heteroatoms, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur (“5-10 membered heterocyclyl”). In some embodiments, a heterocyclyl group is a 5-8 membered non-aromatic ring system having ring carbon atoms and 1-4 ring heteroatoms, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur (“5-8 membered heterocyclyl”). In some embodiments, a heterocyclyl group is a 5-6 membered non-aromatic ring system having ring carbon atoms and 1-4 ring heteroatoms, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur (“5-6 membered heterocyclyl”). In some embodiments, the 5-6 membered heterocyclyl has 1-3 ring heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, the 5-6 membered heterocyclyl has 1-2 ring heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, the 5-6 membered heterocyclyl has 1 ring heteroatom selected from nitrogen, oxygen, and sulfur. [0027] Exemplary 3-membered heterocyclyl groups containing 1 heteroatom include, without limitation, azirdinyl, oxiranyl, and thiiranyl. Exemplary 4-membered heterocyclyl groups containing 1 heteroatom include, without limitation, azetidinyl, oxetanyl, and thietanyl.

Exemplary 5-membered heterocyclyl groups containing 1 heteroatom include, without limitation, tetrahydrofuranyl, dihydrofuranyl, tetrahydrothiophenyl, dihydrothiophenyl, pyrrolidinyl, dihydropyrrolyl, and pyrrolyl-2,5-dione. Exemplary 5-membered heterocyclyl groups containing 2 heteroatoms include, without limitation, dioxolanyl, oxathiolanyl and dithiolanyl. Exemplary 5-membered heterocyclyl groups containing 3 heteroatoms include, without limitation, triazolinyl, oxadiazolinyl, and thiadiazolinyl. Exemplary 6-membered heterocyclyl groups containing 1 heteroatom include, without limitation, piperidinyl, tetrahydropyranyl, dihydropyridinyl, and thianyl. Exemplary 6-membered heterocyclyl groups containing 2 heteroatoms include, without limitation, piperazinyl, morpholinyl, dithianyl, and dioxanyl. Exemplary 6-membered heterocyclyl groups containing 3

heteroatoms include, without limitation, triazinyl. Exemplary 7-membered heterocyclyl groups containing 1 heteroatom include, without limitation, azepanyl, oxepanyl and thiepanyl. Exemplary 8-membered heterocyclyl groups containing 1 heteroatom include, without limitation, azocanyl, oxecanyl and thiocanyl. Exemplary bicyclic heterocyclyl groups include, without limitation, indolinyl, isoindolinyl, dihydrobenzofuranyl,

dihydrobenzothienyl, tetrahydrobenzothienyl, tetrahydrobenzofuranyl, tetrahydroindolyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, decahydroquinolinyl, decahydroisoquinolinyl, octahydrochromenyl, octahydroisochromenyl, decahydronaphthyridinyl, decahydro-1,8- naphthyridinyl, octahydropyrrolo[3,2-b]pyrrole, indolinyl, phthalimidyl, naphthalimidyl, chromanyl, chromenyl, 1H-benzo[e][1,4]diazepinyl, 1,4,5,7-tetrahydropyrano[3,4-b]pyrrolyl, 5,6-dihydro-4H-furo[3,2-b]pyrrolyl, 6,7-dihydro-5H-furo[3,2-b]pyranyl, 5,7-dihydro-4H- thieno[2,3-c]pyranyl, 2,3-dihydro-1H-pyrrolo[2,3-b]pyridinyl, 2,3-dihydrofuro[2,3- b]pyridinyl, 4,5,6,7-tetrahydro-1H-pyrrolo[2,3-b]pyridinyl, 4,5,6,7-tetrahydrofuro[3,2- c]pyridinyl, 4,5,6,7-tetrahydrothieno[3,2-b]pyridinyl, 1,2,3,4-tetrahydro-1,6-naphthyridinyl, and the like.

[0028] The term“aryl” refers to a radical of a monocyclic or polycyclic (e.g., bicyclic or tricyclic) 4n+2 aromatic ring system (e.g., having 6, 10, or 14 pi electrons shared in a cyclic array) having 6-14 ring carbon atoms and zero heteroatoms provided in the aromatic ring system (“C_6-14 aryl”). In some embodiments, an aryl group has 6 ring carbon atoms (“C₆ aryl”; e.g., phenyl). In some embodiments, an aryl group has 10 ring carbon atoms (“C₁₀ aryl”; e.g., naphthyl such as 1-naphthyl and 2-naphthyl). In some embodiments, an aryl group has 14 ring carbon atoms (“C₁₄ aryl”; e.g., anthracyl).“Aryl” also includes ring systems wherein the aryl ring, as defined above, is fused with one or more carbocyclyl or heterocyclyl groups wherein the radical or point of attachment is on the aryl ring, and in such instances, the number of carbon atoms continue to designate the number of carbon atoms in the aryl ring system. Unless otherwise specified, each instance of an aryl group is independently unsubstituted (an“unsubstituted aryl”) or substituted (a“substituted aryl”) with one or more substituents. In certain embodiments, the aryl group is an unsubstituted C_6-14 aryl. In certain embodiments, the aryl group is a substituted C_6-14 aryl.

[0029] The term“heteroaryl” refers to a radical of a 5-14 membered monocyclic or polycyclic (e.g., bicyclic, tricyclic) 4n+2 aromatic ring system (e.g., having 6, 10, or 14 pi electrons shared in a cyclic array) having ring carbon atoms and 1-4 ring heteroatoms provided in the aromatic ring system, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur (“5-14 membered heteroaryl”). In heteroaryl groups that contain one or more nitrogen atoms, the point of attachment can be a carbon or nitrogen atom, as valency permits. Heteroaryl polycyclic ring systems can include one or more heteroatoms in one or both rings.“Heteroaryl” includes ring systems wherein the heteroaryl ring, as defined above, is fused with one or more carbocyclyl or heterocyclyl groups wherein the point of attachment is on the heteroaryl ring, and in such instances, the number of ring members continue to designate the number of ring members in the heteroaryl ring system. “Heteroaryl” also includes ring systems wherein the heteroaryl ring, as defined above, is fused with one or more aryl groups wherein the point of attachment is either on the aryl or heteroaryl ring, and in such instances, the number of ring members designates the number of ring members in the fused polycyclic (aryl/heteroaryl) ring system. Polycyclic heteroaryl groups wherein one ring does not contain a heteroatom (e.g., indolyl, quinolinyl, carbazolyl, and the like) the point of attachment can be on either ring, i.e., either the ring bearing a heteroatom (e.g., 2-indolyl) or the ring that does not contain a heteroatom (e.g., 5-indolyl).

[0030] In some embodiments, a heteroaryl group is a 5-10 membered aromatic ring system having ring carbon atoms and 1-4 ring heteroatoms provided in the aromatic ring system, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur (“5-10 membered heteroaryl”). In some embodiments, a heteroaryl group is a 5-8 membered aromatic ring system having ring carbon atoms and 1-4 ring heteroatoms provided in the aromatic ring system, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur (“5-8 membered heteroaryl”). In some embodiments, a heteroaryl group is a 5-6 membered aromatic ring system having ring carbon atoms and 1-4 ring heteroatoms provided in the aromatic ring system, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur (“5-6 membered heteroaryl”). In some embodiments, the 5- 6 membered heteroaryl has 1-3 ring heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, the 5-6 membered heteroaryl has 1-2 ring heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, the 5-6 membered heteroaryl has 1 ring heteroatom selected from nitrogen, oxygen, and sulfur. Unless otherwise specified, each instance of a heteroaryl group is independently unsubstituted (an“unsubstituted heteroaryl”) or substituted (a“substituted heteroaryl”) with one or more substituents. In certain embodiments, the heteroaryl group is an unsubstituted 5-14 membered heteroaryl. In certain embodiments, the heteroaryl group is a substituted 5-14 membered heteroaryl.

[0031] Exemplary 5-membered heteroaryl groups containing 1 heteroatom include, without limitation, pyrrolyl, furanyl, and thiophenyl. Exemplary 5-membered heteroaryl groups containing 2 heteroatoms include, without limitation, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, and isothiazolyl. Exemplary 5-membered heteroaryl groups containing 3 heteroatoms include, without limitation, triazolyl, oxadiazolyl, and thiadiazolyl. Exemplary 5-membered heteroaryl groups containing 4 heteroatoms include, without limitation, tetrazolyl. Exemplary 6-membered heteroaryl groups containing 1 heteroatom include, without limitation, pyridinyl. Exemplary 6-membered heteroaryl groups containing 2 heteroatoms include, without limitation, pyridazinyl, pyrimidinyl, and pyrazinyl. Exemplary 6-membered heteroaryl groups containing 3 or 4 heteroatoms include, without limitation, triazinyl and tetrazinyl, respectively. Exemplary 7-membered heteroaryl groups containing 1 heteroatom include, without limitation, azepinyl, oxepinyl, and thiepinyl. Exemplary 5,6- bicyclic heteroaryl groups include, without limitation, indolyl, isoindolyl, indazolyl, benzotriazolyl, benzothiophenyl, isobenzothiophenyl, benzofuranyl, benzoisofuranyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzoxadiazolyl, benzthiazolyl,

benzisothiazolyl, benzthiadiazolyl, indolizinyl, and purinyl. Exemplary 6,6-bicyclic heteroaryl groups include, without limitation, naphthyridinyl, pteridinyl, quinolinyl, isoquinolinyl, cinnolinyl, quinoxalinyl, phthalazinyl, and quinazolinyl. Exemplary tricyclic heteroaryl groups include, without limitation, phenanthridinyl, dibenzofuranyl, carbazolyl, acridinyl, phenothiazinyl, phenoxazinyl, and phenazinyl.

[0032]“Heteroaralkyl” is a subset of“alkyl” and refers to an alkyl group substituted by a heteroaryl group, wherein the point of attachment is on the alkyl moiety. [0033] The term“unsaturated bond” refers to a double or triple bond.

[0034] The term“unsaturated” or“partially unsaturated” refers to a moiety that includes at least one double or triple bond.

[0035] The term“saturated” refers to a moiety that does not contain a double or triple bond, i.e., the moiety only contains single bonds.

[0036] Affixing the suffix“-ene” to a group indicates the group is a divalent moiety, e.g., alkylene is the divalent moiety of alkyl, alkenylene is the divalent moiety of alkenyl, alkynylene is the divalent moiety of alkynyl, heteroalkylene is the divalent moiety of heteroalkyl, heteroalkenylene is the divalent moiety of heteroalkenyl, heteroalkynylene is the divalent moiety of heteroalkynyl, carbocyclylene is the divalent moiety of carbocyclyl, heterocyclylene is the divalent moiety of heterocyclyl, arylene is the divalent moiety of aryl, and heteroarylene is the divalent moiety of heteroaryl.

[0037] A group is optionally substituted unless expressly provided otherwise. The term “optionally substituted” refers to being substituted or unsubstituted. In certain embodiments, alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl groups are optionally substituted.“Optionally substituted” refers to a group which may be substituted or unsubstituted (e.g.,“substituted” or“unsubstituted” alkyl, “substituted” or“unsubstituted” alkenyl,“substituted” or“unsubstituted” alkynyl, “substituted” or“unsubstituted” heteroalkyl,“substituted” or“unsubstituted” heteroalkenyl, “substituted” or“unsubstituted” heteroalkynyl,“substituted” or“unsubstituted” carbocyclyl, “substituted” or“unsubstituted” heterocyclyl,“substituted” or“unsubstituted” aryl or “substituted” or“unsubstituted” heteroaryl group). In general, the term“substituted” means that at least one hydrogen present on a group is replaced with a permissible substituent, e.g., a substituent which upon substitution results in a stable compound, e.g., a compound which does not spontaneously undergo transformation such as by rearrangement, cyclization, elimination, or other reaction. Unless otherwise indicated, a“substituted” group has a substituent at one or more substitutable positions of the group, and when more than one position in any given structure is substituted, the substituent is either the same or different at each position. The term“substituted” is contemplated to include substitution with all permissible substituents of organic compounds, and includes any of the substituents described herein that results in the formation of a stable compound. The present invention contemplates any and all such combinations in order to arrive at a stable compound. For purposes of this invention, heteroatoms such as nitrogen may have hydrogen substituents and/or any suitable substituent as described herein which satisfy the valencies of the heteroatoms and results in the formation of a stable moiety. The invention is not intended to be limited in any manner by the exemplary substituents described herein.

[0038] Exemplary carbon atom substituents include, but are not limited to, halogen,−CN, −NO₂,−N₃,−SO₂H,−SO₃H,−OH,−OR^aa,−ON(R^bb)₂,−N(R^bb)₂,−N(R^bb) ⁺

3 X⁻,−N(OR^cc)R^bb, −SH,−SR^aa,−SSR^cc,−C(=O)R^aa,−CO₂H,−CHO,−C(OR^cc)₃,−CO₂R^aa,−OC(=O)R^aa, −OCO₂R^aa,−C(=O)N(R^bb)₂,−OC(=O)N(R^bb)₂,−NR^bbC(=O)R^aa,−NR^bbCO₂R^aa,

−NR^bbC(=O)N(R^bb)₂,−C(=NR^bb)R^aa,−C(=NR^bb)OR^aa,−OC(=NR^bb)R^aa,−OC(=NR^bb)OR^aa, −C(=NR^bb)N(R^bb)₂,−OC(=NR^bb)N(R^bb)₂,−NR^bbC(=NR^bb)N(R^bb)₂,−C(=O)NR^bbSO₂R^aa, −NR^bbSO₂R^aa,−SO₂N(R^bb)₂,−SO₂R^aa,−SO₂OR^aa,−OSO₂R^aa,−S(=O)R^aa,−OS(=O)R^aa, −Si(R^aa)₃,−OSi(R^aa)₃−C(=S)N(R^bb)₂,−C(=O)SR^aa,−C(=S)SR^aa,−SC(=S)SR^aa,

−SC(=O)SR^aa,−OC(=O)SR^aa,−SC(=O)OR^aa,−SC(=O)R^aa,−P(=O)(R^aa)₂,−P(=O)(OR^cc)₂, −OP(=O)(R^aa)₂,−OP(=O)(OR^cc)₂,−P(=O)(N(R^bb)₂)₂,−OP(=O)(N(R^bb)₂)₂,−NR^bbP(=O)(R^aa)₂, −NR^bbP(=O)(OR^cc)₂,−NR^bbP(=O)(N(R^bb)₂)₂,−P(R^cc)₂,−P(OR^cc)₂,−P(R^cc) ⁺

3 X⁻,

−P(OR^cc) ⁺

3 X⁻,−P(R^cc)₄,−P(OR^cc)₄,−OP(R^cc)₂,−OP(R^cc) ⁺

3 X⁻,−OP(OR^cc)₂,−OP(OR^cc) ⁺

3 X⁻, −OP(R^cc)₄,−OP(OR^cc)₄,−B(R^aa)₂,−B(OR^cc)₂,−BR^aa(OR^cc), C_1-10 alkyl, C_1-10 perhaloalkyl, C_2-10 alkenyl, C_2-10 alkynyl, heteroC_1-10 alkyl, heteroC_2-10 alkenyl, heteroC_2-10 alkynyl, C_3-10 carbocyclyl, 3-14 membered heterocyclyl, C_6-14 aryl, and 5-14 membered heteroaryl, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R^dd groups; wherein X⁻ is a counterion;

or two geminal hydrogens on a carbon atom are replaced with the group =O, =S, =NN(R^bb)₂, =NNR^bbC(=O)R^aa, =NNR^bbC(=O)OR^aa, =NNR^bbS(=O)₂R^aa, =NR^bb, or =NOR^cc; each instance of R^aa is, independently, selected from C_1-10 alkyl, C_1-10 perhaloalkyl, C_2-10 alkenyl, C_2-10 alkynyl, heteroC_1-10 alkyl, heteroC_2-10 alkenyl, heteroC_2-10 alkynyl, C_3-10 carbocyclyl, 3-14 membered heterocyclyl, C_6-14 aryl, and 5-14 membered heteroaryl, or two R^aa groups are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R^dd groups;

each instance of R^bb is, independently, selected from hydrogen,−OH,−OR^aa, −N(R^cc)₂,−CN,−C(=O)R^aa,−C(=O)N(R^cc)₂,−CO₂R^aa,−SO₂R^aa,−C(=NR^cc)OR^aa, −C(=NR^cc)N(R^cc)₂,−SO₂N(R^cc)₂,−SO₂R^cc,−SO₂OR^cc,−SOR^aa,−C(=S)N(R^cc)₂,−C(=O)SR^cc, −C(=S)SR^cc,−P(=O)(R^aa)₂,−P(=O)(OR^cc)₂,−P(=O)(N(R^cc)₂)₂, C_1-10 alkyl, C_1-10 perhaloalkyl, C_2-10 alkenyl, C_2-10 alkynyl, heteroC_1-10 alkyl, heteroC_2-10 alkenyl, heteroC_{2-1 0}alkynyl, C_3-10 carbocyclyl, 3-14 membered heterocyclyl, C_6-14 aryl, and 5-14 membered heteroaryl, or two R^bb groups are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R^dd groups; wherein X⁻ is a counterion;

each instance of R^cc is, independently, selected from hydrogen, C_1-10 alkyl, C_1-10 perhaloalkyl, C_2-10 alkenyl, C_2-10 alkynyl, heteroC_1-10 alkyl, heteroC_2-10 alkenyl, heteroC_2-10 alkynyl, C_3-10 carbocyclyl, 3-14 membered heterocyclyl, C_6-14 aryl, and 5-14 membered heteroaryl, or two R^cc groups are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R^dd groups;

each instance of R^dd is, independently, selected from halogen,−CN,−NO₂,−N₃, −SO₂H,−SO₃H,−OH,−OR^ee,−ON(R^ff)₂,−N(R^ff)₂,−N(R^ff) ⁺

3 X⁻,−N(OR^ee)R^ff,−SH,−SR^ee, −SSR^ee,−C(=O)R^ee,−CO₂H,−CO₂R^ee,−OC(=O)R^ee,−OCO₂R^ee,−C(=O)N(R^ff)₂,

−OC(=O)N(R^ff)₂,−NR^ffC(=O)R^ee,−NR^ffCO₂R^ee,−NR^ffC(=O)N(R^ff)₂,−C(=NR^ff)OR^ee, −OC(=NR^ff)R^ee,−OC(=NR^ff)OR^ee,−C(=NR^ff)N(R^ff)₂,−OC(=NR^ff)N(R^ff)₂,

−NR^ffC(=NR^ff)N(R^ff)₂,−NR^ffSO₂R^ee,−SO₂N(R^ff)₂,−SO₂R^ee,−SO₂OR^ee,−OSO₂R^ee, −S(=O)R^ee,−Si(R^ee)₃,−OSi(R^ee)₃,−C(=S)N(R^ff)₂,−C(=O)SR^ee,−C(=S)SR^ee,−SC(=S)SR^ee, −P(=O)(OR^ee)₂,−P(=O)(R^ee)₂,−OP(=O)(R^ee)₂,−OP(=O)(OR^ee)₂, C_1-6 alkyl, C_1-6 perhaloalkyl, C_2-6 alkenyl, C_2-6 alkynyl, heteroC_1-6 alkyl, heteroC_2-6 alkenyl, heteroC_2-6 alkynyl, C_3-10 carbocyclyl, 3-10 membered heterocyclyl, C_6-10 aryl, 5-10 membered heteroaryl, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R^gg groups, or two geminal R^dd substituents can be joined to form =O or =S; wherein X⁻ is a counterion;

each instance of R^ee is, independently, selected from C_1-6 alkyl, C_1-6 perhaloalkyl, C_2-6 alkenyl, C_2-6 alkynyl, heteroC_1-6 alkyl, heteroC_2-6 alkenyl, heteroC_2-6 alkynyl, C_3-10 carbocyclyl, C_6-10 aryl, 3-10 membered heterocyclyl, and 3-10 membered heteroaryl, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R^gg groups;

each instance of R^ff is, independently, selected from hydrogen, C_1-6 alkyl, C_1-6 perhaloalkyl, C_2-6 alkenyl, C_2-6 alkynyl, heteroC_1-6 alkyl, heteroC_2-6 alkenyl, heteroC_2-6 alkynyl, C_3-10 carbocyclyl, 3-10 membered heterocyclyl, C_6-10 aryl and 5-10 membered heteroaryl, or two R^ff groups are joined to form a 3-10 membered heterocyclyl or 5-10 membered heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R^gg groups; and

each instance of R^gg is, independently, halogen,−CN,−NO₂,−N₃,−SO₂H,−SO₃H, −OH,−OC ⁺

1_-6 alkyl,−ON(C_1-6 alkyl)₂,−N(C_1-6 alkyl)₂,−N(C_1-6 alkyl)₃ X⁻,−NH(C_1-6 alkyl) ⁺

2 X⁻,−NH₂(C_1-6 alkyl)⁺X⁻,−NH ⁺

3 X⁻,−N(OC_1-6 alkyl)(C_1-6 alkyl),−N(OH)(C_1-6 alkyl), −NH(OH),−SH,−SC_1-6 alkyl,−SS(C_1-6 alkyl),−C(=O)(C_1-6 alkyl),−CO₂H,−CO₂(C_1-6 alkyl),−OC(=O)(C_1-6 alkyl),−OCO₂(C_1-6 alkyl),−C(=O)NH₂,−C(=O)N(C_1-6 alkyl)₂, −OC(=O)NH(C_1-6 alkyl),−NHC(=O)(C_1-6 alkyl),−N(C_1-6 alkyl)C(=O)( C_1-6 alkyl), −NHCO₂(C_1-6 alkyl),−NHC(=O)N(C_1-6 alkyl)₂,−NHC(=O)NH(C_1-6 alkyl),−NHC(=O)NH₂, −C(=NH)O(C_1-6 alkyl),−OC(=NH)(C_1-6 alkyl),−OC(=NH)OC_1-6 alkyl,−C(=NH)N(C_1-6 alkyl)₂,−C(=NH)NH(C_1-6 alkyl),−C(=NH)NH₂,−OC(=NH)N(C_1-6 alkyl)₂,

−OC(=NH)NH(C_1-6 alkyl),−OC(=NH)NH₂,−NHC(=NH)N(C_1-6 alkyl)₂,−NHC(=NH)NH₂, −NHSO₂(C_1-6 alkyl),−SO₂N(C_1-6 alkyl)₂,−SO₂NH(C_1-6 alkyl),−SO₂NH₂,−SO₂(C_1-6 alkyl), −SO₂O(C_1-6 alkyl),−OSO₂(C_1-6 alkyl),−SO(C_1-6 alkyl),−Si(C_1-6 alkyl)₃,−OSi(C_1-6 alkyl)₃ −C(=S)N(C_1-6 alkyl)₂, C(=S)NH(C_1-6 alkyl), C(=S)NH₂,−C(=O)S(C_1-6 alkyl),−C(=S)SC_1-6 alkyl,−SC(=S)SC_1-6 alkyl,−P(=O)(OC_1-6 alkyl)₂,−P(=O)(C_1-6 alkyl)₂,−OP(=O)(C_1-6 alkyl)₂, −OP(=O)(OC_1-6 alkyl)₂, C_1-6 alkyl, C_1-6 perhaloalkyl, C_2-6 alkenyl, C_2-6 alkynyl, heteroC_1-6 alkyl, heteroC_2-6 alkenyl, heteroC_2-6 alkynyl, C_3-10 carbocyclyl, C_6-10 aryl, 3-10 membered heterocyclyl, 5-10 membered heteroaryl; or two geminal R^gg substituents can be joined to form =O or =S; wherein X⁻ is a counterion.

[0039] In certain embodiments, carbon atom substituents include: halogen,−CN,−NO₂,−N₃, −SO₂H,−SO₃H,−OH,−OC_1-6 alkyl,−ON(C_1-6 alkyl)₂,−N(C_1-6 alkyl)₂,−N(C_1-6 alkyl) ⁺

3 X⁻, −NH(C_1-6 alkyl) ⁺

2 X⁻,−NH₂(C_1-6 alkyl)⁺X⁻,−NH ⁺

3 X⁻,−N(OC_1-6 alkyl)(C_1-6 alkyl), −N(OH)(C_1-6 alkyl),−NH(OH),−SH,−SC_1-6 alkyl,−SS(C_1-6 alkyl),−C(=O)(C_1-6 alkyl), −CO₂H,−CO₂(C_1-6 alkyl),−OC(=O)(C_1-6 alkyl),−OCO₂(C_1-6 alkyl),−C(=O)NH₂, −C(=O)N(C_1-6 alkyl)₂,−OC(=O)NH(C_1-6 alkyl),−NHC(=O)(C_1-6 alkyl),−N(C_1-6

alkyl)C(=O)( C_1-6 alkyl),−NHCO₂(C_1-6 alkyl),−NHC(=O)N(C_1-6 alkyl)₂,−NHC(=O)NH(C_1-6 alkyl),−NHC(=O)NH₂,−C(=NH)O(C_1-6 alkyl),−OC(=NH)(C_1-6 alkyl),−OC(=NH)OC_1-6 alkyl,−C(=NH)N(C_1-6 alkyl)₂,−C(=NH)NH(C_1-6 alkyl),−C(=NH)NH₂,−OC(=NH)N(C_1-6 alkyl)₂,−OC(=NH)NH(C_1-6 alkyl),−OC(=NH)NH₂,−NHC(=NH)N(C_1-6 alkyl)₂,

−NHC(=NH)NH₂,−NHSO₂(C_1-6 alkyl),−SO₂N(C_1-6 alkyl)₂,−SO₂NH(C_1-6 alkyl),−SO₂NH₂, −SO₂(C_1-6 alkyl),−SO₂O(C_1-6 alkyl),−OSO₂(C_1-6 alkyl),−SO(C_1-6 alkyl),−Si(C_1-6 alkyl)₃, −OSi(C_1-6 alkyl)₃−C(=S)N(C_1-6 alkyl)₂, C(=S)NH(C_1-6 alkyl), C(=S)NH₂,−C(=O)S(C_1-6 alkyl),−C(=S)SC_1-6 alkyl,−SC(=S)SC_1-6 alkyl,−P(=O)(OC_1-6 alkyl)₂,−P(=O)(C_1-6 alkyl)₂,

alkyl)₂,−OP(=O)(OC_1-6 alkyl)₂, C_1-6 alkyl, C_1-6 perhaloalkyl, C_2-6 alkenyl, C_2-6 alkynyl, heteroC_1-6 alkyl, heteroC_2-6 alkenyl, heteroC_2-6 alkynyl, C_3-10 carbocyclyl, C_6-10 aryl, 3-10 membered heterocyclyl, 5-10 membered heteroaryl; or two geminal R^gg substituents can be joined to form =O or =S; wherein X⁻ is a counterion.

[0040] The term“halo” or“halogen” refers to fluorine (fluoro,−F), chlorine (chloro,−Cl), bromine (bromo,−Br), or iodine (iodo,−I).

[0041] The term“hydroxyl” or“hydroxy” refers to the group−OH. The term“substituted hydroxyl” or“substituted hydroxyl,” by extension, refers to a hydroxyl group wherein the oxygen atom directly attached to the parent molecule is substituted with a group other than hydrogen, and includes groups selected from−OR^aa,−ON(R^bb)₂,−OC(=O)SR^aa,

−OC(=O)R^aa,−OCO₂R^aa,−OC(=O)N(R^bb)₂,−OC(=NR^bb)R^aa,−OC(=NR^bb)OR^aa,

−OC(=NR^bb)N(R^bb)₂,−OS(=O)R^aa,−OSO₂R^aa,−OSi(R^aa)₃,−OP(R^cc)₂,−OP(R^cc) ⁺

3 X⁻, −OP(OR^cc)₂,−OP(OR^cc) ⁺

3 X⁻,−OP(=O)(R^aa)₂,−OP(=O)(OR^cc)₂, and−OP(=O)(N(R^bb)₂)₂, wherein X⁻, R^aa, R^bb, and R^cc are as defined herein.

[0042] The term“amino” refers to the group−NH₂. The term“substituted amino,” by extension, refers to a monosubstituted amino, a disubstituted amino, or a trisubstituted amino. In certain embodiments, the“substituted amino” is a monosubstituted amino or a

disubstituted amino group.

[0043] The term“monosubstituted amino” refers to an amino group wherein the nitrogen atom directly attached to the parent molecule is substituted with one hydrogen and one group other than hydrogen, and includes groups selected from−NH(R^bb),−NHC(=O)R^aa, −NHCO₂R^aa,−NHC(=O)N(R^bb)₂,−NHC(=NR^bb)N(R^bb)₂,−NHSO₂R^aa,−NHP(=O)(OR^cc)₂, and−NHP(=O)(N(R^bb)₂)₂, wherein R^aa, R^bb and R^cc are as defined herein, and wherein R^bb of the group−NH(R^bb) is not hydrogen.

[0044] The term“disubstituted amino” refers to an amino group wherein the nitrogen atom directly attached to the parent molecule is substituted with two groups other than hydrogen, and includes groups selected from−N(R^bb)₂,−NR^bbC(=O)R^aa,−NR^bbCO₂R^aa,

−NR^bbC(=O)N(R^bb)₂,−NR^bbC(=NR^bb)N(R^bb)₂,−NR^bbSO₂R^aa,−NR^bbP(=O)(OR^cc)₂, and −NR^bbP(=O)(N(R^bb)₂)₂, wherein R^aa, R^bb, and R^cc are as defined herein, with the proviso that the nitrogen atom directly attached to the parent molecule is not substituted with hydrogen. [0045] The term“trisubstituted amino” refers to an amino group wherein the nitrogen atom directly attached to the parent molecule is substituted with three groups, and includes groups selected from−N(R^bb)₃ and−N(R^bb) ⁺

3 X⁻, wherein R^bb and X⁻ are as defined herein.

[0046] The term“sulfonyl” refers to a group selected from–SO₂N(R^bb)₂,–SO₂R^aa, and– SO₂OR^aa, wherein R^aa and R^bb are as defined herein.

[0047] The term“sulfinyl” refers to the group–S(=O)R^aa, wherein R^aa is as defined herein.

[0048] The term“acyl” refers to a group having the general formula−C(=O)R^X1,

−C(=O)OR^X1,−C(=O)−O−C(=O)R^X1,−C(=O)SR^X1,−C(=O)N(R^X1)₂,−C(=S)R^X1, −C(=S)N(R^X1)₂,−C(=S)O(R^X1),−C(=S)S(R^X1),−C(=NR^X1)R^X1,−C(=NR^X1)OR^X1, −C(=NR^X1)SR^X1, and−C(=NR^X1)N(R^X1)₂, wherein R^X1 is hydrogen; halogen; substituted or unsubstituted hydroxyl; substituted or unsubstituted thiol; substituted or unsubstituted amino; substituted or unsubstituted acyl, cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic; cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; cyclic or acyclic, substituted or unsubstituted, branched or unbranched alkyl; cyclic or acyclic, substituted or unsubstituted, branched or unbranched alkenyl; substituted or unsubstituted alkynyl; substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, aliphaticoxy, heteroaliphaticoxy, alkyloxy, heteroalkyloxy, aryloxy,

heteroaryloxy, aliphaticthioxy, heteroaliphaticthioxy, alkylthioxy, heteroalkylthioxy, arylthioxy, heteroarylthioxy, mono- or di- aliphaticamino, mono- or di- heteroaliphaticamino, mono- or di- alkylamino, mono- or di- heteroalkylamino, mono- or di-arylamino, or mono- or di-heteroarylamino; or two R^X1 groups taken together form a 5- to 6-membered heterocyclic ring. Exemplary acyl groups include aldehydes (−CHO), carboxylic acids (−CO₂H), ketones, acyl halides, esters, amides, imines, carbonates, carbamates, and ureas. Acyl substituents include, but are not limited to, any of the substituents described herein, that result in the formation of a stable moiety (e.g., aliphatic, alkyl, alkenyl, alkynyl, heteroaliphatic, heterocyclic, aryl, heteroaryl, acyl, oxo, imino, thiooxo, cyano, isocyano, amino, azido, nitro, hydroxyl, thiol, halo, aliphaticamino, heteroaliphaticamino, alkylamino, heteroalkylamino, arylamino, heteroarylamino, alkylaryl, arylalkyl, aliphaticoxy, heteroaliphaticoxy, alkyloxy, heteroalkyloxy, aryloxy, heteroaryloxy, aliphaticthioxy, heteroaliphaticthioxy, alkylthioxy, heteroalkylthioxy, arylthioxy, heteroarylthioxy, acyloxy, and the like, each of which may or may not be further substituted).

[0049] The term“carbonyl” refers a group wherein the carbon directly attached to the parent molecule is sp² hybridized, and is substituted with an oxygen, nitrogen or sulfur atom, e.g., a group selected from ketones (e.g.,–C(=O)R^aa), carboxylic acids (e.g.,–CO₂H), aldehydes (– CHO), esters (e.g.,–CO₂R^aa,–C(=O)SR^aa,–C(=S)SR^aa), amides (e.g.,–C(=O)N(R^bb)₂,– C(=O)NR^bbSO₂R^aa,−C(=S)N(R^bb)₂), and imines (e.g.,–C(=NR^bb)R^aa,–C(=NR^bb)OR^aa),– C(=NR^bb)N(R^bb)₂), wherein R^aa and R^bb are as defined herein.

[0050] The term“silyl” refers to the group–Si(R^aa)₃, wherein R^aa is as defined herein.

[0051] The term“oxo” refers to the group =O, and the term“thiooxo” refers to the group =S.

[0052] Nitrogen atoms can be substituted or unsubstituted as valency permits, and include primary, secondary, tertiary, and quaternary nitrogen atoms. Exemplary nitrogen atom substituents include, but are not limited to, hydrogen,−OH,−OR^aa,−N(R^cc)₂,−CN, −C(=O)R^aa,−C(=O)N(R^cc)₂,−CO₂R^aa,−SO₂R^aa,−C(=NR^bb)R^aa,−C(=NR^cc)OR^aa,

−C(=NR^cc)N(R^cc)₂,−SO₂N(R^cc)₂,−SO₂R^cc,−SO₂OR^cc,−SOR^aa,−C(=S)N(R^cc)₂,−C(=O)SR^cc, −C(=S)SR^cc,−P(=O)(OR^cc)₂,−P(=O)(R^aa)₂,−P(=O)(N(R^cc)₂)₂, C_1-10 alkyl, C_1-10 perhaloalkyl, C_2-10 alkenyl, C_2-10 alkynyl, heteroC_1-10alkyl, heteroC_2-10alkenyl, heteroC_2-10alkynyl, C_3-10 carbocyclyl, 3-14 membered heterocyclyl, C_6-14 aryl, and 5-14 membered heteroaryl, or two R^cc groups attached to an N atom are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R^dd groups, and wherein R^aa, R^bb, R^cc and R^dd are as defined above.

[0053] In certain embodiments, the substituent present on the nitrogen atom is an nitrogen protecting group (also referred to herein as an“amino protecting group”). Nitrogen protecting groups include, but are not limited to,−OH,−OR^aa,−N(R^cc)₂,−C(=O)R^aa,−C(=O)N(R^cc)₂, −CO₂R^aa,−SO₂R^aa,−C(=NR^cc)R^aa,−C(=NR^cc)OR^aa,−C(=NR^cc)N(R^cc)₂,−SO₂N(R^cc)₂, −SO₂R^cc,−SO₂OR^cc,−SOR^aa,−C(=S)N(R^cc)₂,−C(=O)SR^cc,−C(=S)SR^cc, C_1-10 alkyl (e.g., aralkyl, heteroaralkyl), C_2-10 alkenyl, C_2-10 alkynyl, heteroC_1-10 alkyl, heteroC_2-10 alkenyl, heteroC_2-10 alkynyl, C_3-10 carbocyclyl, 3-14 membered heterocyclyl, C_6-14 aryl, and 5-14 membered heteroaryl groups, wherein each alkyl, alkenyl, alkynyl, heteroalkyl,

heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aralkyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R^dd groups, and wherein R^aa, R^bb, R^cc, and R^dd are as defined herein. Nitrogen protecting groups are well known in the art and include those described in detail in Protecting Groups in Organic Synthesis, T. W. Greene and P. G. M. Wuts, 3^rd edition, John Wiley & Sons, 1999, incorporated herein by reference.

[0054] For example, nitrogen protecting groups such as amide groups (e.g.,−C(=O)R^aa) include, but are not limited to, formamide, acetamide, chloroacetamide, trichloroacetamide, trifluoroacetamide, phenylacetamide, 3-phenylpropanamide, picolinamide, 3- pyridylcarboxamide, N-benzoylphenylalanyl derivative, benzamide, p-phenylbenzamide, o- nitophenylacetamide, o-nitrophenoxyacetamide, acetoacetamide, (N’- dithiobenzyloxyacylamino)acetamide, 3-(p-hydroxyphenyl)propanamide, 3-(o- nitrophenyl)propanamide, 2-methyl-2-(o-nitrophenoxy)propanamide, 2-methyl-2-(o- phenylazophenoxy)propanamide, 4-chlorobutanamide, 3-methyl-3-nitrobutanamide, o- nitrocinnamide, N-acetylmethionine derivative, o-nitrobenzamide and o- (benzoyloxymethyl)benzamide.

[0055] Nitrogen protecting groups such as carbamate groups (e.g.,−C(=O)OR^aa) include, but are not limited to, methyl carbamate, ethyl carbamate, 9-fluorenylmethyl carbamate (Fmoc), 9-(2-sulfo)fluorenylmethyl carbamate, 9-(2,7-dibromo)fluoroenylmethyl carbamate, 2,7-di-t- butyl-[9-(10,10-dioxo-10,10,10,10-tetrahydrothioxanthyl)]methyl carbamate (DBD-Tmoc), 4-methoxyphenacyl carbamate (Phenoc), 2,2,2-trichloroethyl carbamate (Troc), 2- trimethylsilylethyl carbamate (Teoc), 2-phenylethyl carbamate (hZ), 1-(1-adamantyl)-1- methylethyl carbamate (Adpoc), 1,1-dimethyl-2-haloethyl carbamate, 1,1-dimethyl-2,2- dibromoethyl carbamate (DB-t-BOC), 1,1-dimethyl-2,2,2-trichloroethyl carbamate

(TCBOC), 1-methyl-1-(4-biphenylyl)ethyl carbamate (Bpoc), 1-(3,5-di-t-butylphenyl)-1- methylethyl carbamate (t-Bumeoc), 2-(2′- and 4′-pyridyl)ethyl carbamate (Pyoc), 2-(N,N- dicyclohexylcarboxamido)ethyl carbamate, t-butyl carbamate (BOC or Boc), 1-adamantyl carbamate (Adoc), vinyl carbamate (Voc), allyl carbamate (Alloc), 1-isopropylallyl carbamate (Ipaoc), cinnamyl carbamate (Coc), 4-nitrocinnamyl carbamate (Noc), 8-quinolyl carbamate, N-hydroxypiperidinyl carbamate, alkyldithio carbamate, benzyl carbamate (Cbz), p-methoxybenzyl carbamate (Moz), p-nitobenzyl carbamate, p-bromobenzyl carbamate, p- chlorobenzyl carbamate, 2,4-dichlorobenzyl carbamate, 4-methylsulfinylbenzyl carbamate (Msz), 9-anthrylmethyl carbamate, diphenylmethyl carbamate, 2-methylthioethyl carbamate, 2-methylsulfonylethyl carbamate, 2-(p-toluenesulfonyl)ethyl carbamate, [2-(1,3- dithianyl)]methyl carbamate (Dmoc), 4-methylthiophenyl carbamate (Mtpc), 2,4- dimethylthiophenyl carbamate (Bmpc), 2-phosphonioethyl carbamate (Peoc), 2- triphenylphosphonioisopropyl carbamate (Ppoc), 1,1-dimethyl-2-cyanoethyl carbamate, m- chloro-p-acyloxybenzyl carbamate, p-(dihydroxyboryl)benzyl carbamate, 5- benzisoxazolylmethyl carbamate, 2-(trifluoromethyl)-6-chromonylmethyl carbamate (Tcroc), m-nitrophenyl carbamate, 3,5-dimethoxybenzyl carbamate, o-nitrobenzyl carbamate, 3,4- dimethoxy-6-nitrobenzyl carbamate, phenyl(o-nitrophenyl)methyl carbamate, t-amyl carbamate, S-benzyl thiocarbamate, p-cyanobenzyl carbamate, cyclobutyl carbamate, cyclohexyl carbamate, cyclopentyl carbamate, cyclopropylmethyl carbamate, p- decyloxybenzyl carbamate, 2,2-dimethoxyacylvinyl carbamate, o-(N,N- dimethylcarboxamido)benzyl carbamate, 1,1-dimethyl-3-(N,N-dimethylcarboxamido)propyl carbamate, 1,1-dimethylpropynyl carbamate, di(2-pyridyl)methyl carbamate, 2-furanylmethyl carbamate, 2-iodoethyl carbamate, isoborynl carbamate, isobutyl carbamate, isonicotinyl carbamate, p-(p’-methoxyphenylazo)benzyl carbamate, 1-methylcyclobutyl carbamate, 1- methylcyclohexyl carbamate, 1-methyl-1-cyclopropylmethyl carbamate, 1-methyl-1-(3,5- dimethoxyphenyl)ethyl carbamate, 1-methyl-1-(p-phenylazophenyl)ethyl carbamate, 1- methyl-1-phenylethyl carbamate, 1-methyl-1-(4-pyridyl)ethyl carbamate, phenyl carbamate, p-(phenylazo)benzyl carbamate, 2,4,6-tri-t-butylphenyl carbamate, 4- (trimethylammonium)benzyl carbamate, and 2,4,6-trimethylbenzyl carbamate.

[0056] Nitrogen protecting groups such as sulfonamide groups (e.g.,−S(=O)₂R^aa) include, but are not limited to, p-toluenesulfonamide (Ts), benzenesulfonamide, 2,3,6-trimethyl-4- methoxybenzenesulfonamide (Mtr), 2,4,6-trimethoxybenzenesulfonamide (Mtb), 2,6- dimethyl-4-methoxybenzenesulfonamide (Pme), 2,3,5,6-tetramethyl-4- methoxybenzenesulfonamide (Mte), 4-methoxybenzenesulfonamide (Mbs), 2,4,6- trimethylbenzenesulfonamide (Mts), 2,6-dimethoxy-4-methylbenzenesulfonamide (iMds), 2,2,5,7,8-pentamethylchroman-6-sulfonamide (Pmc), methanesulfonamide (Ms), β- trimethylsilylethanesulfonamide (SES), 9-anthracenesulfonamide, 4-(4′,8′- dimethoxynaphthylmethyl)benzenesulfonamide (DNMBS), benzylsulfonamide,

trifluoromethylsulfonamide, and phenacylsulfonamide.

[0057] Other nitrogen protecting groups include, but are not limited to, phenothiazinyl-(10)- acyl derivative, N′-p-toluenesulfonylaminoacyl derivative, N′-phenylaminothioacyl derivative, N-benzoylphenylalanyl derivative, N-acetylmethionine derivative, 4,5-diphenyl-3- oxazolin-2-one, N-phthalimide, N-dithiasuccinimide (Dts), N-2,3-diphenylmaleimide, N-2,5- dimethylpyrrole, N-1,1,4,4-tetramethyldisilylazacyclopentane adduct (STABASE), 5- substituted 1,3-dimethyl-1,3,5-triazacyclohexan-2-one, 5-substituted 1,3-dibenzyl-1,3,5- triazacyclohexan-2-one, 1-substituted 3,5-dinitro-4-pyridone, N-methylamine, N-allylamine, N-[2-(trimethylsilyl)ethoxy]methylamine (SEM), N-3-acetoxypropylamine, N-(1-isopropyl- 4-nitro-2-oxo-3-pyroolin-3-yl)amine, quaternary ammonium salts, N-benzylamine, N-di(4- methoxyphenyl)methylamine, N-5-dibenzosuberylamine, N-triphenylmethylamine (Tr), N- [(4-methoxyphenyl)diphenylmethyl]amine (MMTr), N-9-phenylfluorenylamine (PhF), N- 2,7-dichloro-9-fluorenylmethyleneamine, N-ferrocenylmethylamino (Fcm), N-2- picolylamino N’-oxide, N-1,1-dimethylthiomethyleneamine, N-benzylideneamine, N-p- methoxybenzylideneamine, N-diphenylmethyleneamine, N-[(2- pyridyl)mesityl]methyleneamine, N-(N’,N’-dimethylaminomethylene)amine, N,N’- isopropylidenediamine, N-p-nitrobenzylideneamine, N-salicylideneamine, N-5- chlorosalicylideneamine, N-(5-chloro-2-hydroxyphenyl)phenylmethyleneamine, N- cyclohexylideneamine, N-(5,5-dimethyl-3-oxo-1-cyclohexenyl)amine, N-borane derivative, N-diphenylborinic acid derivative, N-[phenyl(pentaacylchromium- or tungsten)acyl]amine, N-copper chelate, N-zinc chelate, N-nitroamine, N-nitrosoamine, amine N-oxide, diphenylphosphinamide (Dpp), dimethylthiophosphinamide (Mpt),

diphenylthiophosphinamide (Ppt), dialkyl phosphoramidates, dibenzyl phosphoramidate, diphenyl phosphoramidate, benzenesulfenamide, o-nitrobenzenesulfenamide (Nps), 2,4- dinitrobenzenesulfenamide, pentachlorobenzenesulfenamide, 2-nitro-4- methoxybenzenesulfenamide, triphenylmethylsulfenamide, and 3-nitropyridinesulfenamide (Npys). In certain embodiments, a nitrogen protecting group is benzyl (Bn), tert- butyloxycarbonyl (BOC), carbobenzyloxy (Cbz), 9-flurenylmethyloxycarbonyl (Fmoc), trifluoroacetyl, triphenylmethyl, acetyl (Ac), benzoyl (Bz), p-methoxybenzyl (PMB), 3,4- dimethoxybenzyl (DMPM), p-methoxyphenyl (PMP), 2,2,2-trichloroethyloxycarbonyl (Troc), triphenylmethyl (Tr), tosyl (Ts), brosyl (Bs), nosyl (Ns), mesyl (Ms), triflyl (Tf), or dansyl (Ds).

[0058] In certain embodiments, the substituent present on an oxygen atom is an oxygen protecting group (also referred to herein as an“hydroxyl protecting group”). Oxygen protecting groups include, but are not limited to,−R^aa,−N(R^bb)₂,−C(=O)SR^aa,−C(=O)R^aa, −CO₂R^aa,−C(=O)N(R^bb)₂,−C(=NR^bb)R^aa,−C(=NR^bb)OR^aa,−C(=NR^bb)N(R^bb)₂,−S(=O)R^aa, −SO₂R^aa,−Si(R^aa)₃,−P(R^cc)₂,−P(R^cc) ⁺

3 X⁻,−P(OR^cc)₂,−P(OR^cc) ⁺

3 X⁻,−P(=O)(R^aa)₂, −P(=O)(OR^cc)₂, and−P(=O)(N(R^bb) ₂)₂, wherein X⁻, R^aa, R^bb, and R^cc are as defined herein. Oxygen protecting groups are well known in the art and include those described in detail in Protecting Groups in Organic Synthesis, T. W. Greene and P. G. M. Wuts, 3^rd edition, John Wiley & Sons, 1999, incorporated herein by reference.

[0059] Exemplary oxygen protecting groups include, but are not limited to, methyl, methoxylmethyl (MOM), methylthiomethyl (MTM), t-butylthiomethyl,

(phenyldimethylsilyl)methoxymethyl (SMOM), benzyloxymethyl (BOM), p- methoxybenzyloxymethyl (PMBM), (4-methoxyphenoxy)methyl (p-AOM), guaiacolmethyl (GUM), t-butoxymethyl, 4-pentenyloxymethyl (POM), siloxymethyl, 2- methoxyethoxymethyl (MEM), 2,2,2-trichloroethoxymethyl, bis(2-chloroethoxy)methyl, 2- (trimethylsilyl)ethoxymethyl (SEMOR), tetrahydropyranyl (THP), 3- bromotetrahydropyranyl, tetrahydrothiopyranyl, 1-methoxycyclohexyl, 4- methoxytetrahydropyranyl (MTHP), 4-methoxytetrahydrothiopyranyl, 4- methoxytetrahydrothiopyranyl S,S-dioxide, 1-[(2-chloro-4-methyl)phenyl]-4- methoxypiperidin-4-yl (CTMP), 1,4-dioxan-2-yl, tetrahydrofuranyl, tetrahydrothiofuranyl, 2,3,3a,4,5,6,7,7a-octahydro-7,8,8-trimethyl-4,7-methanobenzofuran-2-yl, 1-ethoxyethyl, 1- (2-chloroethoxy)ethyl, 1-methyl-1-methoxyethyl, 1-methyl-1-benzyloxyethyl, 1-methyl-1- benzyloxy-2-fluoroethyl, 2,2,2-trichloroethyl, 2-trimethylsilylethyl, 2-(phenylselenyl)ethyl, t- butyl, allyl, p-chlorophenyl, p-methoxyphenyl, 2,4-dinitrophenyl, benzyl (Bn), p- methoxybenzyl, 3,4-dimethoxybenzyl, o-nitrobenzyl, p-nitrobenzyl, p-halobenzyl, 2,6- dichlorobenzyl, p-cyanobenzyl, p-phenylbenzyl, 2-picolyl, 4-picolyl, 3-methyl-2-picolyl N- oxido, diphenylmethyl, p,p’-dinitrobenzhydryl, 5-dibenzosuberyl, triphenylmethyl, α- naphthyldiphenylmethyl, p-methoxyphenyldiphenylmethyl, di(p- methoxyphenyl)phenylmethyl, tri(p-methoxyphenyl)methyl, 4-(4’- bromophenacyloxyphenyl)diphenylmethyl, 4,4′,4″-tris(4,5- dichlorophthalimidophenyl)methyl, 4,4′,4″-tris(levulinoyloxyphenyl)methyl, 4,4′,4″- tris(benzoyloxyphenyl)methyl, 3-(imidazol-1-yl)bis(4′,4″-dimethoxyphenyl)methyl, 1,1- bis(4-methoxyphenyl)-1′-pyrenylmethyl, 9-anthryl, 9-(9-phenyl)xanthenyl, 9-(9-phenyl-10- oxo)anthryl, 1,3-benzodithiolan-2-yl, benzisothiazolyl S,S-dioxido, trimethylsilyl (TMS), triethylsilyl (TES), triisopropylsilyl (TIPS), dimethylisopropylsilyl (IPDMS),

diethylisopropylsilyl (DEIPS), dimethylthexylsilyl, t-butyldimethylsilyl (TBDMS), t- butyldiphenylsilyl (TBDPS), tribenzylsilyl, tri-p-xylylsilyl, triphenylsilyl,

diphenylmethylsilyl (DPMS), t-butylmethoxyphenylsilyl (TBMPS), formate, benzoylformate, acetate, chloroacetate, dichloroacetate, trichloroacetate, trifluoroacetate, methoxyacetate, triphenylmethoxyacetate, phenoxyacetate, p-chlorophenoxyacetate, 3-phenylpropionate, 4- oxopentanoate (levulinate), 4,4-(ethylenedithio)pentanoate (levulinoyldithioacetal), pivaloate, adamantoate, crotonate, 4-methoxycrotonate, benzoate, p-phenylbenzoate, 2,4,6- trimethylbenzoate (mesitoate), methyl carbonate, 9-fluorenylmethyl carbonate (Fmoc), ethyl carbonate, 2,2,2-trichloroethyl carbonate (Troc), 2-(trimethylsilyl)ethyl carbonate (TMSEC), 2-(phenylsulfonyl) ethyl carbonate (Psec), 2-(triphenylphosphonio) ethyl carbonate (Peoc), isobutyl carbonate, vinyl carbonate, allyl carbonate, t-butyl carbonate (BOC or Boc), p- nitrophenyl carbonate, benzyl carbonate, p-methoxybenzyl carbonate, 3,4-dimethoxybenzyl carbonate, o-nitrobenzyl carbonate, p-nitrobenzyl carbonate, S-benzyl thiocarbonate, 4- ethoxy-1-napththyl carbonate, methyl dithiocarbonate, 2-iodobenzoate, 4-azidobutyrate, 4- nitro-4-methylpentanoate, o-(dibromomethyl)benzoate, 2-formylbenzenesulfonate, 2- (methylthiomethoxy)ethyl, 4-(methylthiomethoxy)butyrate, 2- (methylthiomethoxymethyl)benzoate, 2,6-dichloro-4-methylphenoxyacetate, 2,6-dichloro-4- (1,1,3,3-tetramethylbutyl)phenoxyacetate, 2,4-bis(1,1-dimethylpropyl)phenoxyacetate, chlorodiphenylacetate, isobutyrate, monosuccinoate, (E)-2-methyl-2-butenoate, o- (methoxyacyl)benzoate, α-naphthoate, nitrate, alkyl N,N,N’,N’- tetramethylphosphorodiamidate, alkyl N-phenylcarbamate, borate, dimethylphosphinothioyl, alkyl 2,4-dinitrophenylsulfenate, sulfate, methanesulfonate (mesylate), benzylsulfonate, and tosylate (Ts). In certain embodiments, an oxygen protecting group is silyl. In certain embodiments, an oxygen protecting group is t-butyldiphenylsilyl (TBDPS), t- butyldimethylsilyl (TBDMS), triisoproylsilyl (TIPS), triphenylsilyl (TPS), triethylsilyl (TES), trimethylsilyl (TMS), triisopropylsiloxymethyl (TOM), acetyl (Ac), benzoyl (Bz), allyl carbonate, 2,2,2-trichloroethyl carbonate (Troc), 2-trimethylsilylethyl carbonate,

methoxymethyl (MOM), 1-ethoxyethyl (EE), 2-methyoxy-2-propyl (MOP), 2,2,2- trichloroethoxyethyl, 2-methoxyethoxymethyl (MEM), 2-trimethylsilylethoxymethyl (SEM), methylthiomethyl (MTM), tetrahydropyranyl (THP), tetrahydrofuranyl (THF), p- methoxyphenyl (PMP), triphenylmethyl (Tr), methoxytrityl (MMT), dimethoxytrityl (DMT), allyl, p-methoxybenzyl (PMB), t-butyl, benzyl (Bn), allyl, or pivaloyl (Piv).

[0060] In certain embodiments, the substituent present on a sulfur atom is a sulfur protecting group (also referred to as a“thiol protecting group”). Sulfur protecting groups include, but are not limited to,−R^aa,−N(R^bb)₂,−C(=O)SR^aa,−C(=O)R^aa,−CO₂R^aa,−C(=O)N(R^bb)₂, −C(=NR^bb)R^aa,−C(=NR^bb)OR^aa,−C(=NR^bb)N(R^bb)₂,−S(=O)R^aa,−SO₂R^aa,−Si(R^aa)₃, −P(R^cc)₂,−P(R^cc) ⁺

3 X⁻,−P(OR^cc)₂,−P(OR^cc) ⁺

3 X⁻,−P(=O)(R^aa)₂,−P(=O)(OR^cc)₂, and −P(=O)(N(R^bb) ₂)₂, wherein R^aa, R^bb, and R^cc are as defined herein. Sulfur protecting groups are well known in the art and include those described in detail in Protecting Groups in Organic Synthesis, T. W. Greene and P. G. M. Wuts, 3^rd edition, John Wiley & Sons, 1999, incorporated herein by reference. In certain embodiments, a sulfur protecting group is acetamidomethyl, t-Bu, 3-nitro-2-pyridine sulfenyl, 2-pyridine-sulfenyl, or triphenylmethyl.

[0061] A“counterion” or“anionic counterion” is a negatively charged group associated with a positively charged group in order to maintain electronic neutrality. An anionic counterion may be monovalent (i.e., including one formal negative charge). An anionic counterion may also be multivalent (i.e., including more than one formal negative charge), such as divalent or trivalent. Exemplary counterions include halide ions (e.g., F^–, Cl^–, Br^–, I^–), NO^–

3 , ClO^–

4 , OH^–, H ^–

2PO^–

4 , HCO⁻

3 _, HSO₄ , sulfonate ions (e.g., methansulfonate, trifluoromethanesulfonate, p– toluenesulfonate, benzenesulfonate, 10–camphor sulfonate, naphthalene–2–sulfonate, naphthalene–1–sulfonic acid–5–sulfonate, ethan–1–sulfonic acid–2–sulfonate, and the like), carboxylate ions (e.g., acetate, propanoate, benzoate, glycerate, lactate, tartrate, glycolate, gluconate, and the like), BF⁻

4 , PF^–

4 , PF^–

6 , AsF^–

6 , SbF^–

6 , B[3,5-(CF₃)₂C₆H₃]₄]^–, B(C ⁻

6F₅)₄ , BPh^–

4 , Al(OC(CF₃)₃)^–

4 , and carborane anions (e.g., CB₁₁H ^–

1₂ or (HCB₁₁Me₅Br₆)^–).

Exemplary counterions which may be multivalent include CO ^{2− 3−}

3 , HPO ²⁻

4 , PO_{4 ,} B₄O ²⁻

7 , SO ^{2− −}

4 , S₂O ²

3 , carboxylate anions (e.g., tartrate, citrate, fumarate, maleate, malate, malonate, gluconate, succinate, glutarate, adipate, pimelate, suberate, azelate, sebacate, salicylate, phthalates, aspartate, glutamate, and the like), and carboranes.

[0062] As used herein, use of the phrase“at least one instance” refers to 1, 2, 3, 4, or more instances, but also encompasses a range, e.g., for example, from 1 to 4, from 1 to 3, from 1 to 2, from 2 to 4, from 2 to 3, or from 3 to 4 instances, inclusive.

[0063] The term“carbohydrate” or“saccharide” refers to an aldehydic or ketonic derivative of polyhydric alcohols. Carbohydrates include compounds with relatively small molecules (e.g., sugars) as well as macromolecular or polymeric substances (e.g., starch, glycogen, and cellulose polysaccharides). The term“sugar” refers to monosaccharides, disaccharides, or polysaccharides. Monosaccharides are the simplest carbohydrates in that they cannot be hydrolyzed to smaller carbohydrates. Most monosaccharides can be represented by the general formula C_yH_2yO_y (e.g., C₆H₁₂O₆ (a hexose such as glucose)), wherein y is an integer equal to or greater than 3. Certain polyhydric alcohols not represented by the general formula described above may also be considered monosaccharides. For example, deoxyribose is of the formula C₅H₁₀O₄ and is a monosaccharide. Monosaccharides usually consist of five or six carbon atoms and are referred to as pentoses and hexoses, receptively. If the monosaccharide contains an aldehyde it is referred to as an aldose; and if it contains a ketone, it is referred to as a ketose. Monosaccharides may also consist of three, four, or seven carbon atoms in an aldose or ketose form and are referred to as trioses, tetroses, and heptoses, respectively.

Glyceraldehyde and dihydroxyacetone are considered to be aldotriose and ketotriose sugars, respectively. Examples of aldotetrose sugars include erythrose and threose; and ketotetrose sugars include erythrulose. Aldopentose sugars include ribose, arabinose, xylose, and lyxose; and ketopentose sugars include ribulose, arabulose, xylulose, and lyxulose. Examples of aldohexose sugars include glucose (for example, dextrose), mannose, galactose, allose, altrose, talose, gulose, and idose; and ketohexose sugars include fructose, psicose, sorbose, and tagatose. Ketoheptose sugars include sedoheptulose. Each carbon atom of a

monosaccharide bearing a hydroxyl group (−OH), with the exception of the first and last carbons, is asymmetric, making the carbon atom a stereocenter with two possible configurations (R or S). Because of this asymmetry, a number of isomers may exist for any given monosaccharide formula. The aldohexose ^D-glucose, for example, has the formula C₆H₁₂O₆, of which all but two of its six carbons atoms are stereogenic, making D-glucose one of the 16 (i.e., 2⁴) possible stereoisomers. The assignment of D or L is made according to the orientation of the asymmetric carbon furthest from the carbonyl group: in a standard Fischer projection if the hydroxyl group is on the right the molecule is a D sugar, otherwise it is an L sugar. The aldehyde or ketone group of a straight-chain monosaccharide will react reversibly with a hydroxyl group on a different carbon atom to form a hemiacetal or hemiketal, forming a heterocyclic ring with an oxygen bridge between two carbon atoms. Rings with five and six atoms are called furanose and pyranose forms, respectively, and exist in equilibrium with the straight-chain form. During the conversion from the straight-chain form to the cyclic form, the carbon atom containing the carbonyl oxygen, called the anomeric carbon, becomes a stereogenic center with two possible configurations: the oxygen atom may take a position either above or below the plane of the ring. The resulting possible pair of stereoisomers is called anomers. In an α anomer, the−OH substituent on the anomeric carbon rests on the opposite side (trans) of the ring from the−CH₂OH side branch. The alternative form, in which the−CH₂OH substituent and the anomeric hydroxyl are on the same side (cis) of the plane of the ring, is called a β anomer. A carbohydrate including two or more joined monosaccharide units is called a disaccharide or polysaccharide (e.g., a trisaccharide), respectively. The two or more monosaccharide units bound together by a covalent bond known as a glycosidic linkage formed via a dehydration reaction, resulting in the loss of a hydrogen atom from one monosaccharide and a hydroxyl group from another. Exemplary disaccharides include sucrose, lactulose, lactose, maltose, isomaltose, trehalose, cellobiose, xylobiose, laminaribiose, gentiobiose, mannobiose, melibiose, nigerose, or rutinose.

Exemplary trisaccharides include, but are not limited to, isomaltotriose, nigerotriose, maltotriose, melezitose, maltotriulose, raffinose, and kestose. The term carbohydrate also includes other natural or synthetic stereoisomers of the carbohydrates described herein.

[0064] The term“salt” refers to any and all salts, and encompasses pharmaceutically acceptable salts. The term“pharmaceutically acceptable salt” refers to those salts which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic response, and the like, and are commensurate with a reasonable benefit/risk ratio. Pharmaceutically acceptable salts are well known in the art. For example, Berge et al. describe pharmaceutically acceptable salts in detail in J. Pharmaceutical Sciences, 1977, 66, 1-19, incorporated herein by reference. Pharmaceutically acceptable salts of the compounds of this invention include those derived from suitable inorganic and organic acids and bases. Examples of pharmaceutically acceptable, nontoxic acid addition salts are salts of an amino group formed with inorganic acids, such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, and perchloric acid or with organic acids, such as acetic acid, oxalic acid, maleic acid, tartaric acid, citric acid, succinic acid, or malonic acid or by using other methods known in the art such as ion exchange. Other pharmaceutically acceptable salts include adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentanepropionate, digluconate, dodecylsulfate,

ethanesulfonate, formate, fumarate, glucoheptonate, glycerophosphate, gluconate, hemisulfate, heptanoate, hexanoate, hydroiodide, 2-hydroxy-ethanesulfonate, lactobionate, lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2- naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pamoate, pectinate, persulfate, 3-phenylpropionate, phosphate, picrate, pivalate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, p-toluenesulfonate, undecanoate, valerate salts, and the like. Salts derived from appropriate bases include alkali metal, alkaline earth metal, ammonium, and N⁺(C_1-4 alkyl)⁻

4 salts. Representative alkali or alkaline earth metal salts include sodium, lithium, potassium, calcium, magnesium, and the like. Further pharmaceutically acceptable salts include, when appropriate, nontoxic ammonium, quaternary ammonium, and amine cations formed using counterions such as halide, hydroxide, carboxylate, sulfate, phosphate, nitrate, lower alkyl sulfonate, and aryl sulfonate.

[0065] The term“solvent” refers to a substance that dissolves one or more solutes, resulting in a solution. A solvent may serve as a medium for any reaction or transformation described herein. The solvent may dissolve one or more reactants or reagents in a reaction mixture. The solvent may facilitate the mixing of one or more reagents or reactants in a reaction mixture. The solvent may also serve to increase or decrease the rate of a reaction relative to the reaction in a different solvent. Solvents can be polar or non-polar, protic or aprotic. Common organic solvents useful in the methods described herein include, but are not limited to, acetone, acetonitrile, benzene, benzonitrile, 1-butanol, 2-butanone, butyl acetate, tert-butyl methyl ether, carbon disulfide carbon tetrachloride, chlorobenzene, 1-chlorobutane, chloroform, cyclohexane, cyclopentane, 1,2-dichlorobenzene, 1,2-dichloroethane, dichloromethane (DCM), N,N-dimethylacetamide N,N-dimethylformamide (DMF), 1,3- dimethyl-3,4,5,6-tetrahydro-2-pyrimidinone (DMPU), 1,4-dioxane, 1,3-dioxane, diethylether, 2-ethoxyethyl ether, ethyl acetate, ethyl alcohol, ethylene glycol, dimethyl ether, heptane, n- hexane, hexanes, hexamethylphosphoramide (HMPA), 2-methoxyethanol, 2-methoxyethyl acetate, methyl alcohol, 2-methylbutane, 4-methyl-2-pentanone, 2-methyl-1-propanol, 2- methyl-2-propanol, 1-methyl-2-pyrrolidinone, dimethylsulfoxide (DMSO), nitromethane, 1- octanol, pentane, 3-pentanone, 1-propanol, 2-propanol, pyridine, tetrachloroethylene, tetrahyrdofuran (THF), 2-methyltetrahydrofuran, toluene, trichlorobenzene, 1,1,2- trichlorotrifluoroethane, 2,2,4-trimethylpentane, trimethylamine, triethylamine, N,N- diisopropylethylamine, diisopropylamine, water, o-xylene, p-xylene.

[0066]“Oxidant,”“oxidizing agent” or“chemical oxidant” refers to a chemical compound or substance that has the ability to oxidize another compound. Oxidation, as will be appreciated by one of skill in the art, is the loss of electrons– and an oxidizing agent is a chemical agent that removes electrons from another compound. In certain embodiments, the oxidant is a two- electron oxidant (i.e., removed two electrons from the other compound). Examples of chemical oxidants can be found in the literature, e.g., Carey and Sundberg. Advanced

Organic Chemistry Part B: Reactions and Synthesis, Fifth Edition (7007) New York, NY: Springer; 675-783 and references cited therein. Examples of commerically available chemical oxidants can also be found on the internet, e.g., www.sigmaaldrich.com/chemistry/chemistry- products.html?TablePage=16277367.

[0067] The term“small molecule” refers to molecules, whether naturally-occurring or artificially created (e.g., via chemical synthesis) that have a relatively low molecular weight. Typically, a small molecule is an organic compound (i.e., it contains carbon). The small molecule may contain multiple carbon-carbon bonds, stereocenters, and other functional groups (e.g., amines, hydroxyl, carbonyls, and heterocyclic rings, etc.). In certain

embodiments, the molecular weight of a small molecule is not more than about 1,000 g/mol, not more than about 900 g/mol, not more than about 800 g/mol, not more than about 700 g/mol, not more than about 600 g/mol, not more than about 500 g/mol, not more than about 400 g/mol, not more than about 300 g/mol, not more than about 200 g/mol, or not more than about 100 g/mol. In certain embodiments, the molecular weight of a small molecule is at least about 100 g/mol, at least about 200 g/mol, at least about 300 g/mol, at least about 400 g/mol, at least about 500 g/mol, at least about 600 g/mol, at least about 700 g/mol, at least about 800 g/mol, or at least about 900 g/mol, or at least about 1,000 g/mol. Combinations of the above ranges (e.g., at least about 200 g/mol and not more than about 500 g/mol) are also possible. In certain embodiments, the small molecule is a therapeutically active agent such as a drug (e.g., a molecule approved by the U.S. Food and Drug Administration as provided in the Code of Federal Regulations (C.F.R.)). The small molecule may also be complexed with one or more metal atoms and/or metal ions. In this instance, the small molecule is also referred to as a “small organometallic molecule.” Preferred small molecules are biologically active in that they produce a biological effect in animals, preferably mammals, more preferably humans. Small molecules include, but are not limited to, radionuclides and imaging agents. In certain embodiments, the small molecule is a drug. Preferably, though not necessarily, the drug is one that has already been deemed safe and effective for use in humans or animals by the appropriate governmental agency or regulatory body. For example, drugs approved for human use are listed by the FDA under 21 C.F.R. §§ 330.5, 331 through 361, and 440 through 460, incorporated herein by reference; drugs for veterinary use are listed by the FDA under 21 C.F.R. §§ 500 through 589, incorporated herein by reference. All listed drugs are considered acceptable for use in accordance with the present invention.

[0068] A“large organic molecule” or“large molecule” refers to an organic compound that is not a small molecule. In certain embodiments, the molecular weight of a large molecule is greater than about 2,000 g/mol, greater than about 3,000 g/mol, greater than about 4,000 g/mol, or greater than about 5,000 g/mol. In certain embodiments, the molecular weight of a large molecule is at most about 100,000 g/mol, at most about 30,000 g/mol, at most about 10,000 g/mol, at most about 5,000 g/mol, or at most about 2,000 g/mol. Combinations of the above ranges (e.g., greater than about 2,000 g/mol and at most about 10,000 g/mol) are also possible. In certain embodiments, the large molecule is a therapeutically active agent such as a drug (e.g., a molecule approved by the U.S. Food and Drug Administration as provided in the Code of Federal Regulations (C.F.R.)).The large molecule may also be complexed with one or more metal atoms and/or metal ions. In this instance, the large molecule is also referred to as an“large organometallic compound.”

[0069] These and other exemplary substituents are described in more detail in the Detailed Description, Examples, and Claims. The invention is not intended to be limited in any manner by the above exemplary listing of substituents. DETAILED DESCRIPTION OF CERTAIN EMBODIMENTS

[0070] Provided herein are systems, reagents, compounds, and methods for the glycosylation of organic molecules. In one aspect, the invention provides a method for glycosylating a hydroxyl-containing organic compound (i.e., a glycosyl acceptor), the method comprising contacting a glycosyl donor with the hydroxyl-containing organic compound, in the presence of an oxidant, to yield a glycosylated organic compound. [0071] In certain embodiments,“glycosyl donors” useful in the provided methods are of the following formula:

,

and salts thereof, wherein each R is independently a substituent on the pyranose backbone.

[0072] In certain embodiments, each substituent on the sugar backbone (group R) is independently hydrogen, optionally substituted alkyl, optionally substituted hydroxyl, optionally substituted amino, or a carbohydrate. In certain embodiments, R is hydrogen. In certain embodiments, R is optionally substituted alkyl. In certain embodiments, R is optionally substituted hydroxyl. In certain embodiments, R is optionally substituted amino. In certain embodiments, R is a carbohydrate (e.g., sugar or polysaccharide).

[0073] In certain embodiments, each substituent on the sugar backbone (group R) is independently–CH₂OH,–CH₂OBn,–OH,–OBn,–OBz,–OFmoc,–OTBS,–NPhth, –CO₂Bn,–CH₃,–H, or a carbohydrate (e.g., a sugar). As defined herein, Bn is–CH₂Ph; Bz is –C(=O)Ph; Fmoc is 9-fluorenylmethyl carbamate; TBS is tert-butyldimethylsilyl; and NPhth is a phthalimide group.

[0074] In certain embodiments, the glycosyl donor is of the following formula:

,

or a salt thereof. [0075] In certain embodiments, the glycosyl donor is of one of the following formulae:

, or a salt thereof.

[0076] In certain embodiments, the glycosyl donor is of the following formula:

,

or a salt thereof.

[0077] In certain embodiments, the glycosyl donor is of the following formula:

,

or a salt thereof.

[0078] In certain embodiments, the glycosyl donor is of the following formula:

,

or a salt thereof. [0079] In certain embodiments, the glycosyl donor is of one of the following formulae:

, or a salt thereof.

[0080] In certain embodiments, the glycosyl donor is of one of the following formulae:

,

or a salt thereof.

[0081] In certain embodiments, the glycosyl donor is of one of the following formulae:

,

,

or a salt thereof.

[0082] A“glycosyl acceptor” is any hydroxyl-containing organic compound. A hydroxyl- containing organic compound is any organic molecule comprising an–OH group. In certain embodiments, a hydroxyl-containing organic compound is of the formula R²–OH, or a salt thereof, wherein R² is an organic compound. In certain embodiments, R² is a small molecule. In certain embodiments, R² is a large molecule. In certain embodiments, R² is a carbohydrate (e.g., a sugar). In certain embodiments, R² is a monosaccharide, disaccharide, trisaccharide, or polysaccharide.

[0083] In certain embodiments, the method for glycosylating a hydroxyl-containing organic compound comprises contacting a glycosyl donor provided herein, or a salt thereof, with a hydroxyl-containing organic compound of the formula R²–OH, or a salt thereof, in the presence of an oxidant to yield a compound of Formula (S-1):

wherein each R is independently a substituent on the pyranose ring, as defined herein.

[0084] In certain embodiments, each substituent on the sugar backbone (e.g., group R) is independently–CH₂OH,–CH₂OBn,–OH,–OBn,–OBz,–OFmoc,–OTBS,–NPhth,– CO₂Bn,–CH₃,–H, or another carbohydrate (e.g., a sugar).

[0085] In certain embodiments, the grou corres onding to:

is of the following formulae: ,

[0086] In certain embodiments, the grou corres onding to:

is of the following formulae:

.

[0087] In certain embodiments, the grou corres onding to:

is of one of one of the following formulae:

.

[0088] In certain embodiments, the grou corres onding to:

is of one of the following formulae:

.

[0089] In certain embodiments, the grou corres onding to:

is of one of the following formulae:

.

[0090] In certain embodiments, the group corresponding to:

is of one of the following formulae:

,

[0091] In certain embodiments, the grou corres ondin to:

is of one of the following formulae:

,

[0092] As described herein, the“glycosyl acceptor” is a hydroxyl-containing organic molecule, and may be a hydroxyl-containing carbohydrate (e.g., sugar). When the glycosyl acceptor is a hydroxyl-containing monosaccharide, in certain embodiments, the product of the glycosylation is a disaccharide.

[0093] In certain embodiments, the glycosyl acceptor is of one of the following formulae:

, or a pharmaceutically acceptable salt thereof.

[0094] In certain embodiments, each substituent on the sugar backbone (group R) is independently hydrogen, optionally substituted alkyl, optionally substituted hydroxyl, optionally substituted amino, or a carbohydrate. In certain embodiments, R is hydrogen. In certain embodiments, R is optionally substituted alkyl. In certain embodiments, R is optionally substituted hydroxyl. In certain embodiments, R is optionally substituted amino. In certain embodiments, R is a carbohydrate (e.g., sugar or polysaccharide).

[0095] In certain embodiments, each substituent on the sugar backbone (group R) is independently–CH₂OH,–CH₂OBn,–OH,–OBn,–OBz,–OFmoc,–OTBS,–NPhth, –CO₂Bn,–CH₃,–H, or a carbohydrate (e.g., a sugar). As defined herein, Bn is–CH₂Ph; Bz is –C(=O)Ph; Fmoc is 9-fluorenylmethyl carbamate; TBS is tert-butyldimethylsilyl; and NPhth is a phthalimide group. [0096] In certain embodiments, the glycosyl acceptor is of one of the following formulae:

,

or a salt thereof, wherein:

R¹ is optionally substituted alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted carbocyclyl, or optionally substituted acyl.

[0097] In certain embodiments, the glycosyl acceptor is of the formula:

,

or a salt thereof.

[0098] In certain embodiments, the glycosyl acceptor is of the following formula:

,

or a salt thereof.

[0099] As generally defined herein, R¹ is optionally substituted alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted carbocyclyl, or optionally substituted acyl. In certain embodiments, R¹ is optionally substituted alkyl. In certain embodiments, R¹ is optionally substituted aryl. In certain embodiments, R¹ is optionally substituted heteroaryl. In certain embodiments, R¹ is optionally substituted heterocyclyl. In certain embodiments, R¹ is optionally substituted carbocyclyl. In certain embodiments, R¹ is optionally substituted acyl. In certain

embodiments, R¹ is optionally substituted phenyl. In certain embodiments, R¹ is substituted phenyl. In certain embodiments, R¹ is unsubstituted phenyl (i.e.,–Ph).

[00100] Therefore, the glycosyl acceptor is, in certain embodiments, of one of the following formulae:

,

or a salt thereof .

[00101] In certain embodiments, the glcosl accetor is of one of the formula:

or a salt thereof.

[00102] In certain embodiments, the glycosyl acceptor is of the formula:

or a salt thereof.

[00103] In certain embodiments, the glycosyl acceptor is of one of the following formulae:

or a salt thereof .

[00104] In certain embodiments, the glycosyl acceptor is of one of the following formulae:

[00105] In certain embodiments, the glycosyl acceptor is of the following formula:

,

or a salt thereof.

[00106] In certain embodiments, the glycosyl acceptor is of the following formula:

,

or a salt thereof.

[00107] In certain embodiments, the glycosyl acceptor is of the following formula:

,

or a salt thereof. [00108] In certain embodiments, the glycosyl acceptor is of the following formula:

,

or a salt thereof.

[00109] In certain embodiments, the hydroxyl-containing organic compound of the formula R²–OH, or a salt thereof, and the glycosylation product is a compound of Formula (S-1):

(S-1),

wherein each R is independently a substituent on the pyranose ring.

[00110] In certain embodiments, R² is of any one of the following formulae:

_.

[00111] In certain embodiments, R² is of any one of the following formulae:

,

[00112] In certain embodiments, R² is of any one of the following formulae:

[00113] In certain embodiments, R² is of one of the following formulae:

[00114] In certain embodiments, R² is of one of the following formulae:

.

[00115] The methods provided herein comprise a step of glycosylating that is carried out in the presence of an oxidant. In certain embodiments, the oxidant is a chemical oxidant (i.e., oxidizing agent). In certain embodiments, the oxidant is a 2-electron oxidant. In certain embodiments, the oxidant is ceric ammonium nitrate (CAN). In certain embodiments, the oxidant is a hypervalent iodine reagent. In certain embodiments, the oxidant is

(bis(trifluoroacetoxy)iodo)benzene (PIFA). The oxidant may be used in stoichiometric, substoichiometric, catalytic, or excess amounts. In certain embodiments, less than 1 molar equivalent of the oxidant is used relative to the glycosyl donor. In certain embodiments, approximately 1 molar equivalent of the oxidant is used relative to the glycosyl donor. In certain embodiments, more than 1 molar equivalent of the oxidant is used relative to the glycosyl donor (i.e., excess). In certain embodiments, 1-2 molar equivalents (e.g., about 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, or 1.9 molar equivalents) of the oxidant is used relative to the glycosyl donor. In certain embodiments, approximately 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, or 10 equivalents are used.

[00116] The step of glycosylating may be carried out in the presence of one or more additional agents. In certain embodiments, the step of glycosylating is carried out in the presence of a Lewis acid. In certain embodiments, the Lewis acid is a boron species. In certain embodiments, the Lewis acid is boron trifluoride. In certain embodiments, the Lewis acid is boron trifluoride diethyletherate (BF₃•OEt₂). The Lewis acid may be used in stoichiometric, substoichiometric, catalytic, or excess amounts. In certain embodiments, less than 1 molar equivalent of the Lewis acid is used relative to the glycosyl donor. In certain embodiments, about 1 molar equivalent of the Lewis acid is used relative to the glycosyl donor. In certain embodiments, more than 1 molar equivalent of the Lewis acid is used relative to the glycosyl donor. In certain embodiments, 1-2 molar equivalents (e.g., about 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9 molar equivalents) of the Lewis acid is used relative to the glycosyl donor. In certain embodiments, approximately 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, or 10 equivalents are used. [00117] In certain embodiments, the reaction is carried out in the presence of an oxidant and a Lewis acid. In certain embodiments, the reaction is carried out in the presence of an oxidant and BF₃•OEt₂. In certain embodiments, the reaction is carried out in the presence of PIFA and a Lewis acid. In certain embodiments, the reaction is carried out in the presence of PIFA and BF₃•OEt₂. In certain embodiments, the reaction is carried out in the presence of approximately 1.1 equivalents of PIFA and 1 equivalent of BF₃•OEt₂. In certain

embodiments, the reaction is carried out in the presence of PIFA and BF₃•OEt₂, in CH₂Cl₂ and MeCN. In certain embodiments, the reaction is carried out in the presence of

approximately 1.1 equivalents of PIFA and 1 equivalent of BF₃•OEt₂, in CH₂Cl₂ and MeCN. In certain embodiments, the reaction is carried out in the presence of PIFA and BF₃•OEt₂, in CH₂Cl₂ and MeCN, at room temperature. In certain embodiments, the reaction is carried out in the presence of approximately 1.1 equivalents of PIFA and 1 equivalent of BF₃•OEt₂, in CH₂Cl₂ and MeCN, at room temperature. In certain embodiments, the reaction is carried out in the presence of PIFA and BF₃•OEt₂, in CH₂Cl₂ and MeCN, at room temperature, for 30 minutes or more. In certain embodiments, the reaction is carried out in the presence of approximately 1.1 equivalents of PIFA and 1 equivalent of BF₃•OEt₂, in CH₂Cl₂ and MeCN, at room temperature, for 30 minutes or more.

[00118] In certain embodiments, the step of glycosylating is carried out in a solvent. The solvent may be any solvent, including polar and non-polar solvents. In certain embodiments, the solvent is aprotic. In certain embodiments, the solvent is a polar solvent. In certain embodiments, the solvent is an alkyl nitrile. In certain embodiments, the solvent is acetonitrile (MeCN). In certain embodiments, the solvent is CH₂Cl₂. In certain embodiments, the solvent is a mixture of CH₂Cl₂ and MeCN. In certain embodiments, the solvent is a mixture of CH₂Cl₂ and MeCN (1/1).

[00119] The step of glycosylation can be carried out at any temperature. In certain embodiments, the reaction is carried out at or around room temperature (about 21 °C). In certain embodiments, the reaction is carried out at a temperature below room temperature. In certain embodiments, the reaction is carried out at a temperature above room temperature. In certain embodiments, the reaction is carried out at a temperature between 21 °C and 70 °C. In certain embodiments, the reaction is carried out at or around 60 °C.

[00120] Other reagents (e.g., chemical oxidants) and conditions useful in the glycosylation reactions provided herein can be found in the literature. See, e.g., Boons, Geert-Jan; Karl J. Hale (2000). Organic synthesis with carbohydrates. Blackwell Publishing, the entire contents of which is incorporated herein by reference; and Crich, D.; Lim, L. Org. React.2004, 64, 115; Bufali, S.; Seeberger, P. Org. React.2006, 68, 303; and references cited therein, the entire contents of which is incorporated herein by reference.

[00121] In certain embodiments, the methods described herein yield glycosylated organic molecules with anomeric selectivity.“Anomeric selectivity” refers to the amount of one anomer formed in a reaction as compared to the amount of the opposite anomer formed in the reaction.“Anomers” are sugar stereoisomers that are isomeric with respect to the

stereochemistry of the anomeric carbon of the sugar. Anomers are either alpha (α) or beta (β) anomers. For example, α and β anomeric forms are shown for compounds of Formula (S-1) below:

(α anomer) (β anomer)

[00122] In certain embodiments, the step of glycosylating yields a glycosylated organic molecule (e.g., a compound of Formula (S-1)) in a β:α anomeric ratio greater than 1:1. In certain embodiments, the β:α anomeric ratio is greater than 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, 11:1, 12:1, 13:1, 14:1, 15:1, 16:1, 17:1, 18:1, 19:1, 20:1, 21:1, 22:1, 23:1, 24:1, 25:1, 30:1, 35:1, 40:1, 45:1, 50:1, 60:1, 70:1, 80:1, 90:1, or 100:1. In certain embodiments, the β:α anomeric ratio is greater than 3:1. In certain embodiments, the β:α anomeric ratio is greater than 5:1. In certain embodiments, the β:α anomeric ratio is greater than 10:1. In certain embodiments, the β:α anomeric ratio is greater than 15:1. In certain embodiments, the β:α anomeric ratio is greater than 20:1. In certain embodiments, the β:α anomeric ratio is greater than 25:1.

[00123] In certain embodiments, the step of glycosylating yields a glycosylated organic molecule (e.g., a compound of Formula (S-1)) in a α:β anomeric ratio greater than 1:1. In certain embodiments, the α:β anomeric ratio is greater than 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, 11:1, 12:1, 13:1, 14:1, 15:1, 16:1, 17:1, 18:1, 19:1, 20:1, 21:1, 22:1, 23:1, 24:1, 25:1, 30:1, 35:1, 40:1, 45:1, 50:1, 60:1, 70:1, 80:1, 90:1, or 100:1. In certain embodiments, the α:β anomeric ratio is greater than 3:1. In certain embodiments, the α:β anomeric ratio is greater than 5:1. In certain embodiments, the α:β anomeric ratio is greater than 10:1. In certain embodiments, the α:β anomeric ratio is greater than 15:1. In certain embodiments, the α:β anomeric ratio is greater than 20:1. In certain embodiments, the α:β anomeric ratio is greater than 25:1.

[00124] The glycosylated compound can be isolated in any chemical yield. In certain embodiments, the compound is isolated in from 1-10%, 10-20% 20-30%, 30-40%, 40-50%, 50-60%, 60-70%, 70-80%, 80-90%, or 90-100% yield. In certain embodiments, the compound is produced in approximately 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% yield.

[00125] After formation, the product may be purified via one or more purification steps. For example, in certain embodiments, the product is purified by chromatography, extraction, filtration, precipitation, crystallization, or any other method known in the art. In certain embodiments, the compound is carried forward to a subsequent synthetic step without purification (i.e., crude).

[00126] In certain embodiments, the glycosyl acceptor employed in the glycosylation reaction is a sugar that comprises a“latent glycosyl donor” moiety. In certain embodiments, “latent glycosyl donor” moiety is a protected phenol moiety of the following formula:

.

[00127] In certain embodiments,“latent glycosyl donor” moiety is a protected phenol moiety of the following formula:

.

[00128] Deprotection of the“latent glycosyl donor” moiety provides a free phenol, thereby converting the latent glycosyl donor into a glycosyl donor (i.e.,“active” glycosyl donor) that can then be used in a glycosylation reaction provided herein. Iterative steps of glycosylation and deprotection of the latent glycosyl donor moiety can be used to construct trisaccharides, polysaccharides, and complex glycans, among other carbohydrates. This iterative glycosylation/deprotection/glycosylation concept is represented in the following scheme (structures shown are exemplary):

[00129] In certain embodiments, a method for glycosylating a hydroxyl-containing organic compound described herein further comprises the steps of:

(a) deprotecting the glycosylation product (e.g., a compound of Formula (S-1)) to convert the group corresponding to the formula:

,

to a group of the following formula:

(b) contacting the compound provided in step (a) with a hydroxyl-containing organic compound (e.g., a compound of the formula R²–OH), or a salt thereof, in the presence of an oxidant, thereby glycosylating the hydroxyl organic compound.

[00130] Step (b) above is a glycosylation reaction, and therefore any reagents or conditions described herein for a step of glycosylating may be used in this step. Regarding step (a) above, any reagents or conditions may be used in the step of deprotecting.

[00131] In certain embodiments, the step of deprotecting is carried out in the presence of a nucleophile or base. In certain embodiments, the step of deprotecting is carried out in the presence of an alcohol. In certain embodiments, the step of deprotecting is carried out in the presence of hydroxide (e.g., NaOH, KOH, LiOH). In certain embodiments, the step of deprotecting is carried out in the presence of an alkoxide (e.g., methoxide, ethoxide). In certain embodiments, the step of deprotecting is carried out in the presence of ethanolamine. In certain embodiments, the step of deprotecting is carried out in the presence of sodium methoxide.

[00132] In certain embodiments, the step of deprotecting is carried out in a solvent. The solvent may be any solvent, including polar and non-polar solvents. In certain embodiments, the solvent is a polar solvent. In certain embodiments, the solvent is an alcohol. In certain embodiments, the solvent is methanol. In certain embodiments, the solvent is THF.

[00133] In certain embodiments, the deprotection is carried out in the presence of ethanolamine. In certain embodiments, the deprotection is carried out in the presence of excess ethanolamine (i.e., greater than 1 equivalent). In certain embodiments, the

deprotection is carried out in the presence of excess ethanolamine in THF. In certain embodiments, the deprotection is carried out in the presence of excess ethanolamine, in THF, at around room temperature.

[00134] The step of deprotecting can be carried out at any temperature. In certain

embodiments, the reaction is carried out at or around room temperature (about 21 °C). In certain embodiments, the reaction is carried out at a temperature below room temperature. In certain embodiments, the reaction is carried out at a temperature above room temperature. In certain embodiments, the reaction is carried out at a temperature between 21 °C and 100 °C.

[00135] The deprotected product can be isolated in any chemical yield. In certain

embodiments, the compound is isolated in from 1-10%, 10-20% 20-30%, 30-40%, 40-50%, 50-60%, 60-70%, 70-80%, 80-90%, or 90-100% yield. In certain embodiments, the compound is produced in approximately 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% yield.

[00136] After deprotection, the product may be purified via one or more purification steps. For example, in certain embodiments, the product is purified by chromatography, extraction, filtration, precipitation, crystallization, or any other method known in the art. In certain embodiments, the compound is carried forward to a subsequent synthetic step without purification (i.e., crude).

[00137] Any of the methods described herein may further comprise the steps of:

(c) deprotecting a latent glycosyl donor moiety, thereby yielding an active glycosyl donor; and

(d) using the glycosyl donor produced in step (c) in a subsequent glycosylation reaction. [00138] In other embodiments, any of the methods described herein may further comprise the steps of:

(c) deprotecting a hydroxyl group on the glycosylation product, thereby yielding a glycosyl acceptor (i.e., a compound with a free hydroxyl group); and

(d) using the glycosyl acceptor produced in step (c) in a subsequent glycosylation reaction.

[00139] Any of the methods provided herein may further comprise any number of iterative glycosylating/deprotecting steps to provide a trisaccharide, polysaccharide, glycan, etc. In certain embodiments, the method include 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more iterations. Compounds

[00140] The present invention also provides compounds that are useful as glycosyl donors or glycosyl acceptors in the methods provided herein. Provided herein around compounds of the following formula:

,

and salts thereof.

[00141] In certain embodiments, the provided compound is of one of the following formulae:

, or a salt thereof. [00142] In certain embodiments, the provided compound is of one of the following formulae:

, or a salt thereof.

[00143] In certain embodiments, the provided compound is of the following formulae:

,

or a salt thereof.

[00144] In certain embodiments, the provided compound is of the following formulae:

,

or a salt thereof.

[00145] In certain embodiments, the present invention provides compound of the following formula:

,

and salts thereof. [00146] In certain embodiments, the provided compound is of one of the following formulae:

, or a salt thereof.

[00147] In certain embodiments, the provided compound is of one of the following formulae:

, or a salt thereof.

[00148] In certain embodiments, the present invention provides compounds the following formulae:

,

and salts thereof. [00149] In certain embodiments, a provided compound is of one of the following formulae:

,

or a salt thereof.

[00150] In certain embodiments, a provided compound is of one of the following formulae:

or a salt thereof. [00151] Also provided herein are compound of the following formulae:

, and salts thereof, wherein:

R¹ is optionally substituted alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted carbocyclyl, or optionally substituted acyl.

[00152] In certain embodiments, the provided compound is of the following formula:

,

or a salt thereof.

[00153] In certain embodiments, the provided compound is of the following formula:

,

or a salt thereof. [00154] In certain embodiments, the provided compound is of the following formulae:

,

or a salt thereof .

[00155] In certain embodiments, the provided compound is of the formula:

,

or a salt thereof.

[00156] In certain embodiments, the provided compound is of the formula:

,

or a salt thereof.

[00157] In certain embodiments, the provided compound is of one of the following formulae:

,

or a salt thereof .

[00158] In certain embodiments, the provided compound is of one of the following formulae:

69/126

U1195.70042WO00

[00159] In certain embodiments, the provided compound is of the following formula:

,

or a salt thereof.

[00160] In certain embodiments, the provided compound is of the following formula:

,

or a salt thereof.

[00161] In certain embodiments, the provided compound is of the following formula:

,

or a salt thereof. [00162] In certain embodiments, the provided compound us of the following formula:

,

or a salt thereof.

[00163] Furthermore, all compounds disclosed in the Examples below are part of the present invention and are provided herein as compounds.

[00164] Also provided herein are kits comprising one or more compounds provided herein; optionally one or more reagents provided herein; and optionally instructions for use. In certain embodiments, the kit comprises one or more glycosyl donors, one or more glycosyl acceptors; optionally a chemical oxidant (e.g., PIFA); and optionally instructions for use. EXAMPLES

Glycosylation of organic compounds

[00165] For use in glycosylation reactions, a simple hydroquinone was prepared from the commercially available natural product arbutin 14. The tetra-O-benzyl derivative 15 was selected and, using isopropanol as a simple nucleophile, a variety of oxidants were studied in the glycosylation reaction. A select set of these is shown in Table 1. As can be seen in entry 1, oxidants like CAN indeed provide the desired product, answering the question of whether a different oxidant can be employed. However, it was vital to find an inexpensive, commercially available 2-electron oxidant that would be easy to use straight from the bottle and produce byproducts that were straightforward to remove. While there are a variety of two electron oxidants available, attention was focused on hypervalent iodine reagents, as they would meet the aforementioned criteria.

Furthermore, there is ample literature precedent for I(III)-reagents

like(diacetoxyiodo)benzene to oxidize phenols to a variety of products. As shown,

(bis(trifluoroacetoxy)iodo)benzene (PhI(OTFA)₂; also“PIFA”) yielded 16 in 55% yield after 15 minutes (entry 3). The reaction is quenched with aqueous bicarbonate solution, which efficiently removes the TFA byproduct and iodobenzene and benzoquinone are removed during workup and in vacuo. In short, this is a very easy reaction to perform. Table 1. Screening Experiments

[00166] It is noteworthy that glycosyl donors with different auxiliaries were unsuccessful under these conditions. For instance, the reaction shows in the scheme below did not produce the desired product shown.

[00167] Next, it was important to know whether this strategy will enable a latent form of the reagent to be utilized as the glycosyl acceptor. The proper control experiments were needed to determine if the reactivity could be influenced by simply substituting the phenol, as predicted in Scheme 2. To do this a benzoyl substituent was chosen. A benzoyl group (an electron-withdrawing group) may help reduce the propensity for oxidation in this regard, but more importantly, can be removed to reveal the active reagent. The benzoyl substituted compound 17 was prepared from 15 and exposed to the reaction conditions determined in Table 1. After a 15 minute reaction time (same as Table 1), the latent reagent 17 remained untouched. No consumption of the reagent was observed under prolonged reaction times and even addition of TFA (which the latent form will need to tolerate as it is produced in the oxidation of the active form) did not affect 17. As seen in Scheme 2, 95% of 17 was recovered after 6 h, which is 24 times the reaction time (15 min) developed above. Simple benzoyl protection prevents oxidation with PIFA. Scheme 2

[00168] Missing from 17 is a free hydroxyl group to act as an acceptor in glycosylation reactions. A free hydroxyl was incorporated in 18 and the reaction was run under standard reaction conditions (Scheme 3; PIFA, acetonitrile, 15 min at room temperature). Exactly the desired reaction occurred, providing 19 in 75% yield as a 3:1 mixture of anomers, favoring the beta anomer. This stereoselectivity is what should be expected from the all benzyl substrate 17, in agreement with numerous reports using other triggering strategies (see, e.g., Crich, D.“Mechanism of a Chemical Glycosylation Reaction” Acc. Chem. Res.2010, 43, 1144-1153). Scheme 3

[00169] Given that these reagents are solids, the reaction procedures are simple. Using the reaction of 17 and 18 as an example, the solid reagents are added to the flask and a rubber septum put in place before acetonitrile is added. Solid PIFA is then added in one portion (septum removed and poured in) and in 15 minutes the reaction is worked up with aqueous sodium bicarbonate. The solvent quality does not have to be very high, and may contain water. These experiments unequivocally demonstrated that the reactivity concept can and does work and that the reagents are easy to handle, shelf stable solids that are readily employed using simple procedures. With reagents such as 17 in hand, the scope was briefly explored (Table 2). It should be noted that, in addition to a glucose derived reagent, mannose- and galactose-based reagents were also prepared and employed, giving 22 and 23, respectively. TBS groups were also used to protect the glucose-based reagent (compound pictured in Figure 4) to give 24, and other disaccharides such as 25 could be formed. The α:β anomeric ratios observed are in agreement with many related substrates (Bn-protected glucose derivatives) using a variety of methods. (see, e.g., Crich, D.“Mechanism of a Chemical Glycosylation Reaction” Acc. Chem. Res.2010, 43, 1144-1153). Table 2

[00170] To address stereoselectivity, a 2-O-Bz protecting group was included on the mannose substrate instead of 2-O-Bn, resulting in 27 (Scheme 4). Under standard conditions with isopropanol as a nucleophile, 28 was obtained in 22% yield, but with >25:1 selectivity favoring the alpha-anomer, solving the selectivity problem. Use of additives was explored with the rationale that they may help the ionization to form the oxonium ion and increase reactivity. The Lewis acid BF₃•OEt₂ restored reactivity, and 29 was isolated in 77% yield, again in >25:1 anomeric selectivity. The same substrate control element could be incorporated in glucose and the corresponding reagent 30 was prepared and tested with 18 as nucleophile. In the event, the disaccharide 31 was produced in 81% yield and >25:1 diastereoselectivity, favoring the beta-anomer. Changing the 2-O-Bn group to a 2-O-Bz group was a critical change that achieved greatly improved anomeric stereoselectivity. Scheme 4

[00171] A variety of different types of building blocks are important, including amino sugar derivatives. Before using BF₃•OEt₂ as an additive, the N-phthalimido glucose derivative 32 was prepared and used it with the original conditions. The reactions were highly selective, providing essentially one diastereomer (Scheme 5). These results demonstrate that using this new oxidative strategy, stereoselectivity can be controlled by directing groups on the substrate. Scheme 5

[00172] Using the improved conditions with 15 and 35, the disaccharide 26 was obtained in 81% yield (Scheme 6). For comparison, without BF₃•OEt₂, the reaction had to be heated to 60 °C and then 26 was obtained in 63%. These results show that the glycosyl acceptor can be a secondary alcohol on a sugar backbone– a critical result that will allow for the building of diverse glycans. Scheme 6

[00173] For the construction of polysaccharides and complex glycans, a set of common building block materials and for use in iterative glycosylation reactions is essential. Using this pragmatic tenet, a variety of glycosyl donors have been prepared. As can be seen in Scheme 7, the method is straightforward and applies standard chemistry. The strategy was to prepare the trichloroacetimidates and then convert them to the hydroquinone adducts, which have all been stable solids. Following this general route, donors 15, 40-42, and 32 have been prepared. Scheme 7

[00174] An important feature of this invention is use of these compounds in an iterative process, capitalizing on the active/latent properties designed into the system. The next goal was to use the 2-O-benzoyl reagent 48 with a free C6 hydroxyl group as acceptor (Scheme 8), since it contains a latent glycosyl donor (which can be uncovered after the removal of the phenolic benzoyl group).

Scheme 8

[00175] Compound 48 was prepared from glucal 43. Acceptor 48 can react with 30 under the conditions established above (Scheme 4) followed by selective benzoyl deprotection with ethanolamine to yield 50 (Scheme 9; (a) PIFA, BF₃•OEt₂, CH₃CN; (b) ethanolamine, THF). Note that 30 was prepared from 49 under these deacylation conditions. Simple two-step sequences will then sequentially add monosaccharides to the chain to build the linear carbohydrate. These types of iterative glycosylations are provided and described herein. Scheme 9

[00176] A set of common monosaccharide building blocks are needed to prepare both branched and linear glycan structures. It is important to have a protecting group strategy that is common to all reagents to allow them to be used in a mix-and-match approach. The prevalent motif observed in carbohydrate oligomers is for each monosaccharide in the chain to have two or three points of attachment to the neighboring residues (one for terminal branches). When distilled down, every building block needs to have four types of protecting groups: (1) anomeric protection; (2) protecting groups that will only be removed in a global deprotection step at the end of the sequence; (3) a single temporary protecting group; and (4) no protecting group– a free glycosyl acceptor. One strategy provided herein is as follows: Benzyl groups will be utilized to protect alcohols that will be revealed in the final step; Fmoc groups will be used to protect alcohols that will be immediately revealed after glycosylation to act as glycosyl acceptors to introduce branching; Free hydroxyl groups will be revealed directly before use in glycosylation reactions and will largely be protected as silyl ethers during preparation of the building blocks (Scheme 8).

[00177] Seeberger has used an informatics approach to identify the most common building blocks needed to access the largest majority of known mammalian glycans (Seeberger, P. H. “The Logic of Automated Glycan Assembly”, Acc. Chem. Res.2015, 48, 1450-1463; Werz, D. B.; Ranzinger, R.; Herget, S.; Adibekian, A.; Von der Lieth, C-W.; Seeberger, P. H. “Exploring the Structural Diversity of Mammalian Carbohydrates (‘Glycospace’) by Statistical Databank Analysis”, ACS Chem. Bio.2007, 2, 685-691; Adibekian, A.;

Stallforth, P.; Hecht, L.-M.; Werz, D. B.; Gagneux, P.; Seeberger, P. H.“Comparative bioinformatics analysis of the mammalian and bacterial glycomes,” Chem. Sci.2011, 2, 337– 344). Table 3 shows a set of building blocks for use in the present invention, categorized by monosaccharide type. These molecules are latent donors and can be fed into the reaction as acceptors to be glycosylated at the free hydroxyl groups. It is to be understood that all of these compounds can be protected at the free hydroxyl group (with a hydroxyl protecting group) and treated with ethanolamine to produce the corresponding donor molecules. The building blocks are broken up by monosaccharide and it can be seen that there are clearly more prevalent substitution patterns for some types than others. In Table 3, OAr is OC₆H₄p- OBz.

Table 3

[00178] The synthesis of 32a begins from the known phthalimide 56 (See, e.g., Ferrier, R. J.; Hay, R. W.; Vethaviyasar, N.“A potential versatile synthesis of Glycosides,” Carbohydr. Res.1973, 27, 55–61). Protection as the acetal and benzylation of the free hydroxyl group will provide 58 (see, e.g., Nakano, T.; Ito, Y.; Ogawa, T.“Total synthesis of a sulfated glucuronyl glycosphingolipid, IV3GlcA(3- SO3)nLcOse Cer, a carbohydrate epitope of neural cell adhesion molecules”, Tetrahedron Lett.1990, 31, 1597-1600). Oxidative deprotection and introduction of the hydroquinone using the trichloroacetimidate method should afford 60 (see, e.g., Komarova, B.S.; Orekhova, M.V.; Tsvetkov, Y.E.; Nifantiev, N.E. Is an acyl group at O-3 in glucosyl donors able to control α-stereoselectivity of glycosylation? The role of conformational mobility and the protecting group at O-6”, Carb. Res.2014, 384, 70-76. Introduction of the benzoyl group and reductive acetal opening with trifluoroacetic acid and triethylsilane will then give 32a (see, e.g.,“DeNinno, M.P.; Etienne, J.B.; Duplantier, K.C. A method for the selective reduction of carbohydrate 4,6-O- benzylidene acetals”, Tetrahedron Lett.1995, 36, 669-672. The synthesis of 53a will begin from commercially available galactal 61. Selective protection of the primary hydroxyl group as the TBS silyl ether and benzyl protection of the free alcohols will then provide 62 (see, e.g., Paquette, L.A.; Oplinger, J.A.“Synthesis of a structurally modified gl cal. (-)- (2R,4S)-2-Methyl-2-vinyl-4-(benzyloxy)-3,4-dihydro-2H-pyran”, J. Org. Chem.1988, 53, 2953–2959. Dihydroxylation followed by benzoylation and selective cleavage of the anomeric benzoyl group should then yield 64. The hydroquinone will be introduced using the Schmidt method followed by benzoylation of the phenolic hydroxyl group and deprotection of the TBS group using TBAF to provide the target molecule 53a (see, e.g., Schmidt, R. R.; Michel, J.“Facile Synthesis of α- and β-O-Glycosyl Imidates; Preparation of Glycosides and Disaccharides”, Angew. Chem. Int. Ed.1980, 19, 731–732). Scheme 10

Scheme 11

Synthetic Procedures

General Information

[00179] All reactions were carried out under an atmosphere of nitrogen unless otherwise specified. Anhydrous solvents were transferred via syringe to flame-dried glassware, which had been cooled under a stream of dry nitrogen. Anhydrous tetrahydrofuran (THF), acetonitrile, diethyl ether, dichloromethane, toluene, dimethylformamide (DMF) were dried using an mBraun solvent purification system. Analytical thin layer chromatography (TLC) was performed using 250 µm Silica Gel 60 F254 pre-coated plates. Flash column

chromatography was performed using 230-400 Mesh 60A Silica Gel. Proton nuclear magnetic resonance (¹H NMR) spectra were recorded using Varian Unity Inova 500 MHz. Chemical shifts (δ) are reported in parts per million (ppm) downfield relative to

tetramethylsilane (TMS, 0.0 ppm) or CDCl3 (7.26 ppm). Coupling constants (J) are reported in Hz. Multiplicities are reported using the following abbreviations: s, singlet; d, doublet; t, triplet; q, quartet; p, pentet; m, multiplet; b, broad; Carbon-13 nuclear magnetic resonance (¹³C NMR) spectra were recorded using a Varian Unity Inova 500 MHz at 125 MHz.

Chemical shifts are reported in ppm relative to the carbon resonance of CDCl₃ (77.23 ppm). Specific Optical rotations were obtained on a JASCD P - 2000 Series Polarimeter

(wavelength = 589 nm). High-resolution mass spectra (HRMS) were obtained by Mass Spectrometry Core Laboratory of University of Florida, and are reported as m/z (relative ratio). The Instrument ionization source was coupled to the instrument for DART-TOF analysis. Accurate m/z are reported for the molecular ion [M+Na]+. α-Arbutin was purchased from Chem-Impex International, Inc. [Bis(trifluoroacetoxy)iodo]benzene was purchased from Oakwood Chemical. (1R,2S,5R)-(−)-Menthol was purchased from Sigma-Aldrich. All purchased reagents were used without further purification. Preparation of glycosyl donor precursors

[00180] The following compounds were prepared as reported in the literature (see, e.g., Matwiejuk, M.; Thiem, J. Eur. J. Org. Chem.2011, 5860–5878; Lunau, N.; Meier, C. Eur. J. Org. Chem.2012, 6260–6270; Chiara, J. L.; García, A.; Cristóbal-Lumbroso, G. J. Org. Chem.2005, 70 , 4142–4151; Sanapala, S. R.; Kulkarni, S. S. Chem. Eur. J.2014, 20, 3578– 3583; Qian, S.; Chen, Q. L.; Guan, J. L.; Wu, Y.; Wang, Z. Y. Chem. Pharm. Bull.2014, 62, 779–785):

General procedure for synthesis of glycosyl donors

To a stirred solution of a donor precursor (0.2 M) in CH₂Cl₂ was added K₂CO₃ (1 equiv.). After 30 minutes trichloroacetonitrile (10 equiv.) was added dropwise and the reaction mixture was stirred at room temperature. After 12 hours the resulting mixture was filtrated through a pad of Celite®, the filtrate was concentrated under reduced pressure. To the resulting oil, hydroquinone (10 equiv.) was added at room temperature, followed by a mixture CH₂Cl₂: Et₂O (1:1, v:v). The reaction mixture was cooled at 0ºC and stirred for 30 min. BF₃·OEt₂ (0.1 equiv.) was then added dropwise and the reaction mixture was allowed to stirred overnight at room temperature. The solution was concentrated under reduced pressure; the resulting mixture was diluted with CH₂Cl₂, washed with a saturated aqueous solution of K₂CO₃, water and brine. The organic layer was dried over Na₂SO₄, concentrated under reduced pressure and the crude residue was purified with silica gel column chromatography (15% EtOAc/hexane).

[00181] The above compound was prepared in 73% yield (1:6, α:β) as white solid. All data matched reported literature. See, e.g., Wang, Z. X.; et al. Carbohydr. Res.2006, 341, 1945– 1947.

[00182] The above compound was prepared in 70% yield (α only) as white solid. MP = 112.1-114.7 °C; R_f = 0.60 (30% EtOAc /hexane); [α]²³

D = +37.3 (c 1.0, acetone); IR (ATR) = 3370, 1508, 1210, 1088, 732, 695 cm⁻¹; ¹H NMR (500 MHz, CDCl₃) δ 7.39 (m, 18H), 7.17 (m, 2H), 6.88 (d, J = 8.9 Hz, 2H), 6.69 (d, J = 8.9 Hz, 2H), 5.45 (d, J = 2.0 Hz, 1H), 4.90 (d, J = 10.7 Hz, 1H), 4.78 (d, J = 6.3 Hz, 2H), 4.69 (d, J = 3.8 Hz, 2H), 4.63 (d, J = 12.0 Hz, 1H), 4.54 (d, J = 10.8 Hz, 1H), 4.46 (d, J = 12.0 Hz, 1H), 4.09 (dd, J = 5.1, 1.8 Hz, 2H), 3.95 (s, 1H), 3.90 (dp, J = 7.0, 2.0 Hz, 1H), 3.79 (dd, J = 11.0, 4.8 Hz, 1H), 3.69 (dd, J = 11.0, 1.9 Hz, 1H); ¹³C NMR (125 MHz, CDCl₃) δ 151.1, 150.6, 138.79, 138.75, 138.6, 138.5, 128.8, 128.73, 128.72, 128.66, 128.62, 128.59, 128.3, 128.2, 128.1, 128.03, 127.97, 127.95, 127.8, 118.4, 116.3, 97.5, 80.3, 75.5, 75.1, 75.0, 73.6, 73.1, 72.7, 72.6, 69.4. HRMS (ESI) m/z: [M+Na]⁺ Cacld for C₄₀H₄₀O₇655.2666; Found 655.2639.

[00183] The above compound was prepared in 67% yield (mixture of α, β anomers) as white solid.

[00184] The above compound was prepared in 58% yield (>25:1, β:α) as a low melting point solid; R_f = 0.42 (30% EtOAc/hexane); [α]²¹

D = +48.1 (c 1.0, acetone); IR (ATR) = 3391, 1774, 1707, 1508, 1207, 1051, 696 cm⁻¹; ¹H NMR (500 MHz, CDCl₃) δ 7.84-7.60 (m, 4H), 7.41-7.21 (m, 10H), 7.05-6.94 (m, 2H), 6.91-6.82 (m, 3H), 6.77-6.71 (m, 2H), 6.60-6.50 (m, 2H), 5.71-5.55 (m, 1H), 4.97 (s, 1H), 4.86 (d, J = 10.9 Hz, 1H), 4.81 (d, J = 12.1 Hz, 1H), 4.68-4.60 (m, 2H), 4.56 (d, J = 12.1 Hz, 1H), 4.46 (d, J = 12.1 Hz, 1H), 4.44-4.38 (m, 2H), 3.93-3.67 (m, 4H); ¹³C NMR (125 MHz, CDCl₃) δ 151.6, 151.2, 138.4, 138.21, 138.19, 134.16, 128.8, 128.7, 128.4, 128.31, 128.27, 128.2, 128.1, 128.0, 127.7, 123.7, 119.2, 116.5, 116.1, 98.0, 79.9, 79.5, 75.6, 75.4, 75.2, 73.8, 68.9, 56.2. HRMS (ESI) m/z: [M+Na]⁺ Cacld for C₄₁H₃₇O₈N 694.2411; Found 694.2379.

[00185] The above compound was prepared in 68% yield (>25:1, α:β) as white solid. MP = 140.8-142.1 °C; R_f = 0.50 (25% EtOAc/hexane); [α]²²

D = +46.0 (c 1.0, acetone); IR (ATR) = 3345, 1774, 1707, 1508, 1207, 1051, 695 cm⁻¹; ¹H NMR (500 MHz, CDCl₃) δ 8.09 (dt, J = 8.2, 1.5 Hz, 2H), 7.56 (td, J = 7.4, 1.3 Hz, 1H), 7.25 (s, 17H), 6.90 (d, J = 8.9 Hz, 2H), 6.68 (d, J = 8.9 Hz, 2H), 5.77 (dt, J = 3.1, 1.5 Hz, 1H), 5.54 (d, J = 2.0 Hz, 1H), 5.18 (s, 1H), 4.90 (d, J = 10.8 Hz, 1H), 4.84 (d, J = 11.4 Hz, 1H), 4.67 (dd, J = 22.9, 11.6 Hz, 2H), 4.56 (d, J = 10.7 Hz, 1H), 4.48 (d, J = 11.9 Hz, 1H), 4.30 (ddd, J = 9.3, 3.2, 1.4 Hz, 1H), 4.19 (td, J = 9.7, 1.4 Hz, 1H), 4.07-3.96 (m, 1H), 3.88 (dd, J = 11.0, 3.8 Hz, 1H), 3.74 (dd, J = 10.8, 2.0 Hz, 1H); ¹³C NMR (125 MHz, CDCl₃) δ 166.22, 166.21, 151.49, 151.47, 150.2, 138.59, 138.58, 138.2, 133.63, 130.4, 130.0, 128.8, 128.73, 128.69, 128.67, 128.39, 128.36, 128.34, 128.0, 127.91, 127.87, 118.3, 116.4, 97.2, 78.4, 75.7, 74.5, 73.7, 72.4, 72.1, 69.3, 69.2. HRMS (ESI) m/z: [M+Na]⁺ Cacld for C₄₀H₃₈O₈669.2459; Found 669.2475

[00186] The above compound was prepared in 63% yield (>25:1, β:α) as white solid. MP = 155.5-157.1 °C; R_f = 0.30 (25% EtOAc/hexane); [α]²¹

D = +21.4 (c 1.0, acetone); IR (ATR) = 3274, 1724, 1509, 1220, 1055, 1052, 709, 695 cm⁻¹; ¹H NMR (500 MHz, CDCl₃) δ 8.01 (ddd, J = 8.5, 2.5, 1.3 Hz, 2H), 7.62-7.55 (m, 1H), 7.43 (d, J = 7.6 Hz, 2H), 7.33-7.10 (m, 15H), 6.85 (ddd, J = 7.8, 3.8, 1.7 Hz, 2H), 6.63 (ddd, J = 8.9, 4.5, 1.7 Hz, 2H), 5.58-5.41 (m, 1H), 4.96-4.94 (m, 1H), 4.86-4.82 (m, 1H), 4.78-4.74 (m, 1H), 4.68 (dd, J = 11.6, 2.4 Hz, 1H), 4.64-4.54 (m, 4H), 3.88 (td, J = 9.0, 3.6 Hz, 1H), 3.84-3.79 (m, 2H), 3.73 (dd, J = 10.8, 5.2 Hz, 1H), 3.66 (dtd, J = 9.1, 4.0, 1.9 Hz, 1H); ¹³C NMR (125 MHz, CDCl₃) δ 165.6, 151.7, 138.3, 138.1, 138.00, 133.5, 130.13, 130.12, 130.08, 128.80, 128.75, 128.72, 128.69, 128.6, 128.5, 128.4, 128.2, 128.12, 128.10, 128.03, 128.00, 119.3, 116.2, 101.2, 83.0, 78.2, 75.7, 75.4, 74.03, 74.02, 73.9, 69.1. HRMS (ESI) m/z: [M+Na]⁺ Cacld for C₄₀H₃₈O₈669.2459; Found 669.2434.

[00187] ¹H NMR (500 MHz, CDCl₃) δ 8.28– 8.16 (m, 2H), 7.71– 7.62 (m, 1H), 7.55 (t, J = 7.8 Hz, 2H), 7.41– 7.19 (m, 20H), 7.16 (s, 4H), 5.07 (d, J = 11.0 Hz, 1H), 5.03– 5.00 (m, 1H), 4.98 (d, J = 10.9 Hz, 1H), 4.90– 4.81 (m, 3H), 4.68– 4.52 (m, 3H), 3.87– 3.69 (m, 5H), 3.63 (ddd, J = 9.4, 5.0, 1.9 Hz, 1H).¹³C NMR (125 MHz, CDCl₃) δ 165.4, 155.1, 146.0, 138.5, 138.2, 138.1, 138.0, 133.6, 130.17, 130.17, 129.58, 128.58, 128.43, 128.41, 128.39, 128.37, 128.24, 128.0127.9, 127.82, 127.81, 127.76, 127.67, 127.62, 122.58, 117.9, 102.1, 84.7, 82.0, 77.7, 75.8, 75.2, 75.11, 75.07, 73.5, 68.8. Preparation of glycosyl donors

Scheme 12

Procedures for Scheme 12

[00188] To a stirred solution of Arbutin (20 mmol, 5.4 g) in DMF (20 mL) was added anhydrous K₂CO₃ (24 mmol, 5.5 g) and allyl bromide (24 mmol, 2.9 g) at room temperature. After 24h the reaction was filtrated, the solvent was concentrated under reduced pressure and the crude residue was purified with silica gel column chromatography (5% MeOH/CH₂Cl₂) to afford the title compound as a white solid (quantitative yield, 6.2 g). MP = 142-144ºC; R_f = 0.56 (5% MeOH/CH₂Cl₂); [α] ²²

D = -48.94 (c 0.5, acetone); IR (neat) : 3370, 1510, 1229, 1076, 1022, 822 cm^-1 ; ¹H NMR (500 MHz, (CD₃)₂CO) δ 7.04 (d, J = 8.9 Hz, 2H), 6.88 (d, J = 8.9 Hz, 2H), 6.07 (ddt, J = 16.3, 10.5, 5.2 Hz, 1H), 5.41 (d, J = 17.3 Hz, 1H), 5.25 (d, J = 10.5 Hz, 1H), 4.85 (d, J = 7.6 Hz, 1H), 4.64 (s, 1H), 4.54 (d, J = 4.9 Hz, 2H), 4.47 (s, 1H), 4.38 (s, 1H), 3.91 (d, J=10.0 Hz, 1H), 3.78-3.72 (m, 2H), 3.56-3.45 (m, 4H).¹³C NMR (125 MHz, (CD₃)₂CO) δ 153.9, 152.1, 134.1, 117.9, 116.3, 115.3, 102.1, 77.1, 76.8, 73.8, 70.5, 68.8, 61.8. HRMS (ESI) m/z: [M+Na]⁺ cacld for C₁₅H₂₀O₇335.1101; Found 335.1091.

[00189] To a stirred solution of 12-A in pyridine (20mL) was added TBSCl (20 mmol, 3 g) and DMAP (2 mmol, 0.24 g) at 0ºC. The reaction was warmed up to room temperature and stirred for 10h. The solution was quenched with H₂O (60 mL) the product was extracted with CH₂Cl₂ (3x20 mL). The organic layers were dried over Na₂SO₄, concentrated under reduced pressure and the crude residue was purified with silica gel column chromatography (5% MeOH/CH₂Cl₂) to afford the title compound as a colorless solid (6.39 g, 75% yield). MP = 111-113 ºC; R_f = 0.68 (5% MeOH/CH₂Cl ²²

2); [α]_D = -57.1 (c 0.5, acetone); IR (neat) = 3433, 2929, 1641, 1505, 1215, 1109, 1062, 847, 776 cm^-1; ¹H NMR (500 MHz, CDCl₃) δ 6.99 (d, J = 9.0 Hz, 2H), 6.76 (d, J = 9.0 Hz, 2H), 6.04 (ddt, J = 17.3, 10.5, 5.3 Hz, 1H), 5.44-5.24 (m, 3H), 4.79-4.66 (m, 2H), 4.50-4.40 (m, 3H), 3.92 (dd, J = 10.9, 3.2 Hz, 1H), 3.77 (dd, J = 10.5, 6.0 Hz, 1H), 3.68 (d, J = 6.0 Hz, 2H), 3.53 (m, 1H), 3.42 (m, 1H), 0.89 (s, 9H), 0.04 (d, J = 10.5 Hz, 6H).¹³C NMR (125 MHz, CDCl₃) δ 154.3, 151.4, 133.5, 118.5, 117.5, 115.4, 101.6, 76.5, 75.8, 75.7, 73.3, 71.4, 71.3, 69.3, 63.7, 25.9, 18.3, -5.3, -5.4. HRMS (ESI) m/z: [M+Na]⁺ cacld for C₂₁H₃₄O₇Si 449.1966; Found 449.1955.

[00190] To a stirred solution of 12-B (15 mmol, 6.39 g) in DMF (100 mL) was added NaH (45 mmol) (60% dispersion in mineral oil) portionwise at 0ºC. The suspension was stirred for 1h at 0ºC followed by addition of Benzyl bromide (66 mmol, 1.4 mL). The reaction was warmed up to room temperature and stirred for 14h. The solution was cooled down to 0ºC and quenched with slow addition of H₂O (30 mL). The product was extracted with Hexane (3x 50 mL). The organic layers were dried over Na₂SO₄, concentrated under reduced pressure and the crude residue was purified with silica gel column chromatography (5%

EtOAc/hexane) to afford the title compound as colorless oil (9.0 g, 87 % yield). R_f = 0.7 (20% EtOAc/hexane); [α] ²²

D = -8.7 (c 0.5, CH₂Cl₂); IR(neat) = 2952, 1643, 1505.1211, 1069, 835, 778, 734, 697 cm^-1; ¹H NMR (500 MHz, CDCl₃) δ 7.39-7.30 (m, 15H), 7.05 (d, J = 9Hz, 2H), 6.85 (d, J = 9.0 Hz, 2H), 6.07 (ddt, J = 17.3, 10.6, 5.3 Hz, 1H), 5.42 (dq, J = 17.0, 1.5 Hz, 1H), 5.30 (dq, J = 10.5, 1.5 Hz, 1H), 5.08 (d, J = 10.9 Hz, 1H), 4.96 (d, J = 10.8 Hz, 1H), 4.91-4.84 (m, 4H), 4.70 (d, J = 11Hz, 1H), 4.52 (dt, J = 5.4, 1.5 Hz, 2H), 3.89 (dd, J = 11.3, 1.6 Hz, 1H), 3.81-3.62 (m, 4H), 3.42 (ddd, J = 9.6, 5.1, 1.7, 1H), 0.93 (s, 9H), 0.07 (d, J = 15.5 Hz, 6H).¹³C NMR (125 MHz, CDCl₃) δ 154.3, 151.8, 138.6, 138.4, 138.3, 133.5, 128.5, 128.44, 128.43, 128.2, 128.1, 128.0, 127.9, 127.75, 127.71, 118.7, 117.6, 115.5, 103.0, 84.7, 82.3, 77.6, 76.1, 75.9, 75.1, 75.1, 69.4, 62.3, 25.9, 18.3, -5.1, -5.3. HRMS (ESI) m/z: [M+Na]⁺ cacld for C₄₂H₅₂O₇Si 719.3375; Found 719.3343.

[00191] To a stirred solution of 12-C (13 mmol, 9.0 g) in methanol (65 mL) was added anhydrous K₂CO₃ (60 mmol, 8 g) and Pd(Ph₃)₄ (0.26 mmol, 300 mg) at room temperature. The reaction mixture was stirred at room temperature for 24h then filtrated through celite, the solvent was concentrated under reduced pressure and the crude residue was purified with silica gel column chromatography (20% EtOAc/hexane) to afford the title compound as colorless solid (5.9 g, 70% yield). MP = 76-79 ºC; R_f = 0.29 (20% EtOAc/hexane); [α] ²²

D = - 17.4 (c 0.5, CH₂Cl₂); IR(neat) = 3418, 1651, 1509, 1455, 1359, 1212, 1067, 835, 777, 737, 698 cm^-1; ¹H NMR (500 MHz, CDCl₃) δ 7.40-7.31 (m, 15H), 6.80 (d. J = 9 Hz, 2H), 6.70 (d, J = 9 Hz, 2H), 5.08 (d, J = 10.9 Hz, 1H), 5.03 (s, 1H), 4.97 (d, J = 10.5 Hz, 1H), 4.90 (d, J = 11 Hz, 1H), 4.87-4.84 (m, 3H), 4.71 (d, J = 11 Hz, 1H), 3.89 (dd, J =11.5, 1.5 Hz, 1H), 3.81- 3.77 (m, 1H), 3.75 (d, J = 8.5 Hz, 1H), 3.71-3.63 (m, 2H), 3.42 (ddd, J = 9.6, 5.0, 1.8 Hz, 1H), 0.93 (s, 9H), 0.07 (d, J =15.5 Hz, 6H). ¹³C NMR (125 MHz, CDCl₃) δ 151.7, 151.2, 138.5, 138.4, 138.2, 128.52, 128.46, 128.2, 128.11, 128.06, 127.9, 127.8, 127.7, 118.9, 115.9, 103.1, 84.7, 82.3, 77.6, 77.3, 77.1, 76.8, 76.1, 75.9, 75.1, 62.4, 25.9, 18.4, -5.1, -5.3. HRMS (ESI) m/z: [M+Na]⁺ cacld for C₃₉H₄₈O₇Si 679.3062; Found 679.3081.

[00192] To a stirred solution of 12-D (9.1 mmol, 5.9 g) in CH₂Cl₂ (50 mL) was added Et₃N (30 mmol, 4.5 mL) and BzCl (9.1 mmol, 1.1 mL) at room temperature. After 1h the reaction was washed with H₂O (3x20 mL). The orgranic layers were dried over Na₂SO₄, concentrated under reduced pressure and the crude residue was purified with silica gel column

chromatography (5% EtOAc/hexane) to afford the title compound as colorless oil (5.5 g, 80% yield). R_f = 0.9 (20% EtOAc/hexane). [α] ²²

D = -3.4 (c 0.4, CH₂Cl₂); IR(neat) = 1739, 1504, 1264, 1193, 1064, 836, 781, 735, 698 cm^-1; ¹H NMR (500 MHz, CDCl₃) δ 8.25 (d, J = 7.1 Hz, 2H), 7.67 (t, J = 7.4 Hz, 1H), 7.57 (t, J = 7.7 Hz, 2H), 7.42-7.33 (m, 15H), 7.18 (s, 4H), 5.11 (d, J = 11.0 Hz, 1H), 5.02-4.97 (m, 2H), 4.93 (d, J = 11.0 Hz, 1H), 4.89 (dd, J = 11.0, 2.5 Hz, 2H), 4.74 (d, J = 11.0 Hz, 1H), 3.94 (dd, J = 11.3, 1.4 Hz, 1H), 3.86-3.72 (m, 3H), 3.69 (t, J = 9.1 Hz, 1H), 3.49 (ddd, J = 9.7, 5.1, 1.8 Hz, 1H), 0.95 (s, 9H), 0.09 (d, J = 14 Hz, 6H).¹³C NMR (125 MHz, CDCl₃) δ 165.4, 155.4, 146.1, 138.6, 138.4, 138.3, 133.6, 130.2, 129.6, 128.6, 128.5, 128.49, 128.48128.2, 128.09, 128.06, 127.9, 127.83, 127.76, 122.6, 118.3, 102.5, 84.7, 82.3, 77.6, 77.4, 77.1, 76.9, 76.3, 75.9, 75.2, 75.1, 62.3, 25.9, 18.4, -5.1, - 5.3. HRMS (ESI) m/z: [M+Na]⁺ cacld for C₄₆H₅₂O₈Si 783.3324; Found 783.3312.

[00193] Compound 12-E (7.2 mmol, 5.5 g) was suspended in MeOH (35 mL) followed by catalytic amount of p-TsOH at room temperature. The suspension was stirred until full conversion of the starting material. The reaction concentrated under reduced pressure and the crude residue was purified with silica gel column chromatography (EtOAc/hexane: 4/2) to afford the title product as a white solid (4.3g, 92 % yield). MP = 114-117; R_f = 0.6 ( 20% EtOAc/hexane); [α] ²²

D = -12.1(c 0.5, CH₂Cl₂); IR(neat) = 3422, 1732, 1645, 1506, 1455, 1270, 1246, 1195, 1065, 1025 cm^-1; ¹H NMR (500 MHz, CDCl₃) δ 8.21 (d, J = 7.1 Hz, 2H), 7.65 (t, J = 7.5 Hz, 1H), 7.52 (t, J = 7.8 Hz, 2H), 7.38-7.30 (m, 15H), 7.17 (d, J = 9.1 Hz, 2H), 7.09 (d, J = 9.1 Hz, 2H), 5.07 (d, J = 7.5 Hz, 1H), 5.03 (d, J = 10.4 Hz, 1H), 4.98 (d, J = 10.9 Hz, 1H), 4.92-4.83 (m, 3H), 4.70-4.68 (m, 2H), 3.93-3.89 (m, 1H), 3.80-3.65 (m, 4H), 3.52 (ddd, J = 9.7, 4.7, 2.7 Hz, 1 H).¹³C NMR (125 MHz, CDCl₃) δ 165.4, 154.8, 146.1, 138.4, 138.0, 137.8, 133.6, 130.2, 129.4, 128.6, 128.5, 128.5, 128.4, 128.2, 128.1, 128.0, 127.9, 127.9, 127.7, 126.9, 122.8, 117.6, 101.8, 84.4, 81.9, 77.2, 75.8, 75.4, 75.2, 75.2, 61.9. HRMS (ESI) m/z: [M+Na]⁺ cacld for C₄₀H₃₈O₈669.2459; Found 669.2449. Scheme 13

Procedures for Scheme 13

[00194] To a stirred solution of arbutin (10 mmol, 2.7 g) in DMF (10 mL) was added benzaldehyde dimethyl acetal (12 mmol, 1.8 mL) and a catalytic amount of p-TsOH at room temperature. The reaction is heated up to 70 ºC and stirred for 14 h. H₂O (30 mL) was then added, the white precipitate was filtrated and dried under vacuum to afford the title product as a white solid (3.0, 84 % yield). MP: 247-248 ºC R_f: 0.6 (50% Acetone/hexane), [α]²¹

D -40.3 (c 0.60, acetone); MP: 247.1-248.5 °C; IR (ATR) 3336, 1509, 1376, 1215, 1081, 1016, 748, 695 cm⁻¹; ¹H NMR (500 MHz, (CD₃)₂CO) δ 8.15 (s, 1H), 7.64-7.46 (m, 2H), 7.47-7.33 (m, 3H), 7.09-6.90 (m, 2H), 6.92-6.68 (m, 2H), 5.67 (s, 1H), 5.00 (d, J = 7.7 Hz, 1H), 4.80 (d, J = 4.3 Hz, 1H), 4.70 (d, J = 3.9 Hz, 1H), 4.32 (dd, J = 10.3, 4.7 Hz, 1H), 3.99-3.71 (m, 2H), 3.71-3.54 (m, 3H).¹³C NMR (125 MHz, (CD₃)₂CO) δ 153.3, 151.4, 138.7, 129.1, 128.4, 126.9, 118.7, 116.0, 103.2, 101.8, 81.4, 75.3, 74.0, 68.8, 66.8. HRMS (ESI) m/z:[M+Na]⁺ cacld for C₁₉H₂₀O₇383.1101; Found 383.1191.

[00195] To a stirred solution of 13-A (2 mmol, 0.97 g) in CH₂Cl₂ (10 mL) was added Et₃N (18 mmol, 2.6 mL) and Ac₂O (9 mmol, 0.9 mL) at room temperature. After 5 h the reaction was washed with H₂O (3x20 mL). The orgranic layers were dried over Na₂SO₄, concentrated under reduced pressure and the crude residue was purified with silica gel column

chromatography (10% EtOAc/Hexane) to afford the title compound as a white solid (1.7 g, 87% yield). MP = 191-193 ºC; R_f = 0.53 (50% EtOAc/hexane); [α]²¹

D = -34.3 (c 1.2,

CH₂Cl₂); IR (ATR) 1747, 1503, 1365, 1216, 1188, 971, 763, 696 cm⁻¹; ¹H NMR (500 MHz, CDCl₃) δ 7.62-7.39 (m, 2H), 7.40-7.28 (m, 3H), 7.08– 6.95 (m, 4H), 5.53 (s, 1H), 5.40 (t, J = 9.4 Hz, 1H), 5.26 (dd, J = 9.2, 7.7 Hz, 1H), 5.14 (d, J = 7.7 Hz, 1H), 4.40 (dd, J = 10.6, 4.9 Hz, 1H), 3.82 (dt, J = 12.8, 9.9 Hz, 2H), 3.65 (td, J = 9.7, 4.9 Hz, 1H), 2.29 (s, 3H), 2.12-2.00 (m, 6H); ¹³C NMR (125 MHz, CDCl₃) δ 170.4, 167.0, 169.9, 154.7, 146.6, 137.0, 129.5, 128.6, 126.48, 126.47, 122.9, 118.3, 101.9, 100.3, 78.4, 72.4, 72.0, 68.8, 66.9, 21.4, 21.1, 21.00. HRMS (ESI) m/z: [M+Na]⁺ cacld for C₂₅H₂₆O₁₀509.1418; Found 509.1428.

[00196] To a stirred solution of 13-B (1 mmol, 0.49 g) in CH₂Cl₂ (5 mL) was added Et₃SiH (6 mmol, 0.95 mL) followed by slow addition of TFA (6 mmol, 0.46 mL) at 0 ºC. The reaction was stirred at 0 ºC for 30 min, heated up to room temperature and stirred for 2 h. The mixture was diluted with CH₂Cl₂ (10 mL) and washed with a saturated aqueous solution of NaHCO₃ (3x10 mL). The organic layers were dried over Na₂SO₄, concentrated under reduced pressure and the crude residue was purified with silica gel column chromatography (1/1 EtOAc/hexane) to afford the title compound as a white solid (0.39 g, 81% yield). R_f = 0.39 (1/1 EtOAc/hexane), [α] ²¹

D = -24.6 (c 1.0, CH₂Cl₂). IR (ATR) = 1747, 1503, 1365, 1216, 1188, 971, 763, 696 cm⁻¹; ¹H NMR (500 MHz, CDCl₃) δ 7.32 (m, 5H), 7.04-7.96 (m, 4H), 5.23-5.10 (m, 2H), 5.03 (d, J = 7.6 Hz, 1H), 4.63-4.52 (q, J = 12.0, 21.0 Hz, 2H), 3.86-3.73 (m, 3H), 3.67 (dt, J = 9.4, 4.5 Hz, 1H), 3.32 (s, 1H), 2.29 (s, 3H), 2.10 (s, 3H), 2.06 (s, 3H); ¹³C NMR (125 MHz, CDCl₃) δ 171.2, 169.8, 169.7, 154.6, 145.9, 137.7, 128.5, 127.9, 127.7, 122.5, 117.8, 99.3, 75.6, 74.9, 73.7, 71.3, 70.0, 69.6, 21.1, 20.9, 20.7. HRMS (ESI) m/z:[M+Na]⁺ cacld for C₂₅H₂₈O₁₀511.1575; Found 511.1559.

Scheme 14

Procedures for Scheme 14

[00197] To a stirred solution of 13-A (10 mmol, 3.60 g) in DMF (20 mL) was added K₂CO₃ (14 mmol, 1.92 g) and allyl bromide (14 mmol, 1.19 mL) at room temperature. After 24 hours the reaction was quenched with H₂O (100 mL). The white precipitate was collected through vacuum filtration, washed with H₂O (2x50 mL) and dried under vacuum to afford the title compound as a white solid (3.80 g, 95%). MP = 176.5-178.7 °C; R_f = 0.37 (50%

Acetone/hexane); [α]²⁴

D = -32.7 (c 1.0, acetone); IR (ATR) = 3361, 1658, 1506, 1081, 1013, 820, 730, 696 cm⁻¹; ¹H NMR (500 MHz, (CD₃)₂CO) δ 7.55-7.48 (m, 2H), 7.47-7.35 (m, 3H), 7.14-6.98 (m, 2H), 6.96-6.80 (m, 2H), 6.07 (ddt, J = 17.2, 10.5, 5.3 Hz, 1H), 5.59 (s, 1H), 5.43 (dq, J = 17.2, 1.6 Hz, 1H), 5.31 (dq, J = 10.5, 1.4 Hz, 1H), 4.94 (d, J = 7.7 Hz, 1H), 4.53 (dt, J = 5.3, 1.6 Hz, 2H), 4.40 (dd, J = 10.5, 4.9 Hz, 1H), 3.94 (td, J = 9.1, 2.2 Hz, 1H), 3.85 (t, J = 10.3 Hz, 1H), 3.79 (ddd, J = 9.0, 7.7, 2.7 Hz, 1H), 3.67 (t, J = 9.3 Hz, 1H), 3.58 (ddd, J = 9.9, 9.3, 5.0 Hz, 1H), 2.86 (d, J = 2.3 Hz, 1H), 2.77 (d, J = 2.8 Hz, 1H); ¹³C NMR (125 MHz, (CD₃)₂CO) δ 154.8, 152.5, 138.9, 134.7, 129.3, 128.5, 127.0, 118.6, 117.0, 115.9, 103.1, 101.9, 81.5, 75.4, 74.1, 69.5, 69.0, 66.9. HRMS (ESI) m/z: [M+Na]⁺ cacld for C₂₂H₂₄O₇423.1414; Found 423.1393.

[00198] A mixture of 14-A (2.5 mmol, 1.0 g), n-Bu₂SnO (2.94 mmol, 731 mg), benzene (20 mL) was stirred at reflux for 5 h. The benzene was distilled off and the stannylidene derivative was redissolved in toluene (10 mL) and then n-Bu₄NBr (4.01 mmol, 1.29 g) and benzyl bromide (4.04 mmol, 0.48 mL) were added at 60 ^oC. The reaction mixture was stirred for 5 h, concentrated under reduced pressure and the crude residue was purified with silica gel column chromatography (15:1, toluene/EtOAc). The resulting product was dissolved in methanol (50 mL). Potassium carbonate (5 mmol, 690 mg) and Pd(PPh₃)₄ (0.031mmol, 29 mg) were added. The mixture was stirred at room temperature for 24 hours. The resulting mixture was concentrated under reduced pressure, diluted with EtOAc (100 mL) washed with H₂O (50 mL) and brine (50 mL). The orgranic layer was dried over Na₂SO₄, concentrated under reduced pressure and the crude residue was purified with silica gel column

chromatography (7% to 15% Acetone/toluene) to afford the title compound as a white solid (450 mg, 40% yield). MP = 218.8-219.8 °C; R_f = 0.71 (50% ethyl acetate/hexane); [α]²³

D = - 37.3 (c 1.0, acetone); IR (ATR) = 3295, 1508, 12181079, 1056, 824, 692, 657 cm⁻¹; ¹H NMR (500 MHz, (CD₃)₂CO) δ 8.09 (s, 1H), 7.63-7.48 (m, 2H), 7.48-7.36 (m, 5H), 7.37-7.11 (m, 3H), 7.01-6.87 (m, 2H), 6.86-6.67 (m, 2H), 5.72 (s, 1H), 5.07-4.81 (m, 4H), 4.34 (dd, J = 10.2, 4.9 Hz, 1H), 3.84 (t, J = 10.2 Hz, 1H), 3.79-3.71 (m, 3H), 3.71-3.64 (m, 1H); ¹³C NMR (125 MHz, (CD₃)₂CO) δ 153.5, 151.6, 140.1, 138.9, 129.3, 128.6, 128.2, 127.8, 126.9, 119.0, 116.3, 103.6, 101.6, 81.9, 81.8, 75.1, 74.7, 69.1, 66.8. HRMS (ESI) m/z: [M+Na]⁺ cacld for C₂₆H₂₆O₇473.1571; Found 473.1560.

[00199] To a stirred solution of 14-B (1 mmol, 450 mg) in pyridine (10 mL) was added DMAP (5 mg) and benzoylchloride (3 mmol, 420 mg). After 24h the reaction mixture was quenched with water (10 mL), diluted with EtOAc (50 mL) and washed with an aqueous solution of CuSO₄ (2 M, 3x15 mL) and brine (1x10 mL). The organic layer was dried over Na₂SO₄, concentrated under reduced pressure and the crude residue was purified with silica gel column chromatography (10% EtOAc/toluene) to afford the title compound as white solid (532 mg, 81%). MP = 201-201°C; R_f = 0.76 (33% EtOAc/hexane); [α]²³

D = +38.9 (c 1.0, acetone); IR (ATR) = 1722, 1601, 1505, 1267, 1094, 1081, 1067, 707, 694 cm⁻¹; ¹H NMR (500 MHz, CDCl₃) δ 8.23-8.11 (m, 2H), 8.08-7.99 (m, 2H), 7.76-7.58 (m, 2H), 7.59-7.37 (m, 9H), 7.25-7.04 (m, 7H), 7.02 (dd, J = 9.0, 2.6 Hz, 2H), 5.68 (s, 1H), 5.60 (dq, J = 11.2, 4.1, 3.4 Hz, 1H), 5.21 (dd, J = 7.9, 2.7 Hz, 1H), 4.89 (dd, J = 12.1, 2.9 Hz, 1H), 4.77 (dd, J = 12.1, 2.8 Hz, 1H), 4.48 (dd, J = 10.7, 4.9 Hz, 1H), 4.14-3.98 (m, 2H), 3.94 (t, J = 10.3 Hz, 1H), 3.68 (h, J = 4.4 Hz, 1H).¹³C NMR (125 MHz, CDCl₃) δ 165.6, 165.4, 155.1, 146.8, 138.1, 137.5, 134.0, 133.6, 130.5, 130.2, 129.9, 129.8, 129.5, 128.9, 128.8, 128.7, 128.6, 128.4, 128.0, 126.4, 123.0, 118.7, 101.8, 101.0, 81.8, 78.2, 74.4, 73.5, 69.0, 66.9; HRMS (ESI) m/z: [M+Na]⁺ cacld for C₄₀H₃₄O₉681.2095; Found 681.2059.

[00200] 14-C (0.5 mmol, 532 mg), Cu(OTf)₂ (0.020 mmol, 7.3 mg) and BH₃•THF (1 M) (4 mmol, 4.0 mL) were stirred at 0ºC for 12h. After this time the solution was quenched by MeOH (1 mL), concentrated under reduced pressure and the crude residue was purified with silica gel column chromatography (20% EtOAc/toluene) to afford the title compound as white solid (510 mg, 96%). MP = 153.1-154.0 °C; R_f = 0.37 (33% EtOAc/hexane); [α]²³

D = +50.8 (c 1.0, CH₂Cl₂); IR (ATR) = 1743, 1724, 1506, 1059, 744, 705, 696 cm⁻¹; ¹H NMR (500 MHz, CDCl₃) δ 8.23-8.10 (m, 2H), 8.10-7.93 (m, 2H), 7.71-7.52 (m, 2H), 7.52-7.10 (m, 14H), 7.12-7.04 (m, 2H), 6.98 (dt, J = 7.5, 2.7 Hz, 2H), 5.53 (ddd, J = 9.9, 8.0, 2.0 Hz, 1H), 5.23-5.09 (m, 1H), 4.98-4.86 (m, 1H), 4.80 (dd, J = 11.2, 2.0 Hz, 1H), 4.72 (dd, J = 10.8, 1.9 Hz, 2H), 4.08-3.90 (m, 2H), 3.91-3.73 (m, 2H), 3.63 (ddd, J = 9.6, 4.6, 2.3 Hz, 1H), 1.98 (d, J = 7.1 Hz, 1H); ¹³C NMR (125 MHz, CDCl₃) δ 165.7, 165.5, 155.14, 155.12, 146.5, 138.0, 133.9, 133.6, 130.5, 130.1, 130.0, 129.9, 129.7, 128.9, 128.8, 128.6, 128.5, 128.40, 128.39, 128.1, 123.0, 118.18, 118.17, 100.2, 82.8, 77.7, 76.1, 75.54, 75.50, 73.8, 62.1. HRMS (ESI) m/z: [M+Na]⁺ cacld for C₄₀H₃₆O₉683.2252; Found 683.2216.

[00201] The above compound was prepared using known procedure (see, e.g., Shie, C-H.; Tzeng, Z-H.; Kulkarni, S. S.; Uang, B. J.; Hsu, C-Y.; Hung, S-C. Angew. Chem. Int. Ed. 2005, 44, 1665–1668). All the data matched reported literature. General procedure for glycosylation reactions

[00202] To a stirred solution of glycosyl donor (0.1 mmol) and (1R, 2S, 5R)-(-)-Menthol (0.2 mmol, 31 mg) in dry acetonitrile (0.5 mL) was added PIFA (0.12 mmol, 52 mg) in one portion at room temperature. The reaction mixture instantaneously turned yellow. After 15 min, the solution was diluted with CH₂Cl₂ (2 mL) and quenched with a saturated aqueous solution of NaHCO₃ (2 mL). The organic layer was washed with H₂O (3x 5mL), dried over Na₂SO₄, concentrated under reduced pressure and the crude residue was purified with silica gel column chromatography (25% EtOAc/ Hexane).

[00203] The above compound was prepared in 87% yield (59.0 mg, 0.087 mmol; 1:9, α:β) as a white solid. All data matched reported literature. See, e.g., Jansson, K.; Noori, G.;

Magnusson, G. J. Org. Chem.1990, 55, 3181-3185.

[00204] The above compound was prepared in 87% yield (59.0 mg, 0.087 mmol; 1:9, α:β) as a white solid. All data matched reported literature. See, e.g., Hotha, S.; Kashyap, S. J. Am. Chem. Soc.2006, 128, 9620-9621.

[00205] The above compound was prepared in 71% yield (50 mg, 0.071 mmol; 1:1.5, α:β) as colorless oil. α anomer, semi solid, R_f = 0.73 (20% EtOAc/hexane); [α]²¹

D = +4.6 (c 1.0, CH₂Cl₂); IR (ATR) = 3030, 2951, 2921, 1454, 1101, 1154, 733, 696 cm⁻¹; ¹H NMR (500 MHz, CDCl₃ ) δ 7.58-7.10 (m, 2H), 5.01 (d, J = 12.3 Hz, 1H), 4.95 (d, J = 10.8 Hz, 1H), 4.88 (d, J = 12.3 Hz, 1H), 4.71 (d, J = 11.9 Hz, 1H), 4.64-4.56 (m, 3H), 4.56-4.46 (m, 2H), 3.92 (t, J = 9.6 Hz, 1H), 3.88-3.73 (m, 3H), 3.58 (ddd, J = 16.8, 10.1, 3.6 Hz, 2H), 3.47 (ddd, J = 9.9, 4.8, 2.6 Hz, 1H), 2.45 (pd, J = 6.9, 2.4 Hz, 1H), 2.02 (dd, J = 10.2, 6.1 Hz, 1H), 1.79-1.53 (m, 3H), 1.52-1.34 (m, 1H), 1.34-1.19 (m, 2H), 1.12- 0.72 (m, 11H); ¹³C NMR (125 MHz, CDCl₃) δ 139.1, 138.7, 138.5, 138.4, 128.33, 128.32, 128.31, 128.26, 126.2, 127.8, 127.60, 127.56, 127.5, 127.4, 127.2, 97.9, 82.7, 76.1, 75.14, 75.09, 75.0, 73.9, 73.7, 71.3, 70.1, 48.3, 40.5, 34.5, 31.4, 25.3, 23.1, 22.4, 21.2, 16.0. HRMS (ESI) m/z: [M+Na]⁺ cacld for C₄₄H₅₄O₆ 701.3813; Found 701.3839. β amomer, semi solid, R_f = 0.69 (20% EtOAc/hexane); [α]²¹

D = - 74.6 (c 1.0, CH₂Cl₂); IR (ATR) = 3030, 2922, 1497, 1454.08, 1096, 734, 697 cm⁻¹; ¹H NMR (500 MHz, CDCl₃) δ 7.74-6.96 (m, 20H), 5.01-4.91 (m, 2H), 4.80-4.62 (m, 5H), 4.56 (t, J = 12.1 Hz, 2H), 4.09-3.88 (m, 3H), 3.87-3.52 (m, 3H), 3.29 (td, J = 10.6, 4.2 Hz, 1H), 2.19 (dd, J = 10.2, 6.2 Hz, 1H), 1.82 (dqd, J = 13.9, 9.3, 8.1, 4.7 Hz, 1H), 1.67-1.49 (m, 2H), 1.52-1.31 (m, 1H), 1.15 (ddt, J = 13.1, 10.6, 2.9 Hz, 1H), 1.05-0.54 (m, 13H); ¹³C NMR (500 MHz, CDCl₃) δ 138.62, 138.59, 138.5, 138.3, 128.39, 128.37, 128.34, 128.33, 128.25, 128.09, 128.06, 128.0, 127.8, 127.71, 127.67, 127.58, 127.56, 127.4, 99.9, 81.1, 80.1, 75.3, 74.5, 73.2, 72.4, 72.3, 71.8, 64.5, 48.7, 42.9, 34.3, 31.6, 25.8, 23.3, 22.2, 21.1, 16.3. HRMS (ESI) m/z: [M+Na]⁺ cacld for C₄₄H₅₄O₆701.3813; Found 701.3845.

[00206] The above compound was prepared in 83% yield (56.0 mg, 0.083 mmol; 1:3, α:β) as a colorless oil. All data matched reported literature. See, e.g., Hotha, S.; Kashyap, S. J. Am. Chem. Soc.2006, 128, 9620-9621.

[00207] The above compound was prepared in 64% yield (46.0 mg, 0.064 mmol; >25:1, β:α), semi solid, R_f = 0.78 (30% EtOAc/hexane); [α]²¹

D = -17.0 (c 0.74, CH₂Cl₂); IR (ATR) = 2953, 2921, 1721, 1453, 1265, 1050, 711, 695 cm⁻¹; ¹H NMR (500 MHz, CDCl₃) δ 7.88-7.58 (m, 4H), 7.43-7.25 (m, 10H), 7.08-7.00 (m, 2H), 6.96-6.81 (m, 3H), 5.19 (d, J = 8.4 Hz, 1H), 4.87 (d, J = 10.8 Hz, 1H), 4.82 (d, J = 12.1 Hz, 1H), 4.74-4.64 (m, 2H), 4.61 (d, J = 12.2 Hz, 1H), 4.49 (d, J = 12.1 Hz, 1H), 4.40 (dd, J = 10.8, 8.7 Hz, 1H), 4.17 (dd, J = 10.8, 8.4 Hz, 1H), 3.90-3.70 (m, 3H), 3.63 (ddd, J = 9.9, 4.2, 1.8 Hz, 1H), 3.39 (td, J = 10.6, 4.3 Hz, 1H), 2.27 (pd, J = 7.0, 2.6 Hz, 1H), 1.76-1.64 (m, 1H), 1.54 (ddd, J = 11.8, 7.3, 3.7 Hz, 2H), 1.34- 1.15 (m, 1H), 1.04 (tt, J = 10.5, 3.0 Hz, 1H), 0.99-0.88 (m, 1H), 0.84 (d, J = 7.1 Hz, 3H), 0.78 (d, J = 6.9 Hz, 3H), 0.73-0.59 (m, 4H), 0.38 (q, J = 11.8 Hz, 1H); ¹³C NMR (125 MHz, CDCl₃) δ 138.7, 138.5, 138.4, 133.9, 128.8, 128.7, 128.4, 128.3, 128.2, 128.1, 128.0, 127.8, 127.6, 96.3, 80.1, 79.5, 78.0, 75.3, 74.9, 74.1, 69.5, 56.6, 47.7, 40.7, 34.5, 31.5, 25.4, 23.3, 22.3, 21.3, 16.1. HRMS (ESI) m/z: [M+Na]⁺ cacld for C₄₅H₅₁O₇N 740.3558; Found

740.3593. General procedure for glycosylation reactions

To a stirred solution of glycosyl donor (0.1 mmol) and glycosyl acceptor (0.1 mmol) was added BF₃.Et₂O (0.1 mmol, 10

followed by PIFA (0.12 mmol, 52 mg) in one portion at room temperature. The reaction mixture instantaneously turned yellow. After 15 min, (2 mL) was added and the mixture was quenched with a saturated aqueous solution of NaHCO₃ (2 mL). The organic layer was washed with H₂O (3x 5mL), concentrated under reduced pressure and the crude residue was purified with silica gel column chromatography (5%

PhMe/EtOAc).

[00208] The above compound was prepared in 80% yield (56.0 mg, 0.080mmol ; >25 :1, α:β), semi solid, R_f = 0.69 (20% EtOAc/hexane); [α]²¹

D = -22.2 (c 1.0, CH₂Cl₂); IR (ATR) = 2953, 2921, 1721, 1453, 1266, 1050, 711, 695 cm⁻¹; ¹H NMR (500 MHz, CDCl₃) δ 8.14-8.04 (m, 2H), 7.55 (tt, J = 7.3, 1.3 Hz, 1H), 7.40-7.20 (m, 17H), 5.51 (t, J = 2.4 Hz, 1H), 5.04 (d, J = 2.1 Hz, 1H), 4.90 (d, J = 10.7 Hz, 1H), 4.79 (d, J = 11.5 Hz, 1H), 4.74 (d, J = 11.9 Hz, 1H), 4.61 (d, J = 11.5 Hz, 1H), 4.54 (dd, J = 11.3, 2.3 Hz, 2H), 4.17-3.98 (m, 3H), 3.91 (dd, J = 10.7, 3.9 Hz, 1H), 3.77 (dd, J = 10.7, 1.8 Hz, 1H), 3.38 (td, J = 10.6, 4.3 Hz, 1H), 2.24-2.14 (m, 1H), 2.07 (pt, J = 7.6, 3.8 Hz, 1H), 1.63 (td, J = 7.0, 3.3 Hz, 2H), 1.36 (dddt, J = 15.3, 12.2, 8.0, 3.5 Hz, 1H), 1.22 (ddt, J = 15.5, 10.4, 3.1 Hz, 1H), 1.06-0.94 (m, 2H), 0.93 (d, J = 7.0 Hz, 3H), 0.86 (d, J = 6.5 Hz, 3H), 0.83-0.73 (m, 4H)；¹³C NMR (125 MHz, CDCl₃) δ 166.2, 138.85, 138.76, 138.4, 133.4, 130.4, 130.3, 128.70, 128.66, 128.6, 128.42, 128.40, 128.38, 128.0, 127.95, 127.82, 127.76, 99.7, 82.2, 78.3, 75.6, 75.0, 73.7, 72.0, 71.9, 69.9, 69.6, 48.8, 43.0, 34.6, 31.9, 26.3, 23.7, 22.6, 21.3, 16.8. HRMS (ESI) m/z: [M+Na]⁺ cacld for C₄₄H₅₂O₇715.3605; Found 715.3570.

[00209] The above compound was prepared in 75% yield (0.085 mmol, 100 mg; mixture of α and β) as a white solid. α anomer, semi solid, R_f = 0.25 (2.5% CH₂Cl₂/hexane); [α]²⁰

D = +18.0 (c 0.91, CH₂Cl₂); IR (ATR) = 1735, 1506, 1064, 1064, 754, 696 cm⁻¹; ¹H NMR (500 MHz, CDCl₃) δ 8.14 (d, J = 7.6 Hz, 2H), 7.65 (t, J = 7.6 Hz, 1H), 7.50 (t, J = 7.7 Hz, 2H), 7.40 (d, J = 7.2 Hz, 2H), 7.38-7.19 (m, 31H), 7.17-7.09 (m, 6H), 5.04-4.91 (m, 6H), 4.82 (td, J = 9.8, 8.7, 5.8 Hz, 3H), 4.79-4.72 (m, 3H), 4.59 (d, J = 12.2 Hz, 1H), 4.46 (dd, J = 15.9, 11.6 Hz, 2H), 3.98 (t, J = 9.3 Hz, 1H), 3.93-3.50 (m, 12H); ¹³C NMR (125 MHz,CDCl₃) δ 165.6, 155.4, 146.5, 139.2, 138.9, 138.81, 138.77, 138.54, 138.46, 138.3, 133.8, 130.5, 129.9, 128.84, 128.77, 128.7, 128.65, 128.63, 128.5, 128.30, 128.22, 128.18, 128.15, 128.13, 127.97, 127.94, 127.8, 123.0, 118.8, 102.8, 97.7, 84.9, 82.4, 82.1, 80.4, 78.0, 77.9, 76.05, 75.99, 75.5, 75.4, 75.22, 75.18, 73.6, 73.0, 70.5, 68.8, 66.4. HRMS (ESI) m/z: [M+Na]⁺ cacld for C₇₄H₇₂O₁₃1191.4865; Found 1191.4789.

β amomer, white solid. MP = 149.8-151.4 °C; R_f = 0.09 (CH₂Cl₂/hexane, 6:1); [α]²¹

D = -2.2 (c 1.1, CH₂Cl₂); IR (ATR) = 1733, 1506, 1273, 1196, 1064, 750, 694 cm⁻¹; ¹H NMR (500 MHz, CDCl₃) δ 8.18-8.10 (m, 2H), 7.67-7.58 (m, 1H), 7.48 (t, J = 7.7 Hz, 2H), 7.38– 7.20 (m, 33H), 7.15 (dd, J = 7.2, 2.4 Hz, 2H), 7.12-7.09 (m, 2H), 7.05-6.98 (m, 2H), 5.04 (d, J = 10.9 Hz, 1H), 5.01-4.91 (m, 4H), 4.85-4.75 (m, 5H), 4.70 (d, J = 11.1 Hz, 1H), 4.61-4.55 (m, 2H), 4.51 (dd, J = 13.9, 11.5 Hz, 2H), 4.45 (d, J = 7.8 Hz, 1H), 4.17 (dd, J = 10.7, 4.2 Hz, 1H), 3.83-3.64 (m, 6H), 3.61-3.54 (m, 2H), 3.48 (qd, J = 8.6, 4.2 Hz, 2H), 3.41 (dt, J = 9.5, 3.1 Hz, 1H); ¹³C NMR (125 MHz, CDCl₃) δ 165.5, 155.1, 146.2, 139.0, 138.8, 138.7, 138.5, 138.4, 138.2, 133.8, 130.5, 129.9, 128.84, 128.80, 128.76, 128.74, 128.68, 128.66, 128.63, 128.60, 128.58, 128.51, 128.34, 128.27, 128.23, 128.15, 128.03, 128.02, 127.91, 127.89, 127.86, 122.9, 117.8, 104.2, 101.8, 85.0, 84.9, 82.6, 82.3, 78.4, 78.2, 76.1, 75.7, 75.40, 75.37, 75.3, 75.10, 73.8, 69.3, 69.0. HRMS (ESI) m/z: [M+Na]⁺ cacld for C₇₄H₇₂O₁₃1191.4865; Found 1191.4872.

[00210] The above compound was prepared in 75% yield (0.085 mmol, 100 mg; mixture of α and β) as a white solid. All data matched reported literature. See, e.g., Garcia, B. A.; Gin, D. Y. J. Am. Chem. Soc.2000, 122, 4269-4279.

[00211] Semi solid, R_f = 0.70 (33% EtOAc/hexane); [α]²¹

D = +24.8(c 1.3, CH₂Cl₂); IR (ATR) = 1720.45, 1219.23 , 1054.52, 709.07, 696.88 cm⁻¹; ¹H NMR (500 MHz, CDCl₃) δ 7.99 (dd, J = 8.1, 1.5 Hz, 2H), 7.59-7.50 (m, 1H), 7.41-7.02 (m, 32H), 5.71 (t, J = 2.4 Hz, 1H), 5.56 (d, J = 2.1 Hz, 1H), 5.03 (d, J = 10.9 Hz, 1H), 4.84 (d, J = 10.8 Hz, 1H), 4.79 (d, J = 10.8 Hz, 1H), 4.73 (dd, J = 11.7, 7.8 Hz, 2H), 4.67 (d, J = 12.0 Hz, 1H), 4.60 (d, J = 4.0 Hz, 2H), 4.58- 4.51 (m, 2H), 4.51-4.45 (m, 3H), 4.42 (d, J = 12.0 Hz, 1H), 4.09-3.99 (m, 2H), 3.96 (t, J = 9.1 Hz, 1H), 3.90-3.80 (m, 2H), 3.78-3.68 (m, 4H), 3.55 (td, J = 9.5, 8.7, 2.6 Hz, 2H), 3.40 (s, 3H); ¹³C NMR (125 MHz, CDCl₃) δ 165.6, 138.84, 138.82, 138.6, 138.5, 138.4, 138.29, 133.26, 130.28, 130.25, 128.8, 128.62, 128.58, 128.55, 128.51, 128.48, 128.33, 128.29, 128.27, 127.90, 127.87, 127.82, 127.80, 127.77, 127.73, 127.63, 99.6, 98.1, 82.0, 80.5, 78.5, 76.0, 75.7, 75.6, 74.4, 73.8, 73.7, 73.6, 73.0, 71.7, 69.9, 69.6, 69.4, 69.3, 55.6. HRMS (ESI) m/z: [M+Na]⁺ cacld for C₆₂H₆₂O₁₃1023.4290; Found 1023.4230

[00212] The above compound was prepared in 80% yield (0.080 mmol, 93.0 mg; >25:1, α:β) as a semi solid, R ¹

f = (33% EtOAc/hexane); [α]²

D = -10.8(c 0.5, CH₂Cl₂); IR (ATR) = 1730, 1273, 1196, 1064, 751, 696 cm⁻¹; 8.17 (d, J = 7.9 Hz, 2H), 8.13 (d, J = 7.9 Hz, 2H), 7.68 (t, J = 7.5 Hz, 1H), 7.60 (d, J = 7.4 Hz, 1H), 7.54 (t, J = 7.7 Hz, 2H), 7.48-7.10 (m, 36H), 5.75 (s, 1H), 5.14 (d, J = 11.0 Hz, 1H), 5.10-5.01 (m, 3H), 4.98-4.85 (m, 5H), 4.75 (d, J = 12.0 Hz, 1H), 4.65-4.57 (m, 3H), 4.57-4.50 (m, 2H), 4.13 (d, J = 5.8 Hz, 2H), 3.93 (dd, J = 10.9, 6.0 Hz, 2H), 3.87-3.80 (m, 3H), 3.78-3.66 (m, 2H), 3.61 (t, J = 8.9 Hz, 1H); ¹³C NMR (125 MHz, CDCl₃) δ 165.9, 165.6, 155.4, 146.6, 138.9, 138.8, 138.7, 138.5, 138.3, 138.2, 133.8, 133.4, 130.5, 130.3, 130.2, 129.85, 128.82, 128.78, 128.75, 128.71, 128.67, 128.61, 128.57, 128.52, 128.46, 128.42, 128.21, 128.15, 128.10, 128.04, 128.03, 127.9, 127.8, 127.72, 127.70, 123.0, 118.9, 102.8, 98.3, 85.0, 82.3, 78.4, 78.0, 76.1, 75.43, 75.39, 75.3, 74.52, 74.48, 73.6, 72.0, 71.9, 69.2, 69.0, 66.8. HRMS (ESI) m/z: [M+Na]⁺ cacld for C₇₄H₇₀O₁₄1205.4658; Found 1205.4692

[00213] The above compound was prepared in 82% yield (0.082 mmol, 96.0 mg; >25:1, β:α) as a white solid. MP = 138-140 ºC; R_f = 0.75 (50% EtOAc/Hexane); [α]²²

D = -10.78º (c 0.5, CH₂Cl₂); IR (ATR) = 1729, 1642, 1503, 1452, 1266, 1192, 1067 cm ^-1; ¹H NMR (500 MHz, CDCl₃) δ 8.23 (d, J = 7.4 Hz, 2H), 7.94 (d, J = 7.5 Hz, 2H), 7.67 (t, J = 7.5 Hz, 1H), 7.54 (t, J = 7.7 Hz, 2H), 7.48 (t, J = 7.4 Hz, 1H), 7.34-7.13 (m, 36H), 5.37 (t, J = 8 Hz, 1H), 5.03 (d, J = 11Hz, 1H), 4.92 (dd, J = 8.8, 6.6 Hz, 2H), 4.83 (t, J = 11.7 Hz, 2H), 4.77 (dd, J = 11.1, 6.2 Hz, 2H), 4.71-4.64 (m, 3H), 4.62 (dd, J = 11.5, 4.8 Hz, 2H), 4.55 (s, 1H), 4.54-4.47 (m, 1H), 4.17 (d, J = 11.0 Hz, 1H), 3.84-3.72 (m, 5H), 3.69 (t, J = 6.8 Hz, 2H), 3.64 (dd, J = 15.3, 4.3 Hz, 1H), 3.59-3.48 (m, 2H); ¹³C NMR (125 MHz, CDCl₃) δ 165.3, 165.1, 155.1, 146.0, 138.5, 138.20, 138.15, 137.99, 137.93, 137.8, 133.6, 132.9, 130.2, 129.9, 129.7, 129.6, 128.6, 128.42, 128.39, 128.37, 128.35, 128.24, 128.23, 127.99, 127.95, 127.89, 127.81, 127.79, 127.76, 127.6, 122.6, 118.0, 102.2, 100.9, 84.5, 82.9, 81.9, 78.1, 77.4, 75.6, 75.4, 75.1, 74.99, 74.98, 74.87, 73.7, 73.6, 68.9, 67.7. HRMS (ESI) m/z: [M+Na]⁺ cacld for C₇₄H₇₀O₁₄

1219.445; Found 1219.439.

[00214] The above was prepared in 71% yield (0.071 mmol, 70 mg; 1:1.5, α:β). The diastereomers were separated by preparative thin layer chromatography (2.5% CH₃CN/CH₂Cl₂).

α anomer, semi solid, R_f = 0.50 (2.5% CH₃CN/CH₂Cl₂); [α]²⁰

D = +2.5 (c 1.0, CH₂Cl₂); IR (ATR) = 1754, 1503, 1214, 1188, 1038, 1023, 749, 733 cm⁻¹; ¹H NMR (500 MHz, CDCl₃) δ 7.4-7.07 (m, 25H), 7.05-6.90 (m, 4H), 5.40 (t, J = 9.2 Hz, 1H), 5.24 (dd, J = 9.5, 7.8 Hz, 1H), 5.05-4.96 (m, 2H), 4.88 (d, J = 10.9 Hz, 1H), 4.80 (dd, J = 11.0, 6.9 Hz, 2H), 4.64 (s, 2H), 4.59-4.48 (m, 3H), 4.44 (d, J = 10.8 Hz, 1H), 4.38 (d, J = 12.1 Hz, 1H), 4.11 (t, J = 9.2 Hz, 1H), 3.95 (dd, J = 11.2, 4.2 Hz, 1H), 3.89 (t, J = 9.4 Hz, 1H), 3.86-3.76 (m, 2H), 3.66 (ddd, J = 9.8, 4.1, 1.9 Hz, 1H), 3.61-3.51 (m, 2H), 3.47 (dt, J = 9.9, 3.0 Hz, 2H), 2.30 (s, 3H), 2.06 (s, 3H), 1.92 (s, 3H); ¹³C NMR (125 MHz, CDCl₃) δ 170.5, 170.03, 169.99, 155.0, 146.3, 139.0, 138.7, 138.4, 138.20, 138.17, 128.9, 128.74, 128.72, 128.69, 128.66, 128.64, 128.62, 128.57, 128.34, 128.31, 128.24, 128.1, 128.04, 127.95, 127.9, 127.8, 122.8, 118.2, 99.7, 98.4, 81.8, 80.4, 77.9, 76.0, 75.8, 75.3, 74.9, 74.4, 73.74, 73.71, 73.6, 72.1, 71.7, 21.4, 21.3, 21.1. HRMS (ESI) m/z: [M+Na]⁺ cacld for C₄₄H₅₄O₆1133.3981; Found 1133.3941. β amomer, semi solid, R_f = 0.40 (2.5% CH₃CN/CH₂Cl₂); [α]²¹

D = -0.6 (c 0.91, CH₂Cl₂); IR (ATR) = 1753, 1502, 1454, 1276, 1261, 764, 750, 674 cm⁻¹; ¹H NMR (500 MHz, CDCl₃) δ 7.38-7.20 (m, 23H), 7.15 (dd, J = 7.5, 2.0 Hz, 2H), 7.03-6.90 (m, 4H), 5.30-5.16 (m, 2H), 5.00-4.93 (m, 1H), 4.87 (d, J = 11.0 Hz, 1H), 4.82-4.72 (m, 3H), 4.70 (d, J = 11.3 Hz, 1H), 4.54-4.49 (m, 3H), 4.45 (d, J = 11.8 Hz, 1H), 4.39 (d, J = 11.9 Hz, 1H), 4.32 (d, J = 7.8 Hz, 1H), 4.06-3.93 (m, 1H), 3.79 (dd, J = 11.0, 4.2 Hz, 1H), 3.75-3.67 (m, 3H), 3.64 (t, J = 9.4 Hz, 1H), 3.56 (ddd, J = 9.9, 4.2, 1.8 Hz, 1H), 3.51 (t, J = 9.1 Hz, 1H), 3.35-3.25 (m, 2H), 2.28 (s, 3H), 2.05 (s, 3H), 1.99 (s, 3H); ¹³C NMR (125 MHz, CDCl₃) δ 171.09, 170.04, 169.88, 155.1, 146.3, 138.9, 138.7, 138.6, 138.2, 138.1, 128.76, 128.72, 128.70, 128.69, 128.14, 128.07, 128.05, 128.01, 127.96, 127.91, 127.88, 122.8, 118.2, 103.2, 100.0, 85.1, 82.8, 77.9, 75.8, 75.7, 75.4, 75.2, 75.0, 74.8, 73.7, 73.5, 73.0, 71.7, 69.1, 67.8, 21.4, 21.08, 21.05. HRMS (ESI) m/z: [M+Na]⁺ cacld for C₄₄H₅₄O₆1033.3983; Found 1033.3973. Examples of iterative glycosylations

[00215] Scheme 9 shows examples of an iterative glycosylation/deprotection/glycosylation reacrtions to access polysaccharides. Another example of this is shown below in Scheme 15. Scheme 15

Procedures for Scheme 15

[00216] To a stirred solution of 30 (0.1 mmol) and 48 (0.11 mmol) in a mixture of CH₂Cl₂ (0.5 mL) and CH₃CN (0.5 mL) was added BF₃.Et₂O (0.1 mmol, 10 µL) followed by PIFA (0.11 mmol, 48 mg) in one portion at room temperature. The reaction mixture instantaneously turned yellow. After 1 hour, the mixture was quenched with a saturated aqueous solution of NaHCO₃ (2 mL) then diluted with CH₂Cl₂ (20 mL). The organic layer was washed with H₂O (3x 5mL), concentrated under reduced pressure and the crude residue was purified with silica gel column chromatography (5% PhMe/EtOAc) to give 9-A as a semi solid (75%, 0.075 mmol, 88 mg; >25:1, β:α). R_f = 0.70 (33% EtOAc/hexane); [α]²¹

D = +20.5 (c 1.0, THF); IR (ATR) = 1722, 1262, 1107, 1026, 750, 696 cm⁻¹; ¹H NMR (500 MHz, CDCl₃) δ 8.20 (dd, J = 7.9, 1.6 Hz, 2H), 8.02 (dd, J = 8.0, 1.5 Hz, 2H), 7.95 (dd, J = 8.2, 1.5 Hz, 2H), 7.74-7.62 (m, 1H), 7.62-7.55 (m, 1H), 7.55-7.41 (m, 5H), 7.40-7.28 (m, 13H), 7.26-7.12 (m, 14H), 7.03- 6.96 (m, 4H), 5.52 (dd, J = 9.3, 7.7 Hz, 1H), 5.39 (dq, J = 8.6, 7.0 Hz, 1H), 5.01 (d, J = 7.8 Hz, 1H), 4.89-4.81 (m, 1H), 4.78-4.55 (m, 10H), 4.26-4.14 (m, 1H), 3.90-3.74 (m, 7H), 3.70 (t, J = 8.8 Hz, 1H), 3.60 (ddd, J = 9.3, 4.5, 2.2 Hz, 1H); ¹³C NMR (125 MHz, CDCl₃) δ 165.55, 165.49, 165.46, 155.4, 146.4, 138.5, 138.3, 138.12, 138.06, 138.0, 133.8, 133.5, 133.3, 130.4, 130.14, 130.09, 130.06, 130.04, 129.9, 128.9, 128.74, 128.73, 128.71, 128.70, 128.68, 128.64, 128.56, 128.54, 128.35, 128.31, 128.28, 128.27, 128.15, 128.12, 128.09, 128.06, 127.97, 127.9, 122.8, 118.5, 101.3, 100.5, 83.2, 82.8, 78.3, 78.0, 75.6, 75.5, 75.4, 75.30, 75.27, 75.2, 74.0, 73.9, 73.7, 69.18, 68.15. HRMS (ESI) m/z: [M+Na]⁺ cacld for C₇₄H₆₈O₁₅1219.4450; Found 1219.4390.

[00217] To a stirred solution of 9-A (0.075mmol, 86 mg) in THF (2 mL) was added ethanolamine (6 mmol, 366 mg) at room temperature. After for 24 hours the mixture was concentrated under reduced pressure and the crude residue was purified with silica gel column chromatography (15% EtOAc/toluene) to afford the title compound 50 as a semi solid (85%, 0.063 mmol, 69 mg). R_f = 0.33 (33% EtOAc/hexane); [α]²²

D = +22.1 (c 1.0, dichloromethane); IR (ATR) = 3520, 1722, 1512, 1263, 1060, 1026, 733, 707 cm⁻¹; ¹H NMR (500 MHz, CDCl₃) δ 8.04-7.97 (m, 2H), 7.95-7.87 (m, 2H), 7.60-7.55 (m, 1H), 7.52-7.47 (m, 1H), 7.44 (t, J = 7.8 Hz, 2H), 7.37-7.27 (m, 14H), 7.20 (td, J = 7.1, 6.4, 2.1 Hz, 4H), 7.16- 7.10 (m, 9H), 6.88 -6.75 (m, 2H), 6.68-6.52 (m, 2H), 5.45 (dd, J = 9.4, 7.8 Hz, 1H), 5.35-5.26 (m, 1H), 5.17 (d, J = 3.5 Hz, 1H), 4.88 (d, J = 7.8 Hz, 1H), 4.83 (d, J = 11.0 Hz, 1H), 4.76 (d, J = 11.2 Hz, 1H), 4.72-4.60 (m, 6H), 4.60-4.52 (m, 3H), 4.14 (dd, J = 11.5, 1.5 Hz, 1H), 3.83-3.73 (m, 6H), 3.66-3.59 (m, 2H), 3.54 (ddd, J = 9.3, 4.5, 2.1 Hz, 1H); ¹³C NMR (125 MHz, CDCl₃) δ 165.24, 165.22, 151.6, 151.2, 138.1, 137.89, 137.87, 137.7, 133.2, 133.00, 129.90, 129.83, 129.78, 129.76, 128.54, 128.49, 128.45, 128.43, 128.36, 128.29, 128.25, 128.11, 128.05, 128.01, 127.98, 127.94, 127.89, 127.86, 127.83, 127.81, 127.66, 127.64, 119.2, 100.80, 100.75, 82.9, 82.6, 78.2, 77.7, 75.6, 75.2, 75.1, 74.99, 74.95, 73.7, 73.58, 73.56, 68.8, 67.6. HRMS (ESI) m/z: [M+Na]⁺ cacld for C₆₇H₆₄O₁₄1115.3928; Found

1115.3888.

[00218] To a stirred solution of glycosyl donor 50 (0.058 mmol) and glycosyl acceptor 48 (0.064 mmol) in a mixture of CH₂Cl₂ (0.5 mL) and CH₃CN (0.5 mL) was added BF₃.Et₂O (0.058 mmol, 7 µL) followed by PIFA (0.064 mmol, 28 mg) in one portion at room temperature. After 1 hour, the mixture was quenched with a saturated aqueous solution of NaHCO₃ (2 mL) then diluted with CH₂Cl₂ (20 mL). The organic layer was washed with H₂O (3x 5mL), concentrated under reduced pressure and the crude residue was purified with silica gel column chromatography (5% PhMe/EtOAc) to give an inseparable mixture of desired glycosylated product and unreacted glycosyl donor. The mixture was dissolved in THF (2 mL) and ethanol amine (0.1 mL) was added. The mixture was stirred at room temperature. After for 24 hours the mixture was concentrated under reduced pressure and the crude residue was purified with silica gel column chromatography (15% EtOAc/toluene) to afford the title compound as a semi solid (55%, 0.032 mmol, 50 mg).Semi solid, R_f = 0.23 (33%

EtOAc/hexane); [α]²²

D = +4.6 (c 1.0, dichloromethane); IR (ATR) = 3522, 1725, 1265, 1090, 1026, 709, 696 cm⁻¹; ¹H NMR (500 MHz, CDCl₃) δ 8.09-8.00 (m, 2H), 7.96 (dd, J = 7.8, 3.5 Hz, 2H), 7.90 (dd, J = 8.1, 3.5 Hz, 2H), 7.57 (dt, J = 17.6, 9.0 Hz, 2H), 7.45 (ddt, J = 11.4, 7.8, 4.8 Hz, 4H), 7.40-7.01 (m, 38H), 6.87 (dd, J = 9.0, 3.7 Hz, 2H), 6.67 (dd, J = 8.8, 3.6 Hz, 2H), 5.51-5.40 (m, 1H), 5.37 (td, J = 8.7, 3.8 Hz, 1H), 5.32 (d, J = 3.7 Hz, 1H), 5.25 (td, J = 8.3, 3.6 Hz, 1H), 4.97-4.88 (m, 1H), 4.81 (dq, J = 10.8, 7.1, 6.3 Hz, 1H), 4.76 (dd, J = 11.3, 3.6 Hz, 1H), 4.72-4.45 (m, 12H), 4.38 (dd, J = 11.0, 3.5 Hz, 1H), 4.19-4.09 (m, 1H), 4.02- 3.89 (m, 1H), 3.89-3.46 (m, 14H); ¹³C NMR (125 MHz, CDCl₃) δ 165.3, 165.1, 164.9, 151.8, 150.9, 138.1, 137.91, 137.89, 137.85, 137.82, 137.80, 133.11, 133.08, 132.92, 129.95, 129.87, 129.82, 129.79, 129.75, 129.72, 128.47, 128.45, 128.43, 128.41, 128.38, 128.33, 128.31, 128.26, 128.24, 128.19, 128.15, 128.10, 128.06, 127.99, 127.95, 127.92, 127.90, 127.87, 127.86, 127.80, 127.77, 127.75, 127.70, 127.63, 127.55, 127.51, 119.6, 116.0, 101.4, 100.6, 100.5, 82.69, 82.67, 82.64, 78.1, 77.7, 77.5, 77.3, 77.0, 76.8, 75.1, 75.0, 74.9, 74.81, 74.78, 74.74, 74.71, 74.5, 74.0, 73.68, 73.66, 73.5, 68.9, 68.7, 67.2. HRMS (ESI) m/z:

[M+Na]⁺ cacld for C₉₄H₉₀O₂₀1561.5918; Found 1561.5863. EQUIVALENTS AND SCOPE

[00219] In the claims articles such as“a,”“an,” and“the” may mean one or more than one unless indicated to the contrary or otherwise evident from the context. Claims or descriptions that include“or” between one or more members of a group are considered satisfied if one, more than one, or all of the group members are present in, employed in, or otherwise relevant to a given product or process unless indicated to the contrary or otherwise evident from the context. The invention includes embodiments in which exactly one member of the group is present in, employed in, or otherwise relevant to a given product or process. The invention includes embodiments in which more than one, or all of the group members are present in, employed in, or otherwise relevant to a given product or process.

[00220] Furthermore, the invention encompasses all variations, combinations, and permutations in which one or more limitations, elements, clauses, and descriptive terms from one or more of the listed claims is introduced into another claim. For example, any claim that is dependent on another claim can be modified to include one or more limitations found in any other claim that is dependent on the same base claim. Where elements are presented as lists, e.g., in Markush group format, each subgroup of the elements is also disclosed, and any element(s) can be removed from the group. It should it be understood that, in general, where the invention, or aspects of the invention, is/are referred to as comprising particular elements and/or features, certain embodiments of the invention or aspects of the invention consist, or consist essentially of, such elements and/or features. For purposes of simplicity, those embodiments have not been specifically set forth in haec verba herein.

[00221] It is also noted that the terms“comprising” and“containing” are intended to be open and permits the inclusion of additional elements or steps. Where ranges are given, endpoints are included. Furthermore, unless otherwise indicated or otherwise evident from the context and understanding of one of ordinary skill in the art, values that are expressed as ranges can assume any specific value or sub-range within the stated ranges in different embodiments of the invention, to the tenth of the unit of the lower limit of the range, unless the context clearly dictates otherwise.

[00222] This application refers to various issued patents, published patent applications, journal articles, and other publications, all of which are incorporated herein by reference. If there is a conflict between any of the incorporated references and the instant specification, the specification shall control. In addition, any particular embodiment of the present invention that falls within the prior art may be explicitly excluded from any one or more of the claims. Because such embodiments are deemed to be known to one of ordinary skill in the art, they may be excluded even if the exclusion is not set forth explicitly herein. Any particular embodiment of the invention can be excluded from any claim, for any reason, whether or not related to the existence of prior art.

[00223] Those skilled in the art will recognize or be able to ascertain using no more than routine experimentation many equivalents to the specific embodiments described herein. The scope of the present embodiments described herein is not intended to be limited to the above Description, but rather is as set forth in the appended claims. Those of ordinary skill in the art will appreciate that various changes and modifications to this description may be made without departing from the spirit or scope of the present invention, as defined in the following claims.

Claims

CLAIMS What is claimed is:

1. A compound of the following formula:

or a salt thereof.

2. The compound of claim 1, wherein the compound is of one of the following formulae:

or a salt thereof.

3. The compound of claim 2, wherein the compound is of the following formula:

or a salt thereof.

4. A compound of the following formula:

or a salt thereof.

5. The compound of claim 3, wherein the compound is of one of the following formulae:

or a salt thereof.

6. The compound of claim 5, wherein the compound is of the following formula:

or a salt thereof.

7. A compound of one of the following formulae:

or a salt thereof.

8. The compound of claim 5, wherein the compound is of one of the following formulae:

or a salt thereof.

9. A compound of one of the following formulae:

or a salt thereof, wherein:

R¹ is optionally substituted alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted carbocyclyl, or optionally substituted acyl.

10. The compound of claim 9, wherein the compound is of one of the following formulae:

or a salt thereof.

11. The compound of claims 9 or 10, wherein R¹ is optionally substituted aryl, or a salt thereof.

12. The compound of claim 11, wherein R¹ is optionally substituted phenyl, or a salt thereof.

13. The compound of claim 12, wherein R¹ is unsubstituted phenyl, or a salt thereof.

14. The com ound of claim 9 wherein the com ound is of one of the followin formulae:

or a salt thereof .

15. The compound of claim 14, wherein the com ound is of the following formula:

or a salt thereof.

16. The compound of claim 14, wherein the compound is of the following formula:

or a salt thereof.

17. The compound of claim 9, wherein the compound is of one of the following formulae:

or a salt thereof .

18. The compound of claim 17, wherein the com ound is of the following formula:

or a salt thereof.

19. The compound of claim 17, wherein the compound is of the following formula:

or a salt thereof.

20. A method for glycosylating a hydroxyl-containing organic compound, the method comprising contacting a compound of any one of claims 1-8, or a salt thereof, with a hydroxyl-containing organic compound of the formula R²–OH, or a salt thereof, in the presence of an oxidant to yield a glycosylation product of Formula (S-1):

or a salt thereof, wherein the group corres ondin to:

is of one of the following formulae:

and R² is an organic compound.

21. The method of claim 20, wherein the group corresponding to:

is of the following formula:

22. The method of claim 21, wherein the group corresponding to:

is of the following formula:

23. The method of claim 22, wherein the group corresponding to:

is of the following formula:

24. The method of claim 20, wherein the hydroxyl-containing organic compound is a monosaccharide; and the compound of Formula (S-1) is a disaccharide.

25. The method of claim 20, wherein the hydroxyl-containing organic compound is a compound of any one of claims 9-19; and the compound of Formula (S-1) is a disaccharide.

26. The method of claim 25, wherein R² is of any one of the following formulae:

27. The method of claim 25 or 26, wherein R¹ is optionally substituted aryl.

28. The method of claim 27, wherein R¹ is optionally substituted phenyl.

29. The method of claim 28, wherein R¹ is unsubstituted phenyl.

30. The method of any one of claims 20-29, wherein R² is of one of the following formulae:

31. The method of any one of claims 20-30, wherein the compound of Formula (S-1) is formed with a β:α anomeric ratio of greater than 3:1.

32. The method of claim 31, wherein the β:α anomeric ratio is greater than 10:1.

33. The method of claim 31, wherein the β:α anomeric ratio is greater than 20:1.

34. The method of claim 31, wherein the β:α anomeric ratio is greater than 25:1.

35. The method of any one of claims 20-30, wherein the compound of Formula (S-1) is formed with a α:β anomeric ratio of greater than 3:1.

36. The method of claim 35, wherein the α:β anomeric ratio is greater than 10:1.

37. The method of claim 35, wherein the α:β anomeric ratio is greater than 20:1.

38. The method of claim 35, wherein the α:β anomeric ratio is greater than 25:1.

39. The method of any one of claims 20-38, wherein the oxidant is a hypervalent iodine reagent.

40. The method of claim 39, wherein the oxidant is (bis(trifluoroacetoxy)iodo)benzene (PIFA).

41. The method of any one of claims 20-40, wherein approximately 1.0-1.1 equivalents of the oxidant is used.

42. The method of any one of claims 20-41, wherein the step of glycosylating is carried out in the presence of a Lewis acid.

43. The method of claim 42, wherein the Lewis acid is a boron trifluoride diethyletherate (BF₃•OEt₂).

44. The method of claim 42 or 43, wherein approximately 1.0-1.1 equivalents of the Lewis acid is used.

45. The method of any one of claims 20-44, wherein the step of glycosylating is carried out in a solvent.

46. The method of claim 45, wherein the solvent is acetonitrile.

47. The method of claim 45, wherein the solvent is CH₂Cl₂ (DCM).

48. The method of claim 45, wherein the solvent is a acetonitrile/DCM mixture.

49. The method of any one of claims 20-48, wherein the step of glycosylating is carried out at or around room temperature.

50. The method of any one of claims 25-49, further comprising steps of:

(a) deprotecting the phenolic ester of the glycosylation product to convert the group corresponding to the formula:

to a group of the following formula:

(b) contacting the compound provided in step (a) with a hydroxyl-containing organic compound of the formula R²–OH, or salt thereof, in the presence of an oxidant, thereby yielding a second glycosylation product.

51. The method of claim 50, wherein the hydroxyl organic compound of formula R²–OH is a compound of any one of claims 9-19.

52. The method of claim 50, wherein the step of deprotecting is carried out in the presence of an alcohol, hydroxide, alkoxide.

53. The method of claim 50, wherein the step of deprotecting is carried out in the presence of sodium methoxide.

54. The method of claim 50, wherein the step of deprotecting is carried out in the presence of ethanolamine.

55. The method of claim 54, wherein the ethanolamine is used in excess.

56. The method of any one of claims 50-55, wherein the step of deprotection is carried out in a solvent.

57. The method of claim 56, wherein the solvent is THF.

58. The method of any one of claims 20-57 further comprising the steps of: (c) deprotecting a hydroxyl group of a glycosylation product compound to yield a compound comprising a hydroxyl group;

(d) glycosylating the compound provided in step (c) by contacting the hydroxyl- containing organic compound provided in step (c) with a compound of any one of claims 1-9 in the presence of an oxidant, thereby yielding a glycosylation product.

59. The method of any one of claims 20-58 further comprising one or more iterative steps of deprotecting and glycosylating to yield a disaccharide, trisaccharide, polysaccharide, or glycan.

60. A kit comprising one or more compounds according to any one of claims 1-19;

optionally one or more chemical reagents; and optionally instructions for use.