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WO2019168269A1 - Composé organométallique chiral bifonctionnel ayant une excellente énantiosélectivité, son procédé de préparation et procédé pour produire de l'acide gamma-aminé non naturel à partir d'un composé nitré à l'aide de celui-ci - Google Patents

Composé organométallique chiral bifonctionnel ayant une excellente énantiosélectivité, son procédé de préparation et procédé pour produire de l'acide gamma-aminé non naturel à partir d'un composé nitré à l'aide de celui-ci Download PDF

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WO2019168269A1
WO2019168269A1 PCT/KR2019/001003 KR2019001003W WO2019168269A1 WO 2019168269 A1 WO2019168269 A1 WO 2019168269A1 KR 2019001003 W KR2019001003 W KR 2019001003W WO 2019168269 A1 WO2019168269 A1 WO 2019168269A1
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substituted
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groups
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Korean (ko)
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하덕찬
심재호
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Korea University Research and Business Foundation
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Korea University Research and Business Foundation
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Priority to US16/976,151 priority Critical patent/US11465135B2/en
Publication of WO2019168269A1 publication Critical patent/WO2019168269A1/fr
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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J37/00—Processes, in general, for preparing catalysts; Processes, in general, for activation of catalysts
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
    • C07C201/06—Preparation of nitro compounds
    • C07C201/12—Preparation of nitro compounds by reactions not involving the formation of nitro groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
    • C07C205/01—Compounds containing nitro groups bound to a carbon skeleton having nitro groups bound to acyclic carbon atoms
    • C07C205/03—Compounds containing nitro groups bound to a carbon skeleton having nitro groups bound to acyclic carbon atoms of an unsaturated carbon skeleton
    • C07C205/04—Compounds containing nitro groups bound to a carbon skeleton having nitro groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C227/22—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from lactams, cyclic ketones or cyclic oximes, e.g. by reactions involving Beckmann rearrangement
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
    • C07C229/34—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton containing six-membered aromatic rings
    • C07C229/36—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton containing six-membered aromatic rings with at least one amino group and one carboxyl group bound to the same carbon atom of the carbon skeleton

Definitions

  • the present invention relates to a bifunctional organic chiral catalyst compound having excellent stereoselectivity, a method for producing the same, and a method for producing an unnatural gamma-amino acid from a nitro compound using the organic chiral catalyst compound.
  • Amino acids are the basic building blocks of proteins and are divided into natural and unnatural amino acids. Natural amino acids are amino acids that can be obtained in a natural state, mainly used as sweeteners, animal feed, etc., while non-natural amino acids are amino acids that cannot be obtained in a natural state and correspond to isomers of natural amino acids, and are mainly used as raw materials for medicine.
  • Optically pure amino acids are of great industrial importance because they are widely used as ligands for asymmetric catalysts or as starting materials or intermediates for the synthesis of various pharmaceuticals and physiologically active substances.
  • amino acids obtainable through fermentation are limited to L-amino acids among natural amino acids.
  • Optically pure D-amino acids and non-natural amino acids are produced through chrial resolution, optical resolution, and chiral resolution, but due to the high manufacturing costs, natural L-amino acids are produced by fermentation. Compared to this, the unit price is 5-10 times higher and is having difficulty in mass production.
  • the present invention seeks to provide a bifunctional organic chiral catalyst compound having excellent stereoselectivity and a method for preparing the same.
  • the present invention also provides a method for preparing an unnatural gamma amino acid from a nitro compound using the organic chiral catalyst compound according to the present invention.
  • the present invention provides an organic chiral catalyst compound represented by the following [Formula 1] to solve the above problems.
  • the present invention is to provide a method for preparing an organic chiral catalyst compound represented by the above [Formula 1] comprising the following (A) step.
  • the present invention is to provide a method for producing a non-natural gamma amino acid comprising the following (A) step.
  • this functional organic chiral catalyst compound having excellent stereoselectivity can be easily synthesized, and using this, it is possible to obtain a high yield of gamma amino acids having high optical selectivity in an economical and simple manner, as well as a small amount.
  • a variety of gamma amino acids in the (R) -form that do not exist in nature can be produced in large quantities with high optical purity, and thus can be widely used in various industrial fields including the pharmaceutical industry.
  • FIG. 1 illustrates a structure including a substituent for an organic chiral catalyst compound according to an embodiment of the present invention.
  • FIG. 2 shows a synthesis scheme of a single alkylated thiourea catalyst according to one embodiment of the invention.
  • Figure 3 shows a synthesis scheme of an arylated thiourea catalyst according to an embodiment of the present invention.
  • Figure 4 shows the reaction scheme of the Michael addition reaction according to an embodiment of the present invention.
  • Figure 5 shows the reaction scheme of the non-natural gamma amino acid production reaction according to an embodiment of the present invention.
  • FIG. 6 shows a scheme of Michael addition reaction for conducting a reaction test according to an organic chiral catalyst compound, a catalyst usage amount, and a type of a solvent according to an embodiment of the present invention.
  • Figure 7 shows the reaction scheme of Michael addition reaction for performing a reaction test according to the type of ⁇ , ⁇ -unsaturated nitro compound according to an embodiment of the present invention ( a) used 0.4ml on 0.1 mmol scale ).
  • Figure 8 shows the reaction scheme of the non-natural gamma amino acid production reaction according to an embodiment of the present invention.
  • Figure 9 shows the reaction scheme of the non-natural gamma amino acid production reaction according to an embodiment of the present invention.
  • One aspect of the present invention relates to an organic chiral catalyst compound represented by the following [Formula 1].
  • X is any one selected from O, S, PR 3 and NR 4 , and R 1 to R 4 are the same as or different from each other, and each independently hydrogen, deuterium, a substituted or unsubstituted C1 to C30 alkyl group, a substituted or unsubstituted group A substituted C3 to C30 cycloalkyl group, a substituted or unsubstituted C2 to C30 heteroaryl group, a substituted or unsubstituted C6 to C30 aryl group, a substituted or unsubstituted C6 to C30 arylamine group, a substituted or unsubstituted C1 to C30 alkoxy group, substituted or unsubstituted C2 to C30 alkoxycarbonyl group, substituted or unsubstituted C2 to C30 alkoxycarbonylamino group, substituted or unsubstituted C7 to C30 aryloxycarbonylamino group, substituted or unsub
  • R 1 may be hydrogen, 3-pentyl, Ph 2 CH, or 3,5- (CF 3 ) 2 -PhCH 2
  • R 2 is phenyl, 3,5- (CF 3 ) 2 -Ph, p-tolyl, 4-CF 3 -Ph, C 6 F 5 , 4-NO 2 -Ph, 4-CN-Ph, 4-F-Ph, t-butyl, or 3,5- (Me) 2 -Ph.
  • Another aspect of the present invention is to provide a method for preparing an organic chiral catalyst compound represented by the above [Formula 1] comprising the following (A) step.
  • Another aspect of the invention relates to a method for preparing a non-natural gamma amino acid comprising the following (A) step.
  • Michael addition reaction is performed under the use or non-use of water or organic solvent, more preferably Michael addition reaction under the use or non-use of water solvent, Michael addition reaction Nitrostyl is produced as characterized in that.
  • the water is not limited as long as it is a solvent generally called water, lotion, hexagonal water, high temperature vacuum water, distilled water, primary distilled water, secondary distilled water, tertiary distilled water, hydrogen water, extract, salt-containing water, drinking water, sea water , Salt water, brackish water, mineral water, mineral water, rock water, spring water, groundwater, deep water, soft water, tap water, hard water, ionized water, electrolytic water, carbonated water, sweet water, spring water or sea water, the organic solvent is not particularly limited.
  • the present invention is characterized in that it further comprises the step of synthesizing pyrrolidinone represented by the following [Formula 3-1] or [Formula 3-2] using the product produced by the Michael addition reaction.
  • R 1 and R 2 are the same as or different from each other, and each independently, hydrogen, deuterium, a substituted or unsubstituted C1 to C30 ketone group, a substituted or unsubstituted C1 to C30 nitro group, a substituted or unsubstituted C1 to C30 halogen group, substituted or unsubstituted C1 to C30 cyano group, substituted or unsubstituted C1 to C30 ester group, substituted or unsubstituted C1 to C30 alkyl group, substituted or unsubstituted C3 to C30 cycloalkyl group, substituted or Unsubstituted C2 to C30 heteroaryl group, substituted or unsubstituted C6 to C30 aryl group, substituted or unsubstituted C6 to C30 arylamine group, substituted or unsubstituted C1 to C30 alkoxy group, substituted or unsubstituted C2 To
  • the present invention is characterized in that it further comprises the step of preparing a non-natural gamma amino acid represented by the following [Formula 4-1] or [Formula 4-2] by treating pyrrolidinone with hydrochloric acid.
  • R is hydrogen, deuterium, substituted or unsubstituted C1 to C30 ketone group, substituted or unsubstituted C1 to C30 nitro group, substituted or unsubstituted C1 to C30 halogen group, substituted or unsubstituted C1 to C30 cyano Groups, substituted or unsubstituted C1 to C30 ester groups, substituted or unsubstituted C1 to C30 alkyl groups, substituted or unsubstituted C3 to C30 cycloalkyl groups, substituted or unsubstituted C2 to C30 heteroaryl groups, substituted or unsubstituted C6 to C30 aryl group, substituted or unsubstituted C6 to C30 arylamine group, substituted or unsubstituted C1 to C30 alkoxy group, substituted or unsubstituted C2 to C30 alkoxycarbonyl group, substituted or unsubstituted C2 to
  • R 9 is a phenyl group in [Formula 4-1] or [Formula 4-2], it may be represented by the following [Formula 5-1] or [Formula 5-2], and R is hydrogen Or a halogen group.
  • the non-natural gamma amino acid prepared when R is hydrogen is used as a sleep inducing agent as a phenibut (phenibut), and R is chlorine (Cl ),
  • the non-natural amino acid produced is baclofen, which is used as a muscle relaxant.
  • the basic structure for preparing the organic chiral catalyst compound is (R, R) -1,2-diphenylethylenediamine (DPEN) of the following [Formula 2].
  • the basic structure has a structure in which a substituent is bonded toward the amine at position 1,2, and has a form capable of having stereoselectivity at position 1,2.
  • Organic chiral catalyst compound of Formula 1 is thiophenyl the R 2 derivative of the element is expected to be higher in this case the nature of the electronic pulling group (electron withdrawing group) substituent of a case attached to the basic structure, R 2 derivative the reaction yield . In addition, it is expected to have excellent stereoselectivity upon reaction by substituting R 1 for two amine groups.
  • R 1 when R 1 is hydrogen, R 2 is phenyl (Phenyl, ph), it is an organic chiral catalyst compound 1a; When R 1 is hydrogen and R 2 is 3,5- (CF 3 ) 2 -Ph, it is an organic chiral catalyst compound 1b; An organic chiral catalyst compound 1c when R 1 is a 3-pentyl group and R 2 is p-tolyl; When R 1 is a 3-pentyl group and R 2 is 3,5- (CF 3 ) 2 -Ph, it is an organic chiral catalyst compound 1d; An organic chiral catalyst compound 1e when R 1 is a 3-pentyl group and R 2 is 4-CF 3 -Ph; An organic chiral catalyst compound 1f when R 1 is a 3-pentyl group and R 2 is C 6 F 5 ; When R 1 is a 3-pentyl group and R 2 is 4-NO 2 -Ph, it is 1 g of an organic chiral catalyst compound; When R 1 is a 3-p
  • 2-pyrrolidinone is formed as the carboxyl group is dropped through the reaction, and 6N HCl is treated to 2-pyrrolidinone thus formed to the following baclofen of [Formula 4-1] or [Formula 4-2] (Wherein R 9 is phenyl substituted with Cl) or phenibule (unsubstituted phenyl in the formula 4) compound to synthesize (FIGS. 4 and 5).
  • ⁇ , ⁇ -unsaturated nitro compound was prepared in the presence of malonitril (2.0 equivalents) and 1 m (0.1-0.001 mol%) of the organic chiral catalyst compound prepared in Example 1, with water (0.4 ml) as a solvent.
  • the reaction mixture was stirred at room temperature using and mixed with trans- ⁇ -nitrostyrene (1.0 equiv), malononitrile (2.0 equiv).
  • the reaction conversion was monitored by TLC and after completion of the reaction, 6N HCl was added and heated to 65 ° C. for 2 hours. After the reaction mixture was cooled to room temperature, dialkyl carbonate (1.5 equiv) was added and the solution was heated with stirring at 100 ° C. for 3 h.
  • Example 2 Using the organic chiral catalyst compound prepared in Example 1, the Michael addition reaction of Example 2 was carried out in the presence of water or toluene as a solvent to confirm the reaction time and yield according to the type of organic chiral catalyst compound and the solvent. (Fig. 6 and Table 3, Table 4).
  • trifluoromethyl-substituted organic chiral catalyst compounds can be used in water, which means that the interaction of fluorine atoms in water lowers the activation barrier.
  • Example 2 Using the 1 m of the organic chiral catalyst compound prepared in Example 1, the Michael addition reaction of Example 2 was carried out in the presence of water as a solvent, the reaction time and yield according to the type of ⁇ , ⁇ -unsaturated nitro compound Check it. Specifically, to water (0.4 ml) was added trans- ⁇ -nitrostyrene (1.0 equiv), malonitrile (2.0 equiv) and 0.1 to 0.001 mol% of an organic chiral catalyst compound and the reaction mixture was allowed to stand at room temperature (rt). )). Reaction conversion was monitored by TLC. After completion, ethyl acetate (0.2 ml) was added to the reaction mixture.
  • IR spectra were recorded on a NICOLET 380 FT-IR spectrophotometer. Optical rotation was measured with a Rudolph Automatic polarimeter (Model name: A20766 APV / 6w).
  • 1 H NMR spectra were recorded on Varian Mercury 400 (400 MHz) or Varian Mercury 300 (300 MHz) with TMS as internal reference. 13 C NMR was recorded in Varian Mercury 400 (400 MHz) with TMS or CDCl 3 as internal standard.
  • Chiral HPLC analysis was performed on a Jasco LC-1500 Series HPLC system equipped with a UV detector. All reactions were carried out in glassware oven dried under an argon atmosphere. Toluene (CaH 2 ), THF (Na, benzopinone) was dried by distillation before use.
  • this functional organic chiral catalyst compound having excellent stereoselectivity can be easily synthesized, and using this, it is possible to obtain a high yield of gamma amino acids having high optical selectivity in an economical and simple manner, as well as a small amount.
  • a variety of gamma amino acids in the (R) -form which do not exist in nature can be produced in large quantities with high optical purity, and can be widely used in various industrial fields including the pharmaceutical industry.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Materials Engineering (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

La présente invention concerne un composé organométallique chiral bifonctionnel ayant une excellente énantiosélectivité, son procédé de préparation, et un procédé pour produire un acide aminé gamma non naturel à partir d'un composé nitré en utilisant le composé organométallique chiral. Selon la présente invention, le composé organométallique chiral bifonctionnel ayant une excellente énantiosélectivité peut être facilement synthétisé, des acides gamma-aminés ayant une sélectivité optique élevée peuvent être obtenus avec un rendement élevé par un procédé économique et commode utilisant le composé organométallique chiral, et divers acides gamma-aminés de configuration (R)-, qui ne sont pas présents dans la nature, peuvent être produits avec une pureté optique élevée en grandes quantités en utilisant une petite quantité d'un catalyseur, et par conséquent, la présente invention peut être largement utilisée dans divers domaines industriels comprenant l'industrie pharmaceutique.
PCT/KR2019/001003 2018-02-28 2019-01-24 Composé organométallique chiral bifonctionnel ayant une excellente énantiosélectivité, son procédé de préparation et procédé pour produire de l'acide gamma-aminé non naturel à partir d'un composé nitré à l'aide de celui-ci Ceased WO2019168269A1 (fr)

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Application Number Priority Date Filing Date Title
US16/976,151 US11465135B2 (en) 2018-02-28 2019-01-24 Bifunctional chiral organocatalytic compound having excellent enantioselectivity, preparation method therefor, and method for producing non-natural gamma-amino acid from nitro compound by using same

Applications Claiming Priority (4)

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KR10-2018-0024695 2018-02-28
KR20180024695 2018-02-28
KR1020180161967A KR102261108B1 (ko) 2018-02-28 2018-12-14 입체 선택성이 우수한 이 작용성 유기 키랄 촉매 화합물, 이의 제조 방법 및 이를 이용한 나이트로 화합물로부터의 비천연 감마-아미노산의 제조 방법
KR10-2018-0161967 2018-12-14

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112608282A (zh) * 2019-12-20 2021-04-06 山东先达农化股份有限公司 一种含喹唑啉二酮和n-o结构的化合物及其制备方法和应用
CN112608267A (zh) * 2020-12-23 2021-04-06 南京艾斯特医药科技有限公司 一种4-苯基-2-吡咯烷酮的合成方法
CN113735668A (zh) * 2021-10-15 2021-12-03 温州大学 一种手性δ-氨基-β-酮酸酯化合物及其合成方法

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2007332129A (ja) * 2005-12-09 2007-12-27 Sumitomo Chemical Co Ltd 光学活性な４−アミノ−３−置換フェニルブタン酸の製造方法

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2007332129A (ja) * 2005-12-09 2007-12-27 Sumitomo Chemical Co Ltd 光学活性な４−アミノ−３−置換フェニルブタン酸の製造方法

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
HAN, B.: "Discovery of Bifunctional Thiourea/Secondary-Amine Organocatalysts for the Highly Stereoselective Nitro-Mannich Reaction of a-Substituted Nitroacetates", CHEMISTRY-A EUROPEAN JOURNAL, vol. 14, no. 27, 2008, pages 8094 - 8097, XP055634746 *
LU , A: "Enantioselective Synthesis of trans-Dihydrobenzofurans via Primary Amine-Thiourea Organocatalyzed Intramolecular Michael Addition", THE JOURNAL OF ORGANIC CHEMISTRY, vol. 77, no. 14, 21 June 2012 (2012-06-21), pages 6208 - 6214, XP055634732, ISSN: 0022-3263, DOI: 10.1021/jo301006e *
MENINNO, S.: "Stereoselective amine-thiourea-catalysed sulfa-Michael/nitroaldol cascade approach to 3,4,5-substituted tetrahydrothiophenes bearing a quaternary stereocenter", BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY, vol. 12, 2016, pages 643 - 647, XP055634740, DOI: 10.3762/bjoc.12.63 *
ORGANOCATALYTIC ASYMMETRIC MICHAEL ADDITIONS OF KETONES TO ALPHA,BETA-UNSATURATED NITRO COMPOUNDS, vol. 1 - 117, February 2017 (2017-02-01), pages 7 - 19 *
ZHANG, J.: "Michael-Michael Addition Reactions Promoted by Secondary Amine-Thiourea: Stereocontrolled Construction of Barbiturate-Fused Tetrahydropyrano Scaffolds and Pyranocoumarins", THE JOURNAL OF ORGANIC CHEMISTRY, vol. 82, no. 24, 2017, pages 13594 - 13601, XP055634737, ISSN: 0022-3263, DOI: 10.1021/acs.joc.7b01902 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112608282A (zh) * 2019-12-20 2021-04-06 山东先达农化股份有限公司 一种含喹唑啉二酮和n-o结构的化合物及其制备方法和应用
CN112608267A (zh) * 2020-12-23 2021-04-06 南京艾斯特医药科技有限公司 一种4-苯基-2-吡咯烷酮的合成方法
CN112608267B (zh) * 2020-12-23 2022-10-25 赣州中能实业有限公司 一种4-苯基-2-吡咯烷酮的合成方法
CN113735668A (zh) * 2021-10-15 2021-12-03 温州大学 一种手性δ-氨基-β-酮酸酯化合物及其合成方法

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