DD218886A1 - PROCESS FOR THE PREPARATION OF N-URETHANE PROTECTED AMINO ACIDS - Google Patents
PROCESS FOR THE PREPARATION OF N-URETHANE PROTECTED AMINO ACIDS Download PDFInfo
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- DD218886A1 DD218886A1 DD25419883A DD25419883A DD218886A1 DD 218886 A1 DD218886 A1 DD 218886A1 DD 25419883 A DD25419883 A DD 25419883A DD 25419883 A DD25419883 A DD 25419883A DD 218886 A1 DD218886 A1 DD 218886A1
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- German Democratic Republic
- Prior art keywords
- amino acids
- preparation
- protected amino
- urethane
- chem
- Prior art date
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- 150000001413 amino acids Chemical class 0.000 title claims abstract description 15
- 238000000034 method Methods 0.000 title claims description 8
- 238000002360 preparation method Methods 0.000 title claims description 6
- -1 9-methylfluorenyl Chemical group 0.000 claims abstract description 12
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 12
- 150000004649 carbonic acid derivatives Chemical class 0.000 claims abstract description 7
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 6
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims abstract description 4
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 abstract description 4
- ZUSSTQCWRDLYJA-UHFFFAOYSA-N n-hydroxy-5-norbornene-2,3-dicarboximide Chemical compound C1=CC2CC1C1C2C(=O)N(O)C1=O ZUSSTQCWRDLYJA-UHFFFAOYSA-N 0.000 abstract description 4
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 abstract description 3
- 150000001298 alcohols Chemical class 0.000 abstract description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 abstract description 2
- 238000004519 manufacturing process Methods 0.000 abstract description 2
- WZSYICREJGEVIT-UHFFFAOYSA-N 2-((chlorocarbonyl)oxy)-3a,4,7,7a-tetrahydro-4,7-methano-1h-isoindole-1,3(2h)-dione Chemical compound C1=CC2CC1C1C2C(=O)N(OC(=O)Cl)C1=O WZSYICREJGEVIT-UHFFFAOYSA-N 0.000 abstract 1
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 125000006239 protecting group Chemical group 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 238000005684 Liebig rearrangement reaction Methods 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- 244000309464 bull Species 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 238000010647 peptide synthesis reaction Methods 0.000 description 2
- KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 2
- JOYRKODLDBILNP-UHFFFAOYSA-N urethane group Chemical group NC(=O)OCC JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 2
- ZQEBQGAAWMOMAI-ZETCQYMHSA-N (2s)-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid Chemical compound CC(C)(C)OC(=O)N1CCC[C@H]1C(O)=O ZQEBQGAAWMOMAI-ZETCQYMHSA-N 0.000 description 1
- QVHJQCGUWFKTSE-YFKPBYRVSA-N (2s)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound OC(=O)[C@H](C)NC(=O)OC(C)(C)C QVHJQCGUWFKTSE-YFKPBYRVSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- VRPJIFMKZZEXLR-UHFFFAOYSA-N 2-[(2-methylpropan-2-yl)oxycarbonylamino]acetic acid Chemical compound CC(C)(C)OC(=O)NCC(O)=O VRPJIFMKZZEXLR-UHFFFAOYSA-N 0.000 description 1
- JDXQWYKOKYUQDN-UHFFFAOYSA-N 3-hydroxypyrrolidine-2,5-dione Chemical class OC1CC(=O)NC1=O JDXQWYKOKYUQDN-UHFFFAOYSA-N 0.000 description 1
- 101100228196 Caenorhabditis elegans gly-4 gene Proteins 0.000 description 1
- MDXGYYOJGPFFJL-QMMMGPOBSA-N N(alpha)-t-butoxycarbonyl-L-leucine Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)OC(C)(C)C MDXGYYOJGPFFJL-QMMMGPOBSA-N 0.000 description 1
- 238000007098 aminolysis reaction Methods 0.000 description 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
- KTUQUZJOVNIKNZ-UHFFFAOYSA-N butan-1-ol;hydrate Chemical compound O.CCCCO KTUQUZJOVNIKNZ-UHFFFAOYSA-N 0.000 description 1
- KOFZJCYUAVPINT-UHFFFAOYSA-N butyl [[cyano(phenyl)methylidene]amino] carbonate Chemical compound CCCCOC(=O)ON=C(C#N)C1=CC=CC=C1 KOFZJCYUAVPINT-UHFFFAOYSA-N 0.000 description 1
- 125000004744 butyloxycarbonyl group Chemical group 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Substances CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 238000005192 partition Methods 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000004575 stone Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 229960002317 succinimide Drugs 0.000 description 1
- ISHLCKAQWKBMAU-UHFFFAOYSA-N tert-butyl n-diazocarbamate Chemical compound CC(C)(C)OC(=O)N=[N+]=[N-] ISHLCKAQWKBMAU-UHFFFAOYSA-N 0.000 description 1
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Die Erfindung betrifft ein neues Verfahren zur Herstellung urethangeschuetzter Aminosaeuren bzw. Peptiden durch Umsetzung unsymmetrischer Carbonate I mit Aminosaeuren bzw. Peptiden. Die Carbonate I, in denen R1 fuer tert.-Butyl, Alamantyl-(1), 2-Biphenylpropyl, 9-Methylfluorenyl, Methylsulfonylethyl, Benzyl oder andere in der Peptidchemie uebliche Reste steht, werden aus N-(Chlorcarbonyloxy)-5-norbornen-2,3-dicarboximid - erhalten durch Reaktion von N-Hydroxy-5-norbornen-2,3-dicarboximid mit Phosgen - und Alkoholen gewonnen. Formel IThe invention relates to a novel process for preparing urethane-protected amino acids or peptides by reacting asymmetric carbonates I with amino acids or peptides. The carbonates I in which R1 represents tert-butyl, alamantyl- (1), 2-biphenylpropyl, 9-methylfluorenyl, methylsulfonylethyl, benzyl or other radicals usual in peptide chemistry become N- (chlorocarbonyloxy) -5-norbornene -2,3-dicarboximide - obtained by reaction of N-hydroxy-5-norbornene-2,3-dicarboximide with phosgene and alcohols. Formula I
Description
Verfahren zur Herstellung urethangeschützter AminosäurenProcess for the preparation of urethane-protected amino acids
Anwendungsgebiet der Erfindung Field of application of the invention
Die Erfindung betrifft ein neues Verfahren zur Einführung der Urethan-Gruppe in Aminosäuren bzw« Peptiden unter Verwendung unsymmetrischer Carbonate·The invention relates to a novel process for introducing the urethane group into amino acids or peptides using unsymmetrical carbonates.
Anwendungsgebiet der Erfindung ist die pharmazeutische Industrie j speziell die Synthese von Peptiden«Field of application of the invention is the pharmaceutical industry especially the synthesis of peptides «
Charakteristik der bekannten technischen Lösungen Es ist eine Vielzahl symmetrischer Carbonate bekannt, die zur Einführung von Urethan-Sohutzgruppen in Aminosäuren verwendet werden· Die tert#~Butyloxycarbonyl-(Boc)~Gruppe stellt neben der Benzyloxycarbonyl-(Z)-Gruppe. die in der Peptidsynthese am häufigsten benutzte Schutzgruppe dar· Um die in der hohen Toxizität und Explosionsneigung bestehenden Nachteile des bislang meistverwendeten Boc—Ein~ fiihrungsreagenz tert.-Butyloxycarbonylazids (Schwyzer, R·; Sieber, P* ue H« Kappler, HeIv. Chim« Acta, 42« 2622 (1962)) zu vermeiden, wurden eine Vielzahl neuer Einführungsreagenzien entwickelt, wie tertv-Butyl-^o-dimethylpyrimidyl~2~thiol-carbonat (Nagasawa, T,; Kuriowa, K. J Ifarita, Ke u«, Y« Isowa, Bull· Chem. Soc«:(Jap·) 46. U9 A# Ce Mc Gregor, J, Amere Chem« Soc« 7^j. 6180 (1957), terte~Butyloxycarbonyloximino-2-phenylacetonitril (Iteh. M9; Hagiwara, D» u. T· Kamiya, Bull« Chenu Soo« (Jap#) 718 (1977); Tetrahedron Lett. 197^ 4393), IT-(tert.-. Butyloxycarbonyloxy)-phthalimid (Gross, H. u.J I.. Bilk, Liebigs Ann« Chem« 725, 212 (1969), K-(tert«-Butyloxycarbonyloxy)-succinimid (Pranket, M. ladkany, D.j Gilon, Characteristics of known technical solutions A large number of symmetrical carbonates are known which are used for the introduction of urethane protecting groups into amino acids. The tert-butyloxycarbonyl (Boc) group is in addition to the benzyloxycarbonyl (Z) group. · The disadvantages of the hitherto most frequently used Boc introduction reagent tert-butyloxycarbonyl azide (Schwyzer, R · Sieber, P * u e H Kappler, HeIv.), which are the most frequently used in the synthesis of peptides. Chim "Acta, 42" 2622 (1962)), a variety of new incorporation reagents have been developed, such as tert-butyl-o-dimethylpyrimidyl-2-thiol carbonate (Nagasawa, T, Kuriowa, K. J Ifarita, K e ", Y« Isowa, Bull · Chem. Soc « : (Jap ·) 46. U 9 A # C e Mc Gregor, J, Amer e Chem« Soc «7 ^ j 6180 (1957), tert e ~ Butyloxycarbonyloximino-2-phenylacetonitrile (Iteh M 9 , Hagiwara, D »and T · Kamiya, Bull« Chenu Soo »(Jap # ) 718 (1977), Tetrahedron Lett., 197, 4393), IT (tert. butyloxycarbonyloxy) phthalimide (Gross, H. u. J .. I Bilk, Liebigs Ann "Chem" 725, 212 (1969), K (tert "-Butyloxycarbonyloxy) succinimide (Pranket, M. ladkany, Dj Gilon,
C® u« Υ« Wolman, Tetrahedron Lett« 1966<, 4765« Gross, Η® u» L. Bilk, Liebigs Ann· Chem« 725» 212 (1969), W-(terte~ Butyloxycarbonyl)-1H-Butyl-phenylcarbonat (Ragnarsson, U«; K ar Is son, S* Μ« u« Β« E0 Sandberg, Acta Chem« Scand« 26Ai 2550 (1972); Org« Synth. 32x 25 (1973), tert«-Butyl-S-ehinolylcarbonat (Rzesztotarska, B« u« S« Wiejak, Xiebigs Ann« Chem« 716« 216 (1968); Rzesztotarska, B« j Wiejak, S« u« K» Pawelozak, Org« Prep. Proc» Int· 5± 71 (1973), terte-Butyl~2,4,5-trichlorphenylearbonat (Broadbent, We j Morley, I« S. u* Β« E« Stone; J. Chem. Soc. (C), 1967t 2632)% und Di~ terte-butyl-dicarbonat (Tarbell, D· S.; Yamamoto, T· u. B@ M, Pope; Proc· Nat« Acad« Sei. USA 6£± 730 (1972); Org. Synth. £2jl ^5 (1977); Moroder, L.; Hallet, Α.; Wünsch, E.; Keller, 0* u. G. Wünsch, E.; Kelleri 0. u. G. Wersin, Hoppe-Seyler» s Z. Physiol· Chem. 357« 1651 (1976). leben diesen häufig angewandten Schutzgruppen werden für spezielle Syntheseprobleme weitere wichtige Schutzgruppen benötigt* Hier haben sich in den letzten Jahren vor allem Schutzgruppen bewährt, die unter milderen Bedingungen abspaltbar sind» Das sind z.B. die 9-Pluorenylmethyloxycarb©«= nyl-Gruppe (Carpino I«. J. Am. Chem. Soc. 92» 5748 (1970) die Methylsulfonylethoxycarbonyl-Gruppe (G.· Tesser et. al®« Intern« J. Peptide Prot.Res» 2i (1975) 295) oder I-Adamantylocycarbonyl-Schutzgruppe (E. Wünsch, L. Wackerle u. Le Moroder, Hoppe-Seylers Z9 Physiol. Chem. 357« 1647 (1976))« Alle diese letzten Sohutzgruppen werden gewöhnlich über sub-» stituierte Phenole oder li~Hydroxy succinimide st er eingeführt (M9 Bodanszky, Y. S« Klausner u. M.A. Ondetti in: Peptide synthesis, 2nd« ed«1, 3*· Wiley Ν« Υ« 1976 ρ« 32; Η« Groß U* L* Bilk, Ann. Chem« 72^4 212 (1969); A. Paquet, Can« J« Chem« 52a 2775, (1979) und Can. J. Chem. 6O4 (8) 976 (1982)β C® u "Υ" Wolman, Tetrahedron Lett '1966', 4765 'Gross, Η® u »L. Bilk, Liebigs Ann Chem ·" 725 "212 (1969), W (t ~ e butyloxycarbonyl) -1-butyl . -phenylcarbonat (Ragnarsson, U "K ar Is son, S * Μ« u «Β" e 0 Sandberg, Acta Chem "Scand" 26 Ai 2550 (1972); Org "Synth 32x 25 (1973), tert" - Butyl-S-ehinolylcarbonate (Rzesztotarska, B «u« S «Wiejak, Xiebigs Ann« Chem « 716« 216 (1968); Rzesztotarska, B «j Wiejak, S» u «Pawelozak, Org« Prep. Proc »Int · 5 ± 71 (1973), tert-butyl e ~ 2,4,5-trichlorphenylearbonat (Broadbent, We j Morley, I "p u * Β" e "Stone;. J. Chem. Soc (C), 1967t 2632)% and di ~ shouldered-butyl dicarbonate (Tarbell, D · S .; Yamamoto, T · u B @ M, Pope; Proc. Nat · "Acad" Sci USA 6 £ ± 730 (1972.); Org. Synthel, L .; Hallet, Α; Wünsch, E .; Keller, 0 * and G Wünsch, E .; Kelleri, 0, and Wersin, Hoppe-Seyler »Z. Physiol · Chem. 357« 1651 (1976). These commonly used protective groups are used for special purposes Synthesis Problems Further Important Protecting Groups Needed In recent years, protection groups have been found to be most effective in cleavage under milder conditions. "These include, for example, the 9-pluorenylmethyloxycarb © nyl group (Carpino I). J. Am. Chem. Soc. 92 »5748 (1970), the methylsulfonylethoxycarbonyl group (G.Tesser et al., Intern. J. Peptide Prot. Res. 2i (1975) 295) or I-adamantylocy- carbonyl protective group (E. Wünsch, L. Wackerle, et al L e Moroder, Hoppe-Seylers Z 9 Physiol. Chem., 357, 1647 (1976)) "All these last so-protecting groups are usually introduced via substituted phenols or hydroxy-succinimides (M 9 Bodanszky, Y. S «Klausner and MA Ondetti in: Peptide synthesis, 2nd ed« 1 , 3 * · Wiley Ν «Υ« 1976 ρ «32; Η« Big U * L * Bilk, Ann. Chem «72 ^ 4 212 (1969) A. Paquet, Can "J" Chem "52a 2775, (1979) and Can. J. Chem. 6O 4 (8) 976 (1982) β
Die genannten Einführungsreagenzien zeichnen sich z«T« da~ durch aus, daß bemerkenswert hohe Ausbeuten an Urethan-geschützten Aminosäuren erreicht werden« Ihr Nachteil besteht jedoch vor allem darin, daß bei der Mehrzahl sowohl die Syn-The above-mentioned introduction reagents are characterized by the fact that remarkably high yields of urethane-protected amino acids are achieved. Their main disadvantage, however, is that in the majority both the syn-
these der Ausgangsstoffe wie auch die Herstellung des Ein*» führungsreagens mit hohem präparativen bzw. technischem Aufwand verbunden und ihre Lagerstabilität eingeschränkt ist« Oft ist auch die Aminolyse-Geschwindigkeit begrenzt«·synthesis of the starting materials as well as the preparation of the introduction reagent are associated with high preparative or technical effort and their storage stability is limited. "Often, the aminolysis rate is also limited."
Ziel der ErfindungObject of the invention
Es ist das Ziel der Erfindung, ein neues vorteilhaftes Verfahren zur Herstellung von urethangeschützten Aminosäuren in die Peptidsynthese einzuführen· Es soll ein Reagenz gefunden werden, dessen Herstellung sich durch einen geringen technischen Aufwand und gute Zugänglichkeit der Ausgangsprodukte auszeichnet und das eine hohe Reaktionsfähigkeit und Hydrolysestabilität besitzt«It is the object of the invention to introduce a novel advantageous process for the preparation of urethane-protected amino acids in the peptide synthesis · A reagent is to be found whose production is characterized by a low technical complexity and good accessibility of the starting materials and has a high reactivity and hydrolytic stability "
Darlegung des Wesens der Erfindung Explanation of the essence of the invention
Der Erfindung liegt die Aufgabe zugrunde, ein Herstellungsverfahren für urethangeschützte Aminosäuren zu entwiokeln, das von haltbaren und leicht zugänglichen Verbindungen ausgeht· Die Aufgabe wurde dadurch gelöst, daß man unsymmetrische Carbonate I, die durch Reaktion von N-CChlorcarbonyl-' öxy)-5-norbornen-2,3-dicarboximid (Cl-CO-OUB) II mit entsprechenden Alkoholen gewonnen werden, mit Aminosäuren bzw*' Peptlden, die eine ungeschützte Arainogruppe enthalten, um-» setsrt.' Das Cl-CO-OlTB II seinerseits wird aus N-Hydroxy-5-norbornen-2,3-dicarboximid HONB III bzw.' seinem ITatriumsalz IV und Phosgen gewonnen. R1 steht für tert.-Butyl, Adämantyl-O), 2-Biphenylpropyl, 9-Methylfluorenyl, Methylsulf onyl ethyl, Benzyl oder andere in der Peptidchemie übliche Reste (Formelschema), R2 für Aminosäure- bzw·' Peptidreste«The object of the invention is to develop a preparation process for urethane-protected amino acids starting from long-lasting and easily accessible compounds. The object has been achieved by using unsymmetrical carbonates I obtained by reaction of N-chlorocarbonyl-oxy) -5- norbornene-2,3-dicarboximide (Cl-CO-OUB) II are obtained with corresponding alcohols, with amino acids or '' Peptlden containing an unprotected Arainogruppe, ums- 'setsrt.' The Cl-CO-OlTB II in turn is prepared from N-hydroxy-5-norbornene-2,3-dicarboximide HONB III or ' his ITatriumsalz IV and phosgene won. R 1 represents tert-butyl, adamantyl-O), 2-biphenylpropyl, 9-methylfluorenyl, methylsulfonylethyl, benzyl or other radicals customary in peptide chemistry (formula scheme), R 2 represents amino acid or "peptide radicals"
Die Titelverbindungen werden nach einem in der Literatur nicht beschriebenen Verfahren, das die Nachteile der bis~ herigen Methoden ausschließt (pH-Stat, Haltbarkeit der Ausgangsverbindungen j Stabilität, Zugänglichkeit) hergestellt«, Die Erfindung soll anhand von Ausführungsbeispielen näher erläutert werden©The title compounds are prepared by a process not described in the literature, which excludes the disadvantages of previous methods (pH-stat, stability of the starting compounds, stability, accessibility). The invention will be explained in more detail by means of exemplary embodiments
Einfuhrung der Schutzgruppen Introduction of protection groups
Die jeweilige Aminosäure wird in einem Gemisch aus Wasser/ Aceton, Wasser/Dioxan oder Wasser/t-Butanol gelöst (evt«; suspendiert) und mit der zwei bis vierfachen molaren Menge an Triethylamin versetzt. Im Anschluß daran wird das Reagens in einem Überschuß von 10 % zugegeben· Man rührt bei Raumtemperatur mehrere Stunden (abhängig von der Aminosäure, bei Einführung der Bpoc-Schutζgruppe beträgt die Reaktionstemperatur 45 0C). Der organische 18sungsmittelanteil wird im Vakuum entfernt und der verbleibende Rückstand mit 1Obiger KHSO. angesäuert.The respective amino acid is dissolved in a mixture of water / acetone, water / dioxane or water / t-butanol (evt "suspended) and with the two to four times the molar amount of triethylamine added. Subsequently, the reagent is added in an excess of 10% · The mixture is stirred at room temperature for several hours (depending on the amino acid, wherein introduction of the Bpoc Schutζgruppe the reaction temperature is 45 0 C). The organic 18sungsmittelanteil is removed in vacuo and the remaining residue with 1Obiger KHSO. acidified.
Man verteilt zwischen Methylenchlorid und KHSO.-Lösung und trennt die organische Phase ab. Die organische Phase wird zur Entfernung des restlichen HONB gründlich mit WasserPartition between methylene chloride and KHSO.-solution and separate the organic phase. The organic phase is thoroughly removed with water to remove the remaining HONB
( ' , (',
gewaschen und über MgSO. getrocknet. Es wird eingeengt und mit η-Hexan verrieben*washed and over MgSO. dried. It is concentrated and triturated with η-hexane *
2« MO C-OKB2 «MO C-OKB
Derivatderivative
* (0C)* ( 0 C)
Ausbeuteyield
MQC-AIa-OH MOC-GIy-QH MOC-Leu-OH Ä>C-Plie-QH MOC-YaI-OH MOC-Ser-OHMQC-Ala-OH MOC-Gly-QH MOC-Leu-OH Ä> C-Plie-QH MOC-YaI-OH MOC-Ser-OH
144144
172-74 153-55 180-82 142-4^· 86-88172-74 153-55 180-82 142-4 ^ · 86-88
95 87 91 95 85 8795 87 91 95 85 87
( ' ('
fl'0-.C-ORfl'0-.C-OR
0 R2-NH-C-O-R1 0 R 2 -NH-COR 1
2e Verfahren nach Punkt 1, dadurch gekennzeichnet, daß unsymmetrische Carbonate I. Verwendung finden, die durch Umsetzung von Alkoholen mit lf-(Chlorcarbonyloxy)-5»>norbornen-2,3-dicarboximid, das seinerseits durch Reaktion von U»-Hydroxy-5-norbornen-2i3-dicarboximid bzw» seinem üa» triumsalz mit Phosgen erhalten wird, gewonnen werden«2e process according to item 1, characterized in that unsymmetrical carbonates I are used which are obtained by reacting alcohols with L- (chlorocarbonyloxy) -5- > norbornene-2,3-dicarboximide, which in turn is obtained by reaction of U-hydroxy- 5-norbornene-2- i- 3-dicarboximide or "its sodium salt with phosgene is obtained"
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Claims (1)
1.grfindungsanspruch
1.
Priority Applications (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DD25419883A DD218886A1 (en) | 1983-08-25 | 1983-08-25 | PROCESS FOR THE PREPARATION OF N-URETHANE PROTECTED AMINO ACIDS |
| YU01445/84A YU144584A (en) | 1983-08-25 | 1984-08-22 | Process for making n-(chlorocarbonyloxi)-s-norbornen-2,3-dicarboximide |
| EP84110072A EP0134041B1 (en) | 1983-08-25 | 1984-08-23 | N-chlorocarbonyloxy-5-norbornene-2,3-dicarboximide, process for its preparation and its use |
| DE8484110072T DE3470309D1 (en) | 1983-08-25 | 1984-08-23 | N-chlorocarbonyloxy-5-norbornene-2,3-dicarboximide, process for its preparation and its use |
| AT84110072T ATE33386T1 (en) | 1983-08-25 | 1984-08-23 | N-CHLORCARBONYLOXY-5-NORBORNE-2,3-DICARBOXIMIDE PROCESS FOR ITS PRODUCTION AND ITS USE. |
| US06/644,777 US4714768A (en) | 1983-08-25 | 1984-08-27 | N-(chlorocarbonyloxy)-5-norbornene-2,3-dicarboximide, process for its production and its use |
| JP5094791A JPH06122672A (en) | 1983-08-25 | 1993-03-16 | Method of using N- (chlorocarbonyloxy) -5-norbornene-2,3-dicarboximide |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DD25419883A DD218886A1 (en) | 1983-08-25 | 1983-08-25 | PROCESS FOR THE PREPARATION OF N-URETHANE PROTECTED AMINO ACIDS |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DD218886A1 true DD218886A1 (en) | 1985-02-20 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DD25419883A DD218886A1 (en) | 1983-08-25 | 1983-08-25 | PROCESS FOR THE PREPARATION OF N-URETHANE PROTECTED AMINO ACIDS |
Country Status (1)
| Country | Link |
|---|---|
| DD (1) | DD218886A1 (en) |
-
1983
- 1983-08-25 DD DD25419883A patent/DD218886A1/en not_active IP Right Cessation
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| RPI | Change in the person, name or address of the patentee (searches according to art. 11 and 12 extension act) | ||
| ENJ | Ceased due to non-payment of renewal fee |