[go: up one dir, main page]

RU2221046C2 - Method for preparing semi-synthetic aminopenicillins, aminocephalosporins or their n-substituted derivatives - Google Patents

Method for preparing semi-synthetic aminopenicillins, aminocephalosporins or their n-substituted derivatives Download PDF

Info

Publication number
RU2221046C2
RU2221046C2 RU2000101270/13A RU2000101270A RU2221046C2 RU 2221046 C2 RU2221046 C2 RU 2221046C2 RU 2000101270/13 A RU2000101270/13 A RU 2000101270/13A RU 2000101270 A RU2000101270 A RU 2000101270A RU 2221046 C2 RU2221046 C2 RU 2221046C2
Authority
RU
Russia
Prior art keywords
beta
lactam
betalactam
biosynthetic
enzyme
Prior art date
Application number
RU2000101270/13A
Other languages
Russian (ru)
Other versions
RU2000101270A (en
Inventor
П.С. Ныс
В.Б. Курочкина
ренко А.В. Скл
А.В. Скляренко
А.М. Егоров
Original Assignee
Государственный научный центр антибиотиков
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Государственный научный центр антибиотиков filed Critical Государственный научный центр антибиотиков
Priority to RU2000101270/13A priority Critical patent/RU2221046C2/en
Publication of RU2000101270A publication Critical patent/RU2000101270A/en
Application granted granted Critical
Publication of RU2221046C2 publication Critical patent/RU2221046C2/en

Links

Images

Classifications

    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/52—Improvements relating to the production of bulk chemicals using catalysts, e.g. selective catalysts

Landscapes

  • Immobilizing And Processing Of Enzymes And Microorganisms (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Enzymes And Modification Thereof (AREA)

Abstract

FIELD: biotechnology, antibiotics. SUBSTANCE: invention relates to preparing semi-synthetic beta-lactam antibiotics aminopenicillins and aminocephalosporins and their N-substituted derivatives also. Method involves enzymatic transformation of the parent beta-lactam compound in the presence of enzyme system. For realizing method biosynthetic beta-lactam compounds and their chemical analogues are used as parent beta-lactam compounds and biocatalysts of the 2-d generation based on immobilized cells comprising hydrolase for biosynthetic beta-lactams in combination with enzyme amino-beta-lactam synthase specific to derivatives of aminophenylacetic acid are used as enzymes. Amino acid esters are used as acylating agent that are added to reaction mass and flowing molar excess of acylating agent with respect to amino acid is maintained to be 3-4-fold and its total content is 1.9-2.1 M/M of the parent beta-lactam, not above. End products are isolated by direct precipitation as amino-beta- lactams by pH value change, medium dielectric permeability value or by addition of specific precipitating agent, preferably α- naphthol, or as N-substituted derivative by pH value change. Invention provides elevating effectiveness of method with its simultaneous simplification. EFFECT: enhanced yield, improved quality of product. 4 cl, 9 ex

Description

Текст описания в факсимильном виде (см. графическую часть)а Description text in facsimile form (see graphic part) a

Claims (4)

1. Способ получения полусинтетических аминопенициллинов, аминоцефалоспоринов или их N-замещенных производных, включающий ферментативную трансформацию исходного беталактамного соединения в присутствии катализатора с использованием эфира Д-аминокислоты в качестве ацилирующего агента с последующим осаждением целевого продукта, отличающийся тем, что в качестве исходного беталактамного соединения используют биосинтетический беталактам или его химический аналог, а в качестве катализатора ферментативной трансформации используют биокатализатор на основе совместно иммобилизованных микробных клеток, содержащих гидролазу биосинтетического беталактама, и фермента аминобеталактамсинтетазы, специфичной к производным аминофенилуксусной кислоты.1. A method of producing semi-synthetic aminopenicillins, aminocephalosporins or their N-substituted derivatives, comprising the enzymatic transformation of the initial betalactam compound in the presence of a catalyst using an D-amino acid ester as an acylating agent, followed by precipitation of the target product, characterized in that it is used as the initial betalactam compound biosynthetic betalactam or its chemical analogue, and bioca as a catalyst for enzymatic transformation a catalyst based on co-immobilized microbial cells containing a biosynthetic betalactam hydrolase and an aminobetalactam synthetase enzyme specific for aminophenylacetic acid derivatives. 2. Способ по п.1, отличающийся тем, что в качестве исходного беталактамного соединения используют Pen G, Серh G, Glutary-7-АСА или ее С-3 производное.2. The method according to claim 1, characterized in that Pen G, Serh G, Glutary-7-ACA or its C-3 derivative are used as the initial betalactam compound. 3. Способ по п.1, отличающийся тем, что используют водонерастворимый биокатализатор на основе совместно иммобилизованных микробных клеток Е.coli, содержащих пенициллинамидазу, или Pseudomonas sp., содержащих глутарилгидролазу, и фермента аминоцефалоспорин (аминопенициллин) синтетазы из Xanthomonas rubrilineans.3. The method according to claim 1, characterized in that a water-insoluble biocatalyst based on co-immobilized E. coli microbial cells containing penicillin amidase or Pseudomonas sp. Containing glutaryl hydrolase and the enzyme aminocephalosporin (aminopenicillin) synthetase from Xanthomonas ru is used. 4. Способ по любому из пп.1 и 3, отличающийся тем, что используют обратимо растворимый биокатализатор на основе совместно иммобилизованных клеток Е.coli, содержащих пенициллинамидазу, и фермента аминоцефалоспорин (аминопенициллин) синтетазы из Xanthomonas rubrilineans.4. The method according to any one of claims 1 and 3, characterized in that a reversibly soluble biocatalyst is used based on co-immobilized E. coli cells containing penicillin amidase and the enzyme aminocephalosporin (aminopenicillin) synthetase from Xanthomonas rubrilineans.
RU2000101270/13A 2000-01-21 2000-01-21 Method for preparing semi-synthetic aminopenicillins, aminocephalosporins or their n-substituted derivatives RU2221046C2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
RU2000101270/13A RU2221046C2 (en) 2000-01-21 2000-01-21 Method for preparing semi-synthetic aminopenicillins, aminocephalosporins or their n-substituted derivatives

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
RU2000101270/13A RU2221046C2 (en) 2000-01-21 2000-01-21 Method for preparing semi-synthetic aminopenicillins, aminocephalosporins or their n-substituted derivatives

Publications (2)

Publication Number Publication Date
RU2000101270A RU2000101270A (en) 2002-08-27
RU2221046C2 true RU2221046C2 (en) 2004-01-10

Family

ID=32090112

Family Applications (1)

Application Number Title Priority Date Filing Date
RU2000101270/13A RU2221046C2 (en) 2000-01-21 2000-01-21 Method for preparing semi-synthetic aminopenicillins, aminocephalosporins or their n-substituted derivatives

Country Status (1)

Country Link
RU (1) RU2221046C2 (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2535893C1 (en) * 2013-08-20 2014-12-20 Федеральное государственное унитарное предприятие "Государственный научно-исследовательский институт генетики и селекции промышленных микроорганизмов" (ФГУП "ГосНИИгенетика") Method for obtaining heterogenic biocatalyst based on hydrolase of esters of alpha aminoacids, heterogenic biocatalyst obtained by such method, and synthesis method of aminobeta-lactam antibiotic under action of this heterogenic biocatalyst

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0045717B1 (en) * 1980-08-01 1985-09-25 BIOCHEMIE Gesellschaft m.b.H. New cephalosporin derivatives, their production and their use
PT96538A (en) * 1990-01-22 1991-10-15 Biochemie Gmbh Improved process for the preparation of &beta-lactams
RU96103835A (en) * 1995-02-28 1998-05-10 Эй Си Эс Добфар С.п.А. IMPROVED ENZYMATIC METHOD FOR OBTAINING PENICILLINS AND CEFALOSPORINS

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0045717B1 (en) * 1980-08-01 1985-09-25 BIOCHEMIE Gesellschaft m.b.H. New cephalosporin derivatives, their production and their use
PT96538A (en) * 1990-01-22 1991-10-15 Biochemie Gmbh Improved process for the preparation of &beta-lactams
RU96103835A (en) * 1995-02-28 1998-05-10 Эй Си Эс Добфар С.п.А. IMPROVED ENZYMATIC METHOD FOR OBTAINING PENICILLINS AND CEFALOSPORINS

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2535893C1 (en) * 2013-08-20 2014-12-20 Федеральное государственное унитарное предприятие "Государственный научно-исследовательский институт генетики и селекции промышленных микроорганизмов" (ФГУП "ГосНИИгенетика") Method for obtaining heterogenic biocatalyst based on hydrolase of esters of alpha aminoacids, heterogenic biocatalyst obtained by such method, and synthesis method of aminobeta-lactam antibiotic under action of this heterogenic biocatalyst

Similar Documents

Publication Publication Date Title
Kataoka et al. Lactonohydrolase-catalyzed optical resolution of pantoyl lactone: selection of a potent enzyme producer and optimization of culture and reaction conditions for practical resolution
Secundo et al. Optimization of hydrolase efficiency in organic solvents
WO1997004086A1 (en) An improved immobilized penicillin g acylase
RU2221046C2 (en) Method for preparing semi-synthetic aminopenicillins, aminocephalosporins or their n-substituted derivatives
JP2771244B2 (en) Preparation method of β-lactam enzyme
JPS6255097A (en) Production of l-amino acid
EP1275723B1 (en) Recombinant D-hydantoin hydrolases and N-carbamyl-D-amino acid hydrolases, and DNA encoding them; uses thereof for producing D-amino acids
Koreishi et al. Purification and characterization of a novel aminoacylase from Streptomyces mobaraensis
US6060268A (en) Penicillin G acylase immobilized with a crosslinked mixture of gelled gelatin and amino polymer
Scollar et al. Preparative resolution of d, l‐threonine catalyzed by immobilized phosphatase
JP2004081107A (en) Hydrolysis or dehydration condensing enzyme, method for producing the enzyme, and method for synthesizing amide using the enzyme
JPH01199576A (en) Alpha-aminoadipinylmonoamino compound
WO1992017600A1 (en) Enzymatic process for the production of cefonicid
JPH01320991A (en) Production of d-homophenylalanines
Kazan et al. Influence of polyhydric compounds on the pH stability of penicillin G acylase obtained from a mutant of Escherichia coli ATCC 11105
US20050153401A1 (en) Process for preparing optically active beta-aminocarboxylic acids from racemic n-acylated beta-aminocarboxylic acids
RU2000101270A (en) METHOD FOR PRODUCING SEMI-SYNTHETIC AMINOPENICILLINS, AMINOCEPHALOSPORINS AND THEIR N-SUBSTITUTED DERIVATIVES
Adams et al. Biotransformations in Small‐Molecule Pharmaceutical Development
RU2535893C1 (en) Method for obtaining heterogenic biocatalyst based on hydrolase of esters of alpha aminoacids, heterogenic biocatalyst obtained by such method, and synthesis method of aminobeta-lactam antibiotic under action of this heterogenic biocatalyst
JP4765358B2 (en) Process for producing optically active N-protected-propargylglycine
Brask Immobilized enzymes in organic synthesis
JPH0574353B2 (en)
US3716454A (en) PROCESS FOR THE PRODUCTION OF alpha -AMINOBENZLPENICILLIN
Egorov et al. Enzymatic transformation of betalactam antibiotics: Trend of development and approaches to practical implementation
WO1996031616A1 (en) Process for producing l-2-aminoadipic acid

Legal Events

Date Code Title Description
MM4A The patent is invalid due to non-payment of fees

Effective date: 20100122