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US 4,340,672 AGranted
Enzymatic synthesis of .beta.-lactam antibacterials
AssigneeShionogi & Co., Ltd.
InventorsEiji Kondo, Takashi Mitsugi, Tamio Fujiwara, Ryonosuke Muneyuki
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Abstract
Penicillins and cephalosporins can be synthesized by the action of an acylase on a penicillin or cephalosporin nucleus amine as substrate and an ester (I) of the following formula as the acyl source: ##STR1## (wherein RCO is an acyl group in penicillin or cephalosporin side chains; X is a hydrogen atom, lower alkyl group or hydroxy-lower alkyl group; Y is a hydrogen atom or a lower alkyl group; and n is a positive integer). The novel acyl source (I) is also disclosed.
Claims3
A process for the synthesis of a penicillin or cephalosporin comprising the steps of:
- subjecting an amine of the formula:
- H.sub.2 N--Q
- optionally in an enzymatically acceptable conventional salt or ester form to enzymatic catalysis in the presence of an acylase and in the presence of an ester of the formula:
- ##STR30## wherein Q is a group of the formula:
- ##STR31## Z is hydrogen, halogen, or a group which consisting of 1 to 7 carbon atoms selected from the group consisting of methyl, lower alkoxy, monocyclic (O, N or S)-heterocyclic thio, monocyclic lower aralkyl, lower alkanoyloxy, lower alkanoyloxy-lower alkyl, monocyclic (O, N or S)-heterocyclic thio-lower alkyl, or pyridinium-lower alkyl, optionally substituted with lower alkyl, carboxy-lower alkyl, lower alkoxy, carbamoyl or halogen;
- RCO, which contains 1 to 15 carbon atoms, is lower alkanoyl, lower alkenoyl, monocyclic lower aralkanoyl, monocyclic aryloxylower alkanoyl, (O, N or S)-heterocyclic-lower alkanoyl, (O,N or S)-heterocyclic thio-lower alkanoyl, cyanoacetyl, cyanomethylthioacetyl, monocyclic arylglycyl, monocyclic cycloalkenylglycyl, monocyclic arylglycolyl, N-acylarylglycyl, monocyclic arylmalonyl or arylsulfoalkanoyl, optionally substituted with lower alkyl, aminomethyl, halogen, hydroxy, lower alkanoyloxy or lower alkoxy;
- X is hydrogen, lower alkyl or hydroxymethyl;
- Y is hydrogen or lower alkyl;
- and n is an integer of from 1 to 20, to form a penicillin or cephalosporin of the formula:
- RCONH--Q
- wherein R and Q are as defined above.
8 more elements
Dependencies are inferred from the claim text.