method of separation penicillines' natural enzyme and enzyme synthesis penicillines' semi synthetic 'by means of an insoluble enzyme acylase and synthes divisione of composesayant similar therapeutic properties

摘要

1348359 Enzymatic preparation of cepnalosporins and penicillins SNAM PROGETTI SpA 27 April 1972 [28 April 1971] 19726/72 Heading C2A [Also in Division C3] The invention comprises a process for the treatment of a substance which contains a ring structure characteristic of penicillins or cephalosporins to convert it to another substance containing the ring structure, which process comprises contacting a reaction medium containing the substance with a filament in which is distributed in finely divided form at least one enzyme capable of causing the desired conversion, the or each enzyme being encased in the filament in such a manner that the or each enzyme can effect conversion and that it or they are substantially retained in the filament during the contacting. The enzyme or enzymes may be incorporated in a filament formed from a nitrated, esterified or etherified cellulosic polymer, a polyolefine, a polymer or copolymer of acrylonitrile, an acrylate, methacrylate, vinyl ester, vinyl chloride, vinylidene chloride or styrene, a polyamide or polyvinylbutyral. Suitable polymers include ethyl cellulose, poly-- methylglutamate and cellulose triacetate. Hydrolysis of natural penicillins may be carried out by this process. Such penicillins include those of Formula I wherein R is alkyl of 1 to 10 carbon atoms, with from 3 to 10 carbon atoms, aralkyl, RSP1/SPOCH 2 - or RSP1/SPSCH 2 -, wherein RSP1/SP is alkyl, alkenyl, phenyl or optionally substituted phenyl. The pH of the reaction medium may be buffered at 8. The filament may contain an acylase derived from bacterial cells such as E. coli, B. megaterium, Aerobacter aerogenes or Alcaligenes faecalis cells. The filament may contain an enzyme derived from Actinomyces or fungal cells, e.g. Aspergillus, Penicillum, Botrytis cinerea, Fusanium, Mucor, Alternaria or Streptomyces cells. Synthesis of some penicillins, e.g. ampicillin, may be effected by the process of the invention. The invention also comprises a filament in which is distributed in finely divided form at least one enzyme capable of causing conversion of a substance containing a ring structure characteristic of penicillins or cephalosporins to another substance containing the ring structure, the enzyme being present in the filament in a manner such that it is retained in the filament, when the latter is contacted by a reaction medium containing the substance and that it is capable of effecting the conversion whilst being so retained.