| 摘要 |
1,272,769. Enzymic production of carboxyalkyl-cephalosporins. GLAXO LABORATORIES Ltd. 18 July, 1969 [2 Aug., 1968], No. 37113/68. Heading C2A. [Also in Division C3] Novel cephalosporin derivatives having the Formula I and salts thereof, wherein R is -CO.COOH or -COOH and X is an acetate group, a residue of a nucleophile, -OH or hydrogen, are prepared by treating cephalosporin C or a salt or derivative thereof wherein X is as before with a fungal D-amino-acid oxidase under aerobic conditions, catalase activity being present when the group R in the desired product is -CO.COOH. The oxidase may be derived from species of Aspergillas, Penicillium, Neurospora or Aerobacter or the yeast Trigonopsis variabilis, and is prepared as an acetone powder or cell-free extract of the mycelium (see Division C3). Oxidase formation may be induced in the fungus by adding a D- or DL-amino-acid (e.g. DL-alanine, DL-valine or methionine) to the growing cells at the seed stage. The oxidase preparations normally contain some catalase but extra catalase may be added if required. The presence of catalase prevents oxidative decarboxylation via an intermediate wherein R is -CHO and hence R is -CO.COOH in the product. By inhibiting the catalase (e.g. with ascorbic acid, 3-amino-1,2,3-triazole or an inorganic azide) or using a catalase-free aminoacid oxidase preparation, this oxidative decarboxylation is allowed to proceed resulting in a product wherein R is -COOH. The cephalosporin C starting material may be a preferably de-proteinized fermentation broth or a semisynthetic material having the aforesaid substituent X in the 3-position. The product may be isolated by solvent-extraction or by use of ion-exchangers and optionally converted to the 2,4-dinitrophenylhydrazone derivative. The products are useful as intermediates for preparing the corresponding 7-ACA derivatives by N-deacylation.
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