NEUE ANTIBIOTICA

1455016 Dethiacephalosporin derivatives; their preparation and use MERCK & CO Inc 5 Nov 1973 [6 Nov 1972 18 Sept 1973] 51301/73 Headings C2C and C2P Compounds of the formulµ and isomers of the compounds of Formula I, wherein R is an acyl radical, B is H, OCH 3 , CH 3 or SR wherein R is C 1-6 alkyl or aryl R1 is hydrogen or a protecting group, A1 is hydrogen or an organic radical, X is -O-, -CH 2 - or -NY-, wherein Y is hydrogen, benzyl, formyl or C 1-6 alkyl, and R 6 is azido, amino, benzaldimino or substituted benzaldimino, or a non-toxic pharmacologically acceptable salt, ester or amide derivative of such a compound, may be prepared in a number of different ways. The 7- acylamino compounds (Formula I) may be prepared by treating a 7-amino or 7-substituted imino compound of the formula wherein R4 is hydrogen or both R4 groups taken together represent optionally substituted benzylidene, with a suitable acylating agent, generally at -20‹ C. to +100‹ C. and preferably in the presence of a solvent; when an imino compound is employed it is preferably first treated with a metal catalyst. The 7#-amino and 7#-substituted imino compounds may be prepared by various processes depending upon the nature of the X group. When X is methylene, the procedure shown in the following flow diagram (III) may be employed wherein R5 is C 1-5 alkyl or an aryl radical. Compound B is suitably reacted with azidoacetyl chloride in the above flow diagram and the product, compound G, treated with an oxidizing agent; ring closure of compound D may be effected with a base and the product, compound E subsequently reduced, e.g. by treatment with hydrogen in the presence of a noble metal catalyst. Alternatively the oxoazetidinone (D) in the above flow diagram (III) may be obtained by utilizing a valeraldehyde, which contains a 4-carbonyl group precursor or a 4-masked carbonyl group, in place of the 4- methylene valeraldehyde of flow diagram (III), according to the following flow diagram wherein X and Y represent a carboxyl precursor grouping or a masked carboxyl group. Regeneration of the carboxyl group to form the oxoazetidinone (D) may be effected by treating the azetidinone (C1) with an oxidizing agent, in the case of a carboxyl precursor grouping, or employing acid hydrolysis where X and Y represent a masked carboxyl group. 7#-Amino compounds (IIa), wherein X is -O- or -NY-, may be obtained according to the following flow diagram wherein X1 is a divalent radical selected from -O- and -NY