트리아오릴 티오메칠피로리딘을 3번 측쇄에 가진 세파로스포린 유도체의 합성

Synthesis of Cephalosporin Derivatives with Triazolylthiomethylpyrrolidines at the C-3 Side Chain

Synthesis of 7β- [(Z)-2-(2-aminothiazol-4-yl)-2-(1-carboxy-1- methylethoxyimino)acetamido] -3- [ [(3S,5S)-5- [4-phenyl -5- (4- methylphenil or 2- thiophenyl) -4H-1,2,4- triazol -3-yl] thiomethylpyrrolidin-3-yl] ] thiomethyl -3- cephem -4- carboxylic acids (`7a,7b) were described. (2S,4S) -4-acethylthio-2- [4- phenol-5- (4-methylphenyl or 2-thiophenyl)-4H-1,2,4-triazol-3-yl ] thiomethyl-1- tert butoxycarbonylpyrrolidines (4a ,4b) were prepared from trans -4- hydroxy-L -proline with (2S,4R) -absolute configuration as starting material.4-Phenyl- 5-(4-methylphenyl or 2-thiophenyl) -4H-1,2,4-triazol-3-thiols (2a,2b) were prepared from p-toluic anhydride and 2-thiophene carboxylic acid hydrazide, respectively. P- Methowbenzyl 7β-(Z)-2-(2-formamidothiazol 1-4-yl ) -2- (1-tert- butoxycarbonylisopropylimino) acetamido -3- [ [(3S,5S)-5-[4-phenyl-5-(4-methylphenyl or 2-thio phenil)-4H-1,2,3-triazol-3-yl]thiomethyltertbutoxycarbonylpyrroli din -3-yl]] thiomethyl-3-cephem-4-carboxylates (6a ,6b) were achieved by using p- methoxybenfyll 7β- (Z) -2- (2-formamidothiazol -4-yl ) -2- (tert- butoxycarbonylisopropylimino) acetamido-3-chloromethyl-3-cephem-4-carboxylate (5) and (2S,4S)-4-acethylthio-2- [4-phenyl-5-(4-methyl phenyl or 2-thiophenyl) -4H-1,2,4- triazol-3-yl]thiomethyl-1-tert-butoxycarbonyl pyrrolidines (4a,4b) . Removal of formyl, Boc, and p-methoxybenzyl protecting groups were carried out by triflu oroacetic acid and anisole to give the target compounds.