2-羟甲基-青霉烯-3-羧酸对硝基苄酯的制备

目的研究(5R,6S)-2-羟甲基-6-[(1R)-1-叔丁基-2-二甲基硅氧乙基]-青霉烯-3-羧酸对硝基苄酯的合成方法.方法以商品化的小四环为原料,经噻酸亲核取代、与对硝基苄基草酰氯反应、与亚磷酸三乙酯反应、加热环合、脱去保护基生成目标化合物1.结果与结论设计的合成路线经4步反应,总收率为23%,合成路线简便易行,适宜大规模生产.所合成的中间体及目标产物经核磁共振氢谱确证.

Preparation of p-nitrobenzyl(5R,6S)-2-hydroxymethyl-6-[(1R)-1-tert-butyl-dimethylsilyloxyethyl]-penem-3-carboxylate

Aim To improve the synthetic route for p nitrobenzyl( 5R,6S ) 2 hydroxymethyl 6 [( 1R ) 1 tert butyl dimethylsilyloxyethyl] penem 3 carboxylate(1).Methods Displacement of the acetoxy group of the commercially available azetidinone with the protected thioglycolic acid afforded the thioester(2),acylation to provide the oxalamide with p nitrobenzyloxy oxalyl chloride,followed by triethylphosphite induced cyclization to afford the penem(4).Selective deprotection of the primary TBS ether provided the final penem(1).Result and conclusion A facile,low cost synthetic route that is suitable for large scale preparation of the target compound has been provided through a four step procedure with the total yield of 23%,and the structure was verified by 1H NMR.