2-羟甲基-青霉烯-3-羧酸对硝基苄酯的制备

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

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 2 3% ,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。

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.