贝美前列素的合成

Synthesis of Bimatoprost

苯甲酰Corey内酯经Swern氧化得苯甲酰Corey醛,与(2-氧代-4-苯基丁基)磷酸二甲酯经Horner-WadsworthEmmons反应生成(1S,5R,6R,7R)-6-[(E)-3-氧代-5-苯基戊烯-1-基]-7-苯甲酰氧基-2-氧杂二环[3.3.0]辛烷-3-酮,再经硼氢化钠还原、脱保护、还原、与4-羧丁基三苯基溴化鏻进行Wittig反应、甲基化和胺解制得贝美前列素,总收率约31.7%,纯度99.3%。

Bimatoprost was synthesized from （-）-Corey lactone benzoate by Swem oxidation, HWE reaction with dimethyl （2-oxo-4-phenylbutyl） phosphonate to give （1S,5R,6R,7R） -6- [ （E） -3-oxo-5-phenylpent- 1-en- 1-yl] -7- E [ （phenyl） formyl] oxy] -2-oxobicyclo E3.3.0] octan-3-one, which was subjected to reduction with sodium borohydride, deprotection, reduction, Witting reaction with （4-carboxybutyl）triphenylphosphonium bromide, methylation and ammonolysis with an overall yield of about 31.7 % and an HPLC purity of 99.3 %.