24-亚甲基胆甾-5-烯-3β,19-二醇的合成

从豆甾醇出发,通过10步反应,合成得到具有显著细胞毒活性的24-亚甲基胆甾-5-烯-3β,19-二醇(1),总产率为16%.目标产物1的熔点、α]值和波谱数据与天然产物一致.化合物1的合成是首次报道,它对人体鼻咽癌(CN2)和胃癌(Mgc803)细胞有显著抑制活性.

Synthesis of 24-Methylenecholest-5-en-3β, 19-diol

With stigmasterol as the starting material, 24-methylenecholest-5-en-3%β%,19-diol(1), a cytotoxic hydroxylated sterol, was synthesized in 10 steps in 16% overall yield. The side chain of stigmasterol was converted to a keto-containing structure 4 %via% ozonization, the Wittig reaction and hydrogenation. The key intermediate cholest-5-en-24-oxo-3%β%,19-diol(8) from compound 4 was prepared according to the following procedures: HOBr addition, lead tetraacetate/I2-irradiation reaction, zinc dust reduction and KOH/CH3OH hydrolyzation. Finally, the synthesis of the target product 1 was completed by the Wittig reaction with methenetriphenylphosphorane. The physical constants and NMR data of compound 1 were identical with those of the natural product. This is the first report for the synthesis of 24-methylenecholest-5-en-3%β%,19-diol(1). Compound 1 exhibits a significant cytotoxic activity against human CN2 and Mgc803 cell lines with IC50 values of 3.5 and 4.0 μg/mL respectively.