1α-羟基胆固醇的合成工艺改进

Improvement of Synthetic Process of 1α-Hydroxycholesterol

文章对1α-羟基维生素D3关键中间体1α-羟基胆固醇(1)的合成工艺进行改进:以胆固醇(2)为原料,经过氧化脱氢、环氧化、选择性开环、异构化和还原等5步反应得到1。较现有1的制备工艺,该路线一方面规避了液氨/锂于-78℃还原的苛刻条件,操作简单,条件温和;另一方面采用苯硒酚对1α,2α-环氧-4,6-胆甾二烯-3-酮(4)进行选择性开环,并由I2/乙酸异丙烯酯体系实现由烯酮异构化为烯醇酯。采用优化后的工艺,1的总收率达40%,纯度为98%。

An improved synthetic process of la-hydroxycholesterol(1),a key intermediate of lα-hydroxyvitamin D,was reported by using cholesterol as raw material(2)through five steps,including oxidative dehydrogenation,epoxidation,selective ring opening,isomerization and reduction.Compared with the existed preparation process of 1,on the one hand,this route featured simple operation and mild conditions,avoiding the harsh conditions of liquid ammonia/lithium reduction at-78℃.On the other hand,the ring-opening of 1α,2α-epoxy-4,6-cholestadiene-3-one(4)was carried out by using phenylselenol,and the isomerization of ketene to enol ester was achieved by I_(2)/isopropylacetate system.After the optimization,the total yield for synthesis of 1 was 40%with purity of 98%.