1α-羟基胆固醇的合成工艺改进  

Improvement of Synthetic Process of 1α-Hydroxycholesterol

作　　者：张克盛 葛欢恬 孙彬 金灿[1,2] ZHANG Kesheng;GE Huantian;SUN Bin;JIN Can(College of Pharmaceutical Sciences,Zhejiang University of Technology,Hangzhou 310014;National Engineering Research Center for Process Development of Active Pharmaceutical Ingredients,Hangzhou 310014)

机构地区：[1]浙江工业大学药学院,浙江杭州310014 [2]国家化学原料药合成工程技术研究中心,浙江杭州310014

出　　处：《中国医药工业杂志》2023年第8期1198-1201,共4页Chinese Journal of Pharmaceuticals

摘　　要：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%.

关 键 词：1α-羟基胆固醇 1α-羟基维生素D_(3) 中间体 合成 

分 类 号：R914.5[医药卫生—药物化学]