Total synthesis of ent-cholesterol via a steroid C,D-ring side-chain synthon
Total synthesis of ent-cholesterol via a steroid C,D-ring side-chain synthon
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DOI：
10.1021/jo025535k
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发表时间：
2002-07-12
影响因子：
3.6
通讯作者：
Covey, DF
中科院分区：
文献类型：
--
作者：
Jiang, X;Covey, DF
首次通过一种合成路线合成了胆固醇的两种对映体之一（对映胆固醇），该合成路线从含有胆固醇 D 环和整个侧链的前体开始。作为所报道的合成路线的一部分，一种大规模（> 10 g）制备[1α(R*),7aα]-1-(1,5-二甲基己基)-1,2,3,6,7,7a-六氢-7a-甲基-5H-茚-5-酮、C,D环侧链合成子的每种对映体的通用方法，可用于合成维生素D-3、胆固醇、并且还开发了它们的类似物。使用导致对映胆固醇的 C,D 环侧链合成子的对映异构体，从线性片段中精心设计出 A 环和 B 环，该线性片段依次环化形成类固醇 B 环和 A 环。采用该路线，由(1α,5α,6α)-(+/-)-6-甲基-2-氧代-双环[3.1.0]己烷-1-甲酸甲酯经过23步制备对映胆固醇，总产率为2.6%。
For the first time, one of the two enantiomers of cholesterol (ent-cholesterol) has been synthesized by a synthetic route that starts from a precursor containing the D-ring and entire side chain of cholesterol. As part of the reported synthetic route, a method of general utility for the large scale (> 10 g) preparation of each enantiomer of [1alpha(R*),7aalpha]-1-(1,5-dimethylhexyl)-1,2,3,6,7,7a-hexahydro-7a-methyl-5H-inden-5-one, C,D ring-side chain synthons that can be used for the synthesis of enantiomers of vitamin D-3, cholesterol, and their analogues was also developed. Using the enantiomer of the C,D-ring side-chain synthon that leads to ent-cholesterol, the A- and B-rings were elaborated from a linear fragment that is sequentially cyclized to form the steroid B- and A-rings. Using this route, ent-cholesterol was prepared in 23 steps from the methyl ester of (1alpha,5alpha,6alpha)-(+/-)-6-methyl-2-oxo-bicyclo[3.1.0]hexane-1-carboxylic acid in a total yield of 2.6%.