利用薯蓣皂甙元完整骨架形式合成1α,25-二羟基维生素D3

首次利用薯蓣皂甙元的完整骨架经16步反应以7.6%的总收率合成了骨化三醇(1α,25-二羟基维生素D₃)的光化反应前体. 3-苄基保护的薯蓣皂甙元经还原开E/F环产生3,16,26-胆甾三醇-3-苄醚(5). 除去化合物5 C-16羟基后, 其C-26羟基经消除和羟基化反应转移到C-25位. 目标分子A/B环结构单元通过薯蓣皂甙元A/B环的官能团转化被构筑. 按照已知的光化反应, (1S,3R)-胆甾-5,7-二烯-1,3,25-三醇能被转化成为1α,25-二羟基维生素D₃.

Formal Synthesis of 1α,25-Dihydroxyvitamin D3 by Utilizing the Intact Skeleton of Diosgenin

(1S,3R)-Cholesta-5,7-diene-1,3,25-triol, a photochemical reaction precursor for the preparation of 1α,25-dihydroxyvitamin D₃ , was synthesized by utilizing the intact skeleton of diosgenin in 16 steps in 7.6% overall yield. The reductive E/F ring opening of 3-benzyloxy-diosgenin produced 3,16,26-cholesteratriol benzyl ether 5. The C-26 hydroxy group was shifted to C-25 through the elimination and hydroxylation after the selective removal of C-16 hydroxyl group in 5. The A/B structural unit of the target molecule was constructed by the functional transformation of the A/B ring of diosgenin. (1S,3R)-Cholesta-5,7-diene-1,3,25-triol can be converted into 1α,25-dihydroxyvitamin D₃ according to the known photochemical reaction.