生物活性20S-羟基维生素D3的全合成
Total synthesis of biologically active 20S-hydroxyvitamin D3.
作者信息
Wang Qinghui, Lin Zongtao, Kim Tae-Kang, Slominski Andrzej T, Miller Duane D, Li Wei
机构信息
Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN 38163, United States.
Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294, United States; Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, United States.
出版信息
Steroids. 2015 Dec;104:153-62. doi: 10.1016/j.steroids.2015.09.009. Epub 2015 Oct 1.
Abstract
A total synthetic strategy of 20S-hydroxyvitamin D3 [20S-(OH)D3] involving modified synthesis of key intermediates 7 and 12, Grignard reaction to stereoselectively generate 20S-OH and Wittig-Horner coupling to establish D3 framework, was completed in 16 steps with an overall yield of 0.4%. The synthetic 20S-(OH)D3 activated vitamin D receptor (VDR) and initiated the expression of downstream genes. In addition, 20S-(OH)D3 showed similar inhibitory potency as calcitriol [1,25(OH)2D3] on proliferation of melanoma cells.
摘要
一种20S-羟基维生素D3 [20S-(OH)D3]的全合成策略，涉及关键中间体7和12的改进合成、立体选择性生成20S-OH的格氏反应以及构建D3骨架的维蒂希-霍纳尔偶联反应，该策略以16步完成，总产率为0.4%。合成的20S-(OH)D3激活了维生素D受体（VDR）并启动了下游基因的表达。此外，20S-(OH)D3在抑制黑色素瘤细胞增殖方面表现出与骨化三醇[1,25(OH)2D3]相似的效力。
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