（22E，25R）-和（22，25S）-22-脱氢-1α，25-二羟基-26-甲基维生素D3的合成与生物活性

Synthesis and biological activity of (22E,25R)- and (22,25S)-22-dehydro- 1 alpha,25-dihydroxy-26-methylvitamin D3.

作者信息

Hara N, Eguchi T, Ikekawa N, Ishizuka S, Sato J

机构信息

Department of Chemistry, Tokyo Institute of Technology, Meguro-ku, Japan.

出版信息

J Steroid Biochem. 1990 May;35(6):655-64. doi: 10.1016/0022-4731(90)90305-c.

DOI:10.1016/0022-4731(90)90305-c

PMID:2163469

Abstract

Both 25-epimers of (22E)-22-dehydro-1 alpha,25-dihydroxy-26-methylvitamin D3 [22-dehydro-26-methyl-1,25-(OH)2D3] were synthesized. The biological activity of these compounds was tested in binding affinity to chick intestinal receptor protein of 1 alpha,25-dihydroxy-vitamin D3 [1,25-(OH)2D3] and in stimulating for intestinal calcium transport and bone calcium mobilization with vitamin D-deficient rats. The relative potency of (25R)- and (25S)-22-dehydro-26-homo-1,25-(OH)2D3 and 1,25-(OH)2D3 in competing for the intestinal cytosolic binding was 1.7:1.5:1. A similar order of activity was observed on intestinal calcium transport and bone calcium mobilization. In the ability for stimulation of intestinal calcium transport, (25R)- and (25S)-22-dehydro-26-methyl-1,25-(OH)2D3 were about 3.6 and 2.1 times as active as 1,25-(OH)2D3, respectively. In bone calcium mobilization tests, (25R)- and (25S)-22-dehydro-26-methyl-1,25-(OH)2D3 were estimated to be 2.2 and 1.6 times as potent as 1,25-(OH)2D3, respectively.

摘要

合成了(22E)-22-脱氢-1α,25-二羟基-26-甲基维生素D3[22-脱氢-26-甲基-1,25-(OH)2D3]的两种25-差向异构体。在与1α,25-二羟基维生素D3[1,25-(OH)2D3]的鸡肠受体蛋白的结合亲和力以及对维生素D缺乏大鼠的肠钙转运和骨钙动员的刺激作用方面测试了这些化合物的生物活性。(25R)-和(25S)-22-脱氢-26-高-1,25-(OH)2D3与1,25-(OH)2D3在竞争肠胞质结合方面的相对效价为1.7:1.5:1。在肠钙转运和骨钙动员方面观察到了类似的活性顺序。在刺激肠钙转运的能力方面，(25R)-和(25S)-22-脱氢-26-甲基-1,25-(OH)2D3的活性分别约为1,25-(OH)2D3的3.6倍和2.1倍。在骨钙动员试验中，(25R)-和(25S)-22-脱氢-26-甲基-1,25-(OH)2D3的效力分别估计为1,25-(OH)2D3的2.2倍和1.6倍。