Synthesis of 2α- and 2β-substituted-14-epi-previtamin D3 and their genomic activity

被引：18
|
作者：
Sawada, Daisuke [1 ]
Katayama, Tomoyuki [1 ]
Tsukuda, Yuya [1 ]
Saito, Nozomi [1 ]
Saito, Hiroshi [2 ]
Takagi, Ken-ichiro [2 ]
Ochiai, Eiji [2 ]
Ishizuka, Seiichi [2 ]
Takenouchi, Kazuya [2 ]
Kittaka, Atsushi [1 ]
机构：
[1] Teikyo Univ, Fac Pharmaceut Sci, Midori Ku, Kanagawa 2525195, Japan
[2] Teijin Pharma Ltd, Teijin Inst Biomed Res, Tokyo 1918512, Japan
来源：
TETRAHEDRON | 2010年 / 66卷 / 29期
基金：
日本学术振兴会;
关键词：
Vitamin D-3; 14-epi-Previtamin D-3; Osteocalcin; Vitamin D receptor; VITAMIN-D-RECEPTOR; STEREOCONTROLLED TOTAL-SYNTHESIS; CELL-DIFFERENTIATION ACTIVITY; ACTIVATED PROTEIN-KINASE; D ENDOCRINE SYSTEM; 1-ALPHA; 25-DIHYDROXYVITAMIN D-3; A-RING; D ANALOGS; BIOLOGICAL EVALUATION; RAPID STIMULATION;
D O I：
10.1016/j.tet.2010.05.028
中图分类号：
O62 [有机化学];
学科分类号：
070303 ; 081704 ;
摘要：
2 alpha- and 2 beta-Substituted analogs of 14-epi-previtamin D-3 were synthesized and isolated after thermal isomerization of 14-epi-vitamin D-3 triene at 80 degrees C. The VDR binding affinity and transactivation activity of osteocalcin promoter in HOS cells were tested, and the 2 alpha-methyl-substituted analog was found to have greater genomic activity than 14-epi-previtamin D-3. We found that modification at the C2 position of the seco-steroidal skeleton afforded interesting effects for biological genomic activity for the previtamin D form as well as the natural vitamin D form. (C) 2010 Elsevier Ltd. All rights reserved.
引用
收藏
页码：5407 / 5423
页数：17
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