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化学进展 2016, Vol. 28 Issue (6): 839-859 DOI: 10.7536/PC151226 前一篇   后一篇

• 综述与评论 •

活性维生素D3类似物的合成及构效关系研究

胡代花, 陈旺, 王永吉*   

  1. 陕西理工学院 维生素D生理与应用研究所 汉中 723000
  • 收稿日期:2015-12-01 修回日期:2016-02-01 出版日期:2016-06-15 发布日期:2016-03-23
  • 通讯作者: 王永吉 E-mail:yjwang2000@gmail.com
  • 基金资助:
    陕西省自然科学基金项目(No.2014JQ2083)、陕西省重点科技创新团队项目(No.2012KCT-29)和陕西省2011计划陕南秦巴山区生物资源综合开发协同创新中心项目(No.QBXT-Z(P)-15-15)资助
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Synthesis and Structure-Activity Relationship of Active Vitamin D3 Analogues

Hu Daihua, Chen Wang, Wang Yongji*   

  1. Vitamin D Research Institute, Shaanxi University of Technology, Hanzhong 723000, China
  • Received:2015-12-01 Revised:2016-02-01 Online:2016-06-15 Published:2016-03-23
  • Supported by:
    The work was supported by the Natural Science Foundation of Shaanxi Province (No.2014JQ2083),the Key Project of Scientific and Technological Innovation Group of Shaanxi Province(No.2012KCT-29),the 2011 Project of Qinling-Bashan Mountains Bioresources Comprehensive Development C.I.C of Shaanxi Province(No.QBXT-Z(P)-15-15).
1α,25-二羟基维生素D3(1α,25-(OH)2-D3,125D)是维生素D中最具生理活性的代谢产物,但因高钙血症副反应而限制其临床应用。从对构效关系的研究出发,迄今已合成三千多种类似物。本文综述了近年来对某些A环修饰(C2位修饰、C3位修饰、芳香A环类似物、A环开环类似物)、侧链修饰、CD环修饰、seco-B环修饰和非开环甾体的活性维生素 D3 类似物的设计、合成以及构效关系的研究,旨在为新型较佳活性维生素D3类似物的合成及临床开发提供参考。
关键词： 1α,25-二羟基维生素D3, 类似物, 构效关系, 化学合成, 生物活性
1α,25-Dihydroxyvitamin D3(1α,25-(OH)2-D3, 125D)is the most active metabolite of vitamin D3, but the therapeutic application of 125D is limited by induction of hypercalcemia. The need for vitamin D compounds with selective biological profiles has stimulated the synthesis of more than three thousand analogues of 125D. This article reviews the recent progress of vitamin D research in the design and synthesis of the structural modifications in the A ring (including modification in the C2-, and C3-substitued, aromatic A ring and seco-A ring analogues), side chain, CD ring, seco-B ring, and non-secosteroidal vitamin D3 analogs, and the relation between the structure and the biological activities.

Contents
1 Introduction
2 Structure-activity relationship of analogues modified in the A ring
2.1 Analogues modification of C-2-substitued
2.2 Aromatic A-ring 125D analogues
2.3 Ring-A-seco-19-nor analogues
2.4 C-3-subtitued-25-hydroxy analogues
3 Structure-activity relationship of analogues modified in the side chains
3.1 26-Desmethyl-2-methylene-22-ene-19-nor-analogues
3.2 C-22-oxa-analogues
3.3 Analogues with aromatic side chains attached at C-17
3.4 C-2 substituted analogues having ringed side chains
3.5 Analogues of combination of triple bond and adamantane ring on the side chain
4 Structure-activity relationship of analogues modified in CD-ring
4.1 13α-Substituted-des-C-ring-19-nor-125D analogues
4.2 Analogues with α-hydroxyalkyl substituents at C12
4.3 9-Alkylidene-19-nor-125D analogues with unnatural triene system
5 Structure-activity relation of analogues modified substituted in seco-B ring
5.1 6-Substituted analogues of 125D
5.2 C-7-methyl-19-nor-125D analogues
6 Structure-activity relationship of non-secosteroidal vitamin D analogues
6.1 Bis- and tris-aromatic analogues
6.2 p-Carborane-based non-secosteroidal vitamin D analogues
7 Conclusion and outlook

Key words: 1α,25-dihydroxyvitamin D3, analogues, structure-activity relationship, chemical synthesis, biological activities

中图分类号: 

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