(20R)-2-methylene-19,26,27-trinor-1α-hydroxyvitamin D₃

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: (20R)-2-methylene-19,26,27-trinor-1α-hydroxyvitamin D₃
• 英文别名: (20R)-2α-methyl-19,26,27-trinor-1α,25-dihydroxycalciferol
• 化学式: C₂₅H₄₂O₃
• 分子量: 390.607
• InChiKey: YZIQNNXLWCGZKG-SSUAOLEZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.01
• 重原子数：
  28.0
• 可旋转键数：
  6.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.84
• 拓扑面积：
  60.69
• 氢给体数：
  3.0
• 氢受体数：
  3.0

反应信息

• 作为产物：
  描述：

  (S)-2-((3R,3aR,7S,7aR)-octahydro-7-hydroxy-3a-methyl-1H-inden-3-yl)propyl 4-methylbenzenesulfonate 在 吡啶 、 lithium aluminium tetrahydride 、 tris(triphenylphosphine)rhodium(l) chloride 、 pyridinium dichromate 、 nickel(II) chloride hexahydrate 、 氢氟酸 、 氢气 、 4-甲基苯磺酸吡啶 、 苯基锂 、 三乙胺 、 potassium iodide 、 锌 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 环己烷 、 水 、 丙酮 、 乙腈 、 苯 为溶剂， 反应 75.0h， 生成 (20R)-2-methylene-19,26,27-trinor-1α-hydroxyvitamin D₃ 、 (20R)-2β-methyl-19,26,27-trinor-1α-hydroxyvitamin D₃
  参考文献：
  名称：

  26- and 27-Methyl groups of 2-substituted, 19-nor-1α,25-dihydroxylated vitamin D compounds are essential for calcium mobilization in vivo

  摘要：

  Twelve new analogs of 19-nor-1 alpha,25-dihydroxyvitamin D-3 6-17, were prepared by a multi-step procedure from known alcohols 18 and 19. We have examined the influence of removing two methyl groups located at C-25, as well as the 25-hydroxy group, on the biological in vitro and in vivo biological activity. Surprisingly, removal of the 26- and 27-methyl groups from either the 2 alpha-methyl or 2-methylene-19-nor-1 alpha,25-dihydroxyvitamin D-3 reduced vitamin D receptor binding, HL-60 differentiation, and 25-hydroxylase transcription in vitro only slightly to moderately (compounds 6-13). However, these compounds were devoid of in vivo bone mobilization activity and had markedly reduced activity on intestinal calcium transport. The analogs 14-17 with a 2 beta-methyl substitution had little or no activity in vitro and in vivo as expected from previous work. (C) 2013 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bioorg.2013.01.001

文献信息

• 2-Substituted-1Alpha,25-Dihydroxy-19,26,27-Trinor Vitamin D Analogs and Uses Thereof
  申请人：DeLuca F. Hector

  公开号：US20070238704A1

  公开（公告）日：2007-10-11

  Compounds of formula I, II or III are provided where X 1 , X 2 and X 3 are independently selected from H and hydroxy protecting groups and R 1 and R 2 are independently selected from H or straight or branched chain alkyl groups having from 1 to 8 carbon atoms, straight or branched chain alkenyl groups having from 2 to 8 carbon atoms, straight or branched chain hydroxy-substituted alkyl groups having from 1 to 8 carbon atoms, or straight and branched chain hydroxy-substituted alkenyl groups having from 2 to 8 carbon atoms; and R 3 is independently selected from straight or branched chain alkyl groups having from 1 to 8 carbon atoms, straight or branched chain alkenyl groups having from 2 to 8 carbon atoms, straight or branched chain hydroxy-substituted alkyl groups having from 1 to 8 carbon atoms, or straight and branched chain hydroxy-substituted alkenyl groups having from 2 to 8 carbon atoms. Such compounds are used in preparing pharmaceutical compositions and are useful in treating a variety of biological conditions.

  提供了I、II或III式化合物，其中X1、X2和X3独立地选择自H和羟基保护基团，R1和R2独立地选择自具有1至8个碳原子的直链或支链烷基基团、具有2至8个碳原子的直链或支链烯基基团、具有1至8个碳原子的直链或支链羟基取代烷基基团或具有2至8个碳原子的直链和支链羟基取代烯基基团；而R3独立地选择自具有1至8个碳原子的直链或支链烷基基团、具有2至8个碳原子的直链或支链烯基基团、具有1至8个碳原子的直链或支链羟基取代烷基基团或具有2至8个碳原子的直链和支链羟基取代烯基基团。这些化合物用于制备药物组合物，并且在治疗各种生物状况方面非常有用。
• 26- and 27-Methyl groups of 2-substituted, 19-nor-1α,25-dihydroxylated vitamin D compounds are essential for calcium mobilization in vivo
  作者：Pawel Grzywacz、Lori A. Plum、Margaret Clagett-Dame、Hector F. DeLuca

  DOI：10.1016/j.bioorg.2013.01.001

  日期：2013.4

  Twelve new analogs of 19-nor-1 alpha,25-dihydroxyvitamin D-3 6-17, were prepared by a multi-step procedure from known alcohols 18 and 19. We have examined the influence of removing two methyl groups located at C-25, as well as the 25-hydroxy group, on the biological in vitro and in vivo biological activity. Surprisingly, removal of the 26- and 27-methyl groups from either the 2 alpha-methyl or 2-methylene-19-nor-1 alpha,25-dihydroxyvitamin D-3 reduced vitamin D receptor binding, HL-60 differentiation, and 25-hydroxylase transcription in vitro only slightly to moderately (compounds 6-13). However, these compounds were devoid of in vivo bone mobilization activity and had markedly reduced activity on intestinal calcium transport. The analogs 14-17 with a 2 beta-methyl substitution had little or no activity in vitro and in vivo as expected from previous work. (C) 2013 Elsevier Inc. All rights reserved.