(3S,9S,10R,13S,14R,17S)-17-((S)-2-hydroxy-6-methylheptan-2-yl)-10,13-dimethyl-2,3,4,9,10,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | 1252023-07-6

• 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: (3S,9S,10R,13S,14R,17S)-17-((S)-2-hydroxy-6-methylheptan-2-yl)-10,13-dimethyl-2,3,4,9,10,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate
• CAS: 1252023-07-6
• 化学式: C₂₉H₄₆O₃
• 分子量: 442.682
• InChiKey: RSUGRZYUVRDISA-XMKWUEEFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.99
• 重原子数：
  32.0
• 可旋转键数：
  6.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  46.53
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  (3S,9S,10R,13S,14R,17S)-17-((S)-2-hydroxy-6-methylheptan-2-yl)-10,13-dimethyl-2,3,4,9,10,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate 以 甲醇 为溶剂， 反应 0.08h， 生成 (1S)-3-[(E)-2-[(1S,3aR,7aS)-1-[(2S)-2-hydroxy-6-methylheptan-2-yl]-7a-methyl-1,2,3,3a,6,7-hexahydroinden-4-yl]ethenyl]-4-methylcyclohex-3-en-1-ol 、 20-hydroxylumisterol 3 、 20S-Hydroxyvitamin D3
  参考文献：
  名称：

  Chemical synthesis of 20S-hydroxyvitamin D3, which shows antiproliferative activity

  摘要：

  20S-hydroxyvitamin D3 (20S-(OH)D3), an in vitro product of vitamin D3 metabolism by the cytochrome P450scc, was recently isolated, identified and shown to possess antiproliferative activity without inducing hypercalcemia. The enzymatic production of 20S-(OH)D3 is tedious, expensive, and cannot meet the requirements for extensive chemical and biological studies. Here we report for the first time the chemical synthesis of 20S-(OH)D3 which exhibited biological properties characteristic of the P450scc-generated compound. Specifically, it was hydroxylated to 20,23-dihydroxyvitamin D3 and 17,20-dihydroxyvitamin D3 by P450scc and was converted to 1 alpha,20-dihydroxyvitamin 03 by CYP27B1. It inhibited proliferation of human epidermal keratinocytes with lower potency than 1 alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3) in normal epidermal human keratinocytes, but with equal potency in immortalized HaCaT keratinocytes. It also stimulated VDR gene expression with similar potency to 1,25(OH)2D3, and stimulated involucrin (a marker of differentiation) and CYP24 gene expression, showing a lower potency for the latter gene than 1,25(OH)2D3. Testing performed with hamster melanoma cells demonstrated a dose-dependent inhibition of cell proliferation and colony forming capabilities similar or more pronounced than those of 1,25(OH)203. Thus, we have developed a chemical method for the synthesis of 20S-(OH)D3, which will allow the preparation of a series of 20S-(OH)D3 analogs to study structure-activity relationships to further optimize this class of compound for therapeutic use. (C) 2010 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2010.05.021
• 作为产物：
  描述：

  pregna-5,7-diene-3β-ol-20-one acetate 、 1-溴-4-甲基戊烷 在 magnesium 、 盐酸 作用下， 以 四氢呋喃 、 水 为溶剂， 以75%的产率得到(3S,9S,10R,13S,14R,17S)-17-((S)-2-hydroxy-6-methylheptan-2-yl)-10,13-dimethyl-2,3,4,9,10,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate
  参考文献：
  名称：

  Chemical synthesis of 20S-hydroxyvitamin D3, which shows antiproliferative activity

  摘要：

  20S-hydroxyvitamin D3 (20S-(OH)D3), an in vitro product of vitamin D3 metabolism by the cytochrome P450scc, was recently isolated, identified and shown to possess antiproliferative activity without inducing hypercalcemia. The enzymatic production of 20S-(OH)D3 is tedious, expensive, and cannot meet the requirements for extensive chemical and biological studies. Here we report for the first time the chemical synthesis of 20S-(OH)D3 which exhibited biological properties characteristic of the P450scc-generated compound. Specifically, it was hydroxylated to 20,23-dihydroxyvitamin D3 and 17,20-dihydroxyvitamin D3 by P450scc and was converted to 1 alpha,20-dihydroxyvitamin 03 by CYP27B1. It inhibited proliferation of human epidermal keratinocytes with lower potency than 1 alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3) in normal epidermal human keratinocytes, but with equal potency in immortalized HaCaT keratinocytes. It also stimulated VDR gene expression with similar potency to 1,25(OH)2D3, and stimulated involucrin (a marker of differentiation) and CYP24 gene expression, showing a lower potency for the latter gene than 1,25(OH)2D3. Testing performed with hamster melanoma cells demonstrated a dose-dependent inhibition of cell proliferation and colony forming capabilities similar or more pronounced than those of 1,25(OH)203. Thus, we have developed a chemical method for the synthesis of 20S-(OH)D3, which will allow the preparation of a series of 20S-(OH)D3 analogs to study structure-activity relationships to further optimize this class of compound for therapeutic use. (C) 2010 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2010.05.021