(1S,3AR,7AR)-7A-甲基-1-((S)-1-(3-甲基-3-((三甲基甲硅烷基)氧基)丁氧基)乙基)八氢-4H-茚-4-酮 | 192573-33-4

• 物质功能分类: 医药中间体 - 原料药中间体
• 分子结构分类: 有机化合物 - 有机金属化合物 - 有机类金属化合物
• 中文名称: (1S,3AR,7AR)-7A-甲基-1-((S)-1-(3-甲基-3-((三甲基甲硅烷基)氧基)丁氧基)乙基)八氢-4H-茚-4-酮
• 中文别名: 玛莎骨化醇CD环；玛莎骨化醇中间体
• 英文名称: (1S,3aR,7aR)-1-[(S)-1-(3-methyl-3-trimethylsilyloxybutyloxy)ethyl]-7a-methyloctahydro-1H-inden-4-one
• 英文别名: de-A,B-8-oxo-25-(trimethylsilyloxy)-22-oxacholestane；(1S,3AR,7aR)-7a-methyl-1-((S)-1-(3-methyl-3-((trimethylsilyl)oxy)butoxy)ethyl)hexahydro-1H-inden-4(2H)-one；(1S,3aR,7aR)-7a-methyl-1-[(1S)-1-(3-methyl-3-trimethylsilyloxybutoxy)ethyl]-2,3,3a,5,6,7-hexahydro-1H-inden-4-one
• CAS: 192573-33-4
• 化学式: C₂₀H₃₈O₃Si
• 分子量: 354.605
• InChiKey: KOKCWHXZUQQNAX-PFRQMTDMSA-N

物化性质

• 沸点：
  401.3±20.0 °C(Predicted)
• 密度：
  0.963±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.95
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 储存条件：
  室温

反应信息

• 作为反应物：
  描述：

  (1S,3AR,7AR)-7A-甲基-1-((S)-1-(3-甲基-3-((三甲基甲硅烷基)氧基)丁氧基)乙基)八氢-4H-茚-4-酮 在 正丁基锂 、 四丁基氟化铵 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 24.0h， 生成 3-Epi-1alpha,25-dihydroxy-22-oxavitamin D3
  参考文献：
  名称：

  Synthesis and evaluation of A-Ring diastereomers of 1α,25-dihydroxy-22-oxavitamin D 3 (OCT) 1

  摘要：

  A-ring diastereomers of 1 alpha ,25-dihydroxy-22-oxavitamin D-3 (OCT) (2), 3-epi-1 alpha ,25-dihydroxy-22-oxavitamin D-3 (3-epiOCT) (3) and 1,3-diepi-1 alpha ,25-dihydroxy-22-oxavitamin D-3 (1,3-diepiOCT) (4) were synthesized by the convergent method. In vitro binding affinity for rat vitamin D binding protein and calf-thymus vitamin D receptor, differentiation-inducing activity on HL-60 cells, and transcriptional activity of 3-epiOCT (3) and 1,3-diepiOCT (4) were evaluated in comparison with OCT (2), 1-epi-1 alpha ,25-dihydroxy-22-oxavitamin D-3 (1-epiOCT) (5) and 1 alpha ,25-dihydroxyvitamin D-3 (1). (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(00)00259-5
• 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 palladium on activated charcoal N-甲基吗啉 、 咪唑 、 氢氟酸 、 potassium tert-butylate 、 氢气 、 氧气 、 氢化钾 、 碳酸氢钠 、 二甲基亚砜 、 pyridinium chlorochromate 作用下， 以 四氢呋喃 、 乙醚 、 乙醇 、 二氯甲烷 、 异丙醇 、 乙腈 、 叔丁醇 、 苯 为溶剂， 反应 24.0h， 生成 (1S,3AR,7AR)-7A-甲基-1-((S)-1-(3-甲基-3-((三甲基甲硅烷基)氧基)丁氧基)乙基)八氢-4H-茚-4-酮
  参考文献：
  名称：

  A new approach to the synthesis of the 25-hydroxy-22-oxa-vitamin D3 side chain

  摘要：

  An efficient new method is described for the construction of the 25-hydroxy-22-oxavitamin D-3 side-chain, which is present in several analogues of calcitriol with antitumour activity. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0040-4039(97)01056-3

文献信息

• Facile Construction of the 7,8‐Olefin Linkage in Vitamin D₃: A Practical Synthesis Benefiting the Vitamin D₃Analog Study
  作者：Yoshiyuki Ono、Hirotaka Kashiwagi、Tadakatsu Takahashi

  DOI：10.1080/00397910500503645

  日期：2006.5

  Abstract A facile procedure for construction of the 7,8‐olefin linkage in vitamin D3 is described. Treatment of a mixture of A‐ring phosphine oxide and CD‐ring ketone in THF with lithium hexamethyldisilazide (LHMDS) at −20°C followed by gradual heating to 50°C gives the key intermediate of vitamin D3 analogs in excellent yield. This simplified procedure makes possible small‐scale synthesis benefiting

  摘要描述了一种在维生素 D3 中构建 7,8-烯烃键的简便程序。在-20°C 下用六甲基二硅叠氮化锂 (LHMDS) 在 THF 中处理 A 环氧化膦和 CD 环酮的混合物，然后逐渐加热至 50°C，以优异的产率得到维生素 D3 类似物的关键中间体。这种简化的程序使小规模合成成为可能，有利于维生素 D3 类似物研究。
• Catalytic asymmetric synthesis and anticancer effects of the novel non-calcemic analog of vitamin D, 2α-fluoro-19-nor-22-oxa-1α,25-dihydroxyvitamin D3 in metastatic lung carcinoma
  作者：Kimie Nakagawa、Toshio Okano、Keiichi Ozono、Shigeaki Kato、Noboru Kubodera、Shiho Ohba、Yoshimitsu Itoh、Koichi Mikami

  DOI：10.1016/j.jfluchem.2007.03.002

  日期：2007.6

  1 alpha,25-Dihydroxyvitamin D-3 (1 alpha,25-D-3) has potent antiproliferative and anti-invasive properties in vitro in cancer cells. However, the major limitation to its clinical use is that it causes hypercalcemia. Therefore, vitamin D analogs with potent cell regulatory effects but with weaker calcemic effects than 1 alpha,25-D-3 are required. Among them, 22-oxa-1 alpha,25-D-3 and 19-nor-1 alpha,25-D-3 have anti-cancer effects with relatively low calcemic effects. Modifications at the C-2ot position of the A-ring also produced analogs with a unique biological profile. Not only the side-chain but also the A-ring modification thus generates a unique analog with potent cell regulatory effects and low calcemic activity as well. We report here that the hybrid 1 alpha,25-D-3 analog, synthesized via the highly regio- and stereo-selective ring opening 2 alpha-fluorination and catalytic asymmetric carbonyl-ene cyclization, with 2 alpha-fluoro, 19-nor, and 22-oxa modification exhibits unique cell regulatory activities against the development of metastatic lung carcinoma. (c) 2007 Published by Elsevier B.V.