1α,3β-bis-(tert-butyldimethylsilyloxy)-9,10-secopregna-5(Z),7(E),10(19)-triene-20(R)-methyl p-toluenesulfonate | 114694-13-2

• 分子结构分类: 有机化合物 - 脂质和类脂质分子
• 英文名称: 1α,3β-bis-(tert-butyldimethylsilyloxy)-9,10-secopregna-5(Z),7(E),10(19)-triene-20(R)-methyl p-toluenesulfonate
• 英文别名: (5Z,7E)-(1S,3R)-1,3-bis[(t-butyldimethyl-silyl)oxy]-24-(p-toluenesulfonyloxy)-22,23-dinor-9,10-secochola-5,7,10(19)-triene；(5Z,7E,20S)-1α,3β-bis(tert-butyldimethylsilyloxy)-20-(p-tolylsulfonyloxymethyl)-9,10-seco-5,7,10(19)-pregnatriene；(5Z,7E)-(1S,3R,20S)-1,3-bis<(tert-butyldimethylsilyl)oxy>-9,10-seco-22,23-dinor-5,7,10(19)-cholatrienol 22-p-toluenesulfonate；(2S)-2-((1R,3aS,7aR,E)-4-((Z)-2-((3S,5R)-3,5-bis((t-butyldimethylsilyl)oxy)-2-methylenecyclohexylidene)ethylidene)-7a-methyloctahydro-1H-inden-1-yl)propyl 4-methylbenzenesulfonate；[(2S)-2-[(1R,3aS,4E,7aR)-4-[(2Z)-2-[(3S,5R)-3,5-bis[[tert-butyl(dimethyl)silyl]oxy]-2-methylidenecyclohexylidene]ethylidene]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-1-yl]propyl] 4-methylbenzenesulfonate
• CAS: 114694-13-2
• 化学式: C₄₁H₆₈O₅SSi₂
• 分子量: 729.225
• InChiKey: LRDKADGJXOXSQN-NIUVICCHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  11.54
• 重原子数：
  49
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  70.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1α,3β-bis-(tert-butyldimethylsilyloxy)-9,10-secopregna-5(Z),7(E),10(19)-triene-20(R)-methyl p-toluenesulfonate 在 盐酸 、 碳酸氢钠 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 四氢呋喃 、 二甲基亚砜 、 丙酮 为溶剂， 反应 45.0h， 生成 (1R,3S,Z)-5-(2-((1R,3aS,7aR,E)-7a-methyl-1-((R)-1-(pyrrolidin-1-yl)propan-2-yl)octahydro-4H-inden-4-ylidene)ethylidene)-4-methylenecyclohexane-1,3-diol
  参考文献：
  名称：

  [EN] VITAMIN D DERIVATIVE HAVING CYCLIC AMINE IN SIDE CHAIN
  [FR] DÉRIVÉ DE VITAMINE D AYANT UNE AMINE CYCLIQUE DANS LA CHAÎNE LATÉRALE
  [JA] 側鎖に環状アミンを有するビタミンＤ誘導体

  摘要：

  本文提供了一种具有优良中枢移行性的维生素D衍生物，以及其医药上允许的盐或溶剂物。式（1）表示的是这种维生素D衍生物或其医药上允许的盐或溶剂物。

  公开号：

  WO2022059684A1
• 作为产物：
  描述：

  hydroxybisnorcholenic acid 在 吡啶 、 咪唑 、 叔丁基过氧化氢 、 氢氧化钾 、 lithium aluminium tetrahydride 、 selenium(IV) oxide 、 硫酸 、 potassium hydrogencarbonate 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 72.42h， 生成 1α,3β-bis-(tert-butyldimethylsilyloxy)-9,10-secopregna-5(Z),7(E),10(19)-triene-20(R)-methyl p-toluenesulfonate
  参考文献：
  名称：

  Novel convergent synthesis of side-chain-modified analogs of 1.alpha.,25-dihydroxycholecalciferol and 1.alpha.,25-dihydroxyergocalciferol

  摘要：

  DOI：

  10.1021/jo00250a009

文献信息

• An Improved Synthesis of 24,24-Difluoro-1.ALPHA.,25-dihydroxyvitamin D3 from Readily Available Vitamin D2.
  作者：Kaori ANDO、Fumiaki KOIKE、Fumihiro KONDO、Hiroaki TAKAYAMA

  DOI：10.1248/cpb.43.189

  日期：——

  An improved synthesis of a highly potent vitamin D3 analog, 24, 24-difluoro-1α, 25-dihydroxyvitamin D3 (1b)has been accomplished via vitamin D2-SO2 adducts. The introduction of fluorine atoms was performed by treating the α-keto ester (11) with diethylaminosulfur trifluoride. The total yield was 12.5% from inexpensive vitamin D2 in 11 steps. This sequence is sufficiently straightforward to be conducted on a gram scale.

  通过维生素D2-SO2加合物，完成了一种高效能维生素D3类似物24, 24-二氟-1α, 25-二羟基维生素D3 (1b) 的改进合成。引入氟原子的过程是通过用二乙胺硫三氟化物处理α-酮酯（11）来实现的。该方法从廉价的维生素D2中在11个步骤中获得了12.5%的总产率。这一序列简单明了，足以在克级规模上进行。
• VITAMIN D3 LACTONE DERIVATIVE
  申请人：Teijin Pharma Limited

  公开号：EP1589009B1

  公开（公告）日：2014-10-08
• Synthesis and antiproliferative activity of side-chain unsaturated and homologated analogs of 1,25-dihydroxyvitamin D2
  作者：Michał Chodyński、Joanna Wietrzyk、Ewa Marcinkowska、Adam Opolski、Wiesław Szelejewski、Andrzej Kutner

  DOI：10.1016/s0039-128x(02)00038-7

  日期：2002.8

  A series of analogs of 1,25-dihydroxyergocalciferol (1-4) was synthesized and screened for their antiproliferative activity in vitro. The structure of new analogs was designed based on biological activity of the previously obtained side-chain modified analogs of vitamin D-2 and D-3. The analogs were obtained by the Julia olefination of C-22-vitamin D sulfone 11 with side-chain aldehyde 15. The analogs were tested for their antiproliferative activity against the cells of human breast cancer lines T47D and MCF7 as well as human and mouse leukemia lines, HL-60 and WEHI-3, respectively. Analog 2 (PRI-1907) showed the strongest antiproliferative activity out of the present series of analogs of 1,25-dihydroxyvitamin D-2 with the mono homologated and double unsaturated side chain. The activity of 2 was 3-150 times stronger, depending on the cell line, than that of 1,25-dihydroxycholecalciferol (calcitriol), used as standard. (C) 2002 Elsevier Science Inc. All rights reserved.
• EP1477483
  申请人：——

  公开号：——

  公开（公告）日：——
• Practical Synthesis and Evaluation of the Biological Activities of 1α,25-dihydroxyvitamin D₃ Antagonists, 1α,25-dihydroxyvitamin D₃-26,23-lactams. Designed on the Basis of the Helix 12-Folding Inhibition Hypothesis
  作者：Yusuke Nakano、Yuko Kato、Keisuke Imai、Eiji Ochiai、Jun-ichi Namekawa、Seiichi Ishizuka、Kazuya Takenouchi、Aya Tanatani、Yuichi Hashimoto、Kazuo Nagasawa

  DOI：10.1021/jm050738x

  日期：2006.4.1

  A practical synthetic route to novel vitamin D antagonists of DLAM (1 alpha.,25-dihydroxyvitamin D-3-26,23lactam) was developed from vitamin D-2 via the 1,3-dipolar cycloaddition reaction as a key step. Six DLAM derivatives (24 compounds) with a variety of nitrogen substituents and stereochemistries at C23 and C25 were synthesized. Among these new derivatives, (23S,25S)-DLAM isomers bound effectively to VDRs and showed antagonistic activity in the HL-60 cell differentiation inhibition assay. The importance of the substituent on the nitrogen of DLAMs for antagonistic activity was also suggested by computational docking studies.