艾地骨化醇起始物料杂质2 | 215257-72-0

• 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: 艾地骨化醇起始物料杂质2
• 英文名称: [1R-(1β,3aα,7aβ)]-[1S-(4β)]-(1,1-dimethylethyl)dimethyl{[octahydro-7a-methyl-1-(1-methylethenyl)-1H-inden-4-yl]oxy}silane
• 英文别名: [1R-(1α,3aβ,4α,7aα)]-(1,1-dimethylethyl)dimethyl[[octahydro-7a-methyl-1-(1-methylethyl)-1H-inden-4-yl]oxy]silane；[1R-(1α,3aβ,4α,7aα)]-(1,1-dimethylethyl)dimethyl[[octahydro-7a-methyl-1-(1-methylethenyl)-1H-inden-4-yl]oxy]silane；tert-Butyldimethyl(((1R,3aR,4S,7aR)-7a-methyl-1-(prop-1-en-2-yl)octahydro-1H-inden-4-yl)oxy)silane；[(1R,3aR,4S,7aR)-7a-methyl-1-prop-1-en-2-yl-1,2,3,3a,4,5,6,7-octahydroinden-4-yl]oxy-tert-butyl-dimethylsilane
• CAS: 215257-72-0
• 化学式: C₁₉H₃₆OSi
• 分子量: 308.58
• InChiKey: QYSMTSGDQWEEIF-VUHPKUFZSA-N

物化性质

• 沸点：
  331.8±21.0 °C(Predicted)
• 密度：
  0.89±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.17
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  9.2
• 氢给体数：
  0
• 氢受体数：
  1

上下游信息

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  ——	[1S-(1α,3aβ,4α,7aα)]-4-[[Dimethyl(1,1-dimethylethyl)silyl]oxy]-7a-methyl-β-methyleneoctahydro-1H-indene-1-ethanol	337528-61-7	C19H36O2Si	324.579
  ——	[1R-(1α,3aβ,4α,7aα)]-6-[4-[[(1,1-dimethylethyl)dimethylsilyl]oxy]octahydro-7a-methyl-1H-inden-1-yl]-2,10-dimethyl-2,10-undecanediol	215257-75-3	C29H58O3Si	482.863
  ——	[1R-[1α,3aβ,4α,7aα]]-5-[4-[[(1,1-dimethylethyl)dimethylsilyl]oxy]octahydro-7a-methyl-1H-inden-1-yl]nonanedioic acid diethyl ester	215257-74-2	C29H54O5Si	510.83
  ——	[1R-[1α(2E,4E,7E),3aβ,4α,7aα]]-5-[4-[[(1,1-dimethylethyl)dimethylsilyl]oxy]octahydro-7a-methyl-1H-inden-1-yl]-2,4,7-nonatrienedioic acid diethyl ester	215257-73-1	C29H48O5Si	504.783
  ——	8β-[(tert-butyldimethylsilyl)oxy]de-A,B-androstan-17β-ol	140659-45-6	C16H32O2Si	284.514
  ——	[1S-(1β,4β,7aβ)]-[1R-(3aα)]-octahydro-1-acetyl-4-[(tert-butyldimethylsilyl)oxy]-7a-methyl-1H-indene	140659-43-4	C18H34O2Si	310.552
  ——	8β-[(tert-butyldimethylsilyl)oxy]de-A,B-androstan-17β-one	140659-26-3	C16H30O2Si	282.498
  ——	<1S-(1α,3aβ,4α,7aα)>-Octahydro-1-(acetyloxy)-4-<(tert-butyldimethylsilyl)oxy>-7a-methyl-1H-indene	140659-44-5	C18H34O3Si	326.552

反应信息

• 作为反应物：
  描述：

  艾地骨化醇起始物料杂质2 在 palladium on activated charcoal 重铬酸吡啶 、 六氟合硅酸 、 氢气 、 二氯乙基铝 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 乙酸乙酯 、 乙腈 为溶剂， 反应 56.5h， 生成 [1S-(1α,3aβ,7aα)]-octahydro-7a-methyl-1-[5-methyl-1-[4-methyl-4-[(trimethylsilyl)oxy]pentyl]-5-[(trimethylsilyl)oxy]hexyl]-4H-inden-4-one
  参考文献：
  名称：

  Characterization of a Novel Analogue of 1α,25(OH)₂-Vitamin D₃ with Two Side Chains:  Interaction with Its Nuclear Receptor and Cellular Actions

  摘要：

  The hormone 1 alpha,25(OH)(2)-vitamin D-3 (125D) binds to its nuclear receptor (VDR) to stimulate gene transcription activity. Inversion of configuration at C-20 of the side chain to generate 20-epi-1 alpha,25(OH)(2)Da (20E-125D) increases transcription 200-5000-fold over 125D with its 20-normal (20N) side chain. This enhancement has been attributed to the VDR ligand-binding domain (LBD) having different contact sites for 20N and 20E side chains that generate different VDR conformations. We synthesized 1 alpha,25-dihydroxy-21-(3-hydroxy-3-methylbutyl) vitamin D-3 (Gemini) with two six-carbon side chains (both 20N and 20E orientations). Energy minimization calculations indicate the Gemini side chain possesses significantly more energy minima than either 125D or 20E-125D (2346, 207, and 127 minima, respectively). We compared activities of 125D, 20E-125D, and Gemini, respectively,in several assays: binding to wild-type (100%, 147%, and 38%)and C-terminal-truncated mutant VDR; transcriptional activity (of the transfected osteopontin promoter in ROS 17/2.8 cells: ED50 10, 0.005, and 1.0 nM) mediation of conformational changes in VDR assessed by protease clipping major trypsin-resistant fragment of 34, 34, and 28 kDa). For inhibition of cellular clonal growth of human leukemia (HL-60) and breast cancer (MCF7) cell lines, the ED50(125D)/ED50(Gem) was respectively 380 and 316. We conclude that while Gemini readily binds to the VDR and generates unique conformational changes, none of them is able to permit a superior gene transcription activity despite the presence of a 20E side chain.

  DOI：

  10.1021/jm0000160
• 作为产物：
  描述：

  艾地骨化醇起始原料杂质1 在 potassium tert-butylate 作用下， 以 四氢呋喃 、 二甲基亚砜 为溶剂， 反应 0.67h， 以84%的产率得到艾地骨化醇起始物料杂质2
  参考文献：
  名称：

  atrans-Hydrindanone，用于制备维生素 D 类似物的前体的合成

  摘要：

  基于 Criegee 重排，我们开发了一种非常有效且实用的方法，用于大规模合成与维生素 D 相关的反式三氢呋喃衍生物。这种酮是用于制备双子型维生素 D 类似物或其他在 C-20、C-21 或 D 环上修饰的骨化三醇类似物的有价值的合成子。在考虑效率和便利时，我们的方法优于先前报告的方法。

  DOI：

  10.1002/ejoc.201300528

文献信息

• A facile stereoselective route to a C/D-ring synthon for 20-epi-22-oxavitamin D3 analogues
  作者：Susumi Hatakeyama、Tatsuhiko Ikeda、Hiroshi Irie、Chino Izumi、Hisato Mori、Kohsei Uenoyama、Hidetoshi Yamada、Mugio Nishizawa

  DOI：10.1039/c39950001959

  日期：——

  An efficient method for the preparation of a C/D-ring synthon for 20-epi-22-oxavitamin D3 analogues is developed based on Me3SiOSO2CF3 catalysed reductive etherification of a ketone with an alkoxytrimethylsilane in the presence of triethylsilane.

  在三乙基硅烷存在下，基于Me 3 SiOSO 2 CF 3催化的酮与烷氧基三甲基硅烷的还原性醚化作用，开发了一种有效的方法来制备20-表-22-恶维他命D 3类似物的C / D环合成子。
• WO2008/43857
  申请人：——

  公开号：——

  公开（公告）日：——
• WO2008/34908
  申请人：——

  公开号：——

  公开（公告）日：——
• Novel side chain analogs of 1α,25-dihydroxyvitamin D3: design and synthesis of the 21,24-methano derivatives
  作者：Martin J. Calverley

  DOI：10.1016/s0039-128x(00)00156-2

  日期：2001.3

  The syntheses of the new 21,24-methane derivatives of 1 alpha ,25-dihydroxyvitamin D-3 [viz. 1(S),3(R)-dihydroxy-17(R)-(1',4'-cis-(4'-(1'hydroxy-1'- hydroxy-1'-methylethyl)-cyclo-hexyl))-9, 10-seco-androsta-5(Z),7(E), 10(19)-triene (MC 2108) and its(1',4'-trans)-isomer (MC 2110)] are described. The key step is the establishment, by Diels-Alder reaction on a CD-ring side chain diene intermediate prepared from vitamin D-2, of a 1,4-disubstituted cyclohexene moiety in the side chain. Hydrogenation to a 1:1 mixture of cis and trans cyclohexane derivatives and separation of the two series at a stage prior to the standard Horner-Wittig coupling with the (Hoffmann-La Roche) ring-A building block were other important steps in the syntheses of the target analogs. The relative configurations of intermediates were assigned by NMR spectroscopy. MC 2108 and MC 2110 are of interest as conformationally locked side chain derivatives to probe the receptor interactions of not only the parent vitamin D hormone but also its biologically active symmetrical 'double side chain' analog [21-(3'-hydroxy-3'methylbutyl)-9, 10-seco-cholesta-5(Z),7(E), 10(19)-triene-1 (S),3(R),25-triol (MC 2100)], 'both' side chains of which can formally be traced out in the new analogs. The preferred conformations, inferred from an analysis of C-13-NMR characteristics, notably the chemical shift of C-17 in a series of analogs, to have the tertiary alcohol (1'-hydroxy-1'-methylethyl) substituent equatorial on the cyclohexane chair, are confirmed by molecular modeling. (C) 2001 Elsevier Science Inc. All rights reserved.
• J. Org. Chem. 1986, 51, 3098-3108
  作者：

  DOI：——

  日期：——