[1S-(1α,3aβ,4α,7aα)]-4-[[Dimethyl(1,1-dimethylethyl)silyl]oxy]-7a-methyl-β-methyleneoctahydro-1H-indene-1-ethanol | 337528-61-7

• 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
• 英文名称: [1S-(1α,3aβ,4α,7aα)]-4-[[Dimethyl(1,1-dimethylethyl)silyl]oxy]-7a-methyl-β-methyleneoctahydro-1H-indene-1-ethanol
• 英文别名: 2-[(1S,3aR,4S,7aR)-4-[tert-butyl(dimethyl)silyl]oxy-7a-methyl-1,2,3,3a,4,5,6,7-octahydroinden-1-yl]prop-2-en-1-ol
• CAS: 337528-61-7
• 化学式: C₁₉H₃₆O₂Si
• 分子量: 324.579
• InChiKey: ZGDYHTPBWHDQMY-VUHPKUFZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.14
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  29.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  [1S-(1α,3aβ,4α,7aα)]-4-[[Dimethyl(1,1-dimethylethyl)silyl]oxy]-7a-methyl-β-methyleneoctahydro-1H-indene-1-ethanol 在 potassium tert-butylate 、 戴斯-马丁氧化剂 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 tert-Butyl-dimethyl-[(1R,3aR,4S,7aR)-7a-methyl-1-(1-methylene-allyl)-octahydro-inden-4-yloxy]-silane
  参考文献：
  名称：

  Novel side chain analogs of 1α,25-dihydroxyvitamin D3: design and synthesis of the 21,24-methano derivatives

  摘要：

  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.

  DOI：

  10.1016/s0039-128x(00)00156-2
• 作为产物：
  描述：

  艾地骨化醇起始原料杂质1 在 magnesium isopropyl-cyclohexylamide 、 potassium tert-butylate 、 间氯过氧苯甲酸 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 为溶剂， 生成 [1S-(1α,3aβ,4α,7aα)]-4-[[Dimethyl(1,1-dimethylethyl)silyl]oxy]-7a-methyl-β-methyleneoctahydro-1H-indene-1-ethanol
  参考文献：
  名称：

  Novel side chain analogs of 1α,25-dihydroxyvitamin D3: design and synthesis of the 21,24-methano derivatives

  摘要：

  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.

  DOI：

  10.1016/s0039-128x(00)00156-2

文献信息

• 20-position modified pharmaceutically active vitamin D series compounds
  申请人：Schering Aktiengesellschaft

  公开号：US05585368A1

  公开（公告）日：1996-12-17

  The invention relates to vitamin D derivatives, modified in 20-position, of general formula I ##STR1## in which X, Y, Z, R.sub.1, R.sub.2 as well as R.sub.3 have the meaning indicated in the description, process for their production and their use as agents for treatment of hyperproliferative diseases of the skin.

  该发明涉及一种改变20位位置的维生素D衍生物，其一般式为I ##STR1## 其中X、Y、Z、R.sub.1、R.sub.2以及R.sub.3的含义如描述中所示，以及它们的制备过程和作为治疗皮肤过度增生疾病的药物的用途。
• 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.