(3S,4R,5R)-3,5-bis(tert-butyldimethylsilanyloxy)-4-methyl-oct-1-en-7-yne | 215394-15-3

• 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: (3S,4R,5R)-3,5-bis(tert-butyldimethylsilanyloxy)-4-methyl-oct-1-en-7-yne
• 英文别名: (3S,4R,5R)-3,5-bis[(tert-butyldimethylsilyl)oxy]-4-methyloct-1-en-7-yne；(3S,4R,5R)-3,5-bis(t-butyldimethylsilyloxy)-4-methyl-1-octen-7-yne；tert-butyl-[(3S,4R,5R)-5-[tert-butyl(dimethyl)silyl]oxy-4-methyloct-1-en-7-yn-3-yl]oxy-dimethylsilane
• CAS: 215394-15-3
• 化学式: C₂₁H₄₂O₂Si₂
• 分子量: 382.734
• InChiKey: ISAIOCNIQWJIBA-GBESFXJTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.61
• 重原子数：
  25
• 可旋转键数：
  10
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  18.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (3S,4R,5R)-3,5-bis(tert-butyldimethylsilanyloxy)-4-methyl-oct-1-en-7-yne 在 tris(dibenzylideneacetone)dipalladium(0) chloroform complex 、 camphor-10-sulfonic acid 、 三乙胺 、 三苯基膦 作用下， 以 甲苯 为溶剂， 反应 22.0h， 生成 (5Z,7E)-(1R,2R,3R,20S)-2-Methyl-9,10-seco-5,7,10(19)-cholestatriene-1,3,25-triol
  参考文献：
  名称：

  Synthesis, Biological Evaluation, and Conformational Analysis of A-Ring Diastereomers of 2-Methyl-1,25-dihydroxyvitamin D₃ and Their 20-Epimers:  Unique Activity Profiles Depending on the Stereochemistry of the A-Ring and at C-20

  摘要：

  All eight; possible A-ring diastereomers of 2-methyl-1,25-dihydroxyvitamin D-3 (2) and 2-methyl-20-epi-1,25-dihydroxyvitamin D-3 (3) were convergently synthesized. The A-ring enyne synthons 19 were synthesized starting with methyl(S)-(+)- or (R)-(-)-3-hydroxy-2-methylpropionate (8). This was converted to the alcohol 14 as a 1:1 epimeric mixture in several steps. After having been separated by column chromatography, each isomer led to the requisite A-ring enyne synthons 19 again as 1:1 mixtures at C-1. Coupling of the resulting A-ring enynes 20a-h with the CD-ring portions 5a,b in the presence of a Pd catalyst afforded the 2-methyl analogues 2a-h and 3a-h in good yield. In this way, all possible A-ring diastereomers were synthesized. The synthesized analogues were biologically evaluated both in vitro and in vivo. The potency was highly dependent on the stereochemistry of each isomer. In particular, the alpha alpha beta -isomer 2g exhibited 4-fold higher potency than 1 alpha ,25-dihydroxyvitamin D-3 (1) both in bovine thymus VDR binding and in elevation of rat serum calcium concentration and was twice as potent, as the parent compound in HL-60 cell differentiation. Furthermore, its 20-epimer, that is, 20epi-alpha alpha beta 3g, exhibited exceptionally high activities: 12-fold higher in VDR binding affinity, 7-fold higher in calcium mobilization, and 590-fold higher in HL-60 cell differentiation, as compared to 1 alpha ,25-dihydroxyvitamin D3 (1). Accordingly, the double modification of 2-methyl substitution and 20-epimerization resulted in unique activity profiles. Conformational analysis of the A-ring by H-1 NMR and an X-ray crystallographic analysis of the alpha alpha beta -isomer 2g are also described.

  DOI：

  10.1021/jm000261j
• 作为产物：
  描述：

  (4R,5S)-6-[(tert-butyldiphenylsilyl)oxy]-5-methyl-4-[(2-tetrahydropyranyl)oxy]-1-(trimethylsilyl)hex-1-yne 在 2,6-二甲基吡啶 、 cerium(III) chloride 、 swern reagent 、 四丁基氟化铵 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 生成 (3S,4R,5R)-3,5-bis(tert-butyldimethylsilanyloxy)-4-methyl-oct-1-en-7-yne
  参考文献：
  名称：

  一种新颖实用的途径，用于1个α，25-二羟基维生素D3类似物的A环烯炔合子：1个α，25-二羟基维生素D2和3-甲基-1,25-二羟基维生素D3的A环非对映异构体的合成。

  摘要：

  开发了一种新颖而实用的通往A环烯炔合子（2）的途径，该途径可用于多种1α，25-二羟基维生素D3（1）的A环类似物。这种新方法改进了1的A环非对映异构体，化合物13-15的合成，以及新的类似物2-甲基-1,25-二羟基维生素D3（4）及其所有可能的非对映异构体的合成。对2-甲基类似物的生物学评估表明，α-α-β-异构体的效力比1。

  DOI：

  10.1016/s0960-894x(97)10204-9

文献信息

• Synthesis of 2α- and 2β-substituted-14-epi-previtamin D3 and their genomic activity
  作者：Daisuke Sawada、Tomoyuki Katayama、Yuya Tsukuda、Nozomi Saito、Hiroshi Saito、Ken-ichiro Takagi、Eiji Ochiai、Seiichi Ishizuka、Kazuya Takenouchi、Atsushi Kittaka

  DOI：10.1016/j.tet.2010.05.028

  日期：2010.7

  and 2β-Substituted analogs of 14-epi-previtamin D3 were synthesized and isolated after thermal isomerization of 14-epi-vitamin D3 triene at 80 °C. The VDR binding affinity and transactivation activity of osteocalcin promoter in HOS cells were tested, and the 2α-methyl-substituted analog was found to have greater genomic activity than 14-epi-previtamin D3. We found that modification at the C2 position

  14-表位-维生素D 3三烯在80°C下热异构化后，合成并分离了14-表位-维生素D 3的2α和2β取代类似物。在HOS细胞骨钙蛋白启动子的VDR结合亲和力和反式激活活性进行了测试，并且2α甲基取代的类似物被发现具有更大的基因组活性比14-外延-previtamin d 3。我们发现，在修改的C2位置塞科-steroidal骨架提供了对前维生素d形式的生物基因组活动以及天然维生素d形式有趣的效果。
• Synthesis and biological activity of 2-methyl-20-epi analogues of 1α,25-dihydroxyvitamin D3
  作者：Toshie Fujishima、Zhaopeng Liu、Daishiro Miura、Manabu Chokki、Seiichi Ishizuka、Katsuhiro Konno、Hiroaki Takayama

  DOI：10.1016/s0960-894x(98)00363-1

  日期：1998.8

  Synthesis and biological evaluation of all eight possible A-ring diastereomers of 2-methyl-20-epi-1,25-dihydroxyvitamin D-3 are described. Among the analogues synthesized, 2 alpha-methyl-20-epi-1 alpha,25-dihydroxyvitamin D-3 exhibited exceptionally high potency. The double modification of 2-methyl substitution and 20-epimerization yielded analogues with unique activity profiles. (C) 1998 Elsevier Science Ltd. All rights reserved.