(3R,4R,5R)-4-methyloct-1-en-7-yne-3,5-diol | 215394-09-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (3R,4R,5R)-4-methyloct-1-en-7-yne-3,5-diol
• 英文别名: (3R,4R,5R)-3,5-dihydroxy-4-methyl-1-octen-7-yne
• CAS: 215394-09-5
• 化学式: C₉H₁₄O₂
• 分子量: 154.209
• InChiKey: QJLPSSSPXITMCC-DJLDLDEBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  11
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  40.5
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (3R,4R,5R)-4-methyloct-1-en-7-yne-3,5-diol 在 2,6-二甲基吡啶 、 tris(dibenzylideneacetone)dipalladium(0) chloroform complex 、 camphor-10-sulfonic acid 、 三乙胺 、 三苯基膦 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 23.0h， 生成 (5Z,7E)-(1S,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：

  (R)-4-[(tert-butyldiphenylsilyl)oxy]-3-methylbut-1-ene 在 正丁基锂 、 cerium(III) chloride 、 swern reagent 、 三氟化硼乙醚 、 四丁基氟化铵 、 对甲苯磺酸 、 间氯过氧苯甲酸 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 生成 (3R,4R,5R)-4-methyloct-1-en-7-yne-3,5-diol
  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

• VITAMIN D3 DERIVATIVES AND PROCESS FOR PRODUCING THE SAME
  申请人：TEIJIN LIMITED

  公开号：EP0957088B1

  公开（公告）日：2002-12-18
• JPH11116551A
  申请人：——

  公开号：JPH11116551A

  公开（公告）日：1999-04-27
• US6982257B1
  申请人：——

  公开号：US6982257B1

  公开（公告）日：2006-01-03