16α-hydroxymethyl-3-benzyloxyestra-1,3,5(10)-trien-17β-ol | 438536-56-2

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: 16α-hydroxymethyl-3-benzyloxyestra-1,3,5(10)-trien-17β-ol
• 英文别名: 3-benzyloxy-16α-hydroxymethylestra-1,3,5(10)-trien-17β-ol
• CAS: 438536-56-2
• 化学式: C₂₆H₃₂O₃
• 分子量: 392.538
• InChiKey: ZBNNWEFLYICGDH-CAVKYZKFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  29.0
• 可旋转键数：
  4.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  49.69
• 氢给体数：
  2.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  16α-hydroxymethyl-3-benzyloxyestra-1,3,5(10)-trien-17β-ol 在 四溴化碳 、 三苯基膦 作用下， 以 二氯甲烷 为溶剂， 以79%的产率得到3-benzyloxy-16α-bromomethylestra-1,3,5(10)-trien-17β-ol
  参考文献：
  名称：

  Neighboring group participation

  摘要：

  The four possible isomers of 3-benzyloxy-16-hydroxymethylestra-1,3,5(10)-trien-17-ol (1a-4a) with proven configurations were converted into the corresponding 3-benzyloxy-16-bromomethylestra-1,3,5(10)-triene-3,17-diols (5e-8e). Depending on the reaction conditions the cis isomers of 3-benzyloxy-16-hydroxymethylestra-1,3,5(10)-trien-17-ol (1a and 2a) were transformed into 3-benzyloxy-16-bromomethylestra-1,3,5(10)-trien-17-yl acetate (5b and 6b) or 16-bromomethyl-3-hydroxyestra-1,3,5(10)-trien-17-yl acetate (5c and 6c) on treatment with HBr and acetic acid. The mechanism of the process can be interpreted as involving front-side neighboring group participation. Under similar experimental conditions, the trans isomers (3a and 4a) yielded only 3-benzyloxy-16-acetoxymethylestra-1,3,5(10)-trien-17-yl acetates (3b and 4b) or 16-acetoxymethylestra-1,3,5(10)-triene-3,17-diyl diacetates (3d and 4d). Both the cis (1a and 2a) and the trans (3a, and 4a) isomers were transformed into 16-bromomethylestra-1,3,5(10)-trien-17-ol (5a-8a) by the Appel reaction on treatment with CBr4/Ph3P. Debenzylation of 5a-8a was carried out with HBr and acetic acid to yield 5e-8e. The debenzylation process in the presence of acetic anhydride produces the diacetates 5d-8d. The structures of the compounds were determined by means of MS, H-1 NMR and C-13 NMR spectroscopic methods. Compounds 5c-8c and 5e-8e were tested in a radioligand-binding assay. Except for the affinity of 7e for the estrogen receptor (K-1 = 2.55 nM), thew affinities of the eight compounds (5c-8c and 5e-8e) for the estrogen, androgen and progesterone receptors are low (K-i > 0.55, 0.52 and 0.21 mu M, respectively). (c) 2005 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2005.09.008
• 作为产物：
  描述：

  3-O-苄基雌酮 在 钾硼氢 、 sodium methylate 作用下， 以 乙醇 、 苯 为溶剂， 反应 30.0h， 生成 16α-hydroxymethyl-3-benzyloxyestra-1,3,5(10)-trien-17β-ol
  参考文献：
  名称：

  Synthesis and receptor-binding examination of 16-hydroxymethyl-3,17-estradiol stereoisomers

  摘要：

  The four 16-hydroxyniethylestra-1,3,5(10)-triene-3,17-diol isomers were synthesized and tested in a radioligand-binding assay. The estrogen receptor recognizes these compounds, but their relative binding affinities are lower than 2.0% relative to that of the reference molecule estra-1,3,5(10)-triene-3,17beta-diol. The affinities of the tested compounds for the androgen and progesterone receptors are very low (K-i > 100 mum and 1 muM, respectively). The prepared 16-hydroxymethylestra-1,3,5(10)-triene-3,17-diol isomers are therefore estrogen receptor-selective molecules. (C) 2002 Elsevier Science Inc. All rights reserved.

  DOI：

  10.1016/s0039-128x(01)00191-x

文献信息

• Stereocontrolled synthesis of the four possible 3-methoxy and 3-benzyloxy-16-triazolyl-methyl-estra-17-ol hybrids and their antiproliferative activities
  作者：Anita Kiss、János Wölfling、Erzsébet Mernyák、Éva Frank、Zsanett Benke、Seyyed Ashkan Senobar Tahaei、István Zupkó、Sándor Mahó、Gyula Schneider

  DOI：10.1016/j.steroids.2019.108500

  日期：2019.12

  The four possible isomers of each of 3-methoxy- and 3-benzyloxyestra-1,3,5(10)-trien-17-ols (5-8 and 9-12) were converted through 16-p-tosylorcymethyl- or 16-bromomethyl derivatives into their 3-methoxy- and 3-benzyloxy-16-azidomethylestra(1,3,5(10)-triene derivatives (13-16 and 17-20). The regioselective Cu(I)-catalyzed 1,3-dipolar cycloaddition of these compounds with different terminal alkynes afforded novel 1,4-disubstituted diastereomers (21a-f, 22a-f, 23a-f, 24a-f and 25a-f, 26a-f, 27a-f, 28a-f). The antiproliferative activities of the structurally related triazoles were determined in vitro with the microculture tetrazolium assay on four malignant human cell lines of gynecological origin (Hela, SiHa, MCF-7 and MDA-MB-231).