3-<3',17'β-di-(tert-butyldimethylsilyloxy)-1',3',5'(10')-estratrien-16'α-yl>propanol | 160840-42-6

• 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: 3-<3',17'β-di-(tert-butyldimethylsilyloxy)-1',3',5'(10')-estratrien-16'α-yl>propanol
• 英文别名: 3-[(8R,9S,13S,14S,16R,17S)-3,17-bis[[tert-butyl(dimethyl)silyl]oxy]-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-16-yl]propan-1-ol
• CAS: 160840-42-6
• 化学式: C₃₃H₅₈O₃Si₂
• 分子量: 558.993
• InChiKey: MBUIVWUDKHNDCX-YVIPJWCCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.32
• 重原子数：
  38
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  38.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-<3',17'β-di-(tert-butyldimethylsilyloxy)-1',3',5'(10')-estratrien-16'α-yl>propanol 在 4 A molecular sieve 、 sodium acetate 、 pyridinium chlorochromate 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以85%的产率得到3-<3',17'β-di-(tert-butyldimethylsilyloxy)-1',3',5'(10')-estratrien-16α-yl>propanal
  参考文献：
  名称：

  N-butyl, N-methyl, 11-[3′,17′ β-(dihydroxy)-1′,3′,5′(10′)- estratrien-16′ α-yl]-9(R/S)-bromo undecanamide: synthesis and 17β-HSD inhibiting, estrogenic and antiestrogenic activities

  摘要：

  The synthesis of a 16 alpha-(bromoalkylamide) derivative of estradiol (N-butyl, N-methyl, 11-[3',17'beta-(dihydroxy)-1',3',5'(10')-estratrien-16'alpha-yl]-9(R/S)-bromo undecanamide) was performed by two different approaches starting from estrone. Each approach hers the same key intermediate, containing an aldehyde group, but differs by the bromination step and the timing of formation of the amide group. This compound was found to cause, at 100 mu M, a complete inhibition of 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) responsible for the interconversion of estrone and estradiol. The corresponding IC50 value was 10.6 mu M. In the estrogen-sensitive ZR-75-1 human breast cancer cell line, this estradiol derivative has no estrogenic activity at 30 nM and only a minimal estrogenic activity (10% above the basal level) at 1 mu M. At this latter concentration, this compound causes a 28% inhibition of 0.1 nM EI-induced cel[proliferation (antiestrogenic activity). Thus, the introduction of a side-chain with a secondary bromide and a butyl methyl amide group at the 16 alpha-position of estradiol has two interesting effects; namely an inhibition of cytosolic 17 beta-HSD and a blockade of the estrogenic effect of estradiol.

  DOI：

  10.1016/0039-128x(94)90072-8
• 作为产物：
  描述：

  3-(O-tert-butyl(dimethyl)silyl)estrone 在 咪唑 、 sodium hydroxide 、 lithium aluminium tetrahydride 、 正丁基锂 、 硼烷 、 双氧水 、 二异丙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 21.0h， 生成 3-<3',17'β-di-(tert-butyldimethylsilyloxy)-1',3',5'(10')-estratrien-16'α-yl>propanol
  参考文献：
  名称：

  N-butyl, N-methyl, 11-[3′,17′ β-(dihydroxy)-1′,3′,5′(10′)- estratrien-16′ α-yl]-9(R/S)-bromo undecanamide: synthesis and 17β-HSD inhibiting, estrogenic and antiestrogenic activities

  摘要：

  The synthesis of a 16 alpha-(bromoalkylamide) derivative of estradiol (N-butyl, N-methyl, 11-[3',17'beta-(dihydroxy)-1',3',5'(10')-estratrien-16'alpha-yl]-9(R/S)-bromo undecanamide) was performed by two different approaches starting from estrone. Each approach hers the same key intermediate, containing an aldehyde group, but differs by the bromination step and the timing of formation of the amide group. This compound was found to cause, at 100 mu M, a complete inhibition of 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) responsible for the interconversion of estrone and estradiol. The corresponding IC50 value was 10.6 mu M. In the estrogen-sensitive ZR-75-1 human breast cancer cell line, this estradiol derivative has no estrogenic activity at 30 nM and only a minimal estrogenic activity (10% above the basal level) at 1 mu M. At this latter concentration, this compound causes a 28% inhibition of 0.1 nM EI-induced cel[proliferation (antiestrogenic activity). Thus, the introduction of a side-chain with a secondary bromide and a butyl methyl amide group at the 16 alpha-position of estradiol has two interesting effects; namely an inhibition of cytosolic 17 beta-HSD and a blockade of the estrogenic effect of estradiol.

  DOI：

  10.1016/0039-128x(94)90072-8

文献信息

• Synthesis of a First Estradiol-Adenosine Hybrid Compound
  作者：Donald Poirier、Roch P. Boivin、Marie Bérubé、Sheng-Xiang Lin

  DOI：10.1081/scc-120023440

  日期：2003.9

  An estradiol derivative, bearing an adenosine residue linked at C-16alpha by a three-carbon side chain, provides access to a new series of substrate-cofactor hybrid compound designed to potentially interact with two binding domains of the enzyme type 1 17alpha-hydroxysteroid dehydrogenase (17beta-HSD). The synthesis of 5'-O-[3-(3',17'beta-dihydroxy-1',3',5'(10')-estratrien-16'alpha-yl)propanoyl]adenosine (7) is reported focusing on the crucial last steps: the coupling of adenosine residue to estradiol side chain by an ester link and the appropriate final cleavage of three protecting groups.
• N-butyl, N-methyl, 11-[3′,17′ β-(dihydroxy)-1′,3′,5′(10′)- estratrien-16′ α-yl]-9(R/S)-bromo undecanamide: synthesis and 17β-HSD inhibiting, estrogenic and antiestrogenic activities
  作者：Joëlle D. Pelletier、Fernand Labrie、Donald Poirier

  DOI：10.1016/0039-128x(94)90072-8

  日期：1994.9

  The synthesis of a 16 alpha-(bromoalkylamide) derivative of estradiol (N-butyl, N-methyl, 11-[3',17'beta-(dihydroxy)-1',3',5'(10')-estratrien-16'alpha-yl]-9(R/S)-bromo undecanamide) was performed by two different approaches starting from estrone. Each approach hers the same key intermediate, containing an aldehyde group, but differs by the bromination step and the timing of formation of the amide group. This compound was found to cause, at 100 mu M, a complete inhibition of 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) responsible for the interconversion of estrone and estradiol. The corresponding IC50 value was 10.6 mu M. In the estrogen-sensitive ZR-75-1 human breast cancer cell line, this estradiol derivative has no estrogenic activity at 30 nM and only a minimal estrogenic activity (10% above the basal level) at 1 mu M. At this latter concentration, this compound causes a 28% inhibition of 0.1 nM EI-induced cel[proliferation (antiestrogenic activity). Thus, the introduction of a side-chain with a secondary bromide and a butyl methyl amide group at the 16 alpha-position of estradiol has two interesting effects; namely an inhibition of cytosolic 17 beta-HSD and a blockade of the estrogenic effect of estradiol.