3-<3',17'β-di-(tert-butyldimethylsilyloxy)-1',3',5'(10')-estratrien-16α-yl>propanal | 160840-44-8

• 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-16α-yl>propanal
• 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]propanal
• CAS: 160840-44-8
• 化学式: C₃₃H₅₆O₃Si₂
• 分子量: 556.977
• InChiKey: UWDUAXPPHPQHJV-YVIPJWCCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.52
• 重原子数：
  38
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 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-16α-yl>propanal 在 chromium(VI) oxide 、 盐酸 、 amberlyst-15 、 三正丁胺 、 硫酸 、 溴 、 三苯基膦 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成
  参考文献：
  名称：

  Synthesis and evaluation of estradiol derivatives with 16α-(bromoalkylamide), 16α-(bromoalkyl) or 16α-(bromoalkynyl) side chain as inhibitors of 17β-hydroxysteroid dehydrogenase type 1 without estrogenic activity

  摘要：

  To develop inhibitors of 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) without residual estrogenic activity, the synthesis of 16 alpha-(bromoalkylamide) derivatives of estradiol was performed starting from a key intermediate aldehyde obtained from commercially available estrone. In addition, series of 16 alpha-(bromoalkyl) and 16 alpha-(bromoalkynyl) derivatives of estradiol were also prepared as model compounds. All new compounds inhibited human placental cytosolic 17 beta-HSD (type 1) with IC50 values ranging from 1.7 to 10.6 mu M. From these results, we observed that a primary bromide produces a greater inhibition of 17 beta-HSD activity than secondary bromide, and that a shorter 16 alpha-side chain increases the inhibiting activity. In the estrogen-sensitive ZR-75-1 human breast cancer cell line, the 16 alpha-(bromoalkylamide)-estradiol series had no estrogenic activity at 30 nM, and only the compound with a shorter side chain length showed an estrogenic activity at 1000 nM. Interestingly, at this concentration, the compound with an intermediate side chain length showed an antiestrogenic activity of 74%, whereas the compound with the longer side chain length showed 34% of antiestrogenic activity. In this test, other 17 beta-HSD inhibitors (without bromoalkylamide side chain) were fully estrogenic. Among synthesized compounds, the estradiol derivative 4 (N-butyl, N-methyl, 9-[3',17'beta-(dihydroxy)-1',3',5'(10')-estratrien-16'alpha-yl]-7-bromononamide) was the best compromise for a dual-action inhibitor. This compound inhibited moderately and reversibly the 17 beta-HSD type 1 activity, but possessed no estrogenic activity and exhibited antiestrogenic activity in the ZR-75-1 cell line. Copyright (C) 1996 Elsevier Science Ltd

  DOI：

  10.1016/0968-0896(96)00154-x
• 作为产物：
  描述：

  (8R,9S,13S,14S,16R,17S)-16-Allyl-3-(tert-butyl-dimethyl-silanyloxy)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-17-ol 在 咪唑 、 sodium hydroxide 、 4 A molecular sieve 、 硼烷 、 双氧水 、 sodium acetate 、 pyridinium chlorochromate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 22.0h， 生成 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

文献信息

• O-Methoxycarbonyl Cyanohydrin as a New Protective Group for Carbonyls
  作者：David Berthiaume、Donald Poirier

  DOI：10.1016/s0040-4020(00)00535-4

  日期：2000.8

  O-Methoxycarbonyl cyanohydrin, a new protective group of carbonyls, was prepared in high yields by an efficient one-step procedure using methyl cyanoformate and a secondary alkylamine at room temperature. Herein, we report efficient methods for the formation and cleavage of the protective group. Also, the ability of different types of carbonyls to be protected and the protective group's behavior under different

  通过高效的一步法，在室温下使用氰基甲酸酯甲酯和仲烷基胺，高产率地制备了O-甲氧羰基氰醇，一种新的羰基保护基团。在此，我们报道了形成和裂解保护基的有效方法。此外，研究了不同类型的羰基被保护的能力以及保护基在不同化学条件下的行为。