3β-(tert-butyldimethylsilyloxy)pregna-5,16-dien-20-one | 58701-41-0

• 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: 3β-(tert-butyldimethylsilyloxy)pregna-5,16-dien-20-one
• 英文别名: 3β-tert-butyl-dimethylsilyloxy-pregna-5,16-dien-20-one；3β-tert-butyl-dimethylsilyloxypregn-5,16-dien-20-one；3β-(t-butyldimethylsilyloxy)pregna-5,16-dien-20-one；3β-t-butyldimethylsilyloxy-pregna-5,16-dien-20-one
• CAS: 58701-41-0
• 化学式: C₂₇H₄₄O₂Si
• 分子量: 428.731
• InChiKey: TUBMAQIAKDQSQY-MSFOBWSXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.46
• 重原子数：
  30.0
• 可旋转键数：
  3.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  26.3
• 氢给体数：
  0.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  3β-(tert-butyldimethylsilyloxy)pregna-5,16-dien-20-one 在 四丁基氟化铵 、 异丙基溴化镁 作用下， 以 四氢呋喃 为溶剂， 反应 15.0h， 生成 3β-hydroxy-16α-(pyridin-2-yl)-pregnan-5-en-20-one
  参考文献：
  名称：

  噻唑/吡啶侧链甾体C-20叔醇的立体选择性合成和抑菌活性

  摘要：

  利用甾体酮和噻唑/吡啶溴化镁的格氏反应，实现了具有噻唑和吡啶侧链的新型甾体C-20叔醇的立体选择性合成。在体外评估这些分子的抗真菌和抗菌活性。大多数化合物对所有测试菌株均表现出显着的抗真菌和抗菌活性。

  DOI：

  10.1016/j.ejmech.2011.05.032
• 作为产物：
  描述：

  16-脱氢孕烯醇酮乙酸酯 在 咪唑 、 水 、 potassium hydroxide 作用下， 以 N,N-二甲基甲酰胺 、 叔丁醇 为溶剂， 反应 12.0h， 生成 3β-(tert-butyldimethylsilyloxy)pregna-5,16-dien-20-one
  参考文献：
  名称：

  噻唑/吡啶侧链甾体C-20叔醇的立体选择性合成和抑菌活性

  摘要：

  利用甾体酮和噻唑/吡啶溴化镁的格氏反应，实现了具有噻唑和吡啶侧链的新型甾体C-20叔醇的立体选择性合成。在体外评估这些分子的抗真菌和抗菌活性。大多数化合物对所有测试菌株均表现出显着的抗真菌和抗菌活性。

  DOI：

  10.1016/j.ejmech.2011.05.032

文献信息

• Synthesis of hydroxylated steroid hormones via conjugate addition of a silyl-cuprate reagent
  作者：Diana Garside、David N. Kirk、Norman M. Waldron

  DOI：10.1016/0039-128x(94)90102-3

  日期：1994.12

  several hydroxylated steroids via conjugate addition of Fleming's silyl-cuprate reagent, (PhMe2Si)2CuLi, a masked hydroxyl group, to the appropriate enone was studied. By this means 7 alpha-hydroxytestosterone (7) was obtained in good yield from 17 beta-hydroxyandrosta-4,6-dien-3-one (1a), though similar reactions on 17 beta-hydroxyandrosta-1,4-dien-3-one (8) gave a low yield of 1 alpha-hydroxytestosterone

  研究了通过将Fleming的甲硅烷基-杯酸酯试剂（PhMe2Si）2CuLi，一种被掩蔽的羟基缀合到适当的烯酮中来合成几种羟基化的类固醇。通过这种方法，从17个β-羟基雄甾烯-4,6-dien-3-one（1a）以良好的收率获得了7个α-羟基睾丸激素（7），尽管对17个β-羟基雄甾烯-1,4-dien-3的反应相似-一（8）产生低产率的1α-羟基睾丸酮（13）的主要原因是苯基甲硅烷基中间体向卤代硅烷的转化率低。以类似的方式从3 beta-hydroxy-5 alpha-pregn-16-en-20-one和5 alpha-cholestane-1获得3 beta，16 alpha-Dihydroxy-5 alpha-pregnan-20-one（18b）。通过共轭加成甲硅烷基，还原羰基官能团，由1-en-3-one（14）生成alpha，3 alpha-diol（17），
• Ionic hydrogenation-directed stereoselective construction of C-20(H) stereogenic center in steroid side chains: Scope and limitations
  作者：Bapurao B. Shingate、Braja G. Hazra

  DOI：10.1016/j.tet.2017.03.029

  日期：2017.4

  Stereoselective synthesis of steroidal C-20 tertiary alcohols with n-butyl, vinyl, furyl, thienyl, thiazolyl, aryl and pyridyl side chains via Grignard reaction or organolithium reagents have been realized starting from readily available 16-dehydropregnenolone acetate. The ionic hydrogenation of steroidal C-20 tertiary alcohols having furyl, methylfuryl, thienyl, phenyl and 4-methoxyphenyl side chains, resulted

  用甾族C-20叔醇的立体选择性合成Ñ丁基，乙烯基，呋喃基，噻吩基，噻唑基，芳基和吡啶基的侧链通过从容易获得的16-脱氢孕烯醇酮乙酸酯开始已经实现了格氏反应或有机锂试剂。具有呋喃基，甲基呋喃基，噻吩基，苯基和4-甲氧基苯基侧链的甾族C-20叔醇的离子加氢，以优异的产率得到具有C-20天然构型的脱氧产物。然而，在相同反应条件下，烷基，噻唑基和吡啶基并入的甾族C-20叔醇失败。通过用呋喃基，噻吩基和4-甲氧基苯基侧链将甾体C-20，21-烯化合物立体选择性还原，得到具有C-20天然构型的饱和化合物，可以进一步突出离子氢化的范围。
• Synthesis of 21,21-Difluoro-3β-hydroxy-20-methylpregna-5,20-diene and 5,16,20-Triene as potential inhibitors of steroid C17(20) lyase
  作者：Philip M Weintraub、Amy K Holland、Cynthia A Gates、William R Moore、Robert J Resvick、Philippe Bey、Norton P Peet

  DOI：10.1016/s0968-0896(02)00434-0

  日期：2003.2

  Novel 21,21-difluorovinyl steroids, designed as difluorinated C20(21) enol mimics of pregnenolone, were targeted as potential mechanism-based inhibitors of C17(20) lyase, a crucial enzyme in the biosynthesis of testosterone. Addition of (difluoromethyl)diphenylphosphine oxide reagent to 17-acetyl steroids was the approach chosen for the construction of these compounds. Of particular interest were the

  新颖的21,21-二氟乙烯基类固醇，被设计为孕烯醇酮的二氟化C20（21）烯醇模拟物，被靶向作为潜在的基于机制的C17（20）裂合酶抑制剂，C17（20）裂合酶是睾丸激素生物合成中的关键酶。将（二氟甲基）二苯基膦氧化物试剂加到17-乙酰基甾族化合物中是用于构建这些化合物的选择方法。在尝试制备三烯9期间形成的异常Wittig产物尤其令人关注。发现目标二氟烯烃3是该酶的中度有效，时间依赖性抑制剂。
• Acetylenic Inhibitors of C-22 Hydroxylase of Ecdysone Biosynthesis
  作者：A. Mauvais、A. Burger、J.P. Roussel、C. Hetru、B. Luu

  DOI：10.1006/bioo.1994.1003

  日期：1994.3

  Acetylenic derivatives of cholesterol designed to be inhibitors of ecdysteroid biosynthesis were prepared. The side chains of these compounds differ additionally from that of cholesterol by stereochemical modifications at C-17 and C-20. A bicyclic acetylenic compound containing the partial structure of the C and D rings of the cholesterol nucleus was also synthesized. These compounds were devised with the aim of inhibiting the C-22 hydroxylation of ecdysone biosynthesis by a suicide substrate mechanism. One of these molecules inhibits very efficiently the synthesis of ecdysone in prothoracic glands in vitro. (C) 1994 Academic Press, Inc.
• Synthesis of novel galeterone derivatives and evaluation of their in vitro activity against prostate cancer cell lines
  作者：Radek Jorda、Eva Řezníčková、Urszula Kiełczewska、Jadwiga Maj、Jacek W. Morzycki、Leszek Siergiejczyk、Václav Bazgier、Karel Berka、Lucie Rárová、Agnieszka Wojtkielewicz

  DOI：10.1016/j.ejmech.2019.06.040

  日期：2019.10

  Prostate cancer is one of the main causes of male cancer-related deaths worldwide and the suppression of androgen receptor signalling is established as an effective strategy for the treatment. A series of galeterone analogues including several steroid-fused azacycles, as well as 17-(benzimidazol-1-ylimino), 16 alpha-(benzimidazol-2-ylamino), and 16 alpha-(benzothiazol-2-ylamino) steroid derivatives, were synthesized and tested against prostate cancer cell lines. Candidate compound 3f was shown to reduce AR-regulated transcription in a dose-dependent manner in nanomolar ranges and suppress expression of AR-regulated proteins Nkx3.1 and PSA in 22Rv1-ARE14 and VCaP cancer cell lines. Flexible docking study revealed similar position of 3f within AR binding site in comparison of galeterone even with stronger binding energy. (C) 2019 Elsevier Masson SAS. All rights reserved.