6β-methylandrost-4-ene-3,17-dione | 5696-36-6

• 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: 6β-methylandrost-4-ene-3,17-dione
• 英文别名: 6β-methyl-androst-4-ene-3,17-dione；6β-Methyl-androst-4-en-3,17-dion；6β-Methyl-androsten-(4)-dion-(3.17)；6β-Methyl-androsten-(4)-dion-(3,17)；6β-Methyl-androst-en-3,17-dion；(6R,8R,9S,10R,13S,14S)-6,10,13-trimethyl-2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthrene-3,17-dione
• CAS: 5696-36-6
• 化学式: C₂₀H₂₈O₂
• 分子量: 300.441
• InChiKey: GZSCFURMBHMSCE-LVWDTYCVSA-N

物化性质

• 熔点：
  212-213 °C
• 沸点：
  437.2±45.0 °C(Predicted)
• 密度：
  1.10±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  22
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  34.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  6β-methylandrost-4-ene-3,17-dione 在 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 苯 为溶剂， 反应 18.0h， 以68%的产率得到(6R,8R,9S,10R,13S,14S)-6,10,13-trimethyl-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthrene-3,17-dione
  参考文献：
  名称：

  时间依赖性灭活的6-烷基androsta-1,4-diene-3,17-diones芳香化酶。长度和6-烷基构型的影响。

  摘要：

  合成了一系列6α-和6β-烷基雄甾烯-1,4-二烯-3,17-二酮（3和4），并作为人类胎盘微粒体中芳香化酶的时间依赖性灭活剂进行了评估，以了解其结构活性关系。将6-正烷基取代基（C-1--C-7）改变为随时间变化的灭活活性。合成的所有抑制剂均是芳香酶的良好竞争抑制剂，其表观Ki范围为4.7至54 nM。6beta-乙基（4b）和6beta-n-戊基（4e）化合物是其中最有效的化合物（4b和4e的Ki分别为4.7和5.0 nM）。在一系列的6-α-烷基甾族化合物中，在6-位具有C-1--C-4的抑制剂3a-d以及6个α-正庚基（3g）化合物没有。相反，在6β-烷基甾族化合物系列中，只有甲基类似物4a会以时间依赖性方式使芳香化酶失活，而在C-6beta处具有两个以上碳原子的其他烷基类固醇则没有。底物雄烯二酮可防止失活，并且在每种情况下均未观察到L-半胱氨酸对失活的显着影响。这些结果以及使用P

  DOI：

  10.1021/jm950720u
• 作为产物：
  描述：

  3,3:17,17-bis(ethylendioxy)-5α,6α-epoxyandrostane 在 吡啶 、 氯化亚砜 、 高氯酸 作用下， 以 四氢呋喃 为溶剂， 反应 6.05h， 生成 6β-methylandrost-4-ene-3,17-dione
  参考文献：
  名称：

  6-Alkyl- and 6-Arylandrost-4-ene-3,17-diones as Aromatase Inhibitors. Synthesis and Structure-Activity Relationships

  摘要：

  Two series of 6 beta- and 6 alpha-substituted androst-4-ene-3,17-diones (5 and 6) were synthesized as aromatase inhibitors to gain insights of structure-activity relationships of varying substituents (methyl, ethyl, n-propyl, isopropyl, n-butyl, phenyl, benzyl, vinyl, and ethynyl) to the inhibitory activity. All of the inhibitors synthesized prevented human placental aromatase in a competitive manner. The inhibition activities of all the 6-n-alkylated steroids 5a-d and 6a-d (K-i = 1.4-12 nM) as well as the 6 beta-vinyl (5h), 6 alpha-benzyl (6g), and 6-methylene (10) compounds (K-i = 5.1, 10, and 4.9 nM, respectively) were very powerful whereas those of the g-isopropyl (5e and 6e), 6-phenyl (5f and 6f), 6 beta-benzyl (5g), and 6 beta-ethynyl (5i) steroids, having a bulky or polar substituent, were relatively weak. The 6 beta-ethyl derivative 5b was the most potent inhibitor among those synthesized. Inhibitors 5a, 5f, 5h, 5i, 6b, and 10 did not cause a time-dependent inactivation of aromatase. The 6 beta-alkyl steroids essentially had higher affinity for the enzyme than the corresponding 6 alpha-isomers, whereas the opposite relation was observed in a series of the aryl steroids. These results along with molecular modeling with the PM3 method clearly indicate that aromatase has a hydrophobic binding pocket with a limited accessible volume in the active site in the region corresponding to the beta-side rather than the alpha-side of the C-6 position of the substrate.

  DOI：

  10.1021/jm00035a011

文献信息

• Direct organocatalytic stereoselective transfer hydrogenation of conjugated olefins of steroids
  作者：Dhevalapally B. Ramachary、Rajasekar Sakthidevi、P. Srinivasa Reddy

  DOI：10.1039/c3ra41519h

  日期：——

  catalyst 1b·D-CSA is mild enough to activate the various chiral cyclic enones through iminium ion formation during the organocatalytic transfer hydrogenations with Hantzsch ester 2a as a hydrogen source. Further, clear evidence for the selective formation of intermediate iminium species [I]+ have been characterized through on-line monitoring of controlled experiments by NMR and ESI-HRMS analyses.

  通过动力学控制和有机催化的顺-选择性转移氢化已成功地证明了各种类固醇的烯酮官能团的还原。在此，已经报道了通过有机催化的许多5β-类固醇的非对映选择性合成，其具有广泛的医学和药学应用。机理研究和产物的选择性清楚地表明，催化剂1b · D -CSA足够温和，可以在以汉茨sch酸酯2a为氢源的有机催化转移加氢过程中通过亚胺离子的形成来活化各种手性环状烯酮。此外，有明确的证据表明可以选择性地形成中间亚胺鎓类物质[ I] +通过NMR和ESI-HRMS分析对受控实验进行在线监测来表征。
• 571. Modified steroid hormones. Part XVII. Some 6-methyl-4,6-dien-3-ones
  作者：B. Ellis、D. N. Kirk、V. Petrow、B. Waterhouse、D. M. Williamson

  DOI：10.1039/jr9600002828

  日期：——
• 6-Methyl Steroids in the Androstane Series¹
  作者：J Allan Campbell、John C. Babcock、John A. Hogg

  DOI：10.1021/ja01550a073

  日期：1958.9
• Microbial transformation of 3-hydroxy-5,6-cyclopropanocholestanes - An alternative route to 6-methylsteroids
  作者：Jiann-Long Yan、Shoei-Sheng Lee、K.C. Wang

  DOI：10.1016/s0039-128x(00)00170-7

  日期：2000.12

  Incubation of 3 beta -hydroxy-5,6 beta alpha cyclopropano-5 alpha -cholestane (4), 3 beta -hydroxy-5,6 beta -cyclopropano-5 beta -cholestane (5), and 3 beta -hydroxy-5,6 alpha -cyclopropano-5 alpha -cholest-7-ene (6) with Mycobacterium sp. (NRRL B-3805) gave a mixture of side chain cleaved 17-keto steroids as the major products in 52, 57, and 69% yields, respectively. Among these 17-keto steroids, the cyclopropyl ring eliminated product, androst-4-ene-3,17-dione (9), was isolated in 6, 4, and 8% yields, respectively. A cyclopropyl ring migration product, 6 alpha ,7 alpha -cyclopro-panoandrost-4-ene-3,17-dione (16), was isolated from the incubation mixture of 6 in 4% yield, also 10% yield of 16 was obtained when 5,6 alpha -cyclopropano-5 alpha -androst-7-ene-3, 17-dione (12) was incubated. The cyclopropyl ring opening and subsequent reduction followed by oxidation of the two major biotransformation products, 5,6 beta -cyclopropano-5 beta -androsta-3, 17-dione (10) and 5,6 alpha -cyclopropano-5 alpha -androsta-3,17-dione (7), gave 6 beta- and 6 alpha -methylandrost-4-ene-3,17-dione in 60, and 45% yields, respectively. (C) 2000 Elsevier Science Inc. All rights reserved.
• Ackroyd et al., Journal of the Chemical Society, 1957, p. 4099,4101
  作者：Ackroyd et al.

  DOI：——

  日期：——