3β-hydroxy-17aα-methyl-17-oxa-D-homo-5-androsten-16-one | 849425-36-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 萘并吡喃类
• 英文名称: 3β-hydroxy-17aα-methyl-17-oxa-D-homo-5-androsten-16-one
• 英文别名: 3β-hydroxy-17aα-methyl-17-oxa-17a-homoandrost-5-en-16-one；(1S,4aS,4bR,8S,10aR,10bS,12aS)-8-hydroxy-1,10a,12a-trimethyl-1,4,4a,4b,5,7,8,9,10,10b,11,12-dodecahydronaphtho[2,1-f]isochromen-3-one
• CAS: 849425-36-1
• 化学式: C₂₀H₃₀O₃
• 分子量: 318.456
• InChiKey: NFWVIRXDFSLOMP-CWXIGQHFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  23
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3β-hydroxy-17aα-methyl-17-oxa-D-homo-5-androsten-16-one 在 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 1,4-二氧六环 为溶剂， 反应 18.0h， 以74%的产率得到17aα-methyl-17-oxa-D-homo-1,4,6-androstatrien-3,16-dione
  参考文献：
  名称：

  Synthesis and anti-aromatase activity of some new steroidal D-lactones

  摘要：

  Starting from D-seco derivatives of 5-androstene 1-3, the D-homo lactones, 4 and 5, were synthesized. By the Oppenauer oxidation and/or by dehydration of 4 and 5 with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) or 2,3,5,6-tetrachloro-1,4-betizoquinone (chloranil), the corresponding D-lactones 6-12 were obtained. The structures of 6 and 10 were unambiguously proved by the appropriate X-ray structural analysis. Anti-aromatase assay showed that tested compounds possess inhibition potency, however. two to four times smaller (IC50 from 0.2 to 0.7 mum, respectively) in comparison to aminoglutethimide (AG). (C) 2004 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2004.10.005
• 作为产物：
  描述：

  3β,17-dihydroxy-17-methyl-16-nitrile-16,17-seco-5-androstene 在 氢氧化钾 作用下， 以 乙二醇 为溶剂， 反应 3.5h， 以84%的产率得到3β-hydroxy-17aα-methyl-17-oxa-D-homo-5-androsten-16-one
  参考文献：
  名称：

  Synthesis and anti-aromatase activity of some new steroidal D-lactones

  摘要：

  Starting from D-seco derivatives of 5-androstene 1-3, the D-homo lactones, 4 and 5, were synthesized. By the Oppenauer oxidation and/or by dehydration of 4 and 5 with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) or 2,3,5,6-tetrachloro-1,4-betizoquinone (chloranil), the corresponding D-lactones 6-12 were obtained. The structures of 6 and 10 were unambiguously proved by the appropriate X-ray structural analysis. Anti-aromatase assay showed that tested compounds possess inhibition potency, however. two to four times smaller (IC50 from 0.2 to 0.7 mum, respectively) in comparison to aminoglutethimide (AG). (C) 2004 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2004.10.005

文献信息

• Synthesis and Biological Activity of Some 17a-Substituted Homolactones of Androst-5-ene Derivatives
  作者：Katarina M. Penov Gaši、Srdjan Z. Stojanović、Marija N. Sakač、Evgenija A. Djurendić、János J. Csanádi、Dora Molnar-Gabor、Dušan Lazar、Radmila M. Kovačević

  DOI：10.1135/cccc20051387

  日期：——

  Some new 17a-homolactones were prepared from 3β-hydroxy-16-(hydroxyimino)androst-5-en-17-one (1) as a starting compound, which was transformed first to the corresponding 17α-phenyl and 17α-benzyl derivatives 2 and 3. The structure of compound 3 was confirmed by X-ray structure analysis. Beckmann fragmentation of compounds 2 and 3 yielded 16,17-seco-cyano ketones 4-7, whose reduction with NaBH₄ gave 16,17-seco-cyano alcohols 8-11, whereby the structure of compound 7 was established by X-ray structural analysis. Compounds 8-11 served as the starting compounds for obtaining lactones 12 and 13 in a reaction with potassium hydroxide in ethylene glycol. One-pot procedures were also developed for preparing 17a-homolactones 12, 13 and 16 from the hydroxyimino alcohols 2, 3 and 14. Compounds 12 and 13 showed an inhibitory activity against the enzyme aromatase (63 and 59%, respectively).

  一些新的17a-同型内酯是从3β-羟基-16-(羟肟)雄烯-5-烯-17-酮（1）作为起始化合物制备的，首先转化为相应的17α-苯基和17α-苄基衍生物2和3。化合物3的结构经X射线结构分析确认。化合物2和3的贝克曼分解产生16,17-戊二酮4-7，它们与NaBH4还原后得到16,17-戊二醇8-11，其中化合物7的结构通过X射线结构分析确定。化合物8-11作为起始化合物，通过与乙二醇中的氢氧化钾反应获得内酯12和13。还开发了一锅法制备17a-同型内酯12、13和16，其起始物为羟肝醇2、3和14。化合物12和13显示对芳香化酶的抑制活性分别为63%和59%。