3β,17β-dihydroxy-17α-methyl-16-oximino-5-androstene | 361342-62-3

• 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,17β-dihydroxy-17α-methyl-16-oximino-5-androstene
• CAS: 361342-62-3
• 化学式: C₂₀H₃₁NO₃
• 分子量: 333.471
• InChiKey: QCOTXJZQFHXINW-HOSJZOFRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  24.0
• 可旋转键数：
  0.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  73.05
• 氢给体数：
  3.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  3β,17β-dihydroxy-17α-methyl-16-oximino-5-androstene 在 sodium 、 水杨酸甲酯 作用下， 以 甲苯 为溶剂， 反应 0.25h， 以53%的产率得到2-[(2S,4aS,4bR,7S,10aR)-2-acetyl-7-hydroxy-2,4b-dimethyl-1,3,4,4a,5,6,7,8,10,10a-decahydrophenanthren-1-yl]acetonitrile
  参考文献：
  名称：

  estra-1,3,5（10）-三烯和雄烯-5-烯的水杨酰衍生物的合成，抗氧化活性和细胞毒性

  摘要：

  由于许多雌激素和雄甾烷衍生物表现出细胞毒性，抗氧化或抗激素活性，因此从合适的雌激素或雄激素前体合成了新的甾体衍生物，从而获得了治疗类固醇依赖性疾病的潜在疗法。从雌二醇（I）开始，制备了6-氧代衍生物V和VII。通过化合物V或VII与水杨酸甲酯在钠存在下的反应，合成了17种β-水杨酰基-6-氧代衍生物VI和VIII。17 β -Salicyloyloxy雌二醇IX由雌二醇制备。用水杨酸甲酯对16-氧亚氨基醇XII和XIII进行贝克曼裂解，得到相应的D-seco衍生物XIV和XV。化合物XII的同时断裂和酰化产生了3种β-水杨酰基-D-seco衍生物XVI，其也从化合物XIV获得。与标准抗氧化剂BHA和BHT相比，新合成的化合物V-IX，XIV和XVI的抗氧化剂测定表明，其清除羟自由基的能力较强，而清除DPPH自由基的能力较弱。化合物V，XIV和XVI表现出与BHT更高或相同的活性。评价了新化

  DOI：

  10.2478/s11696-012-0150-6
• 作为产物：
  描述：

  去氢表雄酮 在 亚硝酸正戊酯 、 potassium tert-butylate 作用下， 以 四氢呋喃 、 乙醚 、 叔丁醇 为溶剂， 生成 3β,17β-dihydroxy-17α-methyl-16-oximino-5-androstene
  参考文献：
  名称：

  estra-1,3,5（10）-三烯和雄烯-5-烯的水杨酰衍生物的合成，抗氧化活性和细胞毒性

  摘要：

  由于许多雌激素和雄甾烷衍生物表现出细胞毒性，抗氧化或抗激素活性，因此从合适的雌激素或雄激素前体合成了新的甾体衍生物，从而获得了治疗类固醇依赖性疾病的潜在疗法。从雌二醇（I）开始，制备了6-氧代衍生物V和VII。通过化合物V或VII与水杨酸甲酯在钠存在下的反应，合成了17种β-水杨酰基-6-氧代衍生物VI和VIII。17 β -Salicyloyloxy雌二醇IX由雌二醇制备。用水杨酸甲酯对16-氧亚氨基醇XII和XIII进行贝克曼裂解，得到相应的D-seco衍生物XIV和XV。化合物XII的同时断裂和酰化产生了3种β-水杨酰基-D-seco衍生物XVI，其也从化合物XIV获得。与标准抗氧化剂BHA和BHT相比，新合成的化合物V-IX，XIV和XVI的抗氧化剂测定表明，其清除羟自由基的能力较强，而清除DPPH自由基的能力较弱。化合物V，XIV和XVI表现出与BHT更高或相同的活性。评价了新化

  DOI：

  10.2478/s11696-012-0150-6

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%。
• New D-modified androstane derivatives as aromatase inhibitors☆
  作者：Katarina M. Penov Gaši、Slobodanka M. Stanković、János J. Csanádi、Evgenija A. Djurendić、Marija N. Sakač、Ljubica Medić Mijačević、Otto N. Arcson、Srdjan Z. Stojanović、Silvana Andrić、Dora Molnar Gabor、Radmila Kovačević

  DOI：10.1016/s0039-128x(01)00096-4

  日期：2001.8

  Starting from a 16-oximino derivative of 5-androstene the newly-synthesized 16-oximino-17-hydroxy-17-substituted derivatives 2-4 gave by the Beckmann fragmentation reaction the corresponding D-seco derivatives 6-9. Besides, in the case of the 17-hydroxy-17-methyl-16-oximino derivative 2, as a result of the rearrangement, the hydrolysis product 5 of the 16-oximino group with the opposite configuration

  从5-雄甾烯的16-氧亚氨基衍生物开始，新合成的16-氧亚氨基17-羟基-17-取代的衍生物2-4通过贝克曼裂解反应得到相应的D-seco衍生物6-9。此外，在17-羟基-17-甲基-16-肟基衍生物2的情况下，由于重排，获得了在C-17处具有相反构型的16-肟基的水解产物5。通过Oppenauer氧化和/或用2,3-二氯-5,6-二氰基苯并醌（DDQ）脱水7，可获得相应的衍生物12、13和14。通过适当的X射线结构分析明确证明了6和12的结构。抗芳香化酶活性的动力学分析表明，与其他雄烯衍生物相比，化合物12在去核大鼠卵巢中的表达最高（IC（50）为0.42 microM）。与氨基戊二酰亚胺（AG）活性相比，它低3.5倍。抑制是竞争性的，K（i）为0.27 microM。在D-seco衍生物中引入其他不饱和单元（化合物13和14）不会增加抗芳香化酶活性。
• Synthesis, X-ray crystal structures and biological activity of 16-amino-17-substituted-D-homo steroid derivatives
  作者：Katarina M. Penov Gaši、Dušan A. Miljković、Ljubica D. Medić Mijačević、Evgenija A. Djurendić、Srdjan Z. Stojanović、Marija N. Sakač、Maja Dj. Djurendić、Slobodanka M. Stanković、Dušan Lazar、Silvana Andrić、Radmila Kovačević

  DOI：10.1016/s0039-128x(03)00097-7

  日期：2003.9

  Homo derivatives in the androstane and estrane series, 12-19, were synthesized by a fragmentation-cyclization reaction of 16-oximino-17-hydroxy-17-substituted derivatives 3-9, or by cyclization of the corresponding D-seco derivatives 20-26. The structures were confirmed by X-ray analysis of compounds 12 and 16. Preliminary assessment of inhibitory effects of D-homo derivatives from androstane series towards aromatase, 3beta-hydroxysteroid dehydrogenase (3beta-HSD), 17alpha-hydroxylase/C17-20 lyase (P450c17) and 17beta-HSD indicated much lower inhibitory potential compared to previously tested activity of another type of D-modified steroids, namely D-seco derivatives. Also, assessment of potential antiestrogenic activity of derivatives from estrane series showed absence of such an activity. (C) 2003 Elsevier Inc. All rights reserved.
• Structural Analysis and Antitumor Activity of Androstane D-Seco-mesyloxy Derivatives
  作者：Aleksandar M. Oklješa、Suzana S. Jovanović-Šanta、Olivera R. Klisurić、Marija N. Sakač、Evgenija A. Djurendić、Dimitar S. Jakimov、Lidija D. Aleksić、Katarina M. Penov Gaši

  DOI：10.5935/0103-5053.20130206

  日期：——

  The study of the influence of steroidal compounds on tumor cell cultures, cell growth, induction of apoptosis and/or cell cycle changes, is a common way of discovering potential therapeutics for treating people suffering from hormone-dependent problems and diseases. Because of the very high mortality rate associated with this class of disease, therapeutics for treating different types of cancers are among the most important. This work presents the synthesis of two stereoisomeric 16,17-secoandrostane mesyloxy derivatives and their 17-hydroxy precursors. Compounds were structurally analyzed by X-ray crystallography, and their antiproliferative activity, influence on the cell cycle and potential to induce apoptosis were investigated.