19-(tert-butyldimethylsiloxy)androst-5-en-17-one | 157022-94-1

• 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: 19-(tert-butyldimethylsiloxy)androst-5-en-17-one
• 英文别名: (8R,9S,10S,13S,14S)-10-[[tert-butyl(dimethyl)silyl]oxymethyl]-13-methyl-1,2,3,4,7,8,9,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-17-one
• CAS: 157022-94-1
• 化学式: C₂₅H₄₂O₂Si
• 分子量: 402.693
• InChiKey: WFTCMHSFBSXITC-MNUZBTPPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.91
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  19-(tert-butyldimethylsiloxy)androst-5-en-17-one 在 高氯酸 、 jones reagent 、 乙醇 、 溴 、 对甲苯磺酸 、 溶剂黄146 、 calcium carbonate 、 锌 、 N-溴代乙酰胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 丙酮 为溶剂， 反应 23.4h， 生成 19-acetoxyandrost-5-ene-4,17-dione
  参考文献：
  名称：

  芳香酶竞争性抑制剂5-雄烯-4,17-二酮的19-氧化衍生物的合成。

  摘要：

  由19-（叔丁基二甲基甲硅烷氧基）androst-5合成了19-羟基-甾醇13和19-oxo-甾族化合物13和15，它们是芳香酶抑制剂5-雄甾烯-4,17-二酮（3）的潜在代谢物。 -en-17-one（5）或4beta-acetoxyandrost-5-en-17-one（16），分别通过5alpha-bromo-4beta-hydroxy-6beta，19-epoxyandrostan + ++-17-one（10）作为每个序列中的关键中间体。19-甲硅烷氧基化合物5与Br2的反应生成5α-溴-6β，19-环氧化合物8，将其用N，N'-二甲基乙酰胺处理，然后与N-溴乙酰胺和0.28 M HCIO4反应，得到化合物10。另一方面，用N-溴乙酰胺-HClO 4处理4β-乙酰氧基甾族化合物16，然后在辐射下用Pb（IV）乙酸和I 2氧化，再用K 2 CO 3水解，也制得化合物10，产率比上述合成更好。琼斯氧化4beta-ol

  DOI：

  10.1016/s0039-128x(98)00113-5
• 作为产物：
  描述：

  3β-<(p-tolylsulfonyl)oxy>-19-(tert-butyldimethylsiloxy)androst-5-en-17-one 在 水 、 sodium iodide 、 锌 作用下， 以 乙二醇二甲醚 为溶剂， 反应 3.5h， 以86%的产率得到19-(tert-butyldimethylsiloxy)androst-5-en-17-one
  参考文献：
  名称：

  Synthesis of Androst-5-en-7-ones and Androsta-3,5-dien-7-ones and Their Related 7-Deoxy Analogs as Conformational and Catalytic Probes for the Active Site of Aromatase

  摘要：

  A series of androst-5-en-7-ones and androsta-3,5-dien-7-ones and their 7-deoxy derivatives, respectively, were synthesized and tested for their abilities to inhibit aromatase in human placental microsomes. All the steroids inhibited the enzyme in a competitive manner with K-i's ranging from 0.058 to 45 mu M. The inhibitory activities of 17-oxo compounds were much more potent than those of the corresponding 17 beta-alcohols in each series. Steroids having an oxygen function (hydroxy or carbonyl) at C-19 were less potent inhibitors than the corresponding parent compounds having a 19-methyl group. 3,5-Dien-7-one 24 and its 19-hydroxy and 19-oxo derivatives (12 and 13) as well as 19-oxo-5-en-7-one 3 caused a time-dependent inactivation of aromatase only in the presence of NADPH in which the k(inact) values of 19-als 3 and 13 (0.143 and 0.189 min(-1), respectively) were larger than those of the corresponding 19-methyl (23 and 24) and 19-hydroxy (1 and 12) steroids, respectively. 19-Nor-5-en-7-one 4 but not its 3,5-diene derivative 14 also inactivated the enzyme in a time-dependent manner. In contrast, 7-deoxy steroids 21 and 27, having a 19-methyl group, did not cause it. The inactivations were prevented by the substrate androstenedione, and no significant effects of L-cysteine on the inactivations were observed in each case. The results suggest that oxygenation at C-19 would be at least in part involved in the inactivations caused by the inhibitors 23 and 24. The conjugated enone structures should play a critical role in the inactivation sequences.

  DOI：

  10.1021/jm00040a012

文献信息

• Synthesis of 19-oxygenated derivatives of the competitive inhibitor of aromatase, 5-androstene-4,17-dione
  作者：Mitsuteru Numazawa、Keiko Yamada

  DOI：10.1016/s0039-128x(98)00113-5

  日期：1999.5

  HCIO4, to yield compound 10. On the other hand, treatment of the 4beta-acetoxy steroid 16 with N-bromoacetamide-HCI04 followed by oxidation with Pb (IV) acetic acid and I2 under irradiation and subsequent hydrolysis with K2CO3 also produced compound 10 and in better yield than that in the above synthesis. Jones oxidation of the 4beta-ol 10 followed by reductive debromination with zinc dust yielded the

  由19-（叔丁基二甲基甲硅烷氧基）androst-5合成了19-羟基-甾醇13和19-oxo-甾族化合物13和15，它们是芳香酶抑制剂5-雄甾烯-4,17-二酮（3）的潜在代谢物。 -en-17-one（5）或4beta-acetoxyandrost-5-en-17-one（16），分别通过5alpha-bromo-4beta-hydroxy-6beta，19-epoxyandrostan + ++-17-one（10）作为每个序列中的关键中间体。19-甲硅烷氧基化合物5与Br2的反应生成5α-溴-6β，19-环氧化合物8，将其用N，N'-二甲基乙酰胺处理，然后与N-溴乙酰胺和0.28 M HCIO4反应，得到化合物10。另一方面，用N-溴乙酰胺-HClO 4处理4β-乙酰氧基甾族化合物16，然后在辐射下用Pb（IV）乙酸和I 2氧化，再用K 2 CO 3水解，也制得化合物10，产率比上述合成更好。琼斯氧化4beta-ol
• Synthesis of Androst-5-en-7-ones and Androsta-3,5-dien-7-ones and Their Related 7-Deoxy Analogs as Conformational and Catalytic Probes for the Active Site of Aromatase
  作者：Mitsuteru Numazawa、Ayako Mutsumi、Mii Tachibana、Kumiko Hoshi

  DOI：10.1021/jm00040a012

  日期：1994.7

  A series of androst-5-en-7-ones and androsta-3,5-dien-7-ones and their 7-deoxy derivatives, respectively, were synthesized and tested for their abilities to inhibit aromatase in human placental microsomes. All the steroids inhibited the enzyme in a competitive manner with K-i's ranging from 0.058 to 45 mu M. The inhibitory activities of 17-oxo compounds were much more potent than those of the corresponding 17 beta-alcohols in each series. Steroids having an oxygen function (hydroxy or carbonyl) at C-19 were less potent inhibitors than the corresponding parent compounds having a 19-methyl group. 3,5-Dien-7-one 24 and its 19-hydroxy and 19-oxo derivatives (12 and 13) as well as 19-oxo-5-en-7-one 3 caused a time-dependent inactivation of aromatase only in the presence of NADPH in which the k(inact) values of 19-als 3 and 13 (0.143 and 0.189 min(-1), respectively) were larger than those of the corresponding 19-methyl (23 and 24) and 19-hydroxy (1 and 12) steroids, respectively. 19-Nor-5-en-7-one 4 but not its 3,5-diene derivative 14 also inactivated the enzyme in a time-dependent manner. In contrast, 7-deoxy steroids 21 and 27, having a 19-methyl group, did not cause it. The inactivations were prevented by the substrate androstenedione, and no significant effects of L-cysteine on the inactivations were observed in each case. The results suggest that oxygenation at C-19 would be at least in part involved in the inactivations caused by the inhibitors 23 and 24. The conjugated enone structures should play a critical role in the inactivation sequences.