17-羟基-16beta-甲基孕甾-1,4,9(11)-三烯-3,20-二酮 21-(乙基碳酸酯) | 56665-79-3

• 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
• 中文名称: 17-羟基-16beta-甲基孕甾-1,4,9(11)-三烯-3,20-二酮 21-(乙基碳酸酯)
• 中文别名: 17-羟基-16beta-甲基孕甾-1,4,9(11)-三烯-3,20-二酮21-(乙基碳酸酯)
• 英文名称: 17α-hydroxy-16β-methyl-21-ethoxycarbonyloxypregna-1,4,9(11)-triene-3,20-dione
• 英文别名: 16β-methyl-3,20-dioxopregna-1,4,9(11)-triene-17α,21-diol 21-(ethylcarbonate)；17-Hydroxy-16beta-methylpregna-1,4,9(11)-triene-3,20-dione 21-(ethylcarbonate)；ethyl [2-[(8S,10S,13S,14S,16S,17R)-17-hydroxy-10,13,16-trimethyl-3-oxo-7,8,12,14,15,16-hexahydro-6H-cyclopenta[a]phenanthren-17-yl]-2-oxoethyl] carbonate
• CAS: 56665-79-3
• 化学式: C₂₅H₃₂O₆
• 分子量: 428.525
• InChiKey: DADGESXUBSRHSL-ZUGRACOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  89.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  17-羟基-16beta-甲基孕甾-1,4,9(11)-三烯-3,20-二酮 21-(乙基碳酸酯) 在 高氯酸 、 1,3-二溴-5,5-二甲基海因 、 sodium hydroxide 作用下， 以 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 倍他米松环氧水解物
  参考文献：
  名称：

  Process Improvements in the Synthesis of Corticosteroid 9,11β-Epoxides

  摘要：

  Corticosteroid 9,11 beta -epoxides are key intermediates in the preparation of pharmaceutically important compounds such as betamethasone, mometasone, beclomethasone, and dexamethasone. A new process for the 9,11 beta -epoxide was developed using a PCl5-mediated regioselective dehydration of II alpha -hydroxysteroid to form the corresponding Delta (9,11) double bond. The olefin is then converted into 9 alpha ,11 beta -bromoformate by treatment with 1,3-dibromo-5, 5-dimethyl hydantoin (DBH) in DMF and subsequently cyclized to produce the desired 9,11 beta -epoxide upon treatment with NaOH. Major process-related impurities such as 21-OH-Delta (9,11)-triene, 21-OH-Delta (11,12)-triene, 21-Cl-Delta (9,11)-triene, and beta -epoxide-21-cathylate as well as 11 beta -Cl are all eliminated or minimized. This new process has been implemented in our manufacturing facility in full-scale production and proved to raise the overall yield and the quality of the product dramatically compared to the existing process.

  DOI：

  10.1021/op0102013
• 作为产物：
  描述：

  11-chloro-17α-hydroxy-16-methyl-21-ethoxycarbonyloxypregna-1,4-diene-3,20-dione 以 二甲基亚砜 为溶剂， 反应 3.0h， 以97%的产率得到17-羟基-16beta-甲基孕甾-1,4,9(11)-三烯-3,20-二酮 21-(乙基碳酸酯)
  参考文献：
  名称：

  Process Improvements in the Synthesis of Corticosteroid 9,11β-Epoxides

  摘要：

  Corticosteroid 9,11 beta -epoxides are key intermediates in the preparation of pharmaceutically important compounds such as betamethasone, mometasone, beclomethasone, and dexamethasone. A new process for the 9,11 beta -epoxide was developed using a PCl5-mediated regioselective dehydration of II alpha -hydroxysteroid to form the corresponding Delta (9,11) double bond. The olefin is then converted into 9 alpha ,11 beta -bromoformate by treatment with 1,3-dibromo-5, 5-dimethyl hydantoin (DBH) in DMF and subsequently cyclized to produce the desired 9,11 beta -epoxide upon treatment with NaOH. Major process-related impurities such as 21-OH-Delta (9,11)-triene, 21-OH-Delta (11,12)-triene, 21-Cl-Delta (9,11)-triene, and beta -epoxide-21-cathylate as well as 11 beta -Cl are all eliminated or minimized. This new process has been implemented in our manufacturing facility in full-scale production and proved to raise the overall yield and the quality of the product dramatically compared to the existing process.

  DOI：

  10.1021/op0102013

文献信息

• 一种倍他米松环氧水解物的合成方法
  申请人：浙江仙居仙乐药业有限公司

  公开号：CN104945464B

  公开（公告）日：2016-10-26

  本发明属于甾体激素类药物合成领域，具体涉及一种倍他米松环氧水解物的合成方法，包括以倍他米松消除物为原料，经溴羟化反应和环氧水解反应得到倍他米松环氧水解物成品，从减少水析跑料来提高倍他米松环氧水解物的总体收率。本发明减少了溴羟物在反应中的水解，并将环氧、水解两布工序合并成一步，从而提高了倍他米松环氧水解物的收率。
• Barton, Derek H. R.; Hesse, Robert H.; Lindell, Stephen D., Journal of the Chemical Society. Perkin transactions I, 1991, # 11, p. 2855 - 2858
  作者：Barton, Derek H. R.、Hesse, Robert H.、Lindell, Stephen D.、Pechet, Maurice M.

  DOI：——

  日期：——
• A regioselective PCl5 mediated dehydration for preparing Δ9,11 corticosteroids
  作者：Xiaoyong Fu、Chou-Hong Tann、T.K Thiruvengadam、Junning Lee、Cesar Colon

  DOI：10.1016/s0040-4039(01)00274-x

  日期：2001.4

  A regioselective PCl5-induced dehydration of 11 alpha -hydroxy corticosteroids was invented to provide the corresponding Delta (9.11) double bond trienes in excellent yield (>90%) with 99:1 regioisomeric ratio to the Delta (11.12) isomers. A syn-elimination mechanism was proposed for this reaction. (C) 2001 Elsevier Science Ltd. All rights reserved.