6α-fluoro-3α-hydroxy-7-oxo-5β-cholan-24-oic acid methyl ester | 132056-36-1

• 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: 6α-fluoro-3α-hydroxy-7-oxo-5β-cholan-24-oic acid methyl ester
• 英文别名: methyl 3α-hydroxy-6α-fluoro-7-keto-5β-cholanoate；Methyl 3alpha-hydroxy-6alpha-fluoro-7-keto-5beta-cholanoate；methyl (4R)-4-[(3R,5R,6R,8S,9S,10R,13R,14S,17R)-6-fluoro-3-hydroxy-10,13-dimethyl-7-oxo-1,2,3,4,5,6,8,9,11,12,14,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]pentanoate
• CAS: 132056-36-1
• 化学式: C₂₅H₃₉FO₄
• 分子量: 422.581
• InChiKey: MGKONVRVVWADMW-WKGRRQNDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6α-fluoro-3α-hydroxy-7-oxo-5β-cholan-24-oic acid methyl ester 在 4-二甲氨基吡啶 、 platinum(IV) oxide 、 氢气 、 三乙胺 作用下， 以 溶剂黄146 、 甲苯 、 乙腈 为溶剂， 55.0~75.0 ℃ 、275.8 kPa 条件下， 反应 18.0h， 生成 methyl (3α,5β,6α,7α)-3-acetoxy-6-fluoro-7-(methylsulfonyloxy)cholan-24-oate
  参考文献：
  名称：

  An Expedient Synthesis of 6α-Fluoroursodeoxycholic Acid

  摘要：

  Optimization of the synthesis of 6a-fluoroursodeoxycholic acid 1 is described starting from the commercially available 2. The penultimate intermediate 16 was made in eight synthetic steps but in only four operations in an overall yield of 57%. The highlights are flourination of hydroxyketo acid 11 using Selectfluor through the intermediacy of silyl enol ether 12, conversion of 13 to 14 via equilibration of fluoroketone, esterification, and acylation. The drug substance I was prepared from mesylate 16 using potassium superoxide followed by a mild reductive workup using methoxydiethylborane.

  DOI：

  10.1021/op0255433
• 作为产物：
  描述：

  (3α,5β)-6-fluoro-3-hydroxy-7-oxocholan-24-oic acid 、 sodium methylate 在 三甲基氯硅烷 作用下， 以 甲醇 为溶剂， 反应 6.25h， 生成 6α-fluoro-3α-hydroxy-7-oxo-5β-cholan-24-oic acid methyl ester
  参考文献：
  名称：

  An Expedient Synthesis of 6α-Fluoroursodeoxycholic Acid

  摘要：

  Optimization of the synthesis of 6a-fluoroursodeoxycholic acid 1 is described starting from the commercially available 2. The penultimate intermediate 16 was made in eight synthetic steps but in only four operations in an overall yield of 57%. The highlights are flourination of hydroxyketo acid 11 using Selectfluor through the intermediacy of silyl enol ether 12, conversion of 13 to 14 via equilibration of fluoroketone, esterification, and acylation. The drug substance I was prepared from mesylate 16 using potassium superoxide followed by a mild reductive workup using methoxydiethylborane.

  DOI：

  10.1021/op0255433

文献信息

• Fluorinated bile acid derivatives, processes for the preparation thereof
  申请人：Giuliani S.p.A.

  公开号：US05175320A1

  公开（公告）日：1992-12-29

  Compounds of general formula I ##STR1## wherein R.sub.1 is hydrogen or hydroxy, and the hydroxy group at the 7-position can be either in .alpha. or .beta. configuration, are valuable in human therapy. Compounds I can be prepared by fluorination of the suitably protected 6.alpha.-hydroxy-7-keto-derivatives.

  通式I的化合物其中R.sub.1是氢或羟基，而7位的羟基可以是α或β构型，在人类治疗中具有价值。化合物I可通过适当保护的6-α-羟基-7-酮衍生物的氟化制备。
• 7α-OH epimerisation of bile acids via oxido-reduction with Xanthomonas maltophilia
  作者：Alessandro Medici、Paola Pedrini、Ercolina Bianchini、Giancarlo Fantin、Alessandra Guerrini、Benedetto Natalini、Roberto Pellicciari

  DOI：10.1016/s0039-128x(01)00136-2

  日期：2002.1

  The microbial 7 alpha -OH epimerisation of cholic, chenodeoxycholic, and 12-ketochenodeoxycholic acids (7 alpha -OH bile acids) with Xanthomonas maltophilia CBS 827.97 to corresponding 7 beta -OH derivatives with scarcity of oxygen is described. With normal pressure of oxygen the 7-OH oxidation products are obtained. No biotransformations are achieved in anaerobic conditions. The microbial 7 alpha -OH epimerisation is achieved by oxidation of 7-OH function and subsequent reduction. Partial purification, in fact, of the enzymatic fraction revealed the presence of two hydroxysteroid dehydrogenases (HSDH) alpha- and beta -stereospecific together with a glycocholate hydrolase. On the basis of these results a further application is the microbial reduction of 6 alpha -fluoro and 6 beta -fluoro-3 alpha -hydroxy-7-oxo-5 beta -cholan-24-oic acid methyl esters to the corresponding 7 alpha -OH and 7 beta -OH derivatives. (C) 2002 Elsevier Science Inc. All rights reserved.
• Fluorinated bile acid derivatives, processes for the preparation thereof and pharmaceutical compositions containing them
  申请人：GIULIANI S.p.A.

  公开号：EP0393493B1

  公开（公告）日：1995-12-06
• US5061701A
  申请人：——

  公开号：US5061701A

  公开（公告）日：1991-10-29
• US5175320A
  申请人：——

  公开号：US5175320A

  公开（公告）日：1992-12-29