(6α,9β,11β,16α,17α)-9,11-epoxy-6-fluoro-17-hydroxy-16-methyl-3-oxo-androsta-1,4-diene-17-carboxylic acid | 192191-46-1

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: (6α,9β,11β,16α,17α)-9,11-epoxy-6-fluoro-17-hydroxy-16-methyl-3-oxo-androsta-1,4-diene-17-carboxylic acid
• 英文别名: 9β,11β-epoxy-6α-fluoro-17α-hydroxy-16α-methyl-3-oxoandrosta-1,4-diene-17β-carboxylic acid；6α-fluoro-9β,11β-epoxy-17α,-hydroxy-16α-methyl-3-oxoandrosta-1,4-diene-17β-carboxylic acid；(1S,2S,8S,10S,11S,13R,14R,15S,17S)-8-fluoro-14-hydroxy-2,13,15-trimethyl-5-oxo-18-oxapentacyclo[8.8.0.01,17.02,7.011,15]octadeca-3,6-diene-14-carboxylic acid
• CAS: 192191-46-1
• 化学式: C₂₁H₂₅FO₅
• 分子量: 376.425
• InChiKey: SRQZVTLCVKHAFB-FGVNNXKRSA-N

物化性质

• 沸点：
  566.0±50.0 °C(Predicted)
• 密度：
  1.39±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  27
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  87.1
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (6α,9β,11β,16α,17α)-9,11-epoxy-6-fluoro-17-hydroxy-16-methyl-3-oxo-androsta-1,4-diene-17-carboxylic acid 在 硫化氢 、 二乙胺 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.25h， 生成 6α,9β,11β,16α,17β-9,11-epoxy-6-fluoro-16-methyl-3-oxo-17-propionyloxy-androsta-1,4-diene-17-carbothioic acid
  参考文献：
  名称：

  Automated radiosynthesis of no-carrier-added [S-fluoromethyl- 18F]fluticasone propionate as a radiotracer for lung deposition studies with PET

  摘要：

  Fluticasone propionate [(S)-fluoromethyl-6 alpha,9 alpha-difluoro-11 beta-hydroxy-16 alpha-methyl-3-oxo-17 alpha-(propionyloxy)-androsta-1,4-diene-17 beta-carbothioate; FP] is a potent anti-inflammatory steroid with several therapeutic indications, including use as an anti-asthmatic drug when administered as sized particles by inhalation from a pressurised metered-dose inhaler (pMDI). FP was successfully labelled with fluorine-18 (t(1/2) = 109.6 min; beta(+) = 100%) by displacement of tosylate with cyclotron-produced no-carrier-added [F-18]fluoride in an (S)-tosylmethyl precursor prepared from the known (S)-chloromethyl analogue of FP. Radiochemically pure [S-fluoromethyl-F-18]FP was separated by reverse phase HPLC in 35% radiochemical yield (decay-corrected) within 80 min form the end of radionuclide production (as verified by, radio-HPLC, LC-MS and LC-NMR). The radiosynthesis was automated for the safe production of high radioactivities (20-50 mCi) of [F-18]FP in a lead-shielded hot-cell for subsequent incorporation into formulated FP particles within a pMDI and subsequent study of FP deposition in human lung using positron emission tomography (PET).

  DOI：

  10.1002/(sici)1099-1344(199707)39:7<567::aid-jlcr999>3.0.co;2-p
• 作为产物：
  描述：

  (6alpha,9beta,11beta,16alpha)-9,11-环氧-6-氟-17,21-二羟基-16-甲基-孕甾-1,4-二烯-3,20-二酮 在 高碘酸 、 次磷酸 作用下， 以 2-甲基四氢呋喃 、 水 为溶剂， 反应 12.25h， 以94%的产率得到(6α,9β,11β,16α,17α)-9,11-epoxy-6-fluoro-17-hydroxy-16-methyl-3-oxo-androsta-1,4-diene-17-carboxylic acid
  参考文献：
  名称：

  A Streamlined Synthesis of Androstadiene C-17 Ester Derivatives

  摘要：

  展示了一种完全伸缩合成的方法，可以制备出一种基于环氧甲酸甲酯的雄甾二烯C-17酯衍生物。这种简化流程可以在每个合成步骤后消除分离和溶剂更换。因此，它不仅大大减少了溶剂浪费，还最大限度地减少了对高活性中间体的潜在暴露，从而提高了总产率。通过应用标准的绿色指标，直观明显地展示了降低溶剂数量的固有优势。

  DOI：

  10.2533/chimia.2011.877

文献信息

• [EN] 17.BETA- (ALPHA-HYDROXY) -ESTERS OF ANDROSTANES AS INTERMEDIATES FOR THE PREPARATION FOR THE PREPARATION OF 17.BETA.-FLUORINATED-ANDROSTANE ESTERS<br/>[FR] ESTERS DE 17-BETA-(ALPHA-HYDROXY) D'ANTROSTANES, UTILISES COMME INTERMEDIAIRES DANS LA PREPARATION D'ESTERS D'ANDROSTANE 15-BETA FLUORES.
  申请人：FARMABIOS SRL

  公开号：WO2004052912A1

  公开（公告）日：2004-06-24

  Process for the preparation of polyhalogenated steroids, in particular of androstanic fluoro derivatives corticosteroids by means of the formation of new androstanic S-hydroxy alkyl or aralkyl-17-carbothioate intermediates.

  通过形成新的雄甾烷S-羟基烷基或芳基-17-羰硫酸酯中间体，制备多卤代类固醇，特别是雄甾烷氟衍生物皮质类固醇的方法。
• 17.Beta-(alpha-hydroxy)-esters of androstanes as intermediates for the preparation of 17.beta-fluorinated-androstane esters
  申请人：Cainelli Adele Gianfranco

  公开号：US20060116359A1

  公开（公告）日：2006-06-01

  Process for the preparation of polyhalogenated steroids, in particular of androstanic fluoro derivatives corticosteroids by means of the formation of new androstanic S-hydroxy alkyl or aralkyl-17-carbothioate intermediates.

  通过形成新的雄甾烷 S-羟基烷基或芳烷基-17-硫代碳酸酯中间体，制备多卤代类固醇，特别是雄甾烷氟衍生物皮质类固醇的工艺。
• Synthesis and biological properties of novel glucocorticoid androstene C-17 furoate esters
  作者：David A. Sandham、Lucy Barker、David Beattie、David Beer、Louise Bidlake、David Bentley、Keith D. Butler、Sarah Craig、David Farr、Claire Ffoulkes-Jones、John R. Fozard、Sandra Haberthuer、Colin Howes、Deborah Hynx、Sarah Jeffers、Thomas H. Keller、Paul A. Kirkham、Janet C. Maas、Lazzaro Mazzoni、Andrew Nicholls、Gaynor E. Pilgrim、Elisabeth Schaebulin、Gillian M. Spooner、Rowan Stringer、Pamela Tranter、Katharine L. Turner、Morris F. Tweed、Christoph Walker、Simon J. Watson、Bernard M. Cuenoud

  DOI：10.1016/j.bmc.2004.06.027

  日期：2004.10

  A series of novel corticosteroid derivatives featuring C-17 furoate ester functionality have been synthesised. Profiling in vitro and in vivo has resulted in the identification of a compound with a longer duration of action and a lower oral side effect profile in rodents compared to budesonide. (C) 2004 Elsevier Ltd. All rights reserved.
• Use of steroids for the inhibition of angiogenesis
  申请人：ALCON LABORATORIES, INC.

  公开号：EP0533703B1

  公开（公告）日：2000-03-15