(3R)-[(tert-butyldimethylsilyl)oxy]-7-[4-(4-fluorophenyl)-2-isopropyl-1-(methanesulfonyl)-5-methyl-1H-pyrrol-3-yl]-5-oxo-6-heptenoic acid methyl ester | 160204-82-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: (3R)-[(tert-butyldimethylsilyl)oxy]-7-[4-(4-fluorophenyl)-2-isopropyl-1-(methanesulfonyl)-5-methyl-1H-pyrrol-3-yl]-5-oxo-6-heptenoic acid methyl ester
• 英文别名: methyl (E,3R)-3-[tert-butyl(dimethyl)silyl]oxy-7-[4-(4-fluorophenyl)-5-methyl-1-methylsulfonyl-2-propan-2-ylpyrrol-3-yl]-5-oxohept-6-enoate
• CAS: 160204-82-0
• 化学式: C₂₉H₄₂FNO₆SSi
• 分子量: 579.805
• InChiKey: HBJIBMLBHSJMGL-RFAWQRTRSA-N

物化性质

• 沸点：
  637.109±65.00 °C(Press: 760.00 Torr)(predicted)
• 密度：
  1.117±0.14 g/cm3(Temp: 25 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.46
• 重原子数：
  39
• 可旋转键数：
  13
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  100
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (3R)-[(tert-butyldimethylsilyl)oxy]-7-[4-(4-fluorophenyl)-2-isopropyl-1-(methanesulfonyl)-5-methyl-1H-pyrrol-3-yl]-5-oxo-6-heptenoic acid methyl ester 在 二乙基甲氧基硼烷 、 氢氟酸 作用下， 以 四氢呋喃 、 甲醇 、 乙腈 为溶剂， 反应 2.83h， 生成 (3R,5S)-7-[4-(4-fluorophenyl)-2-isopropyl-1-(methanesulfonyl)-5-methyl-1H-pyrrol-3-yl]-3,5-dihydroxy-6-heptenoic acid methyl ester
  参考文献：
  名称：

  Optical Resolution of 3-(Silyloxy)glutaric Acid Half Esters and Their Utilization for Enantioconvergent Synthesis of a HMG-CoA Reductase Inhibitor

  摘要：

  Useful chiral synthons, (3R)- and (3S)-[(tert-butyldimethylsilyl)oxy]penta acid monomethyl ester, (R)-1 and (S)-1, were obtained by optical resolution of a racemic mixture of 1. Sulfoxide 8 has been developed from(S)-1 as a new building block for preparing HMG-CoA reductase inhibitors. Two alternate chiral synthons 2 and 8, synthesized from (R)-1 and(S)-1, respectively, were employed for enantioconvergent synthesis of potent inhibitor 15 containing a pyrrole moiety.

  DOI：

  10.1021/jo9722156
• 作为产物：
  描述：

  [[4-(4-fluorophenyl)-2-isopropyl-5-methyl-1H-pyrrol-3-yl]methyl]dimethylamine 在 potassium tert-butylate 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二氯甲烷 、 甲苯 、 叔丁醇 为溶剂， 反应 10.25h， 生成 (3R)-[(tert-butyldimethylsilyl)oxy]-7-[4-(4-fluorophenyl)-2-isopropyl-1-(methanesulfonyl)-5-methyl-1H-pyrrol-3-yl]-5-oxo-6-heptenoic acid methyl ester
  参考文献：
  名称：

  Optical Resolution of 3-(Silyloxy)glutaric Acid Half Esters and Their Utilization for Enantioconvergent Synthesis of a HMG-CoA Reductase Inhibitor

  摘要：

  Useful chiral synthons, (3R)- and (3S)-[(tert-butyldimethylsilyl)oxy]penta acid monomethyl ester, (R)-1 and (S)-1, were obtained by optical resolution of a racemic mixture of 1. Sulfoxide 8 has been developed from(S)-1 as a new building block for preparing HMG-CoA reductase inhibitors. Two alternate chiral synthons 2 and 8, synthesized from (R)-1 and(S)-1, respectively, were employed for enantioconvergent synthesis of potent inhibitor 15 containing a pyrrole moiety.

  DOI：

  10.1021/jo9722156

文献信息

• Practical Synthesis of Chiral Synthons for the Preparation of HMG-CoA Reductase Inhibitors
  作者：Toshiro Konoike、Yoshitaka Araki

  DOI：10.1021/jo00104a049

  日期：1994.12

  A practical procedure for the enantioselective preparation of optically pure (R)- and (S)-monomethyl esters of 3-[(tert-butyldimethylsilyl)oxy]pentanedioic acid has been developed by diastereoselective ring-opening of 3-[(tert-butyldimethylsilyl)oxy]pentanedioic anhydride 5 by benzyl (R)- and (S)-mandelate, respectively. These half-esters afforded chiral Wittig reagent 2 and Horner-Wadsworth-Emmons (HWE) reagent 1 efficiently which have been proved to be useful in the synthesis of HMG-CoA reductase inhibitors. The method is applied to the synthesis of the (R)-3-methylglutaric acid, monomethyl ester.
• Synthesis and Biological Activity of Methanesulfonamide Pyrimidine- and N-Methanesulfonyl Pyrrole-Substituted 3,5-Dihydroxy-6-heptenoates, a Novel Series of HMG-CoA Reductase Inhibitors
  作者：Masamichi Watanabe、Haruo Koike、Teruyuki Ishiba、Tetsuo Okada、Shujiro Seo、Kentaro Hirai

  DOI：10.1016/s0968-0896(96)00248-9

  日期：1997.2

  A novel series of methanesulfonamide pyrimidine- and N-methanesulfonyl pyrrole-substituted 3,5-dihydroxy-6-heptenoates were synthesized and evaluated for their ability to inhibit the enzyme HMG-CoA reductase in vitro. Monocalcium bis(+)-7-[4-(4-fluorophenyl)-6-isopropyl-2-(N-methanesulfonylaminopyrimidin)-5-yl]-(3R,5S)-dihydroxy-(E)-6-heptenoate (3a,S-4522) was selected as a candidate for further evaluation. Compound 3a was approximately four times more potent than lovastatin sodium salt (in inhibiting HMG-CoA reductase in vitro (IC50 = 11 nM). Compound 3a was shown to be the most potent cholesterol biosynthesis inhibitor in this series (IC50 = 1.12 nM) in rat isolated hepatocytes; its inhibitory activity was approximately 100 times more potent than pravastatin. (C) 1997, Elsevier Science Ltd.
• Optical Resolution of 3-(Silyloxy)glutaric Acid Half Esters and Their Utilization for Enantioconvergent Synthesis of a HMG-CoA Reductase Inhibitor
  作者：Toshiro Konoike、Tetsuo Okada、Yoshitaka Araki

  DOI：10.1021/jo9722156

  日期：1998.5.1

  Useful chiral synthons, (3R)- and (3S)-[(tert-butyldimethylsilyl)oxy]penta acid monomethyl ester, (R)-1 and (S)-1, were obtained by optical resolution of a racemic mixture of 1. Sulfoxide 8 has been developed from(S)-1 as a new building block for preparing HMG-CoA reductase inhibitors. Two alternate chiral synthons 2 and 8, synthesized from (R)-1 and(S)-1, respectively, were employed for enantioconvergent synthesis of potent inhibitor 15 containing a pyrrole moiety.