(1S,3R,4S,4aS,7S,8S,8aS)-4-氯-8-{2-[(2R,4R)-4-{[二甲基(2-甲基-2-丙基)硅烷基]氧基}-6-氧代四氢-2H-吡喃-2-基]乙基}-4A-羟基-3,7-二甲基-1,2,3,4,4A,7,8,8A-八氢-1-萘基2,2-二甲基丁酸酯 | 123852-10-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酯类
• 中文名称: (1S,3R,4S,4aS,7S,8S,8aS)-4-氯-8-{2-[(2R,4R)-4-{[二甲基(2-甲基-2-丙基)硅烷基]氧基}-6-氧代四氢-2H-吡喃-2-基]乙基}-4A-羟基-3,7-二甲基-1,2,3,4,4A,7,8,8A-八氢-1-萘基2,2-二甲基丁酸酯
• 中文别名: β.-D-核-六吡喃糖,1,6-脱水-4-O-(环丁基甲基)-3-脱氧-2-O-甲基-
• 英文名称: 6(R)-<2-<5(S)-Chloro-4a(S)-hydroxy-8(S)-((2,2-dimethylbutyryl)oxy)-2(S),6(R)-dimethyl-1,2,4a,5,6,7,8,8a(S)-octahydronaphth-1(S)-yl>ethyl>-4(R)-((tert-butyldimethylsilyl)oxy)-3,4,5,6-tetrahydro-2H-pyran-2-one
• 英文别名: 6(R)-[2-[5(S)-Chloro-4a(S)-hydroxy-8(S)-(2,2-dimethylbutyryloxy)-2(S),6(R)-dimethyl-1,2,-4a,5,6,7,8,8a(S)-octahydronaphthyl-1(S)]-ethyl]-4-(R)-(t-butyldimethylsilyloxy)-3,4,5,-6-tetrahydro-2H-pyran-2-one；6(R)-[2-[5(S)-Chloro-4a(S)-hydroxy-8(S)-(2,2-dimethylbutyryloxy)-2(S),6(R)-dimethyl-1,2,4a,5,6, 7,8,8a(S)-octahydronaphthyl-1(S)]ethyl]-4(R)-(t-butyldimethylsilyloxy)-3,4,5,6-tetrahydro-2H-pyran-2-one；6(R)-[2-[5(S)-Chloro-4a(S)-hydroxy-8(S)-(2,2-dimethylbutyryloxy)-2(S),6(R)-dimethyl-1,2,4a,5,6,7,8,8a(S)-octahydronaphthyl-1(S)]-ethyl]-4(R)-(t-butyldimethylsilyloxy)-3,4,5,6-tetrahydro-2H-pyran-2-one；6(R)-[2-[5(S)-Chloro-4a-(S)-hydroxy-8(S)-(2,2-dimethylbutyryloxy)-2(S),6(R)-dimethyl-1,2,4a,5,6,7,8,8a(S)-octahydronaphthyl-1(S)]ethyl]-4(R)-(t-butyldimethylsilyloxy)-3,4,5,6-tetrahydro-2H-pyran-2-one；6(R)-[2-[5(S)-Chloro-4a(S)-hydroxy-8(S)-(2,2-dimethylbutyryloxy)-2(S),6(R)-dimethyl-1,2,4a,5,6,7,8,8a(S)-octahydronaphthyl-1(S)]ethyl]-4(R)-(t-butyldimethylsilyloxy)-3,4,5,6-tetrahydro-2H-pyran-2-one；6(R)-[2-[8(S)-(2,2-dimethylbutyryloxy)-2(S), 6(R)-dimethyl-4a(S)-hydroxy-5(S)-chloro-1,2,4a,5,6,7,8,8a(S)-octahydronaphthyl-1(S)]-ethyl]-4(R)-t-butyldimethylsilyloxy-3,4,5,6-tetrahydro-2H-pyran-2-one；4-tert-Butyldimethylsilyl-5'-chloro-4a'-hydroxy Simvastatin；[(1S,3R,4S,4aS,7S,8S,8aS)-8-[2-[(2R,4R)-4-[tert-butyl(dimethyl)silyl]oxy-6-oxooxan-2-yl]ethyl]-4-chloro-4a-hydroxy-3,7-dimethyl-2,3,4,7,8,8a-hexahydro-1H-naphthalen-1-yl] 2,2-dimethylbutanoate
• CAS: 123852-10-8
• 化学式: C₃₁H₅₃ClO₆Si
• 分子量: 585.297
• InChiKey: DUYDNPDLGLCXCC-FSYOVWAKSA-N

物化性质

• 熔点：
  49-51°C
• 沸点：
  618.9±55.0 °C(Predicted)
• 密度：
  1.09±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于氯仿、二氯甲烷、乙酸乙酯、甲醇

计算性质

• 辛醇/水分配系数(LogP)：
  7.03
• 重原子数：
  39
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.87
• 拓扑面积：
  82.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (1S,3R,4S,4aS,7S,8S,8aS)-4-氯-8-{2-[(2R,4R)-4-{[二甲基(2-甲基-2-丙基)硅烷基]氧基}-6-氧代四氢-2H-吡喃-2-基]乙基}-4A-羟基-3,7-二甲基-1,2,3,4,4A,7,8,8A-八氢-1-萘基2,2-二甲基丁酸酯 在 偶氮二异丁腈 、 n-Bu₄SnH 作用下， 以 苯 为溶剂， 反应 2.0h， 以92%的产率得到(1S,3R,4aS,7S,8S,8aS)-8-{2-[(2R,4R)-4-{[二甲基(2-甲基-2-丙基)硅烷基]氧基}-6-氧代四氢-2H-吡喃-2-基]乙基}-4A-羟基-3,7-二甲基-1,2,3,4,4A,7,8,8A-八氢-1-萘基2,2-二甲基丁N酸酯
  参考文献：
  名称：

  Synthesis of L-669,262, a Potent HMG-CoA Reductase Inhibitor

  摘要：

  Synthesis of L-669,262, isosimvastatin-3-one, has been achieved in seven steps from simvastatin (MK-733) and has been shown to be one of the most potent inhibitors of HMG-CoA reductase found to date. The synthesis of the 6-methyl homolog of simvastatin is also described.

  DOI：

  10.1021/jo00099a030
• 作为产物：
  描述：

  辛伐他汀 在 咪唑 、 苯基氯化硒 、 双氧水 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 6.5h， 生成 (1S,3R,4S,4aS,7S,8S,8aS)-4-氯-8-{2-[(2R,4R)-4-{[二甲基(2-甲基-2-丙基)硅烷基]氧基}-6-氧代四氢-2H-吡喃-2-基]乙基}-4A-羟基-3,7-二甲基-1,2,3,4,4A,7,8,8A-八氢-1-萘基2,2-二甲基丁酸酯
  参考文献：
  名称：

  Synthesis of L-669,262, a Potent HMG-CoA Reductase Inhibitor

  摘要：

  Synthesis of L-669,262, isosimvastatin-3-one, has been achieved in seven steps from simvastatin (MK-733) and has been shown to be one of the most potent inhibitors of HMG-CoA reductase found to date. The synthesis of the 6-methyl homolog of simvastatin is also described.

  DOI：

  10.1021/jo00099a030

文献信息

• Novel HMG-CoA reductase inhibitors
  申请人：Merck & Co., Inc.

  公开号：US04857547A1

  公开（公告）日：1989-08-15

  Novel 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors are useful as antihypercholesterolemic agents and are represented by the following general structural formulae (I) and (II): ##STR1##

  新型3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶抑制剂作为降低胆固醇的药物是有用的，其通式如下（I）和（II）： ##STR1##
• Intermediates and processes for 6-hydroxymethyl HMG-CoA reductable
  申请人：Merck & Co., Inc.

  公开号：US04894465A1

  公开（公告）日：1990-01-16

  This invention discloses intermediates and processes for the preparation of 6-desmethyl-6-.alpha. hydroxymethyl derivatives of lovastatin and analogs thereof at the 8-acyl side chain.

  本发明揭示了一种中间体和制备洛伐他汀及其类似物8-酰基侧链的6-脱甲基-6-.alpha.羟甲基衍生物的方法。
• LEE, TA J.;HOFFMAN, WILLIAM F.
  作者：LEE, TA J.、HOFFMAN, WILLIAM F.

  DOI：——

  日期：——
• Synthesis of L-669,262, a Potent HMG-CoA Reductase Inhibitor
  作者：Gerald E. Stokker

  DOI：10.1021/jo00099a030

  日期：1994.10

  Synthesis of L-669,262, isosimvastatin-3-one, has been achieved in seven steps from simvastatin (MK-733) and has been shown to be one of the most potent inhibitors of HMG-CoA reductase found to date. The synthesis of the 6-methyl homolog of simvastatin is also described.