辛伐他汀杂质ZA-Ⅲ-01 | 134970-32-4

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 中文名称: 辛伐他汀杂质ZA-Ⅲ-01
• 英文名称: 2,2-Dimethyl-butyric acid (1S,3R,7S,8S,8aR)-8-[(3R,5R)-3,5-bis-(tert-butyl-dimethyl-silanyloxy)-6-(butyl-methyl-carbamoyl)-hexyl]-3,7-dimethyl-1,2,3,7,8,8a-hexahydro-naphthalen-1-yl ester
• CAS: 134970-32-4
• 化学式: C₄₂H₇₉NO₅Si₂
• 分子量: 734.264
• InChiKey: SUKGPYIDIDAMAR-UTFAGHIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  11.34
• 重原子数：
  50.0
• 可旋转键数：
  17.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  65.07
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为产物：
  描述：

  N-丁基-7-(1,2,6,7,8α(R)-六氢-2(S),6(R)-二甲基-8(S)-((2)-甲基丁酰基)氧基)-1 -(S)萘基)-3(R),5(R)-双((叔丁基二甲基甲硅烷基)-氧基)庚酸酰胺 、 碘甲烷 在 lithium pyrrolidide 作用下， 生成 N-butyl-7-<1,2,6,7,8,8a(R)-hexahydro-2(S),6(R)-dimethyl-8(S)-<<2,2-dimethylbutanoyl>oxy>-1(S)-naphthyl>-3(R),5(R)-bis<(tert-butyldimethylsilyl)oxy>heptanoic acid amide 、 辛伐他汀杂质ZA-Ⅲ-01
  参考文献：
  名称：

  Synthesis of synvinolin: extremely high conversion alkylation of an ester enolate

  摘要：

  A efficient process for the commercial preparation of the therapeutically important cholesterol lowering drug synvinolin (2: simvastatin, ZOCOR) from mevinolin (1: lovastatin, MEVACOR) is reported. The synthesis relies upon deactivation of the delta-lactone carbonyl toward enolization via conversion to the bis[(tert-butyldimethylsilyl)oxy] butylamide 7. An extremely high conversion (99.7%) ester enolate alkylation of 7 affords 8 and 9. Subsequent desilylation and intramolecularly assisted basic amide hydrolysis in the presence of the dimethylbutyrate ester moiety yields 12, which is lactonized to 2. The overall yield from 1 to 2 is 86%.

  DOI：

  10.1021/jo00016a023