(S)-2-Methyl-butyric acid (1S,3R,4aR,7S,8S,8aS)-8-hydroxymethyl-3,7-dimethyl-1,2,3,4,4a,7,8,8a-octahydro-naphthalen-1-yl ester | 158041-72-6

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: (S)-2-Methyl-butyric acid (1S,3R,4aR,7S,8S,8aS)-8-hydroxymethyl-3,7-dimethyl-1,2,3,4,4a,7,8,8a-octahydro-naphthalen-1-yl ester
• 英文别名: [(1S,3R,4aR,7S,8S,8aS)-8-(hydroxymethyl)-3,7-dimethyl-1,2,3,4,4a,7,8,8a-octahydronaphthalen-1-yl] (2S)-2-methylbutanoate
• CAS: 158041-72-6
• 化学式: C₁₈H₃₀O₃
• 分子量: 294.434
• InChiKey: CRHSRBBNTWOBJT-NBCJBSOISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S)-2-Methyl-butyric acid (1S,3R,4aR,7S,8S,8aS)-8-hydroxymethyl-3,7-dimethyl-1,2,3,4,4a,7,8,8a-octahydro-naphthalen-1-yl ester 在 sodium tetrahydroborate 、 Wilkinson's catalyst 、 草酰氯 、 二乙基甲氧基硼烷 、 氢氟酸 、 caesium carbonate 、 二甲基亚砜 、 三乙胺 作用下， 以 异丙醇 、 乙腈 、 苯 为溶剂， 反应 9.08h， 生成 (3R,5R)-7-[(1S,2S,4aR,6R,8S,8aS)-2,6-Dimethyl-8-((S)-2-methyl-butyryloxy)-1,2,4a,5,6,7,8,8a-octahydro-naphthalen-1-yl]-3,5-dihydroxy-heptanoic acid methyl ester
  参考文献：
  名称：

  Enantioselective Total Synthesis of (+)-6-epi-Mevinolin and Its Analogs. Efficient Construction of the Hexahydronaphthalene Moiety by High Pressure-Promoted Intramolecular Diels−Alder Reaction of (R,2Z,8E,10E)-1-[(tert-Butyldimethylsilyl)oxy]-6-methyl-2,8,10-dodecatrien-4-one

  摘要：

  3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, (+)-6-epi-mevinolin (2a) and (+)-6-epi-4a,5-dihydromevinolin (2b), were prepared by combining two nonracemic units, phosphonate 3 and decalin 4, which were prepared from enantiopure 3-substituted pentanedioic acid monoesters 5a and 5b, respectively. Each acid was synthesized from cyclic anhydrides 7a and 7b by diastereoselective ring opening by means of (S)-benzyl mandelate as a common chiral auxiliary. The construction of decalin moiety 4 was accomplished by asymmetric intramolecular Diels-Alder (IMDA) reaction of nonracemic trienone 6 bearing a methyl group as a chiral controller. The IMDA diastereoselectivity of trienone 6 is discussed in terms of the configuration of(E)- and (Z)-dienophiles which are activated by an endogenous carbonyl group. The IMDA reaction of(R)-(Z)-6 under high pressure is highly selective and gives cis-decalins exclusively with preferential formation of 4 over 16. The inhibitory activity of (+)-6-epi-mevinolin (2a) and several analogs against HMG-CoA reductase was compared with mevinolin (1b). (+)-6-epi-Mevinolin (2a) was shown to be half as potent as mevinolin (1b) while (+)-6-epi-4a,5-dihydromevinolin (2b) was as potent as mevinolin.

  DOI：

  10.1021/jo970444m
• 作为产物：
  描述：

  (3R,4aR,7S,8S,8aS)-8-(tert-Butyl-dimethyl-silanyloxymethyl)-3,7-dimethyl-3,4,4a,7,8,8a-hexahydro-2H-naphthalen-1-one 在 4-二甲氨基吡啶 、 sodium hydroxide 、 氢氟酸 、 双氧水 、 L-Selectride 作用下， 以 吡啶 、 乙腈 为溶剂， 反应 49.75h， 生成 (S)-2-Methyl-butyric acid (1S,3R,4aR,7S,8S,8aS)-8-hydroxymethyl-3,7-dimethyl-1,2,3,4,4a,7,8,8a-octahydro-naphthalen-1-yl ester
  参考文献：
  名称：

  Enantioselective Total Synthesis of (+)-6-epi-Mevinolin and Its Analogs. Efficient Construction of the Hexahydronaphthalene Moiety by High Pressure-Promoted Intramolecular Diels−Alder Reaction of (R,2Z,8E,10E)-1-[(tert-Butyldimethylsilyl)oxy]-6-methyl-2,8,10-dodecatrien-4-one

  摘要：

  3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, (+)-6-epi-mevinolin (2a) and (+)-6-epi-4a,5-dihydromevinolin (2b), were prepared by combining two nonracemic units, phosphonate 3 and decalin 4, which were prepared from enantiopure 3-substituted pentanedioic acid monoesters 5a and 5b, respectively. Each acid was synthesized from cyclic anhydrides 7a and 7b by diastereoselective ring opening by means of (S)-benzyl mandelate as a common chiral auxiliary. The construction of decalin moiety 4 was accomplished by asymmetric intramolecular Diels-Alder (IMDA) reaction of nonracemic trienone 6 bearing a methyl group as a chiral controller. The IMDA diastereoselectivity of trienone 6 is discussed in terms of the configuration of(E)- and (Z)-dienophiles which are activated by an endogenous carbonyl group. The IMDA reaction of(R)-(Z)-6 under high pressure is highly selective and gives cis-decalins exclusively with preferential formation of 4 over 16. The inhibitory activity of (+)-6-epi-mevinolin (2a) and several analogs against HMG-CoA reductase was compared with mevinolin (1b). (+)-6-epi-Mevinolin (2a) was shown to be half as potent as mevinolin (1b) while (+)-6-epi-4a,5-dihydromevinolin (2b) was as potent as mevinolin.

  DOI：

  10.1021/jo970444m

文献信息

• Enantioselective Total Synthesis of (+)-6-<i>epi</i>-Mevinolin and Its Analogs. Efficient Construction of the Hexahydronaphthalene Moiety by High Pressure-Promoted Intramolecular Diels−Alder Reaction of (<i>R</i>,2<i>Z</i>,8<i>E</i>,10<i>E</i>)-1-[(<i>tert</i>-Butyldimethylsilyl)oxy]-6-methyl-2,8,10-dodecatrien-4-one
  作者：Yoshitaka Araki、Toshiro Konoike

  DOI：10.1021/jo970444m

  日期：1997.8.1

  3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, (+)-6-epi-mevinolin (2a) and (+)-6-epi-4a,5-dihydromevinolin (2b), were prepared by combining two nonracemic units, phosphonate 3 and decalin 4, which were prepared from enantiopure 3-substituted pentanedioic acid monoesters 5a and 5b, respectively. Each acid was synthesized from cyclic anhydrides 7a and 7b by diastereoselective ring opening by means of (S)-benzyl mandelate as a common chiral auxiliary. The construction of decalin moiety 4 was accomplished by asymmetric intramolecular Diels-Alder (IMDA) reaction of nonracemic trienone 6 bearing a methyl group as a chiral controller. The IMDA diastereoselectivity of trienone 6 is discussed in terms of the configuration of(E)- and (Z)-dienophiles which are activated by an endogenous carbonyl group. The IMDA reaction of(R)-(Z)-6 under high pressure is highly selective and gives cis-decalins exclusively with preferential formation of 4 over 16. The inhibitory activity of (+)-6-epi-mevinolin (2a) and several analogs against HMG-CoA reductase was compared with mevinolin (1b). (+)-6-epi-Mevinolin (2a) was shown to be half as potent as mevinolin (1b) while (+)-6-epi-4a,5-dihydromevinolin (2b) was as potent as mevinolin.