6(R)-[2-[8(S)-(2(S)-methylbutyryloxy)-2(S),6(S)-dimethyl-1,2,6,7,8,8a(R)-hexahydronaphthyl-1(S)]ethyl]-4(R)-hydroxy-3,4,5,6 tetrahydro-2H-pyran-2-one | 123049-73-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酯类
• 英文名称: 6(R)-[2-[8(S)-(2(S)-methylbutyryloxy)-2(S),6(S)-dimethyl-1,2,6,7,8,8a(R)-hexahydronaphthyl-1(S)]ethyl]-4(R)-hydroxy-3,4,5,6 tetrahydro-2H-pyran-2-one
• 英文别名: [(1S,3S,7S,8S,8aR)-8-[2-[(2R,4R)-4-hydroxy-6-oxooxan-2-yl]ethyl]-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl] (2S)-2-methylbutanoate
• CAS: 123049-73-0
• 化学式: C₂₄H₃₆O₅
• 分子量: 404.547
• InChiKey: PCZOHLXUXFIOCF-QEAVJYPTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  72.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 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 吡啶 、 4-二甲氨基吡啶 、 sodium hydroxide 、 sodium tetrahydroborate 、 Wilkinson's catalyst 、 草酰氯 、 二乙基甲氧基硼烷 、 氢氟酸 、 四丁基氟化铵 、 双氧水 、 溴 、 L-Selectride 、 caesium carbonate 、 溶剂黄146 、 二甲基亚砜 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 作用下， 以 四氢呋喃 、 吡啶 、 氯仿 、 异丙醇 、 乙腈 、 苯 为溶剂， 反应 30.08h， 生成 6(R)-[2-[8(S)-(2(S)-methylbutyryloxy)-2(S),6(S)-dimethyl-1,2,6,7,8,8a(R)-hexahydronaphthyl-1(S)]ethyl]-4(R)-hydroxy-3,4,5,6 tetrahydro-2H-pyran-2-one
  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

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

  公开号：EP0306264A2

  公开（公告）日：1989-03-08

  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):

  新型 3-羟基-3-甲基戊二酰辅酶 A（HMG-CoA）还原酶抑制剂可用作抗胆固醇药物，其结构通式（I）和（II）如下：
• A METHOD OF FERMENTATION PREPARATION OF LOVASTATIN BY AN $i(ASPERGILLUS TERREUS) STRAIN AND THE STRAIN FOR PERFORMING THE METHOD
  申请人：Biotika A.S.

  公开号：EP1047768A1

  公开（公告）日：2000-11-02
• [EN] A METHOD OF FERMENTATION PREPARATION OF LOVASTATIN BY AN ASPERGILLUS TERREUS STRAIN AND THE STRAIN FOR PERFORMING THE METHOD<br/>[FR] PROCEDE DE PREPARATION PAR FERMENTATION DE LOVASTINE A L'AIDE D'UNE SOUCHE D'ASPERGILLUS TERREUS ET SOUCHE UTILISEE POUR METTRE EN OEUVRE LE PROCEDE
  申请人：BIOTIKA A.S.

  公开号：WO1999019458A1

  公开（公告）日：1999-04-22

  (EN) The new strain $i(Aspergillus terreus) CCM 8236 was obtained by means of classic mutagenesis procedures. The process of aerobic fermentation of lovastatin by the strain of $i(Aspergillus terreus) CCM 8236 in the form of acid in a submersion culture in a laboratory scale is described. The inoculum was prepared in a broth having low pH value. The mixture of glucose and lactose (at the ratio of 1:22) at the high concentration and Pharmamedia is used as the carbon and nitrogen source, respectively. The strain produced more than 2000 mg/l of lovastatin during 170 hours in the above-mentioned broth.(FR) On a produit la nouvelle souche $i(Aspergillus terreus) CCM 8236 au moyen de procédures de mutagénèse classiques. On décrit le procédé de fermentation aérobie de lovastine à l'aide de la souche d'$i(Aspergillus terreus) CCM 8236 sous forme d'acide dans une culture en submersion réalisée dans une bascule de laboratoire. L'inoculat a été préparé dans un bouillon de culture ayant un faible pH. Le mélange de glucose et de lactose (suivant le rapport de 1:22) à une concentration élevée et le Pharmamédia est utilisé respectivement en tant que source de carbone et d'azote. La souche a produit plus de 2000 mg par litre de lovastine pendant 170 heures dans le bouillon de culture mentionné ci-dessus.
• 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.