(1S,2S,4aR,6S,8S,8aS)-1,2,4a,5,6,7,8,8a-octahydro-8-(hydroxymethyl)-7-methyl-3-<(E)-prop-1-enyl>-1-naphthalenyl 2,2-dimethylbutyrate | 143633-52-7

• 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: (1S,2S,4aR,6S,8S,8aS)-1,2,4a,5,6,7,8,8a-octahydro-8-(hydroxymethyl)-7-methyl-3-<(E)-prop-1-enyl>-1-naphthalenyl 2,2-dimethylbutyrate
• 英文别名: [(1S,3S,4aR,7S,8S,8aS)-8-(hydroxymethyl)-7-methyl-3-[(E)-prop-1-enyl]-1,2,3,4,4a,7,8,8a-octahydronaphthalen-1-yl] 2,2-dimethylbutanoate
• CAS: 143633-52-7
• 化学式: C₂₁H₃₄O₃
• 分子量: 334.499
• InChiKey: SNXFYYUEPYMGPN-MPDGVJHPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.76
• 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：

  (1S,2S,4aR,6S,8S,8aS)-1,2,4a,5,6,7,8,8a-octahydro-8-(hydroxymethyl)-7-methyl-3-<(E)-prop-1-enyl>-1-naphthalenyl 2,2-dimethylbutyrate 在 重铬酸吡啶 、 3 A molecular sieve 、 溶剂黄146 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以84%的产率得到(1S,3S,4aR,7S,8S,8aS)-8-formyl-1,2,3,4,4a,7,8,8a-octahydro-7-methyl-3-<(E)-prop-1-enyl>-1-naphthalenyl 2,2-dimethylbutyrate
  参考文献：
  名称：

  Total synthesis of dihydromevinolin and a series of related 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors

  摘要：

  The natural product dihydromevinolin, 2, and a series of structurally related 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, 3-6, have been synthesized. The key features are an intramolecular Diels-Alder reaction to form a functionalized decalin skeleton with six asymmetric centers in a stereocontrolled manner, the selective manipulation of the functional groups, and an improved method for the introduction and elaboration of the delta-lactone portion. Analogue 6 was approximately 10-fold more potent than 2 as an inhibitor and was produced in multigram quantities.

  DOI：

  10.1021/jo00047a011
• 作为产物：
  描述：

  (+)-(1S,2S,4aR,6S,8S,8aS)-1-(ethoxycarbonyl)-1,2,4a,5,6,7,8,8a-octahydro-2-methyl-6,8-naphthalenecarbolactone 在 吡啶 、 chromium dichloride 、 4-二甲氨基吡啶 、 重铬酸吡啶 、 3 A molecular sieve 、 sodium hexamethyldisilazane 、 三乙基硼氢化锂 、 溶剂黄146 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 49.33h， 生成 (1S,2S,4aR,6S,8S,8aS)-1,2,4a,5,6,7,8,8a-octahydro-8-(hydroxymethyl)-7-methyl-3-<(E)-prop-1-enyl>-1-naphthalenyl 2,2-dimethylbutyrate
  参考文献：
  名称：

  Total synthesis of dihydromevinolin and a series of related 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors

  摘要：

  The natural product dihydromevinolin, 2, and a series of structurally related 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, 3-6, have been synthesized. The key features are an intramolecular Diels-Alder reaction to form a functionalized decalin skeleton with six asymmetric centers in a stereocontrolled manner, the selective manipulation of the functional groups, and an improved method for the introduction and elaboration of the delta-lactone portion. Analogue 6 was approximately 10-fold more potent than 2 as an inhibitor and was produced in multigram quantities.

  DOI：

  10.1021/jo00047a011

文献信息

• [EN] SYNTHETIC PROCESS
  申请人：BRITISH BIO-TECHNOLOGY LIMITED

  公开号：WO1992020644A1

  公开（公告）日：1992-11-26

  (EN) Compounds of general formula (I), wherein R1 represents a C1-8 alkyl group; R2 represents C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C3-8 cycloalkyl (C1-8)alkyl, C1-8 hydroxyalkyl, C1-8 alkylthio, phenyl, substituted phenyl or C1-6 alkyl substituted with an optionally substituted phenyl group. R3 represents C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, CO2(C1-8)alkyl, CO2(C2-8)alkenyl, C1-8 alkylthio, (C1-2)alkyl CO2(C1-8)alkyl or C1-8 aldehydoalkyl where the aldehyde function is protected by a suitable protecting group (for example, an acetal such as a dimethyl acetal); R4 represents a hydrogen atom, C1-8 alkyl or C2-8 alkenyl; Z represents a group (CH2)n or a branched alkyl chain; n is 0 to 8; and each of a, b and c is independently a single or double bond; can be prepared relatively easily and in good yield at room temperature by reacting a compound of general formula (II), wherein R2, R3, R4, Z, a, b and c are as defined in general formula (I); with a compound of general formula (III): CHI2R1 wherein R1 is as defined in general formula (I); in the presence of metal ions such as chromium (II) ions. The severe conditions of the Wittig reaction can therefore be avoided. Compounds of formula (I) are useful intermediates in the synthesis of mevinic acids, which are potent inhibitors of HMG-CoA reductase and which are useful in the treatment of hypocholesterolaemia and hyperlipidaemia.(FR) Composé de la formule générale (i) dans laquelle R1 représente un groupe alkyle C1-8; R2 représente alkyle C1-8, alcényle C2-8, alkynyle C2-8, cycloalkyle C3-8, alkyle C1-8, hydroxyalkyle C1-8, alkylthio C1-8, phényle, phényle substitué ou alkyle C1-6 substitué par un groupe phényle éventuellement substitué. R3 représente alkyle C1-8 alcényle C2-8, alkynyle C2-8, CO2alkyle(C1-8), CO2alcényle(C2-8), alkylthio C1-8, alkyle (C1-2) CO2alkyle(C1-8) ou aldéhydoalkyle C1-8 où la fonction aldéhyde est protégée par un groupe de protection approprié (par exemple un acétal tel qu'un acétal diméthyle); R4 représente un atome d'hydrogène, alkyle C1-8 ou alcényle C2-8; Z représente un groupe (CH2)n ou une chaîne alkyle ramifiée; n représente 0 à 8; et chacun de a, b et c représente indépendamment une liaison simple ou une liaison double. Ces composés peuvent être préparés relativement facilement et avec un bon rendement à température ambiante par la réaction d'un composé de la formule générale (II), dans laquelle R2, R3, R4, Z, a, b et c sont représentés tels que définis dans la formule générale (I), avec un composé de la formule générale CHI2R1 dans laquelle R1 est représenté tel que défini dans la formule générale (I), en présence d'ions métalliques tels que des ions de chrome (II). Les conditions sévères de la réaction Wittig peuvent être ainsi évitées. Des composés de la formule (I) sont des intermédiaires utiles dans la synthèse d'acides méviniques qui sont de puissants inhibiteurs de la HMG-CoA réductase, ainsi que dans le traitement de l'hypocholestérolémie et de l'hyperlipidémie.
• Total synthesis of dihydromevinolin and a series of related 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors
  作者：Christopher M. Blackwell、Alan H. Davidson、Steven B. Launchbury、Christopher N. Lewis、Elizabeth M. Morrice、Maxwell M. Reeve、Jonathon A. R. Roffey、Andrew S. Tipping、Richard S. Todd

  DOI：10.1021/jo00047a011

  日期：1992.10

  The natural product dihydromevinolin, 2, and a series of structurally related 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, 3-6, have been synthesized. The key features are an intramolecular Diels-Alder reaction to form a functionalized decalin skeleton with six asymmetric centers in a stereocontrolled manner, the selective manipulation of the functional groups, and an improved method for the introduction and elaboration of the delta-lactone portion. Analogue 6 was approximately 10-fold more potent than 2 as an inhibitor and was produced in multigram quantities.