(+)-(1S,2S,4aR,6S,8S,8aS)-1-(ethoxycarbonyl)-1,2,4a,5,6,7,8,8a-octahydro-2-methyl-6,8-naphthalenecarbolactone | 116097-23-5

• 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: (+)-(1S,2S,4aR,6S,8S,8aS)-1-(ethoxycarbonyl)-1,2,4a,5,6,7,8,8a-octahydro-2-methyl-6,8-naphthalenecarbolactone
• 英文别名: ethyl (1S,2S,3S,4S,7R,9S)-4-methyl-10-oxo-11-oxatricyclo[7.2.1.02,7]dodec-5-ene-3-carboxylate
• CAS: 116097-23-5
• 化学式: C₁₅H₂₀O₄
• 分子量: 264.321
• InChiKey: VWWOOLRTZKKJLO-RHIYVLOFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  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 水 、 双氧水 、 溴 、 sodium ethanolate 、 三氟乙酸 、 三氟乙酸酐 、 lithium hexamethyldisilazane 作用下， 以 四氯化碳 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 7.92h， 生成 (1R,2R,4aS,6R,8S,8aR)-6-Acetoxy-3,4-dibromo-8-hydroxy-2-methyl-decahydro-naphthalene-1-carboxylic acid ethyl ester
  参考文献：
  名称：

  二氢胃抑素，一种新型的3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂的合成和生物学评估。

  摘要：

  描述了新型羟基化的HMG-CoA还原酶抑制剂二氢他汀（7）的全合成。关键的C-3羟基是通过Baeyer-Villiger反应在甲基酮17上引入的，甲基酮是在三个高产率步骤中从已知的三环内酯12获得的。在分离的酶分析中，二氢西他汀的IC50与美维诺林相似，但在如果使用Hep G2和HES 9细胞系进行细胞分析，则二氢胃抑素的效力要差得多。在两个细胞系之间没有观察到选择性。

  DOI：

  10.1021/jm00096a015
• 作为产物：
  描述：

  (3S,5S)-3-<2'(E),4'(E)-hexadienyl>-5-<2-(ethoxycarbonyl)-(E)-ethenyl>tetrahydrofuran-2-one 在 2,6-二叔丁基-4-甲基苯酚 作用下， 以 均三甲苯 为溶剂， 反应 264.0h， 以73%的产率得到(+)-(1S,2S,4aR,6S,8S,8aS)-1-(ethoxycarbonyl)-1,2,4a,5,6,7,8,8a-octahydro-2-methyl-6,8-naphthalenecarbolactone
  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

• Putative Diels−Alder-Catalyzed Cyclization during the Biosynthesis of Lovastatin
  作者：David J. Witter、John C. Vederas

  DOI：10.1021/jo952117p

  日期：1996.1.1

  polyketide synthase assembly of the bicyclic core of lovastatin (1) (mevinolin) by Aspergillus terreus MF 4845 was examined via the synthesis of the N-acetylcysteamine (NAC) thioester of [2,11-(13)C(2)]-(E,E,E)-(R)-6-methyldodecatri-2,8,10-enoate (5a). In vitro Diels-Alder cyclization of the corresponding unlabeled NAC ester 5b, ethyl ester 18b, and acid 20b yielded two analogous diastereomers in each

  通过合成[2,11-（-）的N-乙酰半胱胺（NAC）硫辛酸酯，研究了拟由地曲霉MF 4845合成的洛伐他汀（1）（mevinolin）双环核的聚酮化合物合酶组装过程中发生的Diels-Alder环化反应。 13）C（2）]-（E，E，E）-（R）-6-甲基十二碳三烯基2,8,10-烯酸酯（5a）。在热或路易斯酸催化条件下，相应的未标记NAC酯5b，乙酯18b和酸20b的体外Diels-Alder环化在每种情况下均产生两个类似的非对映异构体。硫酯5的反应在22℃下在水性介质中容易进行。对于18b，一种产品是（1R，2R，4aS，6R，8aR）-1,2,4a，5,6,7,8,8a-八氢-2,6-二甲基萘-1-羧酸乙酯（ 30）（内基产物），另一个是顺式稠合乙基（1R，2S，4aR，6R，8aR）-1,2,4a，5,6,7,8,8a-八氢-2，6-二甲基萘-1-甲酸（31）（exo产物）。通过转
• The enantiospecific synthesis of dihydromevinolin from L-glutamic acid
  作者：Alan H. Davidson、Andrew J. Jones、Chris D. Floyd、Christopher Lewis、Peter L. Myers

  DOI：10.1039/c39870001786

  日期：——

  An enantiospecific synthesis of the diol (3), a compound which has previously been converted into dihydromevinolin, is reported.

  据报道二醇（3）的对映体特异性合成，该化合物先前已被转化为二氢甲基乙烯基。
• 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.
• The synthesis and biological evaluation of dihydroeptastatin, a novel inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase
  作者：Elisabeth A. Bone、Alan H. Davidson、Christopher N. Lewis、Richard S. Todd

  DOI：10.1021/jm00096a015

  日期：1992.9

  The total synthesis of the novel hydroxylated HMG-CoA reductase inhibitor dihydroeptastatin (7) is described. The key C-3 hydroxyl group is introduced via a Baeyer-Villiger reaction on the methyl ketone 17 which is obtained in three high-yielding steps from the known tricyclic lactone 12. In an isolated enzyme assay dihydroeptastatin had a similar IC50 to mevinolin but in cellular assays using Hep

  描述了新型羟基化的HMG-CoA还原酶抑制剂二氢他汀（7）的全合成。关键的C-3羟基是通过Baeyer-Villiger反应在甲基酮17上引入的，甲基酮是在三个高产率步骤中从已知的三环内酯12获得的。在分离的酶分析中，二氢西他汀的IC50与美维诺林相似，但在如果使用Hep G2和HES 9细胞系进行细胞分析，则二氢胃抑素的效力要差得多。在两个细胞系之间没有观察到选择性。