lepadin E

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉类
• 英文名称: lepadin E
• 英文别名: [(2S,3R,4aS,5S,8aR)-5-[(5R)-5-hydroxyoctyl]-2-methyl-1,2,3,4,4a,5,6,7,8,8a-decahydroquinolin-3-yl] (E)-oct-2-enoate
• 化学式: C₂₆H₄₇NO₃
• 分子量: 421.664
• InChiKey: QNAATLGQMSSVEO-HOLZRJRLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.2
• 重原子数：
  30
• 可旋转键数：
  14
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  58.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  (R)-(-)-hexane-1,3-diol 在 palladium on activated charcoal 三丁基膦 、 四丁基氟化铵 、 氢气 、 sodium hexamethyldisilazane 、 碳酸氢钠 、 N,N-二异丙基乙胺 、 间氯过氧苯甲酸 、 三氟乙酸 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 苯 为溶剂， 反应 95.5h， 生成 lepadin E
  参考文献：
  名称：

  Facile Entry to Substituted Decahydroquinoline Alkaloids. Total Synthesis of Lepadins A−E and H

  摘要：

  Condensation of a L-alanine derived delta-bromo-beta-silyloxy-propylamine with 1,3-cyclohexadione followed by alkylative cyclization produces a bicyclic enone. Diastereoselective Pt/C-catalyzed hydrogenation of this enone in HOAc provides a 5-oxo-cis-fused decahydroquinoline. Wittig olefination of this decahydroquinoline and subsequent epimerization of the resulting 5-formyl intermediate gives rise to a 5-beta-formyl decahydroquinoline exclusively. In a parallel procedure, Peterson reaction of this decahydroquinoline and subsequent hydrogenation of the generated 5-exo-olefin provides a decahydroquinoline with a 5-alpha-substituent predominantly. For these two diastereoselective processes, using the intermediates without N-protection as the substrates is essential because the corresponding N-Boc intermediates give poor diastereoselectivity. The intermediate with beta-form side chain is further converted into lepadins A-C via carbon chain elongation, while the intermediate with alpha-form side chain is transformed into lepadins D, E, and H and corresponding 5'-epimers via connection with two sulfones generated from two Sharpless epoxidation products. By comparison of the rotations and NMR data, the stereochemistry of lepadins D, E, and H is assigned as 2S, 3R, 4aS, 5S, 8aR, 5'R.

  DOI：

  10.1021/jo061070c

文献信息

• A Flexible Approach to the Synthesis of Type II and III Lepadin Alkaloids
  作者：Xiaochuan Chen、Yue Hu、He Gu、Yuanliang Jia、Guiyin Luo

  DOI：10.1055/a-1681-4067

  日期：2022.3

  A flexible approach to both type II and III lepadin alkaloids is developed for the first time. A key Diels–Alder reaction based on a novel chiral ketolactone dienophile is employed to obtain the desirable all-cis-trisubstituted cyclohexene with excellent regio- and stereoselectivity. As the subsequent closure of the piperidine ring is devised at the N1 and C2 position via an intramolecular nucleophilic

  首次开发了针对 II 型和 III 型lepadin 生物碱的灵活方法。采用基于新型手性酮内酯亲二烯体的关键 Diels-Alder 反应来获得具有优异区域和立体选择性的理想全顺式三取代环己烯。由于哌啶环的后续闭合是通过分子内亲核胺化在 N1 和 C2 位置设计的，因此可以从常见的中间体方便地获得在 C2 处具有相反构型的两种立体化学类型的 lepadin 框架。通过该方法，lepadins D、E（II 型）和 F（III 型）是由 L-乳酸乙酯立体选择性合成的。
• Total Synthesis of Lepadins B, D, E, and H; Determination of the Configuration of the Latter Three Alkaloids
  作者：Xiaotao Pu、Dawei Ma

  DOI：10.1002/anie.200460128

  日期：2004.8.13
• Facile Entry to Substituted Decahydroquinoline Alkaloids. Total Synthesis of Lepadins A−E and H
  作者：Xiaotao Pu、Dawei Ma

  DOI：10.1021/jo061070c

  日期：2006.8.1

  Condensation of a L-alanine derived delta-bromo-beta-silyloxy-propylamine with 1,3-cyclohexadione followed by alkylative cyclization produces a bicyclic enone. Diastereoselective Pt/C-catalyzed hydrogenation of this enone in HOAc provides a 5-oxo-cis-fused decahydroquinoline. Wittig olefination of this decahydroquinoline and subsequent epimerization of the resulting 5-formyl intermediate gives rise to a 5-beta-formyl decahydroquinoline exclusively. In a parallel procedure, Peterson reaction of this decahydroquinoline and subsequent hydrogenation of the generated 5-exo-olefin provides a decahydroquinoline with a 5-alpha-substituent predominantly. For these two diastereoselective processes, using the intermediates without N-protection as the substrates is essential because the corresponding N-Boc intermediates give poor diastereoselectivity. The intermediate with beta-form side chain is further converted into lepadins A-C via carbon chain elongation, while the intermediate with alpha-form side chain is transformed into lepadins D, E, and H and corresponding 5'-epimers via connection with two sulfones generated from two Sharpless epoxidation products. By comparison of the rotations and NMR data, the stereochemistry of lepadins D, E, and H is assigned as 2S, 3R, 4aS, 5S, 8aR, 5'R.