(8R,8_αS)-8-hydroxy-8-methyl-6-((Z)-2(R)-methyl-hexylidene)octahydroindolizin-7-one | 91550-12-8

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 普米里奥毒素、同普米里奥毒素和别普米里奥毒素
• 英文名称: (8R,8_αS)-8-hydroxy-8-methyl-6-((Z)-2(R)-methyl-hexylidene)octahydroindolizin-7-one
• 英文别名: (6E,8R,8aS)-8-hydroxy-8-methyl-6-[(2R)-2-methylhexylidene]-2,3,5,8a-tetrahydro-1H-indolizin-7-one
• CAS: 91550-12-8
• 化学式: C₁₆H₂₇NO₂
• 分子量: 265.396
• InChiKey: HPKCYGQIIPLKNN-ANXUWLIDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  40.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (8R,8_αS)-8-hydroxy-8-methyl-6-((Z)-2(R)-methyl-hexylidene)octahydroindolizin-7-one 在 tetramethylammonium triacetoxyborohydride 作用下， 以 溶剂黄146 、 丙酮 为溶剂， 以95%的产率得到(+)-allopumiliotoxin 267 A
  参考文献：
  名称：

  对映体纯的2,3-二氢-4-吡啶酮类化合物作为合成中间体：（+）-铝光毒素267A的简明不对称合成。

  摘要：

  [图：见正文]使用对映体纯的二氢吡啶酮结构单元已完成了（+）-allopumillotoxin 267A的简明不对称合成。合成是高度立体选择性的，需要使用容易获得的材料进行10个步骤。

  DOI：

  10.1021/ol0069709
• 作为产物：
  描述：

  (R)-2-Hydroxy-2-(S)-pyrrolidin-2-yl-propionic acid methyl ester 在 titanium(IV) isopropylate 、 异丙基氯化镁 、 碳酸氢钠 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 50.17h， 生成 (8R,8_αS)-8-hydroxy-8-methyl-6-((Z)-2(R)-methyl-hexylidene)octahydroindolizin-7-one
  参考文献：
  名称：

  Efficient and Practical Method for Synthesizing N-Heterocyclic Compounds Using Intramolecular Nucleophilic Acyl Substitution Reactions Mediated by Ti(O-i-Pr)₄/2i-PrMgX Reagent. Synthesis of Quinolones, Pyrroles, Indoles, and Optically Active N-Heterocycles Including Allopumiliotoxin Alkaloid 267A

  摘要：

  Treatment of N-(2- or 3-alkynyl)amino esters with a low-valent titanium reagent diisopropoxy(eta(2)-propene)titanium (1), generated in situ by the reaction of Ti(O-i-Pr)(4) and 2i-PrMgCl, resulted in an intramolecular nucleophilic acyl substitution (INAS) reaction to afford alpha-alkylidene-pyrrolidinones or -piperidinones. Thus, treatment of N-propargyl-anthranilates 5, -indole-2-carboxylates 10, or -pyrrole-2-carboxylates 13 with 1 gave 4-quinolones 7, [1,2-a]indoles, or [1,2-a]pyrroles, respectively. Similarly, N-alkynylated alpha- or beta-amino esters 14 or 15 with 1 afforded N-heterocycles 18 or 19. In the reaction of N-(2- or 3-alkenyl)amino esters with 1, the resulting INAS product underwent intramolecular carbonyl addition (ICA) reaction to afford the N-heterocyclic compounds having a cyclopropanol moiety in good to excellent yields. Thus, the treatment of N-alkenyl-anthranilate 4a, -indole-2-carboxylates 8 and 9, or -pyrrole-2-carboxylates 11 and 12 with 1 gave the corresponding quinoline derivative 6a, [1,2-a]indoles, or [1,2-a]pyrroles, respectively. The optically active N-heterocyclic compounds 20 and 21 were obtained from N-alkenylated alpha- or beta-amino esters 16 or 17. A highly efficient total synthesis of allopumiliotoxin alkaloid 267A has also been accomplished. Thus, the N-propargyl-2[(1-hydroxy-1-methoxycarbonyl)ethyl]pyrrolidine 24 (from L-proline in six steps) reacted with 1 to afford the corresponding indolidinone 25 in 67% yield, which has previously been converted to allopumiliotoxin 267A.

  DOI：

  10.1021/ja970810j

文献信息

• Enantiopure 2,3-Dihydro-4-pyridones as Synthetic Intermediates:  A Concise Asymmetric Synthesis of (+)-Allopumiliotoxin 267A
  作者：Daniel L. Comins、Shenlin Huang、Cheryl L. McArdle、Charles L. Ingalls

  DOI：10.1021/ol0069709

  日期：2001.2.1

  [figure: see text] A concise asymmetric synthesis of (+)-allopumillotoxin 267A has been accomplished using an enantiopure dihydropyridone building block. The synthesis is highly stereoselective and requires 10 steps from readily available material.

  [图：见正文]使用对映体纯的二氢吡啶酮结构单元已完成了（+）-allopumillotoxin 267A的简明不对称合成。合成是高度立体选择性的，需要使用容易获得的材料进行10个步骤。
• The first enantioselective total syntheses of the allopumiliotoxin A alkaloids 267A and 339B
  作者：Steven W. Goldstein、Larry E. Overman、Michael H. Rabinowitz

  DOI：10.1021/jo00030a026

  日期：1992.2

  Short, highly stereocontrolled, asymmetric total synthesis of the title amphibian alkaloids are described. In the first stage the indolizidine ketone 11 is assembled from L-proline in enantiomerically pure form. This short sequence proceeds in five laboratory operations and involves the novel intermediacy of an "unprotected" 2-acylpyrrolidine intermediate (Scheme VII). The (Z)-alkylidene side chain of the target alkaloids are introduced by stereocontrolled aldol dehydration sequences (Schemes X and XI). These enantioselective total syntheses confirm the structures and absolute configurations of the allopumiliotoxins 267A and 339B.
• Enantioselective total synthesis of allopumiliotoxin A alkaloids 267A and 339B
  作者：Larry E. Overman、Steven W. Goldstein

  DOI：10.1021/ja00330a059

  日期：1984.9
• Efficient and Practical Method for Synthesizing N-Heterocyclic Compounds Using Intramolecular Nucleophilic Acyl Substitution Reactions Mediated by Ti(O-<i>i</i>-Pr)₄/2<i>i</i>-PrMgX Reagent. Synthesis of Quinolones, Pyrroles, Indoles, and Optically Active N-Heterocycles Including Allopumiliotoxin Alkaloid 267A
  作者：Sentaro Okamoto、Masayuki Iwakubo、Katsushige Kobayashi、Fumie Sato

  DOI：10.1021/ja970810j

  日期：1997.7.1

  Treatment of N-(2- or 3-alkynyl)amino esters with a low-valent titanium reagent diisopropoxy(eta(2)-propene)titanium (1), generated in situ by the reaction of Ti(O-i-Pr)(4) and 2i-PrMgCl, resulted in an intramolecular nucleophilic acyl substitution (INAS) reaction to afford alpha-alkylidene-pyrrolidinones or -piperidinones. Thus, treatment of N-propargyl-anthranilates 5, -indole-2-carboxylates 10, or -pyrrole-2-carboxylates 13 with 1 gave 4-quinolones 7, [1,2-a]indoles, or [1,2-a]pyrroles, respectively. Similarly, N-alkynylated alpha- or beta-amino esters 14 or 15 with 1 afforded N-heterocycles 18 or 19. In the reaction of N-(2- or 3-alkenyl)amino esters with 1, the resulting INAS product underwent intramolecular carbonyl addition (ICA) reaction to afford the N-heterocyclic compounds having a cyclopropanol moiety in good to excellent yields. Thus, the treatment of N-alkenyl-anthranilate 4a, -indole-2-carboxylates 8 and 9, or -pyrrole-2-carboxylates 11 and 12 with 1 gave the corresponding quinoline derivative 6a, [1,2-a]indoles, or [1,2-a]pyrroles, respectively. The optically active N-heterocyclic compounds 20 and 21 were obtained from N-alkenylated alpha- or beta-amino esters 16 or 17. A highly efficient total synthesis of allopumiliotoxin alkaloid 267A has also been accomplished. Thus, the N-propargyl-2[(1-hydroxy-1-methoxycarbonyl)ethyl]pyrrolidine 24 (from L-proline in six steps) reacted with 1 to afford the corresponding indolidinone 25 in 67% yield, which has previously been converted to allopumiliotoxin 267A.
• Efficient Construction of Stereodefined α-Alkylidene Aza-cycloketones via β-Amino-alkenyllithium: Straightforward and Protection-Free Synthesis of Allopumiliotoxin 267A
  作者：Bing Wang、Zheng Zhong、Guo-Qiang Lin

  DOI：10.1021/ol900452n

  日期：2009.5.7

  Intramolecular nucleophilic acyl substitution of highly functionalized beta-amino-alkenyllithium species provided facile access to alpha-alkylidene aza-cycloketones with defined olefin geometry and rich structural diversity. A concise total synthesis of allopumiliotoxin 267A has been accomplished in 5 steps from 4 featuring this key transformation.