Benzyl <3S*-(3α,5β,15α,19α,20β)>-1,3,5,6,14,15,16,17,20,21-decahydro-19-methyl-17-oxo-19H-indolo<2,3-a>pyrano<3,4-g>quinolizine-5-carboxylate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: Benzyl <3S*-(3α,5β,15α,19α,20β)>-1,3,5,6,14,15,16,17,20,21-decahydro-19-methyl-17-oxo-19H-indolo<2,3-a>pyrano<3,4-g>quinolizine-5-carboxylate
• 英文别名: benzyl (1S,12R,15R,16R,20R)-16-methyl-18-oxo-17-oxa-3,13-diazapentacyclo[11.8.0.02,10.04,9.015,20]henicosa-2(10),4,6,8-tetraene-12-carboxylate
• 化学式: C₂₇H₂₈N₂O₄
• 分子量: 444.53
• InChiKey: BLLWZBKUIRSRGK-SRIDNHHFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  33
• 可旋转键数：
  4
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  71.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  Benzyl <3S*-(3α,5β,15α,19α,20β)>-1,3,5,6,14,15,16,17,20,21-decahydro-19-methyl-17-oxo-19H-indolo<2,3-a>pyrano<3,4-g>quinolizine-5-carboxylate 在 palladium dihydroxide 氢气 作用下， 以 乙醇 、 乙酸乙酯 为溶剂， 反应 1.5h， 以98%的产率得到<3S*-(3α,5β,15α,19α,20β)>-1,3,5,6,14,15,16,17,20,21-Decahydro-19-methyl-17-oxo-19H-indolo<2,3-a>pyrano<3,4-g>quinolizine-5-carboxylic acid
  参考文献：
  名称：

  Applications of Vinylogous Mannich Reactions. Asymmetric Synthesis of the Heteroyohimboid Alkaloids (-)-Ajmalicine, (+)-19-epi-Ajmalicine, and (-)-Tetrahydroalstonine

  摘要：

  The vinylogous Mannich additions of 1-[(trialkylsilyl)oxy]butadienes to the acyl iminium salt derived from 7 proceeded with a modest degree of stereoselectivity to give a mixture (1.8:1) of 8 and 9. The triene 8 underwent an intramolecular hetero Diels-Alder reaction to give the pentacyclic intermediate 10. Decarboxylation of 10 according to the Barton protocol led to 13, which was then elaborated to (-)-tetrahydroalstonine (1) by a straightforward sequence of reactions. This asymmetric synthesis of 1 required only 10 steps from readily available L-tryptophan. On the other hand, the related vinylogous Mannich addition of a vinyl ketene acetals to 16 were highly stereoselective giving the corresponding trans-substituted hydrocarboline as the only detectable product. Subsequent reaction of this adduct with methyl vinyl ketone followed by cyclization of the intermediate 18 gave the key tetracyclic intermediate 19. Removal of the carboxyl group from the C(5) position of 19 following the Barton procedure gave the ketone 20, which was converted into (-)-ajmalicine (2) in three steps by a known procedure. Alternatively, hydride reduction of the tetracyclic amine 19 gave the alcohol 22, which was subjected to a modified Mitsunobu reaction; selective hydrolysis of the intermediate triester led to the lactone 24. Radical decarboxylation via the Barton procedure gave an intermediate lactone that was converted into (+)-19-epi-ajmalicine (3) in two steps. Removal of the carboxyl presented pathways to both (-)-ajmalicine (2) and (+)-19-epi-ajmalicine (3). Thus, the asymmetric syntheses of 2 and 3 were completed by concise sequences of reactions requiring only 11 and 13 steps, respectively, from D-tryptophan.

  DOI：

  10.1021/jo00115a044
• 作为产物：
  描述：

  Benzyl <3S*-(3α,5β,15α,16β)>-1,3,5,6,14,15,16,17-octahydro-16-<1'(S)-<<(p-nitrophenyl)carbonyl>oxy>ethyl>-15-<(methoxycarbonyl)methyl>indolo<2,3-a>quinolizine-5-carboxylate 在 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 1.0h， 以86%的产率得到Benzyl <3S*-(3α,5β,15α,19α,20β)>-1,3,5,6,14,15,16,17,20,21-decahydro-19-methyl-17-oxo-19H-indolo<2,3-a>pyrano<3,4-g>quinolizine-5-carboxylate
  参考文献：
  名称：

  Applications of Vinylogous Mannich Reactions. Asymmetric Synthesis of the Heteroyohimboid Alkaloids (-)-Ajmalicine, (+)-19-epi-Ajmalicine, and (-)-Tetrahydroalstonine

  摘要：

  The vinylogous Mannich additions of 1-[(trialkylsilyl)oxy]butadienes to the acyl iminium salt derived from 7 proceeded with a modest degree of stereoselectivity to give a mixture (1.8:1) of 8 and 9. The triene 8 underwent an intramolecular hetero Diels-Alder reaction to give the pentacyclic intermediate 10. Decarboxylation of 10 according to the Barton protocol led to 13, which was then elaborated to (-)-tetrahydroalstonine (1) by a straightforward sequence of reactions. This asymmetric synthesis of 1 required only 10 steps from readily available L-tryptophan. On the other hand, the related vinylogous Mannich addition of a vinyl ketene acetals to 16 were highly stereoselective giving the corresponding trans-substituted hydrocarboline as the only detectable product. Subsequent reaction of this adduct with methyl vinyl ketone followed by cyclization of the intermediate 18 gave the key tetracyclic intermediate 19. Removal of the carboxyl group from the C(5) position of 19 following the Barton procedure gave the ketone 20, which was converted into (-)-ajmalicine (2) in three steps by a known procedure. Alternatively, hydride reduction of the tetracyclic amine 19 gave the alcohol 22, which was subjected to a modified Mitsunobu reaction; selective hydrolysis of the intermediate triester led to the lactone 24. Radical decarboxylation via the Barton procedure gave an intermediate lactone that was converted into (+)-19-epi-ajmalicine (3) in two steps. Removal of the carboxyl presented pathways to both (-)-ajmalicine (2) and (+)-19-epi-ajmalicine (3). Thus, the asymmetric syntheses of 2 and 3 were completed by concise sequences of reactions requiring only 11 and 13 steps, respectively, from D-tryptophan.

  DOI：

  10.1021/jo00115a044

文献信息

• Applications of Vinylogous Mannich Reactions. Asymmetric Synthesis of the Heteroyohimboid Alkaloids (-)-Ajmalicine, (+)-19-epi-Ajmalicine, and (-)-Tetrahydroalstonine
  作者：Stephen F. Martin、Cameron W. Clark、Jeffrey W. Corbett

  DOI：10.1021/jo00115a044

  日期：1995.5

  The vinylogous Mannich additions of 1-[(trialkylsilyl)oxy]butadienes to the acyl iminium salt derived from 7 proceeded with a modest degree of stereoselectivity to give a mixture (1.8:1) of 8 and 9. The triene 8 underwent an intramolecular hetero Diels-Alder reaction to give the pentacyclic intermediate 10. Decarboxylation of 10 according to the Barton protocol led to 13, which was then elaborated to (-)-tetrahydroalstonine (1) by a straightforward sequence of reactions. This asymmetric synthesis of 1 required only 10 steps from readily available L-tryptophan. On the other hand, the related vinylogous Mannich addition of a vinyl ketene acetals to 16 were highly stereoselective giving the corresponding trans-substituted hydrocarboline as the only detectable product. Subsequent reaction of this adduct with methyl vinyl ketone followed by cyclization of the intermediate 18 gave the key tetracyclic intermediate 19. Removal of the carboxyl group from the C(5) position of 19 following the Barton procedure gave the ketone 20, which was converted into (-)-ajmalicine (2) in three steps by a known procedure. Alternatively, hydride reduction of the tetracyclic amine 19 gave the alcohol 22, which was subjected to a modified Mitsunobu reaction; selective hydrolysis of the intermediate triester led to the lactone 24. Radical decarboxylation via the Barton procedure gave an intermediate lactone that was converted into (+)-19-epi-ajmalicine (3) in two steps. Removal of the carboxyl presented pathways to both (-)-ajmalicine (2) and (+)-19-epi-ajmalicine (3). Thus, the asymmetric syntheses of 2 and 3 were completed by concise sequences of reactions requiring only 11 and 13 steps, respectively, from D-tryptophan.