(-)-methyl (2S,3aS,5R,11bR)-3-benzyl-2,3,3a,4,5,7-hexahydro-3,5-ethano-12-(Z)-<(methoxycarbonyl)methylene>-1H-pyrrolo<2,3-d>carbazole-6-carboxylates | 219650-30-3

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 马钱子生物碱
• 英文名称: (-)-methyl (2S,3aS,5R,11bR)-3-benzyl-2,3,3a,4,5,7-hexahydro-3,5-ethano-12-(Z)-<(methoxycarbonyl)methylene>-1H-pyrrolo<2,3-d>carbazole-6-carboxylates
• 英文别名: methyl (1R,11S,12Z,17S)-12-(2-methoxy-2-oxoethylidene)-8,14-diazapentacyclo[9.5.2.01,9.02,7.014,17]octadeca-2,4,6,9-tetraene-10-carboxylate
• CAS: 219650-30-3
• 化学式: C₂₁H₂₂N₂O₄
• 分子量: 366.417
• InChiKey: OOYRKRPZZUSSGP-RAJGEZMASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  67.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (-)-methyl (2S,3aS,5R,11bR)-3-benzyl-2,3,3a,4,5,7-hexahydro-3,5-ethano-12-(Z)-<(methoxycarbonyl)methylene>-1H-pyrrolo<2,3-d>carbazole-6-carboxylates 在 三氟化硼乙醚 、 二异丁基氢化铝 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以65%的产率得到(-)-methyl (2S,3aS,5R,11bR)-3-benzyl-2,3,3a,4,5,7-hexahydro-3,5-ethano-12-(Z)-<(hydroxymethyl)methylene>-1H-pyrrolo<2,3-d>carbazole-6-carboxylates
  参考文献：
  名称：

  Syntheses of Strychnan- and Aspidospermatan-Type Alkaloids. 10. An Enantioselective Synthesis of (−)-Strychnine through the Wieland−Gumlich Aldehyde

  摘要：

  Condensations of L-tryptophan-derived 2-[(methoxycarbonyl)methyl]-3-[2(S)-(benzyloxycarbonyl)- 2-(N-b-benzylamino)ethyl]indole (6) with 4,4-dimethoxyacrolein or with 2,4-hexadienal, followed by removal of the tryptophanyl ester function, respectively gave the tetracyclic acetal (-)-methyl (2S, 3aS,5R,11bR)-3-benzyl-2,3,3a,4,5,7-hexahydro-5-(dimethoxymethyl)-1H-pyrrolo[2,3-d]carbazole-6-carboxylate (10) or the tetracyclic olefin (-)-methyl (2S,3aS,5R,11bR)-3-benzyl-2,3,3a,4,5,7-hexahydro-5-(1-propenyl)-1H-pyrrolo[2,3-d]carbazole-6-carboxylate (14). Their respective hydrolysis or oxidation provided, enantioselectively, the tetracyclic aldehyde (-)-methyl (2S,3aS,5R,11bR)3-benzyl-2,3,3a,4,5,7-hexahydro-5-formyl-1H-pyrrolo[2,3-d]carbazole-6-carboxylate (5). Its reaction with tri-n-butyl-1-(ethoxy)ethoxymethyltin and n-butyllithium, followed by oxidation of the resultant alcohol (-)-methyl (2S,3aS,5R,11bR)-3-benzyl-2,3,3a,4,5,7-hexahydro-5-(1 xi-hydroxy-2-((1-ethoxy-ethoxy))ethyl-1H-pyrrolo[2,3-d]carbazole-6-carboxylate (16) and cyclization furnished the pentacyclic ketone (-)-methyl (2S,3aS,5R,11bR)-3-benzyl-2,3,3a,4,5,7-hexahydro-3,5-ethano-12-oxo-1H-pyrrolo-2,3-d]carbazole-6-carboxylate (15). A Horner-Emmons condensation led to the unsaturated esters (-)-methyl (2S,3aS,5R,11bR)-3-benzyl-2,3,3a,4,5,7-hexahodro-3,5-ethano-12-(E and Z)-[(methoxycarbonyl)-methylene]-1H-pyrrolo[2,3-d]carbazole-6-carboxylates(19 and 20) with 17:1 E/Z selectivity. Reductions of the ester and vinylogous urethane functions in 19 led to the Wieland-Gumlich aldehyde 3 as a 6:1 anomeric hemiacetal mixture. Its condensation with malonic acid provided (-)-strychnine (1) in 5.3% overall yield and 14 steps from the tryptophan derivative 6.

  DOI：

  10.1021/jo9813989
• 作为产物：
  描述：

  methyl N-benzyl-L-tryptophanate 在 palladium dichloride 4-二甲氨基吡啶 、 potassium osmate(VI) 、 N-氯代丁二酰亚胺 、 正丁基锂 、 钾硼氢 、 potassium metaperiodate 、 potassium hexamethyldisilazane 、 二甲基硫 、 三氟甲磺酸三甲基硅酯 、 氨 、 水 、 氢气 、 对甲苯磺酸 、 三乙胺 、 N,N-二异丙基乙胺 、 对苯二酚 、 苯甲酸 、 三氟乙酸酐 、 lithium chloride 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 正己烷 、 二氯甲烷 、 水 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 、 甲苯 、 苯 为溶剂， -78.0~135.0 ℃ 、101.33 kPa 条件下， 反应 154.17h， 生成 (-)-methyl (2S,3aS,5R,11bR)-3-benzyl-2,3,3a,4,5,7-hexahydro-3,5-ethano-12-(Z)-<(methoxycarbonyl)methylene>-1H-pyrrolo<2,3-d>carbazole-6-carboxylates
  参考文献：
  名称：

  Syntheses of Strychnan- and Aspidospermatan-Type Alkaloids. 10. An Enantioselective Synthesis of (−)-Strychnine through the Wieland−Gumlich Aldehyde

  摘要：

  Condensations of L-tryptophan-derived 2-[(methoxycarbonyl)methyl]-3-[2(S)-(benzyloxycarbonyl)- 2-(N-b-benzylamino)ethyl]indole (6) with 4,4-dimethoxyacrolein or with 2,4-hexadienal, followed by removal of the tryptophanyl ester function, respectively gave the tetracyclic acetal (-)-methyl (2S, 3aS,5R,11bR)-3-benzyl-2,3,3a,4,5,7-hexahydro-5-(dimethoxymethyl)-1H-pyrrolo[2,3-d]carbazole-6-carboxylate (10) or the tetracyclic olefin (-)-methyl (2S,3aS,5R,11bR)-3-benzyl-2,3,3a,4,5,7-hexahydro-5-(1-propenyl)-1H-pyrrolo[2,3-d]carbazole-6-carboxylate (14). Their respective hydrolysis or oxidation provided, enantioselectively, the tetracyclic aldehyde (-)-methyl (2S,3aS,5R,11bR)3-benzyl-2,3,3a,4,5,7-hexahydro-5-formyl-1H-pyrrolo[2,3-d]carbazole-6-carboxylate (5). Its reaction with tri-n-butyl-1-(ethoxy)ethoxymethyltin and n-butyllithium, followed by oxidation of the resultant alcohol (-)-methyl (2S,3aS,5R,11bR)-3-benzyl-2,3,3a,4,5,7-hexahydro-5-(1 xi-hydroxy-2-((1-ethoxy-ethoxy))ethyl-1H-pyrrolo[2,3-d]carbazole-6-carboxylate (16) and cyclization furnished the pentacyclic ketone (-)-methyl (2S,3aS,5R,11bR)-3-benzyl-2,3,3a,4,5,7-hexahydro-3,5-ethano-12-oxo-1H-pyrrolo-2,3-d]carbazole-6-carboxylate (15). A Horner-Emmons condensation led to the unsaturated esters (-)-methyl (2S,3aS,5R,11bR)-3-benzyl-2,3,3a,4,5,7-hexahodro-3,5-ethano-12-(E and Z)-[(methoxycarbonyl)-methylene]-1H-pyrrolo[2,3-d]carbazole-6-carboxylates(19 and 20) with 17:1 E/Z selectivity. Reductions of the ester and vinylogous urethane functions in 19 led to the Wieland-Gumlich aldehyde 3 as a 6:1 anomeric hemiacetal mixture. Its condensation with malonic acid provided (-)-strychnine (1) in 5.3% overall yield and 14 steps from the tryptophan derivative 6.

  DOI：

  10.1021/jo9813989

文献信息

• Syntheses of Strychnan- and Aspidospermatan-Type Alkaloids. 10. An Enantioselective Synthesis of (−)-Strychnine through the Wieland−Gumlich Aldehyde
  作者：Martin E. Kuehne、Feng Xu

  DOI：10.1021/jo9813989

  日期：1998.12.1

  Condensations of L-tryptophan-derived 2-[(methoxycarbonyl)methyl]-3-[2(S)-(benzyloxycarbonyl)- 2-(N-b-benzylamino)ethyl]indole (6) with 4,4-dimethoxyacrolein or with 2,4-hexadienal, followed by removal of the tryptophanyl ester function, respectively gave the tetracyclic acetal (-)-methyl (2S, 3aS,5R,11bR)-3-benzyl-2,3,3a,4,5,7-hexahydro-5-(dimethoxymethyl)-1H-pyrrolo[2,3-d]carbazole-6-carboxylate (10) or the tetracyclic olefin (-)-methyl (2S,3aS,5R,11bR)-3-benzyl-2,3,3a,4,5,7-hexahydro-5-(1-propenyl)-1H-pyrrolo[2,3-d]carbazole-6-carboxylate (14). Their respective hydrolysis or oxidation provided, enantioselectively, the tetracyclic aldehyde (-)-methyl (2S,3aS,5R,11bR)3-benzyl-2,3,3a,4,5,7-hexahydro-5-formyl-1H-pyrrolo[2,3-d]carbazole-6-carboxylate (5). Its reaction with tri-n-butyl-1-(ethoxy)ethoxymethyltin and n-butyllithium, followed by oxidation of the resultant alcohol (-)-methyl (2S,3aS,5R,11bR)-3-benzyl-2,3,3a,4,5,7-hexahydro-5-(1 xi-hydroxy-2-((1-ethoxy-ethoxy))ethyl-1H-pyrrolo[2,3-d]carbazole-6-carboxylate (16) and cyclization furnished the pentacyclic ketone (-)-methyl (2S,3aS,5R,11bR)-3-benzyl-2,3,3a,4,5,7-hexahydro-3,5-ethano-12-oxo-1H-pyrrolo-2,3-d]carbazole-6-carboxylate (15). A Horner-Emmons condensation led to the unsaturated esters (-)-methyl (2S,3aS,5R,11bR)-3-benzyl-2,3,3a,4,5,7-hexahodro-3,5-ethano-12-(E and Z)-[(methoxycarbonyl)-methylene]-1H-pyrrolo[2,3-d]carbazole-6-carboxylates(19 and 20) with 17:1 E/Z selectivity. Reductions of the ester and vinylogous urethane functions in 19 led to the Wieland-Gumlich aldehyde 3 as a 6:1 anomeric hemiacetal mixture. Its condensation with malonic acid provided (-)-strychnine (1) in 5.3% overall yield and 14 steps from the tryptophan derivative 6.