(+/-)-2,3-didehydro-1-<(p-methoxyphenyl)sulfonyl>aspidospermidin-10-one | 85924-18-1

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 冬青素型生物碱
• 英文名称: (+/-)-2,3-didehydro-1-<(p-methoxyphenyl)sulfonyl>aspidospermidin-10-one
• 英文别名: (1S,12R,19R)-12-ethyl-8-(4-methoxyphenyl)sulfonyl-8,16-diazapentacyclo[10.6.1.01,9.02,7.016,19]nonadeca-2,4,6,9-tetraen-17-one
• CAS: 85924-18-1
• 化学式: C₂₆H₂₈N₂O₄S
• 分子量: 464.585
• InChiKey: YAZBMYBWEHVMOA-TWJOJJKGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  33
• 可旋转键数：
  4
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  75.3
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (+/-)-2,3-didehydro-1-<(p-methoxyphenyl)sulfonyl>aspidospermidin-10-one 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 48.0h， 以68%的产率得到(+)-aspidospermidine
  参考文献：
  名称：

  Stereocontrolled Elaboration of Quaternary Carbon Centers through the Asymmetric Michael Reaction Using Chiral Imines: Enantioselective Synthesis of (+)-Aspidospermidine

  摘要：

  An enantioselective synthesis of (+)-aspidospermidine (1b) has been developed. The key strategic element was the stereocontrolled elaboration of quaternary carbon centers through the asymmetric Michael reaction, using chiral imines under neutral conditions. Thus, addition of imine 21, prepared from 2-ethylcyclohexanone and (R)-1-phenylethylamine, to methyl acrylate, led to cyclohexanone (S)-20 with 90% stereoselectivity (Scheme 3). The latter compound was then converted in six steps into dione 19 (Chart 6). Synthesis of [ABC]-type tricyclic carbazolone 18 was next accomplished, starting from this dione, by using the indole synthesis protocol developed by Suzuki. Critical to the success of this approach was the evolution, after extensive experimentation, of an efficient sequence for assembling D ring to carbazolone 18, having controlled during the events the ''natural'', cis CD ring junction. Thus, treatment of alcohol 57 with trifluoroacetic acid led to tetracycle 58 obtained as a single isomer with 94% yield (Chart 10). The intramolecular capture of a putative intermediary iminium ion, as illustrated in 52, by the carbamate nitrogen atom of 57 has been evoked to rationalize the observed stereoselectivity. The strategy we have adopted for the construction of the fifth E ring of 1b was in fact the methodology proposed by Magnus, based on an intramolecular Pummerer rearrangement (17 --> 59). Thus, synthesis of (+)-aspidospermidine (1b) has been achieved by a linear sequence of 22 chemical operations, starting with 2-ethylcyclohexanone, with an overall yield of 2.7%.

  DOI：

  10.1021/jo00088a008
• 作为产物：
  描述：

  (+)-(R)-1-Ethyl-2-oxo-4-(phenylthio)-3-cyclohexene-1-propanoic acid methyl ester 在 盐酸 、 4-二甲氨基吡啶 、 sodium hydroxide 、 sodium tetrahydroborate 、 sodium periodate 、 copper(l) iodide 、 sodium azide 、 W-2 Raney nickel 、 双氧水 、 sodium methylate 、 四丁基硫酸氢铵 、 sodium hydride 、 三乙基硼氢化锂 、 对甲苯磺酸 、 三乙胺 、 三苯基膦 、 三氟乙酸 、 三氟乙酸酐 作用下， 以 四氢呋喃 、 甲醇 、 六甲基磷酰三胺 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 104.33h， 生成 (+/-)-2,3-didehydro-1-<(p-methoxyphenyl)sulfonyl>aspidospermidin-10-one
  参考文献：
  名称：

  Stereocontrolled Elaboration of Quaternary Carbon Centers through the Asymmetric Michael Reaction Using Chiral Imines: Enantioselective Synthesis of (+)-Aspidospermidine

  摘要：

  An enantioselective synthesis of (+)-aspidospermidine (1b) has been developed. The key strategic element was the stereocontrolled elaboration of quaternary carbon centers through the asymmetric Michael reaction, using chiral imines under neutral conditions. Thus, addition of imine 21, prepared from 2-ethylcyclohexanone and (R)-1-phenylethylamine, to methyl acrylate, led to cyclohexanone (S)-20 with 90% stereoselectivity (Scheme 3). The latter compound was then converted in six steps into dione 19 (Chart 6). Synthesis of [ABC]-type tricyclic carbazolone 18 was next accomplished, starting from this dione, by using the indole synthesis protocol developed by Suzuki. Critical to the success of this approach was the evolution, after extensive experimentation, of an efficient sequence for assembling D ring to carbazolone 18, having controlled during the events the ''natural'', cis CD ring junction. Thus, treatment of alcohol 57 with trifluoroacetic acid led to tetracycle 58 obtained as a single isomer with 94% yield (Chart 10). The intramolecular capture of a putative intermediary iminium ion, as illustrated in 52, by the carbamate nitrogen atom of 57 has been evoked to rationalize the observed stereoselectivity. The strategy we have adopted for the construction of the fifth E ring of 1b was in fact the methodology proposed by Magnus, based on an intramolecular Pummerer rearrangement (17 --> 59). Thus, synthesis of (+)-aspidospermidine (1b) has been achieved by a linear sequence of 22 chemical operations, starting with 2-ethylcyclohexanone, with an overall yield of 2.7%.

  DOI：

  10.1021/jo00088a008

文献信息

• Pentacyclic systems of indole alkaloids. Formation of the C11-C12 bond. Two syntheses of (.+-.)-aspidospermidine
  作者：Timothy Gallagher、Philip Magnus、John C. Huffman

  DOI：10.1021/ja00352a038

  日期：1983.7
• Stereocontrolled Elaboration of Quaternary Carbon Centers through the Asymmetric Michael Reaction Using Chiral Imines: Enantioselective Synthesis of (+)-Aspidospermidine
  作者：Didier Desmaeele、Jean d'Angelo

  DOI：10.1021/jo00088a008

  日期：1994.5

  An enantioselective synthesis of (+)-aspidospermidine (1b) has been developed. The key strategic element was the stereocontrolled elaboration of quaternary carbon centers through the asymmetric Michael reaction, using chiral imines under neutral conditions. Thus, addition of imine 21, prepared from 2-ethylcyclohexanone and (R)-1-phenylethylamine, to methyl acrylate, led to cyclohexanone (S)-20 with 90% stereoselectivity (Scheme 3). The latter compound was then converted in six steps into dione 19 (Chart 6). Synthesis of [ABC]-type tricyclic carbazolone 18 was next accomplished, starting from this dione, by using the indole synthesis protocol developed by Suzuki. Critical to the success of this approach was the evolution, after extensive experimentation, of an efficient sequence for assembling D ring to carbazolone 18, having controlled during the events the ''natural'', cis CD ring junction. Thus, treatment of alcohol 57 with trifluoroacetic acid led to tetracycle 58 obtained as a single isomer with 94% yield (Chart 10). The intramolecular capture of a putative intermediary iminium ion, as illustrated in 52, by the carbamate nitrogen atom of 57 has been evoked to rationalize the observed stereoselectivity. The strategy we have adopted for the construction of the fifth E ring of 1b was in fact the methodology proposed by Magnus, based on an intramolecular Pummerer rearrangement (17 --> 59). Thus, synthesis of (+)-aspidospermidine (1b) has been achieved by a linear sequence of 22 chemical operations, starting with 2-ethylcyclohexanone, with an overall yield of 2.7%.