(S)-8-Chloromethyl-4-hydroxy-6-(5,6,7-trimethoxy-1H-indole-2-carbonyl)-7,8-dihydro-6H-furo[3,2-e]indole-2-carboxylic acid methyl ester

• 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: (S)-8-Chloromethyl-4-hydroxy-6-(5,6,7-trimethoxy-1H-indole-2-carbonyl)-7,8-dihydro-6H-furo[3,2-e]indole-2-carboxylic acid methyl ester
• 英文别名: methyl (8S)-8-(chloromethyl)-4-hydroxy-6-(5,6,7-trimethoxy-1H-indole-2-carbonyl)-7,8-dihydrofuro[3,2-e]indole-2-carboxylate
• 化学式: C₂₅H₂₃ClN₂O₈
• 分子量: 514.919
• InChiKey: JZNVEWDCJFMIGH-GFCCVEGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  36
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  124
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  5,6,7-三甲氧基-1H-吲哚-2-羧酸 在 palladium on activated charcoal ammonium formate 、 碳酸氢钠 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 23.0h， 生成 (S)-8-Chloromethyl-4-hydroxy-6-(5,6,7-trimethoxy-1H-indole-2-carbonyl)-7,8-dihydro-6H-furo[3,2-e]indole-2-carboxylic acid methyl ester
  参考文献：
  名称：

  Total Synthesis of Seco (+)- and ent-(−)-Oxaduocarmycin SA:  Construction of the (Chloromethyl)indoline Alkylating Subunit by a Novel Intramolecular Aryl Radical Cyclization onto a Vinyl Chloride

  摘要：

  A practical, total synthesis of seco-(+)-oxaduocarmycin 3a, an analogue of the highly cytotoxic natural product, duocarmycin SA (1), is described. The 13-step synthesis features a novel and efficient intramolecular aryl radical cyclization onto a vinyl chloride as a direct entry to the (chloromethyl)indoline alkylating subunit 14. Subsequent resolution, utilizing a preparative Chiralpak AD column, provided enantiomerically pure alkylating subunits 14a and 14b which were elaborated to seco-(+) and ent-(-)-oxaduocarmycins, 3a and 3b, respectively. The natural enantiomer 3a was active at pM concentrations and exhibited 7-50-fold higher potentcy than its enantiomer 3b in in vitro cytotoxicity assays.

  DOI：

  10.1021/jo971880b

文献信息

• Total Synthesis of Seco (+)- and <i>ent</i>-(−)-Oxaduocarmycin SA:  Construction of the (Chloromethyl)indoline Alkylating Subunit by a Novel Intramolecular Aryl Radical Cyclization onto a Vinyl Chloride
  作者：Vinod F. Patel、Sherri L. Andis、Julia K. Enkema、David A. Johnson、Joseph H. Kennedy、Fariborz Mohamadi、Richard M. Schultz、Daniel J. Soose、Michael M. Spees

  DOI：10.1021/jo971880b

  日期：1997.12.1

  A practical, total synthesis of seco-(+)-oxaduocarmycin 3a, an analogue of the highly cytotoxic natural product, duocarmycin SA (1), is described. The 13-step synthesis features a novel and efficient intramolecular aryl radical cyclization onto a vinyl chloride as a direct entry to the (chloromethyl)indoline alkylating subunit 14. Subsequent resolution, utilizing a preparative Chiralpak AD column, provided enantiomerically pure alkylating subunits 14a and 14b which were elaborated to seco-(+) and ent-(-)-oxaduocarmycins, 3a and 3b, respectively. The natural enantiomer 3a was active at pM concentrations and exhibited 7-50-fold higher potentcy than its enantiomer 3b in in vitro cytotoxicity assays.