Methyl 7-hydroxy-5-[(2-methylpropan-2-yl)oxycarbonylamino]-1-benzofuran-2-carboxylate | 199280-10-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并呋喃
• 英文名称: Methyl 7-hydroxy-5-[(2-methylpropan-2-yl)oxycarbonylamino]-1-benzofuran-2-carboxylate
• CAS: 199280-10-9
• 化学式: C₁₅H₁₇NO₆
• 分子量: 307.303
• InChiKey: QSMYGORRBUHACU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  98
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  Methyl 7-hydroxy-5-[(2-methylpropan-2-yl)oxycarbonylamino]-1-benzofuran-2-carboxylate 在 N-溴代丁二酰亚胺(NBS) 、 偶氮二异丁腈 、 硫酸 、 三正丁基氢锡 、 sodium hydride 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 苯 为溶剂， 反应 37.0h， 生成 6-O-tert-butyl 2-O-methyl 8-(chloromethyl)-4-phenylmethoxy-7,8-dihydrofuro[3,2-e]indole-2,6-dicarboxylate
  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
• 作为产物：
  描述：

  methyl 7-hydroxy-5-nitro-1-benzofuran-2-carboxylate 在 palladium/alumina 氢气 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 25.0 ℃ 、413.69 kPa 条件下， 反应 28.0h， 生成 Methyl 7-hydroxy-5-[(2-methylpropan-2-yl)oxycarbonylamino]-1-benzofuran-2-carboxylate
  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

• EP1011665A4
  申请人：——

  公开号：EP1011665A4

  公开（公告）日：2001-09-12
• HETEROCYCLIC AGENTS
  申请人：ELI LILLY AND COMPANY

  公开号：EP1011665A1

  公开（公告）日：2000-06-28
• [EN] HETEROCYCLIC AGENTS<br/>[FR] AGENTS HETEROCYCLIQUES
  申请人：ELI LILLY AND COMPANY

  公开号：WO1998040068A1

  公开（公告）日：1998-09-17

  (EN) This inventin relates to heterocyclic antineoplastic agents, including certain substituted furano[3,2-e]-indole-7-carboxylic acid derivatives, as well as to processes for their preparation, pharmaceutical compositions comprising the heterocyclic agents and methods for their use.(FR) La présente invention concerne des agents antinéoplasiques hétérocycliques, parmi lesquels certains dérivés d'acide furano[3,2-e]-indole-7-carboxylique substitué, ainsi que des procédés permettant leur préparation. L'invention se rapporte également à des compositions pharmaceutiques contenant des agents hétérocycliques et des procédés permettant leur utilisation.