title: Efficient synthesis of achiral seco-cyclopropylbenz[2,3-e]indoline analogues: [4-amino-2-(5,6,7-trimethoxyindole-2-carboxamido)naphthalen-1-yl]ethyl chloride and [4-hydroxy-2-(5,6,7-trimethoxyindole-2-carboxamido)naphthalen-1-yl]ethyl chloride.
abstract: Achiral seco-aminocyclopropylbenz[2,3-e]indoline and seco-hydroxycyclopropylbenz[2,3-e]indoline (seco-CBI) analogues of the duocarmycins and CC-1065, e.g., 7 and 8, are potent anticancer agents. This paper describes significantly improved synthetic strategies for preparing these compounds. Starting from Martius acid (9), the new strategy gave a 13-fold increase in the overall yield of 7, and the use of di-tert-butyl malonate was economically beneficial. For compound 8, the new strategy employed an Emmons-Horner reaction, followed by a Stobbe condensation, and the overall yield was improved 15-fold.
authors.affiliation: Taiho Pharmaceutical Co., Ltd., 1-27, Misugidai Hanno-City, Saitama, 357-8527, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sato
authors.forename: Adrienne
authors.initials: A
authors.lastname: Scott
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Asao
authors.forename: Moses
authors.initials: M
authors.lastname: Lee
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis; D007211:Indoles / Q000138:chemical synthesis*; D009281:Naphthalenes / Q000138:chemical synthesis
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D009281:Naphthalenes; C057812:indoline