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-(+)-oxaducocarmycin 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 preparationve Chiralpak AD column, provided enantiomerically pure alkylating subunits 14a and 4b which were Elaborated to seco-(+) and ent-(-)-oxaduocarmycins, 3a and 3b, respectively.