| Abstract
| - A practical, total synthesis of seco-(+)-oxaduocarmycin3a, an analogue of the highly cytotoxicnatural product, duocarmycin SA (1), is described. The13-step synthesis features a novel andefficient intramolecular aryl radical cyclization onto a vinyl chlorideas a direct entry to the(chloromethyl)indoline alkylating subunit 14.Subsequent resolution, utilizing a preparativeChiralpak AD column, provided enantiomerically pure alkylating subunits14a and 14b which wereelaborated to seco-(+) and ent-(−)-oxaduocarmycins,3a and 3b, respectively. Thenaturalenantiomer 3a was active at pM concentrations and exhibited7−50-fold higher potentcy than itsenantiomer 3b in in vitro cytotoxicityassays.
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