Total Synthesis of Seco (+)- andent-(−)-Oxaduocarmycin SA: Construction of the (Chloromethyl)indoline Alkylating Subunit by a Novel Intramolecular Aryl Radical Cyclization onto a Vinyl Chloride
The Journal of Organic Chemistry1997Vol. 62(25), pp. 8868–8874
Citations Over TimeTop 10% of 1997 papers
Vinod F. Patel, Sherri L. Andis, Julia K. Enkema, David A. Johnson, Joseph H. Kennedy, F. MOHAMADI, Richard M. Schultz, Daniel J. Soose, M. M. SPEES
Abstract
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.
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