Regiocontrol by Remote Substituents. An Enantioselective Total Synthesis of Frenolicin B via a Highly Regioselective Diels-Alder Reaction

George A. Kraus, Iowa State University
Jun Li, Iowa State University
Mark S. Gordon, Iowa State University
Jan H. Jensen, Iowa State University

Reprinted (adapted) with permission from Journal of the American Chemical Society 115 (1993): 5859, doi:10.1021/ja00066a078. Copyright 1993 American Chemical Society.

Abstract

The quinone subunit is contained in a broad range ofbiologically Important natural products.1 This subunit is present in anticancer agents such as the anthracyclines, antibiotics such as the rifamycins, antifungal agents such as kalafungin, and anticoccidial agents such as frenolicin B.2 The latter two compounds are members of the pyranonaphthoquinone family. The diverse biological activity of quinones has led to the development of several new synthetic methods for quinones. A number of methods involving cycloadditions, 3 carbanion-mediated annulations, 4 and nucleophilic and electrophilic reactionss have been reported. Among the pathways featuring a cycloaddition reaction, one of the most general methods for the regiospecific synthesis of substituted quinones was pioneered by Rapoport and others.6 This method involves the Diels-Alder reaction of a substituted quinone and is depicted below. The X group is usually chlorine or bromine, but nitrites and sulfoxides7 can also be employed.