Biomimetic Synthesis of Deca- and Dodecaketide-Derived Quinone Antibiotics

Abstract

Two ketide side chains are positioned in vicinal position on a planar aromatic or quinoid core in the biomimetic-type synthesis of ketide-derived quinone antibiotics, described in this article. The close proximity of electrophilic and nucleophilic sites in the side chains restricts the large number of theoretically possible non-enzymatic aldol reactions of the lateral ketide chains during the cyclization. Usually only two cyclization modes are observed: the “linear” or “angular” fashion. An anthraquinone core serves both in the synthesis of the linearly condensed anthracyclinones and the angularly arranged benzo[a]naphthacenequinones. Naphthalenes or naphthoquinones are best suited for the construction of angucyclinones. An advantage of the biomimetic approach to polyketide antibiotics is that all functional groups are “automatically” positioned correctly on the hydroaromatic part. In addition, this approach allows a great flexibility in the kind and location of substituents on the aromatic core. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)