Studies directed towards anthracyclinone syntheses: The use of d-glucose as a chiral auxiliary in asymmetric Diels–Alder reactions

Abstract

Setting up the correct functionality with the correct stereochemistry in the ring-A of anthracycline precursors represents a synthetic challenge. The use of d-glucose as a chiral auxiliary either on the silyloxy diene or naphthoquinone-based dienophile to form the ring-A using asymmetric Diels–Alder reactions as developed by the Stoodley group and is the focus of this review. The endo-transition state is described based on a frontier orbital approach and the HOMO–LUMO energy gaps were estimated using semi-empirical (MNDO) calculations with SPARTAN’08. As anthracyclines are used in chemotherapy, some of their associated biochemistry and clinical effectiveness are also briefly introduced.