The divergent asymmetric synthesis of kalafungin, 5-epi-frenolicin B and related pyranonaphthoquinone antibiotics

Abstract

A divergent, asymmetric method for the synthesis of pyranonaphthoquinones is reported. The synthetic strategy applies a Staunton–Weinreb annulation between substituted ortho-toluates and the (R)-pyran-2-one 7 to construct the key naphthopyranone intermediates. Stereoselective introduction of either a methyl or propyl C5 alkyl substituent by use of Grignard addition/silane-mediated reduction and a sequence of oxidations gave a series of pyranonaphthoquinones including kalafungin 1, 5-epi-9-methoxykalafungin 34 and 5-epi-frenolicin B 24.