Synthesis of model ring systems related to C10–C18 analogues of the mycalamides/theopederins

Abstract

Conjugate addition to d-galactose-derived pyranones 8 and 10, with in situ enolate alkylation, or protonation, provides pyranones 11–13 or 16–19. These are related to the C10–C18 fragment of the mycalamides and provide a short entry to C10, C11, C14 and C15 stereocentres. This approach is relevant to introduction of the side-chain and analogues thereof, and allows for variable C14 functionality. Two side-chain analogues, both C14 monomethylated diastereomers, the C14 unsubstituted system and the natural product-related C14 dimethyl functionality are prepared, and C13 epimeric functionality introduced.