Filipin III: Configuration Assignment and Confirmation by Synthetic Correlation

Abstract

The stereochemical configuration of filipin III (1) was determined using the (13)C acetonide analysis. The relative configurations for the nine stereogenic centers in the top half of filipin were initially identified using just three acetonide derivatives (2, 3, and 4) arising from a two-step protection sequence. The structure was confirmed by synthesis and direct correlation of degradation products 8 (C26-C28) and 10 (C1-C16). Filipin tetraacetonide 2 and triacetonide 4 each contain an anti acetonide in a highly unusual chair conformation. Molecular modeling successfully reproduced the preference for a chair conformation over the normally more stable twist-boat conformation.