Filipin III: Configuration assignment and confirmation by synthetic correlation

The stereochemical configuration of filipin III (1) was determined using the C-13 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.