Total Syntheses of Basiliolide A1, Basiliolide A2, Basiliolide C, and their Structural Analogues

A small focussed library of basiliolides including basiliolide A1, basiliolide A2, basiliolide C, and their structural analogues have been prepared for structure–activity-relationship studies. The synthesis features a cyclopropanation/ring-opening strategy to establish the C-8 stereogenic centre by using the cyclopropanation substrate with the appropriate alkene geometry; an IMDA (intramolecular Diels–Alder) reaction to construct the seco acid derivatives; and a biomimetic O-acylation to form the unprecedented seven-membered acyl ketene acetal ring. The des-D-ring analogues were prepared by an IMDA/decarboxylation strategy. Moreover, an asymmetric catalytic cyclopropanation reaction has been developed; this provided an optically enriched intermediate for asymmetric synthesis.