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

A small focus library of basiliolides including basiliolide A₁, basiliolide A₂, basiliolide C and their structural analogues have been prepared for the structure-activity relationship study. The synthesis features a cyclopropanation/ring-opening strategy for establishing the C8 stereogenic centre by tuning the alkene geometry of the cyclopropanation substrates, IMDA for construction of the seco acid derivatives and biomimetic O-acylation for the unprecedented seven-membered acyl ketene acetal ring formation. The des-D-ring analogues were prepared via an IMDA/decarboxylation strategy. Moreover, an asymmetric catalytic cyclopropanation has been developed and provided an optically enriched intermediate for symmetric syntheses.