Polygalolides A and B are new phenolic lactones that were recently isolated from Polygala fallax, which is a medicinal plant that is found off the southern mainland of China. The species is used by local folk as a tonic and anti-hepatitis drug, although the clinical efficacy of polygalolides A and B remains unknown due to the limited quantities of available material. This proposal represents the first known attempt at synthesizing these natural products, which will be accomplished by utilizing [4 + 3] cycloaddition reactions between 2,3-disubstituted furans and vinyl oxocarbenium ions to generate, in a single step, a complex segment of the molecules' unprecedented fused heterocyclic skeleton. Strategically designed, these cycloadducts enable all subsequent reactions, for achieving polygalolides A and B, to consists of mainly orthogonal protection and deprotection chemistry. To eliminate the production of racemic mixtures, enantioselective [4 + 3] cycloaddition adducts will be engendered by employing, for the first time, an asymmetric Lewis acid catalyst. These cycloaddition methodologies have applications in the synthesis of complex natural products that contain an otherwise difficult to construct internal seven-membered ring.
