Enantioselective synthesis of the aglycone of burnettramic acid A.

Enantioselective total synthesis of the aglycone of burnettramic acid A, an antifungal pyrrolizidinedione with a terminally mannosylated long acyl chain produced by Aspergillus fungi, has been achieved from a known carboxylic acid by a 14-step sequence. The key steps include two-types of asymmetric alkylation, coupling of an acetylide intermediate with (S)-epichlorohydrin to provide an acetylenic epoxide in one pot, and the Birch reduction to effect desulfonylation, semi-reduction of triple bond, and debenzylation in a concurrent manner. Good agreement of the synthetic aglycone with naturally occurring one in 1H and 13C NMR spectra, coupled with previously reported unambiguous stereochemical assignment of the sugar moiety, has confirmed the structure of burnettramic acid A.