Enantiospecific Synthesis of Trisubstituted Butyrolactone Natural Products and Their Analogs

A general methodology for the synthesis of highly substituted butyrolactones in enantiomerically pure form has been developed. The application of this process in a highly efficient synthesis of lactone natural products blastmycinone (1), NFX-2 (2), antimycinone (3), and NFX-4 (4) and two lipid metabolites (5, 6) are described. Additionally, the total synthesis of 5-epi-blastmycinone (22), 5-epi-NFX-2 (21b), 5-epi-NFX-4 (21c), and lipid metabolite analogs (19, 20) are also described. The overall yields for the target molecules are the highest reported so far in the literature.