Total Synthesis of (+)-Blastmycinone, (−)-Litsenolide C₁, and Related Natural Trisubstituted Lactones via Alkynyltungsten Compounds

Abstract

A general method for total synthesis of natural trisubstituted gamma-lactones is developed on the basis of the chemistry of alkynyltungsten compounds. The key step in this approach involves the cycloalkenation of tungsten-eta1-(3R,4S)-pent-1-yne-3,4-diol with aldehydes to give tungsten-oxacarbenium salts, further leading to 3-alkylidene-4-hydroxy-5-methyl-gamma-lactones upon demetalation. This synthetic sequence proceeds well for alkynylaldehydes and the MOM derivative of tungsten-eta1-(3R,4S)-pent-1-yne-3,4-diol. The resulting butyrolactone products are transformed into natural trisubstituted butyrolactones including (+)-blastmycinone, (+)-blastmycinolactol, (+)-antimycinone, NFX-2, and (+)-isodihydromahubanolide A. By using the same approach based on (R)-ethyl lactate, the natural (-)-litsenolide C1 can be prepared in a few steps.