Total Synthesis of the Sensitive Triyne Natural Product (4S,5S)-4,8-Dihydroxy-3,4-dihydrovernoniyne and All of Its Stereoisomers.

An efficient total synthesis of the revised structure of the sensitive triyne natural product, (4S,5S)-4,8-dihydroxy-3,4-dihydrovernoniyne, and all of its stereoisomers, that is, the previously proposed (4S,5R), (4R,5R), and (4R,5S), has been accomplished from chiral pool compounds l-mannonic-γ-lactone and d-glucono-δ-lactone. The key features involve a one-pot conversion of the chiral pool compounds into the γ-vinyl-β-hydroxy-γ-lactones, the heteroatom-directed Wacker oxidation, the Seyferth-Gilbert reaction, and Cadiot-Chodkiewicz coupling. The synthesis also involves minimal protecting groups (only tert-butyldimethylsilyl) and is completed in seven to eight steps.