Enantioselective Total Synthesis of the Guaianolide (-)-Dehydrocostus Lactone by Enediyne Metathesis

The hydroazulene core of the bioactive sesquiterpenoid (-)-dehydrocostus lactone was generated by domino enediyne metathesis. A triple hydroboration/oxidation of the resultant conjugated triene installed three out of four stereogenic centers of the target in a single step. The enantiopure acyclic metathesis substrate was readily available by an asymmetric anti aldol reaction. Masking of the gamma-lactone as an acetal allowed for an efficient completion of the synthesis through late-stage double carbonyl olefination.

Automated summary

In this study, the hydroazulene core of a bioactive sesquiterpenoid was generated by domino enediyne metathesis, with three out of four stereogenic centers of the target installed in a single step through a triple hydroboration/oxidation reaction. The enantiopure acyclic metathesis substrate was easily obtained via an asymmetric anti aldol reaction, and late-stage double carbonyl olefination was efficiently carried out after masking the gamma-lactone as an acetal.