Total Synthesis of Obolactone via Regioselective Carbonyl Desaturation

Total synthesis of the dihydro-γ-pyrone natural product (±)-obolactone is reported. The synthesis relies on regioselective carbonyl desaturation of a tetrahydropyranone precursor via site-selective C-H bond oxidation. Identification of suitable oxidants for this transformation in a model system as well as implementation in a one-pot, double C-O, C-C oxidation procedure that provides direct access to dihydro-γ-pyrones from readily accessible tetrahydropyranols are described. Using this strategy, obolactone was prepared in a single step from the originally proposed structure of cryptoconcatone H and just four steps from C₂ -symmetric (±)-1,8-nonadiene-4,6-diol in 24% overall yield.

Publication History

Received: 20 August 2025

Accepted after revision: 14 September 2025

Accepted Manuscript online:
14 September 2025