Concise syntheses of (+)-maximumins B and C and (+)-ottensinin

Abstract

Maximumin B (1), maximumin C (2), and ottensinin (3) are three rearranged labdane diterpenoids featuring a unique 3-substituted γ-pyrone motif. Herein, we report the first syntheses of (+)-1 and (+)-2 and an improved synthesis of (+)-3 in 4–12 steps. Key features for the syntheses of 1 and 2 include a Pd-catalyzed decarboxylative coupling reaction establishing the 3-substituted γ-pyrone and a Baran decarboxylative coupling enabling ketone formation in the final step. A Ni-catalyzed C(sp²)–C(sp³) cross-electrophile coupling reaction was applied to accomplish the synthesis of 3. Furthermore, in-depth pharmacological screening unveiled ottensinin (3) as a potent KCNQ2 agonist exhibiting comparable potency to retigabine, making it a promising lead for the development of a novel class of anti-epileptic drugs.