An efficient and scalable synthesis of a persistent abscisic acid analog (+)-tetralone ABA

Abstract

The plant hormone (S)-abscisic acid (ABA) is a signalling molecule found in all plants that triggers plants’ responses to environmental stressors such as heat, drought, and salinity. Metabolism-resistant ABA analogs that confer longer lasting effects require multi-step syntheses and high costs that prevent their application in crop protection. To solve this issue, we have developed a two-step, efficient and scalable synthesis of (+)-tetralone ABA from (S)-ABA methyl ester. A challenging three-carbon insertion and a bicyclic ring formation on (S)-ABA methyl ester was achieved through a highly regioselective Knoevenagel condensation, cyclization, and oxidation in one-pot. Further we have studied the biological activity and metabolism of (+)-tetralone ABA in planta and found the analog is hydroxylated similarly to ABA. The biologically active hydroxylated tetralone ABA has greater persistence than 8′-hydroxy ABA as cyclization to the equivalent of phaseic acid is prevented by the aromatic ring. (+)-tetralone ABA complemented the growth retardation of an Arabidopsis ABA-deficient mutant more effectively than (+)-ABA. Taken together, this new synthesis allows the production of the potent ABA agonist efficiently on an industrial scale.