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.

We report here the synthesis and biological testing of 3'-(phenyl alkynyl) abscisic ABA analogs, a new class of potent ABA antagonists. These ABA analogs incorporate a rigid framework of eight carbon atoms attached at the 3'-carbon atom of ABA that prevents folding of the ABA analog-bound receptor required for ABA signalling. The two-step synthesis is based upon the optimized conversion of natural (S)-ABA to 3'-iodo ABA which can be coupled to phenyl acetylenes using Sonogashira conditions, or to styryl compounds through Suzuki chemistry. The parent 3'-(phenyl alkynyl) ABA analog 7 was obtained in 29% yield, 74% yield based on recovered starting material. In a lentil seed germination assay, compound 7 was found to have more potent activity than other known 3'-substituted ABA antagonists to date. In a structure activity study parasubstituted phenyl alkynyl analogs had comparable activity to the analog 7 while the 3'-styryl ABA 18 was only slightly less active. Analog 7 overcame ABA inhibition of germination and seedling growth in a wide range of mono and dicot plant species, including canola, lentil, soybean, rice, wheat, barley, cannabis and canary seed. 3'-(Phenyl alkynyl) ABA analogs have numerous potential practical agricultural applications including promoting ripening of crops, dormancy breaking of seeds and woody perennials, as well as promoting seed germination, and growth under stress conditions as demonstrated in this report.

ABA antagonists have potential application as growth regulators to improve germination and seedling growth at low temperatures for oilseeds and pulses grown in regions with short seasons such as those in western Canada. Towards development of practical ABA antagonists, a series of 3′-substituted ABA analogs were synthesized and screened in seed germination assays in canola (Brassica napus), lentil (Lens culinaris), and soybean (Glycine max) at low temperature and in overcoming exogenous ABA. The most promising analog, ABA 1009, was selected for further germination testing of dose responses in canola, lentil, and soybean. Analog ABA 1009 at 100 µM was effective in overcoming ABA (10 µM)-induced inhibition for canola, lentil, and soybean germination at ambient temperature, and also promoted germination at low temperature for canola (5 °C).