A lead compound for the development of ABA 8′-hydroxylase inhibitors

(1′S*,2′S*)-(±)-6-Nor-2′,3′-dihydro-4′-deoxo-ABA (2) was designed and synthesized as a candidate lead compound for developing a potent and specific inhibitor of ABA 8′-hydroxylase. This compound acted as an effective competitive inhibitor of the enzyme, with a KI value of 0.40 μM, without exhibiting ABA activity. However, compound 2 also functioned as an enzyme substrate, making it a short-lived inhibitor. The 8′-difluorinated derivative of 2 (4) was synthesized as a long-lasting alternative. Compound 4 resisted 8′-hydroxylation, but inhibited ABA 8′-hydroxylation as effectively as 2. These results suggest that compound 2 is a useful lead compound for the future design and development of an ideal ABA 8′-hydroxylase inhibitor.