Synthesis of All Stereoisomers of RK460 and Evaluation of Their Activity and Selectivity as Abscisic Acid Receptor Antagonists

Abstract

The PYR/PYL/RCAR protein families have recently emerged as receptors of the phytohormone abscisic acid (ABA, 1), which regulates plant responses to environmental stress. These families have multiple members with different physiological actions, and so selective agonists or antagonists are needed both as tools to elucidate functional differences and as lead compounds for agrochemicals. We previously identified RK460 (rac‐3 a) as a PYR1‐selective antagonist, and showed that it possesses five stereocenters on a 6,5‐cis‐bicyclo skeleton. Here, we synthesized all the stereoisomers of RK460 and evaluated their activity towards a panel of receptors. Relative stereochemistry as well as absolute stereochemistry was important for selective action.

Direct Catalytic Asymmetric Synthesis of Oxindole-Derived δ-Hydroxy-β-ketoesters by Aldol Reactions

“…δ-Hydroxy-β-ketoesters are useful building blocks for the synthesis of biologically important natural products and pharmaceutical leads. − Common methods to access δ-hydroxy-β-ketoesters include reactions of dianions generated from β-ketoesters by using two or more equivalents of strong base(s) or reactions of preformed silyl dienol ethers or alkyl dienol ether derivatives with carbonyl compounds (Scheme a and b). These methods require either severe conditions or tedious protection and deprotection procedures.…”

Subtype-selective agonists of plant hormone co-receptor COI1-JAZs identified from the stereoisomers of coronatine

“…In addition, chemical genetics is a powerful and promising alternative. Chemical genetics approaches have been successful in analyzing genetically redundant signaling in other hormonal pathways, such as those of abscisic acid and strigolactones, in which specific hormonal agonists activated distinctive receptor subtypes triggering specific responses [18][19][20][21][22][23][24] . Transient inhibition/degradation of a single JAZ protein in a fully developed plant by using chemicals may therefore disclose the specific function of a particular JAZ gene.…”

Click-to-lead design of a picomolar ABA receptor antagonist with potent activity in vivo

“…Dozens of ABA receptor agonists, which reduce transpiration and water use by inducing guard cell closure, have been developed and are being explored as chemical tools for mitigating the effects of drought on crop yields (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23), most of them either being analogs of ABA or sulfonamides similar to quinabactin (24). ABA receptor antagonists could conceivably be useful in cases where water is not limiting, for example, to increase transpiration and gas exchange under elevated CO 2 in glasshouse agriculture, as germination stimulators, and for studying the ABA dependence of physiological processes, among other applications (25)(26)(27)(28)(29)(30)(31). Thus, both ABA receptor agonists and antagonists have potential uses as research tools and for plant biotechnology.…”