3′-(Phenyl alkynyl) analogs of abscisic acid: synthesis and biological activity of potent ABA antagonists

Abstract

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...

Synthesis and biological activity of photostable and persistent abscisic acid analogs

“…Exogenously applied ABA and its analogs are inactivated by hydroxylation of the C8′ methyl group and also by glycosylation of the C1 carboxy group. 2,28 The methyl ester group of (+)-5 may prevent rapid glycosylation of the C1 position and contribute to its persistence in plants, although we cannot exclude the possibility that other pharmacokinetic parameters may contribute to the superior activity of (+)-5.…”

“…Tetralone ABA, a lead compound of (+)-5 and (+)-6, shows higher agonist activity than ABA in Arabidopsis seed germination, 26 probably because of the long life expectancy of the hydroxylated product, 8′-hydroxy-tetralone ABA, which has ABA-like activity in plants. 2,21 Although 8′-hydroxy-ABA possesses biological activity, 27 this compound spontaneously isomerizes to the lower active metabolite PA. Based on these observations, we initially hypothesize that (+)-5 showed stronger bioactivity compared to (+)-BP2A because of the persistence of its hydroxylated product, 8′-hydroxy-tetra-lone-BP2A. However, we found that the bioactivities of (+)-5′ and (+)-6′ (carboxylate forms) were less than those of corresponding methyl esters (Fig.…”

“…Because the function of ABA is closely related to agronomically important plant traits, it is produced in large quantities by fermentation and used commercially in applications such as enhancing the color of red table grapes. 1,2 However, practical uses of ABA have been limited, mainly because of its weak effects in field trials due to its instability under UV irradiation and rapid biodegradation in plants.…”

“…21 This compound is catabolized in plants to 8′-hydroxy-tetralone ABA, which has ABA-like activity but is not converted to a PA-like compound because of the benzene ring fused to the cyclohexenone ring. 2,22 Thus, tetralone ABA shows higher bioactivity than ABA in plant assays. Furthermore, cyano cyclopropyl analogs of ABA (CCPs), in which the cyclohexenone ring of ABA is replaced with a cyano cyclopropyl group, 23 were reported recently.…”

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

“…In principle, there are at least two mechanisms for blocking ABA receptor activation: by preventing gate closure, which is necessary for PP2C binding, or by sterically disrupting the activated, closed-gate receptor conformer from binding to PP2Cs. Prior efforts to design antagonists have focused on the latter strategy and include multiple ABA-derived ligands such as AS6 ( 25 ), PanMe ( 26 ), 3′-alkyl ABA ( 30 – 32 ), 3′-(phenyl alkynyl) ABA ( 33 ), or ligands derived from tetralone ABA ( 34 ) with varying degrees of conformational restriction ( 27 , 28 , 35 ). With the exception of PanMe, these antagonists have linkers attached to the 3′ carbon of ABA or 11′ carbon of tetralone ABA, which is positioned to disrupt receptor–PP2C interactions by protruding through the 3′ tunnel.…”