Synthesis of All Stereoisomers of RK460 and Evaluation of Their Activity and Selectivity as Abscisic Acid Receptor Antagonists
Synthesis of All Stereoisomers of RK460 and Evaluation of Their Activity and Selectivity as Abscisic Acid Receptor Antagonists
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DOI：
10.1002/chem.201806056
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发表时间：
2019-03-07
影响因子：
4.3
通讯作者：
Sodeoka, Mikiko
中科院分区：
文献类型：
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作者：
Mikame, Yu;Yoshida, Kazuko;Sodeoka, Mikiko
PYR/PYL/RCAR蛋白家族最近作为植物激素脱落酸（阿坝，1）的受体出现，脱落酸调节植物对环境胁迫的响应。这些家族具有多个具有不同生理作用的成员，因此需要选择性激动剂或拮抗剂作为阐明功能差异的工具和作为农用化学品的先导化合物。我们先前鉴定RK 460（rac-3a）为PYR 1选择性拮抗剂，并表明其在6，5-顺式双环骨架上具有五个立体中心。在这里，我们合成了RK 460的所有立体异构体，并评估了它们对一组受体的活性。相对立体化学以及绝对立体化学对于选择性作用是重要的。
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.