Biological Activities and Synthetic Advances of Phaseic Acid

doi:10.6023/A26040104

Acta Chimica Sinica ›› 2026, Vol. 84 ›› Issue (7): 1165-1174.DOI: 10.6023/A26040104 Previous Articles Next Articles

Review

红花菜豆酸的生物活性与合成进展

苏芳谊^a, 张焱^b, 宁澄清^b^,^*(), 徐晶^b^,^*()

^a 郑州师范学院生命科学院郑州 450044
^b 南方科技大学化学系格拉布斯研究院光明高等研究院深圳 518055

投稿日期:2026-04-04 发布日期:2026-06-23

作者简介:

苏芳谊, 2015年博士毕业于中国医学科学院药物研究所. 目前在郑州师范学院担任讲师, 主要研究方向为中药药效物质基础及有机合成.

张焱, 2023年博士毕业于南方科技大学, 随后加入南方科技大学从事博士后研究, 主要关注复杂天然产物的全合成研究.

宁澄清, 2015年博士毕业于中南大学, 2015~2017年在南方科技大学从事博士后研究, 2018~至今, 南方科技大学研究助理教授、研究副教授, 主要关注小分子创新药物研究及天然产物结构修饰与成药性研究.

徐晶, 2009年博士毕业于德国莱比锡大学, 2009~2013年在加利福尼亚大学圣迭戈分校从事天然产物全合成博士后研究. 2014年初加入南方科技大学化学系开展独立研究, 任助理教授. 2015年晋升为准聘副教授, 2020年晋升为长聘教授. 主要关注复杂天然产物的全合成研究以及小分子药物研究, 发表学术论文50余篇, 包括J. Am. Chem. Soc.、Angew. Chem. Int. Ed.、Nat. Commun.、Nat. Rev. Chem.、Nat. Prod. Rep.、Acc. Chem. Res.、Eur. J. Med. Chem.、Br. J. Pharmacol.等, 已获得国家级和省市项目二十余项. 独立工作以来, 入选/获得“孔雀计划B类人才”(2014)、“青年千人计划”(2015)、“Thieme Chemistry Journal Award”(2020)、药明康德生命化学研究奖(2022)、深圳市自然科学二等奖(2022, 第一完成人)、深圳市鹏城孔雀计划特聘教授(2023)、南方科技大学杰出科研奖(2023)、教育部“长江学者”(2023)、美国化学会春季年会亚太分会优秀研究生导师(2024)等人才计划与学术荣誉.

基金资助:
郑州师范学院大学生创新训练重点项目(DCZ2024006); 河南省科技攻关研究计划项目(252102110161); 河南省科技攻关研究计划项目(252102110279); 河南省高等学校重点科研项目(23A360027); 河南省高等学校重点科研项目(25B210016); 国家自然科学基金(22401138)

Biological Activities and Synthetic Advances of Phaseic Acid

Fangyi Su^a, Yan Zhang^b, Chengqing Ning^b^,^*(), Jing Xu^b^,^*()

^a School of Life Science, Zhengzhou Normal University, Zhengzhou 450044, China
^b Department of Chemistry and Shenzhen Grubbs Institute and Guangming Advanced Research Institute, Southern University of Science and Technology, Shenzhen 518055, China

Received:2026-04-04 Published:2026-06-23
Contact: * E-mail: ningcq@sustech.edu.cn; xuj@sustech.edu.cn
Supported by:
Key Project of College Students’ Innovation Training, Zhengzhou Normal University(DCZ2024006); Key Science and Technology Research Program of Henan Province(252102110161); Key Science and Technology Research Program of Henan Province(252102110279); Key Scientific Research Project of Colleges and Universities in Henan Province(23A360027); Key Scientific Research Project of Colleges and Universities in Henan Province(25B210016); National Natural Science Foundation of China(22401138)

Phaseic acid (PA), a key oxidative metabolite of the essential plant hormone abscisic acid (ABA) with a unique rigid oxa-bicyclic skeleton, was long regarded merely as an inactive terminal catabolite responsible for ABA signal termination and metabolic clearance in plants. However, accumulating functional and structural evidence over the past decade has definitively established PA as an independent bioactive signaling molecule with distinct physiological functions: in plants, it acts as a biased ligand that selectively activates PYL2-PYL6 subtypes of ABA receptors to precisely regulate seed dormancy, germination inhibition and plant adaptive responses to prolonged drought and salinity stresses; in mammalian systems, endogenous PA has been identified as a potent endogenous neuroprotective agent that alleviates cerebral ischemia-reperfusion injury via reversible inhibition of N-methyl-D-aspartate (NMDA) receptors, showing great potential for ischemic stroke therapeutic development. The remarkable dual applications in crop drought resistance breeding and neuroprotective drug discovery have generated an urgent demand for efficient chemical synthesis of PA, which is severely hindered by its extremely low natural abundance, three contiguous stereogenic centers and the challenging construction of the characteristic rigid fused oxa-bicyclic framework. This review systematically summarizes the landmark advances in the total synthesis of PA since its first isolation and structural characterization in 1960, covering the first racemic synthesis in 1986, the first optically pure synthesis in 1989 and the recent shortest linear sequence of only 7-step highly efficient asymmetric synthesis, with particular emphasis on the stereoselective construction of the conjugated diene side chain and synthetic strategies for PA methyl ester derivatives. The design rationale, core reaction technologies and key intermediates, stereocontrol mechanisms as well as the inherent advantages and practical limitations of representative synthetic routes are comprehensively discussed, aiming to provide systematic theoretical support for the in-depth functional mechanism research, structural modification and cost-effective large-scale industrial application of PA and its derivatives.

Key words: phaseic acid, abscisic acid, plant hormone, sesquiterpene, total synthesis

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Fangyi Su, Yan Zhang, Chengqing Ning, Jing Xu. Biological Activities and Synthetic Advances of Phaseic Acid[J]. Acta Chimica Sinica, 2026, 84(7): 1165-1174.

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Fig. & Tab. 9

Figure 1. ABA metabolic pathways in plants. PAR, phaseic acid reductase; GT, glycosyltransferase

Figure 2. Binding modes and conformational comparison of PA and ABA in the aligned PYL3-PA-HAB1 (cyan, PDB: 5JQ1) and PYR1-ABA-HAB1 (magenta, PDB: 3QN1) complexes

Scheme 1. Synthesis of (±)-methyl phaseates

Scheme 2. Synthesis of (＋)-methyl phaseate

Scheme 3. Conformational analysis and group Kitahara’s synthetic plan

Scheme 4. Group Kitahara’s synthetic route

Scheme 5. Group Abrams’s synthetic route

Scheme 6. Synthetic trials for intermediate 58

Scheme 7. Group Xu’s synthetic route

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红花菜豆酸的生物活性与合成进展

Biological Activities and Synthetic Advances of Phaseic Acid

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