Total Synthesis and Pharmacological Evaluation of Phochrodines A-C.

IF 3.6 2区生物学 Q2 CHEMISTRY, MEDICINAL Journal of Natural Products Pub Date : 2025-04-25 Epub Date: 2025-04-01 DOI:10.1021/acs.jnatprod.5c00104

Jacob L Bouchard, Sichen Chang, Srinivasan Krishnan, Christopher C Presley, Olivier Boutaud, Nathan D Schley, Darren W Engers, Julie L Engers, Craig W Lindsley, Aaron M Bender

引用次数: 0

Abstract

The first syntheses of the Phomopsis-isolated natural products phochrodines A-C are reported. Functional group manipulations on a key 5H-chromeno[4,3-b]pyridine intermediate, itself synthesized from intramolecular Suzuki-Miyaura coupling, enabled facile and high-yielding syntheses of all three natural products. Additionally, sufficient material was generated to enable detailed pharmacological profiling of each compound. Preliminary drug metabolism and pharmacokinetic (DMPK) experiments and ancillary pharmacology screening revealed phochrodine C (3) as an attractive scaffold for further modification, particularly for medicinal chemists working in the antidepressant space.

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Phochrodines A-C的全合成及药理评价。

报道了光合分离天然产物phochrodines A-C的首次合成。关键的5H-chromeno[4,3-b]吡啶中间体（本身由分子内Suzuki-Miyaura偶联合成）上的官能团操纵使这三种天然产物的合成变得容易和高产。此外，还生成了足够的材料，可以对每种化合物进行详细的药理学分析。初步的药物代谢和药代动力学（DMPK）实验和辅助的药理学筛选表明，phochrodine C(3)是一个有吸引力的支架，可以进一步修饰，特别是在抗抑郁药物领域工作的药物化学家。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Natural Products 生物-药学

CiteScore

9.10

自引率

5.90%

发文量

294

审稿时长

2.3 months

期刊介绍： The Journal of Natural Products invites and publishes papers that make substantial and scholarly contributions to the area of natural products research. Contributions may relate to the chemistry and/or biochemistry of naturally occurring compounds or the biology of living systems from which they are obtained. Specifically, there may be articles that describe secondary metabolites of microorganisms, including antibiotics and mycotoxins; physiologically active compounds from terrestrial and marine plants and animals; biochemical studies, including biosynthesis and microbiological transformations; fermentation and plant tissue culture; the isolation, structure elucidation, and chemical synthesis of novel compounds from nature; and the pharmacology of compounds of natural origin. When new compounds are reported, manuscripts describing their biological activity are much preferred. Specifically, there may be articles that describe secondary metabolites of microorganisms, including antibiotics and mycotoxins; physiologically active compounds from terrestrial and marine plants and animals; biochemical studies, including biosynthesis and microbiological transformations; fermentation and plant tissue culture; the isolation, structure elucidation, and chemical synthesis of novel compounds from nature; and the pharmacology of compounds of natural origin.