Divergent Total Synthesis of Isoflavone Natural Products and Their Potential as Therapeutic Agents for TTR Amyloidosis.

IF 3.3 2区生物学 Q2 CHEMISTRY, MEDICINAL Journal of Natural Products Pub Date : 2024-10-27 DOI:10.1021/acs.jnatprod.4c00812

Nguyen Ngoc Thanh Luan, Takuya Okada, Takeshi Yokoyama, Mie Suzuki, Yuko Nabeshima, Mineyuki Mizuguchi, Naoki Toyooka

引用次数: 0

Abstract

We have achieved the divergent total synthesis of nine isoflavone natural products 1-9 starting from commercially available 2,4,6-trihydroxyacetophenone as a starting material. The isoflavone skeleton of 1-9 was constructed by the Suzuki-Miyaura coupling reaction as the key reaction. Investigation of the potential of 1-9 as therapeutic agents for transthyretin (TTR) amyloidosis revealed that millexatin F (3) showed the best efficacy in ex vivo competitive binding experiments and thioflavin-T fluorescence studies. Therefore, millexatin F (3) is promising as a seed compound for a novel TTR amyloidosis therapeutic agent.

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异黄酮天然产品的不同全合成及其作为 TTR 淀粉样变性治疗剂的潜力。

我们以市售的 2,4,6-三羟基苯乙酮为起始原料，实现了九种异黄酮天然产物 1-9 的发散全合成。1-9 的异黄酮骨架是通过关键的铃木-宫浦偶联反应构建的。对 1-9 作为治疗转甲状腺素（TTR）淀粉样变性病的潜在药物的研究表明，在体内外竞争性结合实验和硫黄素-T 荧光研究中，米力铂 F (3) 的疗效最好。因此，millexatin F (3) 有希望成为新型 TTR 淀粉样变性治疗药物的种子化合物。

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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.