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。

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
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引用次数: 0

摘要

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

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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来源期刊
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.
期刊最新文献
Natural Products with Potential for the Treatment of Pain: Global Evidence from the NAPRALERT Database. Divergent Total Synthesis of Isoflavone Natural Products and Their Potential as Therapeutic Agents for TTR Amyloidosis. Revisiting the Cyclocephagenols via Astragalus condensatus: Structural Insights and Configurational Revision. Issue Publication Information Mass Spectrometry Imaging of Coniine and Other Hemlock Alkaloids after On-Tissue Derivatization Reveals Distinct Alkaloid Distributions in the Plant.
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