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多花多孔菌子实体提取物的光反应产物

Photoreaction products of extract from the fruiting bodies of Polyozellus multiplex.

作者信息

Otsuka Hayato, Nakai Keiyo, Shimizu Emi, Yamaguchi Takamasa, Yamano Mitsuhisa, Sasaki Hiroaki, Koyama Kiyotaka, Kinoshita Kaoru

机构信息

Department of Pharmacognosy and Phytochemistry, Meiji Pharmaceutical University, Noshio 2-522-1, Kiyose-Shi, Tokyo, 204-8588, Japan.

Department of Chemistry, Chemical R&D Laboratory, SPERA PHARMA, Inc, 17-85, Jusohonmachi 2-Chome, Yodogawa-Ku, Osaka, 532-0024, Japan.

出版信息

J Nat Med. 2024 Jun;78(3):547-557. doi: 10.1007/s11418-024-01790-6. Epub 2024 Mar 21.

Abstract

Photochemical reactions are powerful tools for synthesizing organic molecules. The input of energy provided by light offers a means to produce strained and unique molecules that cannot be assembled using thermal protocols, allowing for the production of immense molecular complexity in a single chemical step. Furthermore, unlike thermal reactions, photochemical reactions do not require active reagents such as acids, bases, metals, or enzymes. Photochemical reactions play a central role in green chemistry. This article reports the isolation and structure determination of four new compounds (1-4) from the photoreaction products of the Polyozellus multiplex MeOH ext. The structures of the new compounds were elucidated using MS, IR, comprehensive NMR measurements and microED. The four compounds were formed by deacetylation of polyozellin, the main secondary metabolite of P. multiplex, and addition of singlet oxygen generated by sunlight. To develop drugs for treating Alzheimer's disease (AD) on the basis of the amyloid cascade hypothesis, the compounds (1-4) obtained by photoreaction were evaluated for BACE1 inhibitory activity. The hydrolysates (5 and 6) of polyozellin, the main secondary metabolites of P. multiplex, were also evaluated. The photoreaction products (3 and 4) and hydrolysates (5 and 6) of polyozellin showed BACE1 inhibitory activity (IC: 2.2, 16.4, 23.3, and 5.3 μM, respectively).

摘要

光化学反应是合成有机分子的有力工具。光提供的能量输入为生成使用热反应方案无法组装的张力独特分子提供了一种手段,能够在单一化学步骤中产生巨大的分子复杂性。此外,与热反应不同,光化学反应不需要酸、碱、金属或酶等活性试剂。光化学反应在绿色化学中起着核心作用。本文报道了从多孔菌甲醇提取物的光反应产物中分离并确定了四种新化合物(1 - 4)的结构。使用质谱(MS)、红外光谱(IR)、全面的核磁共振测量和微电子衍射(microED)阐明了新化合物的结构。这四种化合物是由多孔菌主要次生代谢产物多孔菌素的脱乙酰化反应以及阳光产生的单线态氧加成反应形成的。为了基于淀粉样蛋白级联假说开发治疗阿尔茨海默病(AD)的药物,对通过光反应获得的化合物(1 - 4)进行了β-分泌酶1(BACE1)抑制活性评估。还评估了多孔菌主要次生代谢产物多孔菌素的水解产物(5和6)。多孔菌素的光反应产物(3和4)以及水解产物(5和6)均表现出BACE1抑制活性(IC分别为2.2、16.4、23.3和5.3 μM)。

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