Design and synthesis of new caged compounds for lipid mediators

脂质介质新型笼状化合物的设计与合成

基本信息

批准号：
13640545
负责人：
FURUTA Toshiaki
金额：
$ 1.92万
依托单位：
Toho University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

项目摘要

Signaling mediated by polyunsaturated fatty acids (PUFAs) has been attracted growing interests. Arachidonic acid (AA) is an essential polyunsaturated fatty acid, and is metabolized to prostaglandins and leukotrienes. To develop a chemical tool to investigate the signaling mediated by such PUFAs, we synthesized Bhc-caged derivatives of PUFAs, arachidonic acid, oleic acid and linoleic acid and found that Bhc-arachidonic acid (Bhc-AA) was photolyzed with quantum yield of 0.05 and overall photosensitivity, the product of quantum yield and molar absorptivity, of about 400. Enzymatic test reveals that Bhc-arachidonic acid has no residual activity against cyclooxygenase-2 (COX-2) which is believed to play important role in carcinogenesis and converts AA to prostaglandins. Furthermore, the enzymatic activity against COX-2 was restored after photo-irradiation (350nm), which also confirms the release of parent arachidonic acid.Furthermore, four photolabile derivatives of bile acids were synthesized through the silver oxide-mediated selective introduction of a 2-nitrobenzyl group to 3α-OH. All of the derivatives showed satisfactory photoreactivity upon irradiation (350 nm) in aqueous solution. Photolysis of 3-NB-CA in methanol produced an unprecedentedly stable nitroso-hemiacetal intermediate whose NMR spectrum could be measured at room temperature. Enzymatic assays of the caged cholic acids revealed that these compounds would be useful as chemical tools to investigate biological processed in which bile acids play key roles.

由多不饱和脂肪酸（PUFA）介导的信号引起了人们日益增长的兴趣。花生四烯酸（AA）是必不可少的多不饱和脂肪酸，被代谢为前列腺素和白三烯。 To develop a chemical tool to investigate the signaling mediated by such PUFAs, we synthesized Bhc-caged derivatives of PUFAs, arachidonic acid, oleic acid and linoleic acid and found that Bhc-arachidonic acid (Bhc-AA) was photolyzed with quantum yield of 0.05 and overall photosensitivity, the product of quantum yield and molar absorption, of about 400. Enzymatic test reveals that BHC-芳基酸没有针对环氧酶-2（COX-2）的残留活性，据信这在癌变中起重要作用，并将AA转化为前列腺素。此外，在光辐照（350nm）之后还恢复针对COX-2的酶活性，这也证实了父蛛网膜酸的释放。曲霉素，通过银氧化物介导的2-硝基苯基团的选择性引入3α-烯二氮基团，通过银氧化物介导的选择性地引入了胆汁酸的四个光刀片衍生物。在水溶液中，所有衍生物在辐照时均显示出令人满意的光反应性（350nm）。甲醇中3-nb-Ca的光解会产生前所未有的稳定的氮气 - 透明质质中间体，其NMR光谱可以在室温下测量。对笼中胆汁酸的酶试验表明，这些化合物可作为研究生物学加工的化学工具，其中胆汁酸起着关键作用。