黄酮类化合物的合成及其血管舒张作用

目的寻找具有较好血管舒张活性的黄酮类化合物。方法以槲皮素为原料，经保护后分别与1-溴代-2，3，4，6-四乙酰基-D-吡喃葡糖等4种溴代糖缩合、脱保护合成了4个槲皮素苷类化合物(1a～d)；以间三酚为原料，按常规方法合成了6个黄酮类化合物(2a～f)；利用IR，¹H NMR，¹³C NMR和MS对合成的化合物进行结构确证。观察了合成的10个槲皮素衍生物及类似物与4个天然黄酮类化合物对大鼠离体胸主动脉环的作用；并用HPLC法测定了这些化合物的相对油水分配系数(logP值)。结果受试的14个黄酮类化合物可以浓度依赖性地舒张PE预收缩的内皮完整的大鼠胸主动脉环，且其血管舒张活性随着其油水分配系数logP值的增加而增大。结论3-溴-5,7二羟基黄酮(2d)的血管舒张作用最强，黄酮类化合物的血管舒张活性与其油水分配系数(logP)具有正相关性。初步的构效关系为开发更有效的具有血管舒张作用的黄酮类化合物提供了一定的实验依据。

Synthesis and vasorelaxation action of flavonoids

Aim To search for flavonoids which possess stronger vasorelaxation action. Methods (Four quercetin) glycosides (1a-d) were synthesized from quercetin in three steps i.e. selective protection of quercetin, condensation with corresponding acetylglycosyl bromide, and then removal of the protecting group; Six flavone compounds (2a-f) were prepared from phloroglucinol according to the conventional methods; The structures of synthetic compounds were confirmed by IR, ~(1)H NMR, ~(13)C NMR and MS. Vasorelaxation action of ten synthetic quercetin derivatives (or analogues) and four natural flavonoids compounds were examined on the isolated rat thoracic aorta rings; Comparative octanol-water partition coefficients (logP) were measured using a reversed-phase HPLC method. Results Most of the tested flavonoids showed concentration dependent relaxation effects against PE-induced contractions of rat aortic rings. These compounds had stronger action with the augment of logP values. Conclusion Compound 3-bromo-5,7-dihydroxyflavone (2d) was identified to have the most potent vasodilating action. These compounds exert vasodilating effects that are related to the logP values. A structure-activity relationship of flavonoids was suggested.