复杂活性黄酮苷的合成研究

Complex flavonoid glycosides montbretin A, apigenin 5-O-glycoside, and carambolaflavone not only possess novel and complex chemical structures, but also have impressive antihyperglycemic activities which render them having promising medicinal future. Launching a synthetic program towards these flavonoid glycosides could on one hand achieve the first total synthesis of them, on the other hand solve the general problems encountered in flavonoid glycoside synthesis, including the establishment of a highly efficient approach to furnish flavonol derivative equippted with appropriate protecting groups, introduction of acyl groups efficiently in the synthesis of acylated flavonoid glycosides, construction of glycosidic linkages of 5-OH which is involved in the formation of intramolecular H-bond and 4’-OH with high efficiency, and the construction of flavonoid C-glycosidic bond convergently. Furthermore, the established synthetic strategies can also be applied in the synthesis of target molecules analogues, facilitating the setting up of a library of flavonoid glycosides and the subsequent investigation of functional mechanism and structure-activity relationship.

复杂黄酮苷montbretin A, 芹菜素-2-O-糖苷及carambolaflavone 不仅具有新颖、复杂的化学结构，而且表现非常优异的抗糖尿病活性，具有很好的药用前景。通过开展全合成研究不仅可以实现目标分子的首次全合成，而且可以解决制约黄酮苷合成的普遍性问题，如黄酮醇的高效合成问题、酰化黄酮苷酰基引入问题、4’-OH糖苷键的高效构建问题、参与形成分子内氢键的5-OH的高效糖苷化问题以及黄酮C-苷键的高效构建问题等，进一步提升复杂黄酮苷的合成水平。所确立的合成方法可应用于一系列目标分子类似物的合成，建立小型黄酮苷类化合物库，为进一步作用机制、构效关系研究奠定基础。

本项目通过对复杂黄酮苷Montbretin A，芹菜素2-O-糖苷以及Carambolaflavone A等分子的合成，新型糖基化给体MPEP以及糖基保护基DMNPA等的研究解决了目前制约黄酮苷合成的普遍性问题，如黄酮醇的高效合成问题，酰化黄酮苷酰基的引入问题，4’-OH，5-OH，7-OH糖苷键的高效构建问题以及黄酮C-苷键的高效构建问题等，进一步提升复杂黄酮苷的合成水平，同时为黄酮类化合物进一步的作用机制以及构效关系等研究奠定基础。