Synthesis Of Hesperidin Derivatives And Study On Their Anti-inflammatory Activities And BINOL Derivatives Were Applied In Asymmetry Reaction

This paper consists of four main components:In the first chapter, a series of new hesperidin derivatives were synthesized by acylation or alkylation of the hydroxyl on the 5, 7 and 3'positions, introducing one or three bromines to the 6, 8 and 2'positions, nitrio or amino to the 5'position of hesperidin, and their anti-inflammatory activities were also studied. Compared with the natural product hesperidin, which has the properties of anti-inflammatory activity, non-toxicity and non-side-effects, most of our synthesized compounds exhibited higher anti-inflammatory activity than that of hesperidin (IC50 = 1.49×10-4 M), especially, the compound 7, 3'- dimethoxy-hesperitin (IC50 = 5.56×10-8 M), about 3,000 times higher than that of hesperidin, is expected to develope as a highly efficient and low toxic anti-inflammatory agentIn the second chapter, a series of 3, 3'-bischiff base ligands with the backbone of BINOL were synthesized by condensation of 3, 3'-diformyl BINOL with primary amine, and they were first applied to enantioselective addition of diethylzinc to aromatic aldehyde. The reaction proceeded with high yield and good enantioselectivity (up to 89% e. e.). During the course of optimizing reaction conditions, we found that the chirality at 3, 3'-substituents has little influence on the enantioselectivity, while the configurations of the products was dominated by the axial chirality of binaphthyl unit; the more bulky substituent on the nitrogen favors the enantioselectivity, while the electron effects of the substrates have little influence on the enantioselectivity.In the third chapter, in view of the 3, 3'-bischiff base BINOL ligands have a good performance in enantioselective addition of diethylzinc to aromatic aldehyde, we further applied these ligands and additional two ligands with multi-coordination sites to the asymmetry pinacol coupling reaction. During the course of optimizing reaction conditions, such as temperature, solvents, the radio of ligand to TiCl4, we found that the stereoselectivity was obviously affected by the structure of the ligands. The larger substituted group at the nitrogen atom, the higher stereoselectivity the products. Increasing the coordination sites, lowering the stereoselectivity of the products, this may due to the uncertain complex manner between central metal and coordination sites that cause an uncertain stereo-reconizing manner.After optimizing reaction conditions, we got the product with high yield and high (dl / meso up to 98 / 2), although the best enantioselectivity is only 42%, however, we are the first to use such ligands in asymmetric pinacol coupling reaction. It will be of values for the further studies of this field.Starting from 3, 3'-dicarboxyl BINOL, we synthesized 3, 3'-bioxazoline BINOL ligands and then reacted with AlMe3 to form the dual-function catalysts, that is the aluminum atoms in the catalysts played the role of Lewis acid and the nitrogen atoms played the role of Lewis base. These dual-function catalysts were applied to the asymmetric addition of TMSCN to benzaldehyde, with high yield and moderate enantioselectivity (63% e. e). During the course of optimizing reaction conditions, we find that the choice of solvent and the structure of the ligand have a significant impact on the enantioselectivity. As a solvent, toluene gave the best results and the configuration of the product was dominated by the axial chirality of binaphthyl unit. When the chirality at 3, 3'-substituents (L-configuration) matchs with that of axial BINOL (S-configuration), the enantioselectivity is superior to that of the mismatch couple (L, R- bioxazoline BINOL).Finally in chapter IV, starting from BINOL, we synthesized several chiral catalysts which contain nucleophilic N or S atoms, intended to use the axial chirality of binaphthyl unit and the nucleophility of the N or S atoms to catalyze the asymmetric Baylis-Hillman reaction and to find effective catalyst with high activity, high enantioselectivity. Thus far, we have successfully synthesized a series of such chiral ligands with innovative structure, however, have not got a breakthrough in catalytic asymmetric baylis-hillman reaction. The further research is kept going on...