Regioselective Enzymatic Synthesis Of Compounds Containing Sugars In Nonaqueous Media

Selective synthesis is an important direction in organic chemistry. Enzymatic synthesis attracts attention because of its high selectivity, mild condition and high rate. CDs and rutin et al. are compounds containing sugar with many similarly active groups. It is important to selectively synthesize their derivatives for developing pro-drug with new structure. Therefore, the study of enzymatic selective synthesis by solvent and substrate engineering plays an important role in theory research and application.The regio-selective transesterification of β-CD, rutin, troxerutin, naringin and hesperidin with divinyl dicarboxylates and vinyl alphatic esters was catalyzed by enzymes. In the thesis, 33 derivatives containing sugar were prepared and 23 products were new compounds. Product structures were characterized and confirmed by ¹H NMR, ¹³C NMR, FTIR, ESI-MS.Influence factors in enzymatic synthesis such as enzyme sources, reaction solvents, chain length of acyl donors, water content and reaction time were studied. Transesterification of β-CD was catalyzed by the alkaline protease from Bacillus subtilis in anhydrous DMF, furnished the corresponding β-CD derivatives with monoacylation occurring at the C-2 secondary hydroxyl groups. Troxerutin was selectively acylated at primary hydroxyl of ethylol catalyzed by the alkaline protease from Bacillus subtilis in anhydrous pyridine. Naringin was acylated at 6"-OH of glucose moiety catalyzed by Novozym 435 in 2-methyl-2-butanol.The controllable regio-selective acylation of rutin was proposed. An efficient synthesis of rutin esters has been developed. Enzymatic selectivity was affected by substrate and solvent. Alkaline protease from Bacillus subtilis obtained 3"-O-substituted rutin esters in pyridine, Novozym 435 provided 4'''-O-substituted rutin esters products in tert-butanol.The influence of ultrasound on the enzymatic reaction was studied. Ultrasound accelerated enzymatic synthesis of glucose esters and troxerutin esters in nonaqueous solvent was investigated, and the influence of the power (50 w, 100 w, 120 w) of the ultrasound, operational manner (continuous ultrasound, 10 min ultrasound / 20 min shaking) and ultrasound time were discussed. The result showed that accelerated effect of ultrasound on enzymatic reaction varied with chain length of acyl donors, and the reaction time was shortened by 80% when divinyl butanedioate was used as acyl donor. The activity of enzyme under pre-ultrasound was also studied. The result showed that ultrasound accelerated the enzymatic synthesis, but did not change the selectivity of enzyme.