Sucralose, a chlorodeoxy derivative of sucrose, is a high intensity sweetener with significant characteristics. In this paper, sucralose was succeeded in synthesizing using two different routes, and the hydroxyl group protection and chlorinating methods were thoroughly studied.1. 6-position hydroxyl group in sucrose is very important to making sucralose in high intensive sweetness. It is necessary to pre-protecting sucrose 6-position hydroxyl group in the process of sucralose preparation.(1) Cyclic 4,6-orthoester is a more selective and effective method of preparing sucrose 6-acetate for protection 6-position hydroxyl group. The reaction of sucrose with triethyl orthoacetate is carried out in DMF solution catalyzed with toluene p-sulphonic acid at ambient. The amount of triethylorthoacetate should be excess over that sucrose required theoretically, typically 1.2 mole equivalent per mole sucrose, the amount of water 6-8 ME(based on sucrose). The reaction to isomerize the 4-ester to the 6-ester can be catalyzed by tert-butylamine, and t-butylamine concentration was about 3.0% by volume to DMF raising the pH to approximately 8-9. In this condition, yield of sucrose 6-acetate was about 75%.(2) Sucrose 6-acetate is essential intermediates for preparing sucralose with selective chlorination. In the first time, sucrose 6-acetate was succeeded in preparing by reacting of sucrose with isopropenyl acetate catalyzed by lipase in inert organic medium, and a new route for synthesis sucralose with enzyme-chemical combination was developed. Pyridine as reaction medium and heptane ad hydrophobicity regulator, lipase activity increased almost by 2 times when pyridine containing about 30-40% heptane by volume. The reaction carried out at 55-65℃ over 84-96hrs containing sucrose 8%, lipase PS Amano 4g/100ml and isopropenyl acetate 20%(v/v). In this condition, the total yield of sucrose 6-acetate was 41%.(3) 2,3,6,3',4'-penta-O-acetylsucrose prepared by tritylation is very complicated.