The Research On Synthesis Of Lamivudine And L-menthyl-α-D-mannopyranoside

Carbohydrates, proteins, nucleic acids and lipids are the four basic substances in Biological molecules, in which sugar is the most widely distributed and the largest number of a class of organic compounds in nature, Many sugar derivatives have a wide applications in the chemical and life sciences fields. This paper investigates the synthesis of two sugar derivatives which are lamivudine and L-menthyl-a-D-mannopyranoside.Lamivudine is a 2',3'-dideoxynucleoside analogue and nucleoside reverse transcriptase inhibitor. Lamivudine was originally used to treat HIV infection, and latter was also found having a significant inhibitory effect on the synthesis of HBV-DNA. Clinical trials have shown that lamivudine have higher antiviral activity and lower cytotoxicity for human cells.. In this article, the intermediates compound L-Menthyl glyoxylate was synthesized with acetic acid or glycoxylic acid as a raw material and the two routes has been improved. In the first route, using acetic acid as a raw material, through a-bromination, esterification, nucleophilic substitution, oxidation reduced to L-Menthyl glyoxylate. We used vacuum distillation and recrystallization to replace the column chromatography method. In the improved method, the ratio of raw materials was changed and the yield was increased. With glyoxylic acid as the raw material through esterification, salification, and then converted to intermediate L-Menthyl glyoxylate. The reaction time was reduced by changing the solution concentration of sodium bisulfite and feed ratio. The excess of raw materials were realized by vacuum distillation. L-Menthyl glyoxylate was reacted to cyclization with 2,5-dihydroxy-1,4-dithiane, subsequently chlorinated, coupled, and reduced to obtain lamivudine. Meanwhile, different reagents and proportion were trying in the synthetic route. The improved technology herein is applicable to industrial production having the advantage of fewer steps, concise and practical operation and low cost.Menthol-glycosides as important glucoside derivatives of menthol which have a better water-solubility and thermal stability than menthol can be widely used in flavor and drug.L-menthyl-a-D-mannopyranoside was synthesized with mannose and menthol as the raw material after multi-step reaction such as protection, coupling and deprotection. Based on discussing the influencing factors for the coupling reaction of 1,2,3,4,6-Pentakis-O-acetyl-D-mannopyranoside and L-menthol, the optimized reaction conditions was as follows:using CH2Cl2 as solvent, n (1,2,3,4,6-Pentakis-O-acetyl-D-mannopyranoside):n (L-menthol):n (BF3-Et2O)=1: 3:4, at 25℃for 9 h, the yield was obtained 47.6%.