Study On Synthesis And Biological Activity Of N-2-deoxy-α-D-glucose Urea Derivatives

Glucosamine is the organism of adaptive molecular, biological processesinvolved in almost all the life body, is a kind of important biological active substance.Studies have shown that it has a certain role in killing tumor cells and anti-virus. Atthe same time, glucosamine has good water solubility, low toxicity, advantages ofeasy decomposition and so on. Lead compounds of glucosamine modified can prolongthe time of drug action, enhance the efficacy and reduce toxicity. Therefore,glucosamine is one of the important raw materials of lead drug modification. Ureacompounds are widely used in the field of medicine and pesticide with the diversity ofstructure variety and biological activities. Taking glucosamine as raw material ofmodified urea compounds in anti-virus and anti-tumor have a unique pharmacologicalactivities.In this article,1,3,4,6-tetra-O-acetyl--D-glucosamine was prepared by directacetylation of D-glucosamine hydrochloride with acetic anhydride. The structures of1,3,4,6-tetra-O-acetyl--D-glucosamine was analyzed by MS,1H NMR, and13CNMR spectroscopy. Then1,3,4,6-tetra-O-acetyl--D-glucosamine were transformedinto the corresponding isocyanate by using triphosgene as the isocyanation agent in anTHF system and four novel N-(1,3,4,6-tetra-O-acetyl)--D-glucose urea wereefficiently synthesized by coupling the isocyanate with aminopydine. The optimalreaction condition was confirmed by investigating ratio of substrate and reactiontemperature on the yield.Subsequently, four new N-2-deoxy--D-glucose urea were synthesized byhydrolysis the acetyl of N-(1,3,4,6-tetra-O-acetyl)--D-glucose urea with sodiummethoxide/methanol, and investigated the factors such as the dosage of sodiummethoxide and post-processing effect on yield.The structures of these8new sugarurea compounds were analyzed by MS, IR, UV,1H NMR, and13C NMR spectroscopy.The results proved that this method was simple and efficient with the target products owning single configurations.At the same time, the anti-tumor activity and anti-virus activity in vitro of these8sugar urea were researched. The results showed that with a strong electronwithdrawing sugar pyridylureas could effectively inhibit the activity of SGC-7901andhave a certain degree of concentration dependent; Compound L10can effectivelyinhibit the activity of influenza a virus...