Study On Improving Synthesis Technology And Bio-Activity Of Anti-Hiv Polysaccharides

The synthesis technology of sulfatized polysaccharide-AZT conjunction has been improved extremely. The detail synthesis process is as following. First step, 3-azido-3-deoxy-5-O-succinyl-thymidine(5x-Suc-AZT) was obtained by reaction of 3-azido-2'3'-dideoxythymidine(AZT) and Succinic anhydride in Pyridine, catalyzed by 4-Dimethylaminopyridine(DMAP), then the pyridine was extracted from reaction solvent after the reaction finished. Followed that, sulfatized Starch-AZT conjunction was obtained by reaction of 5'-Suc-AZT and water-soluble starch in DMSO, catalyzed by DMAP and N,N'-dicyclohexylcarbodiimide (DCC). Second step, After sulfatized by SO3 Py, The sulfatized polysaccharide-AZT conjunction, with DSAZT=0.12-0.20, DSSul=1.0~1.5 and Mn=1.4-2.1X104, was obtained. There were some obvious advantages in improved synthesis technology contrasting with originel one. A lost of reagents and time were used to separate intexmediate product by column chromatography have been sared . because a series of synthesisreactions were made to occur continuonsly. There was no need to separate intermediate product. So improved synthesis technology was veryconveninent to operale, and could economize a lot of labors and money.According to anti-HIV experiment in vitro, It was shown that sulfatized polysaccharide-AZT, with DSAZT=0.13, DSSul=1.0 and Mn=1.6X 104, has very higher anti-HIV selectivity SI, which is 7350, that is 1.8 times that of AZT (SI=4006) and 6.3 times that of DDC(SI=1172). Meanwhile, the toxicity of sulfatized polysaccharide-AZT conjunction(CC50=710.6ug/mL) is 1/10 that of AZT(CC50=68.4ug/mL). As a result, sulfatized polysaccharide-AZT conjunction obtained by improved synthesis technology has higher selectivity and lower toxicity .So that is a kind of potential drug compound to treat AIDS.Through anticoagulation experiments in vitro and in vivo, It was discovered that sulfatized polysaccharide-AZT conjunction has anticoagulation activity. Furthermore, the research results indicated that sulfatized polysaccharide-AZT conjunction was degraded to AZT , succinic acid and SO3 in succession.The extraction water-soluble starch from starch and sulfatization technology have been optimized by orthogonal test. The results as following, 1. The most optimum technology condition for the former is [H+]=0.5 mol L-1 and hydrolyzation for 2h at 70C. 2. to the latter, that is sulfatization reagent is 4.5 times (mol ratio) at 40C for 2.0h...