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Decitabine as a DNA methylation inhibitor , can penetrate the DNA in the role of the bone marrow in myelodysplastic syndrome have a significant effect . Recent studies suggest that decitabine by phosphorylation in the human body and human DNA by direct binding , and ultimately achieve the effect of the inhibition of DNA methylation . Decitabine Pliml and Sorm in 1964 by the first time through the multi-step reaction synthesis, recent studies show that the esterification and glycosylation bases silanated protection as intermediates can be obtained a higher yield . In this thesis, Decitabine Improved synthesis . Determined by analyzing various decitabine synthesis method Synthesis Route: 2 - deoxy -D-ribose with acetic anhydride in pyridine role acetylation, 5 - aza - cytosine silanated protected , again in the presence of a Lewis under the action of an acid both coupled to give 1 - ( 3,5 - two - D - acetyl-2 - deoxy -D -ribose ) -5 - aza- cytosine , and finally deprotected by alkaline , methanol recrystallized decitabine . Focuses on a CN coupling reaction of different catalysts , different amount of catalyst , solvent , and other factors on the reaction results , and post-processing of the exploration and research . Experimental results show that acetylation temperature 15 ° C for the best , the best yield of 83% ; The silanated protection using the one pot method, reflux, can be obtained 95 % yield at 120 ℃ ; the preferred CN coupling the catalyst is anhydrous SnCl4, the optimum amount of 1.5 -fold equivalent , the best solvent for the 1,2 - dichloroethane , this step and the reaction yield was 65% ; hydrolysis using diethylamine , triethylamine as a catalyst, removal of the acetyl protecting , 51.1% yield after recrystallization , the total yield of 26.2% . Improved decitabine synthesis process, using inexpensive SnCl4 Lewis acid catalysts , reagents and processing products and simplify the separation process , making the process more applications prospects , so the research has practical significance .
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