Synthesis Two Fused-Ring Analogues Of Nucleosides

Recnetly confromational restricted nucleosides attract more attections. The specificity nucleosides result from an alkane chain or analogue covalently link two carbon atoms or a carbon and an oxygen of them.The modified nucleosides are modulated and constrained into a specific confromation, their relatively rigid intrastrand structure can dicate different biochemical properties, for example, towards specificty nuclease or other enzymes. Many confromational restricted nucleosides have demonstrated potent antiviral or antitumour activities, and many of them are implanted in antisense oligonucleotides and interferece RNA which is efficient and low toxic theropetic means.The first part of the dissertation, design and synthesis of 2′,3′,5′-condensed nucleoside were introduced, two methods were carried out. The first method resorted to the most usual way of intramolecular nucleophilic 5′-O-NH2 group substititution of 2′,3′-mesylate. Starting from uridine, after a sequence of protecting all the hydroxyl with TBS, selectively deprotecting 5′-TBS, mesylation of 5′-hydroxyl and substitition of 5′-mesthlate with N-hydroxyphthalimide, amination by methylhydrazine, deprotecting the TBS group of 2′and 3′-hydroxy, mesthlation of 2′and 3′-hydroxy gave the precursor compound. Many basic cyclolization were attempted, but only 3′,5′-cyclo-2,2′-anhydrouridine was produced instead of target compound. To avoiding 2,2′-anhydro product we protected 3-N of uridine, after the same synthsis procedure, we got N3-benzyl-5′-O-amino-2′,3′-mesthlate uridine, but after many different conditions only complecated decompose compounds was resulted. We also attempted synthsized the target product through key intermediateof eneselone nucleoside, via Michael addition and nucleophilic substitution. Also starting from uridine, protecting the 5′-hydroxyl with trityl, mesthlation of 2′and 3′-hydroxyl,then treated the intermediate with sodium hydroxide to produce the 2′,3′-epoxide uridine. Nucleophic open epoxide with PhSe anion gave the 3′-phenyl selenyl uridine, elimination of 2′-hydroxyl gave the eneselone uridine, but when attempted to introduce amino group on 5′-position, only decomposed product was obtained because of the disstablization of the eneselone.In the second part synthsis of tetrazole modified 3′,5′-fused nucleoside via 1,3-dipolar cycloaddition between of azido and cyano group was introduced. 3′-α-azido thymidine was obtained via LiN3 attaction 3′-β-mesthlate. After protecting the 3-N with benzyl group, cyanoethyl was introduced on 5′- hydroxyl, the precursor was treated in refluxing xylene, and two main product were got, one of them is target compound and the other is N6,3′-cyclo-5′-O-cyanomethyl-thymidine. Both of the crystal was obtained and characterized by X-ray Single Crystal Diffraction. The conformation of the products was carried out particularly.