Selective Protection Of 2, 5- Or 3, 5-Hydroxyl Groups Of D-ribose And Synthesis Of 4'-Spironucleoside

This dissertation is divided into two chapters. The first chapter deals with the selective protection of 2,5-,3,5-hydroxyl groups of D-ribose. The second chapter deals with the synthesis of the 4′-spironucleoside. All the final products and key intermediates were fully characterized by 1H NMR, 13C NMR.Chapter one, section one describes physical properties, origins and uses of D-ribose. Section two design two methods of the selective protection of 2,5- and 3,5-hydroxyl groups of D-ribose. The first method is selectively protect 2,5- or 3,5-hydroxyl groups of D-ribose with BuSO2 as auxiliaries reagent. In this protocol stannylene species are generated which reacted with BnBr leading to products of O-monobenzylation of 2,3-diols., After trying a mixture of 2,5- and 3,5-protecting D-ribose were produced, with moderate selectivity, and the ratio of two products is 5:2. In the other method, which is better,2,3-O-benzylidene-5-benzyl -5-benzyl-D-ribofuranoside was synthesized from D-ribose, then different reducing conditions were tested for its selectively opening of the five -member ring to produce .2,5- and 3,5-protecting D-ribose with ratio of 1:7.Chapter two, part one provides the background and significance of 4′-spiro nuclesides. Modified nucleoside played an essential role in therapy against epidemical diseases caused by virus infection. Recently some 4′-modified nucleosides are found excellent activities towards HIV and HCV virus. Notably, unlike clinically used NRTIs, the presence of 3′-hydroxyl turned out to be critical for maintaining the activity of 4′-substituted deoxynucleosides. Despite the presence of 3′-hydroxyl, 4′-substituted deoxynucleosides triphosphate acts as a chain terminator upon its incorporation into DNA by RT Part two designs and synthesize of the 4′-spironucleoside were introduced. Two methods in synthesis of the 4′-spironucleoside.One is pure spiro lactone was synthesized enantiomerically,, then coupling with the base; The other is directly modified on the sugar rings of natural nucleotides. This dissertation refers to the second method. First, 4′-azido-uridine has been synthesized through 4 steps according literatures. After protecting 2-,3-hydroxyl groups at the same time with isopropyl, ,allylation on the 5′-hydroxyl was carried out, the product underwent 1,3-dipolar cycloaddition during reaction and resulted a good yield. In these part, we got a efficent method to synthsize 4′-modified spirouridine, with azido and alkyne 1,3-dioplar cycloaddition.