Pyrimidine homonucleoside analogues from 2,5-anhydroaldose derivatives

Article abstract of DOI:10.1016/S0008-6215(00)83491-6

3,4-Di-O-acetyl-2,5-anhydro-D-xylose diisobutyl dithioacetal (1) reacts with bromine to give a monobromo derivative which, on condensation with 2,4-diethoxy-pyrimidine or its 5-methyl analogue, affords the protected nucleoside derivatives 4 and 11, respectively; ammonolysis of 4 gave the cytosine "homonucleoside" 7, and hydrolysis of 11 gave the thymine "homonucleoside" 12. The same type of "homonucleoside" may be produced by cyclization of the sugar chain in a suitable acyclic-sugar nucleoside, as in the conversion of 1-S-ethyl-1-thio-1-(uracil-1-yl)-D-xylitol (16, obtained from tetra-O-acetyl-D-xylose diethyl dithioacetal, 9), by the action of one molar equivalent of p-toluenesulfonyl chloride, into a homonucleoside isolated as its diacetate 17; acyclic-sugar derivatives not susceptible to such cyclization afford instead the 5-p-toluenesulfonates, as exemplified by the conversion of the D-arabino analogue (13) of 16 into the 5′-ester 14. When cyclohexene is used to remove the excess of bromine in the preparation of nucleoside analogues from dithioacetals, the alkylsulfenyl bromide produced may react, by way of its cyclohexene adduct, with the hoterocyclic base to give cyclohexane-base adducts, for example, compounds 6 and 10.