Synthesis of 2,2' -anhydro-2 -hydroxy- and 6,2'-anhydro- 6-hydroxy-1-β-d-arabinofuranqsylniootinamide as conpokmationally restricted nicotinamide nucleoside analogs

1-(β-D-Ribofuranosyl)-2 (1H)-pyridone-3-carboxamide (6a) and the 6(1H)-pyridone derivative (6b) were prepared by condensation of 1,2,3,5-tetra-CHacetyl-/?-D-ribofuranose (3) with 2- and 6-hydroxynicotinic acid, respectively, to 4a and 4b, followed by conversion of the carboxylic acid function of 4a, b into their corresponding carboxamides 5, and then deprotection of 5. Both 6a and 6b were then treated with 1,3-dichloro-1,1,3,3-tetraisopropyldisiloxane to give the corresponding 3', 5'-O-TPDS derivatives, 7a and 7b. Mesylation of 7a,b with mesyl chloride in pyridine afforded the stable, protected mesylates 8a,b. Upon de-O-silylation of 8a,b with Et₃NHF gave a mixture of unprotected mesylates 9a,b and 2,2-anhydro- and 6,2¹-anhydronucleosides, la and lb. Upon storage of 9a,b at room temperature, they are quantitatively converted into la,b. Mild alkaline hydrolysis of la,b afforded their corresponding arabino nucleosides 10a, b.