SYNTHESIS AND PROPERTIES OF 2'-DEOXY-2'-ALPHA-C-BRANCHED NUCLEOSIDES AND NUCLEOTIDES

Four functionalized 2'-deoxy-2'-alpha-C-branched nucleosides, namely, 2'-deoxy-2'-alpha-C-(carboxymethyl)-uridine, 2'-deoxy-2'-alpha-acetami douridine, 2'-deoxy-2'-alpha-C-(hydroxyethyl)uridine, and 2'-deoxy-2'- alpha-C-(2,3-dihydroxypropyl)uridine, have been prepared. Conversion o f these nucleosides to their appropriately protected phosphoramidites, followed by tetrazole-induced reaction with 2',3'-di-O-acetyluridine, oxidation, and subsequent deprotection furnished the corresponding di nucleoside monophosphates. During the oxidation of the amide-derived p hosphite, partial dehydration occurred to give a mixture of the amide- and nitrile-containing dimers. Interestingly, the ratio of amide to n itrile could be largely controlled by choice of oxidant. The hydroxyet hyl- and dihydroxypropyl-modified dimers were particularly resistant t o snake venom phosphodiesterase-catalyzed hydrolysis (relative half-li ves of 129 and 120, respectively, in comparison to UpU). It is anticip ated that these nucleoside analogues will ultimately be used in the co nstruction of ribozymes containing enhanced functionality and nuclease resistance.