A new synthetic use of nucleoside N1-oxides

Abstract

The use of adenosine N/sup 1/-oxide derivatives to prevent intramolecular cyclization during nucleophilic displacement reactions on the sugar moiety is described. This new synthetic use of N/sup 1/-oxides is illustrated by the synthesis of 5'-O-(p-toluenesulfonyl)-2',3'-O-isopropylideneadenosine N/sup 1/-oxide (6) and subsequent displacement of the 5' substituent with iodide or azide under conditions which lead exclusively to N/sup 3/..-->..5' intramolecular cyclization in the absence of the N/sup 1/-oxide. Similarly, reaction of 2',3'-O-isopropylideneadenosine N/sup 1/-oxide with methyltriphenoxyphosphonium iodide produces 5'-iodo-5'-deoxy-2',3'-O-isopropylideneadenosine N/sup 1/-oxide (7) with no observable cyclization. In addition, 2',3'-anhydroadenosine N/sup 1/-oxide (17) is shown to be stable under conditions that lead to complete N/sup 3/..-->..3' intramolecular cyclization in the upprotected 2',3'-anhydroadenosine (14). Reduction of the N/sup 1/-oxide to produce the parent nucleoside is readily achieved by using hexachlorodisilane or by hydrogenating over Raney nickel. The mechanistical rationale and implications for additional nucleoside transformations are discussed. 2 tables, 1 figure.