A New Synthetic Use of Nucleoside N1-Oxides

Article abstract of DOI:10.1021/jo01293a005

The use of adenosine N¹-oxide derivatives to prevent intramolecular cyclization during nucleophilic displacement reactions on the sugar moiety is described.This new synthetic use of N¹-oxides is illustrated by the synthesis of 5'-O-(p-toluenesulfonyl)-2',3'-O-isopropylideneadenosine N¹-oxide (6) and subsequent displacement of the 5' substituent with iodide or azide under conditions which lead exclusively to N³->5' intramolecular cyclization in the absence of the N¹-oxide.Similarly, reaction of 2',3'-O-isopropylideneadenosine N¹-oxide with methyltriphenoxyphosphonium iodide produces 5'-iodo-5'-deoxy-2',3'-O-isopropylideneadenosine N¹-oxide (7) with no observable cyclization.In addition, 2',3'-anhydroadenosine N¹-oxide (17) is shown to be stable under conditions that lead to complete N³->3' intramolecular cyclization in the unprotected 2',3'-anhydroadenosine (14).Reduction of the N¹-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.