Synthetic approaches to carbocyclic nucleosides

Abstract

For the syntheses of (-)-aristeromycin, (-)-neplanocin A and their 4``-modified analogues, key intermediates 44 and 113 were synthesized in two independent routes, and further elaboration was attempted. First, 44 was prepared via intramolecular 1,3-dipolar cycloaddition of nitrone 41 as a key step. Lactol 38, derived from D-isoascorbic acid, was olefinated, oxidized and converted into nitrone 41. Cyclization of nitrone 41 gave the bridged isoxazolidine 42a, of which N-O bond was cleaved and the generated amino group was protected with di-t-butyl dicarbonate. The resulting key intermediate 44 was oxidized to ketone 47 and then hydroxymethyl equivalent was added to 47. In our second synthetic route, stereoselective cyclization of allylic imidate 102 and radical cyclization of iodide 112 were employed as key steps. A stereoselective iodoamination of allylic imidate 102 and the subsequent elimination gave radical cyclization precursor 112, which was cyclized with triphenyltin hydride in the presence of triethylborane to furnish sulfone 113.