Synthesis of 6,2’-Methano-cyclouridine, a Uridine Fixed in High-Anti Conformation (Nucleosides and Nucleotides. LX)

Abstract

The reaction of methylenetriphenylphosphorane with 2’-keto-3’,5’-O-(tetraisopropyldisil-oxane-l,3-diyl)uridine afforded the 2’-methyleneuridine (1). Oxidation of 1 with osmium tetroxide and tert-butyl hydroperoxide or N-methylmorpholine-N-oxide afforded a mixture of a 2’-hydroxymethyluridine (2) and its arabinosyl isomer. Oxidation at lower temperature gave the former as the main product. Compound 2 was converted to the 5-bromo-2’-iodomethyl derivative (3) through the 2’-mesyloxy compound, and 3 was treated with tri-n-butyltin hydride to give the 6,2’-methano-cyclo-5,6-dihydro derivative (4). Compound 4 was dehydrobrominated and deprotected to furnish 6,2’-methano-cyclouridine, a uridine fixed in high-anti conformation. Some results on the synthesis and cleavage of the 2’-spiro-epoxy derivative prepared from the 2’-ketouridine are also presented. © 1985, The Pharmaceutical Society of Japan. All rights reserved.