Carbocyclic Ribosylamines: Synthesis of 5-Substituted Carbocyclic β-Ribofuranosylamines

A synthesis of 5-substituted cyclopentylamine precursors for
5‘-substituted carbocyclic nucleoside analogues was developed. We show that the stereochemistry of the OsO4-catalyzed hydroxylation of an apically brominated lactam,
7-bromo-2-azabicyclo[2.2.1]hept-5-en-3-one, can be controlled through the appropriate selection of the lactam N−H
protecting group. Sterically large groups direct the hydroxylation to the exo-face of the olefin, yielding hydroxylation
products that can be converted into analogues of carbocyclic
ribosides. Conversely, a sterically small protecting group
permits OsO4 approach from the endo-face, yielding hydroxylation products analogous to carbocyclic lyxosides. A
key intermediate for carbocyclic sugar production, (1S,2S,3R,
4R,5S)-1-(tert-butyloxycarbonyl)amino-5-bromo-2,3-(dimethylmethylene)dioxy-4-hydroxymethylcyclopentane, was synthesized starting from a commercially available enantiomerically pure lactam, (1S)-(+)-2-azabicyclo[2.2.1]hept-5-en-3-one, in seven steps in an overall yield of 21%.