Carbocyclic ribosylamines: synthesis of 5-substituted carbocyclic beta-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%.
Slama
James T
JT
Department of Medicinal & Biological Chemistry, University of Toledo, Toledo, Ohio 43606, USA. james.slama@utoledo.edu
Mehta
Nimish
N
Skrzypczak-Jankun
Ewa
E
D000146:Acids, Carbocyclic / Q000138:chemical synthesis*; D000606:Amino Sugars / Q000138:chemical synthesis*; D006900:Hydroxylation; D007769:Lactams / Q000737:chemistry; D012266:Ribose / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D013237:Stereoisomerism
C481638:1-amino-1-deoxyribose; D000146:Acids, Carbocyclic; D000606:Amino Sugars; D007769:Lactams; D012266:Ribose