10.1021/jo060920l.s002
James T. Slama
James T.
Slama
Nimish Mehta
Nimish
Mehta
Ewa Skrzypczak-Jankun
Ewa
Skrzypczak-Jankun
Carbocyclic Ribosylamines: Synthesis of
5-Substituted Carbocyclic β-Ribofuranosylamines
American Chemical Society
2006
hydroxylation products
carbocyclic nucleoside analogues
OsO 4 approach
carbocyclic sugar production
Carbocyclic
apically brominated lactam
2006-09-29 00:00:00
Journal contribution
https://acs.figshare.com/articles/journal_contribution/Carbocyclic_Ribosylamines_Synthesis_of_5_Substituted_Carbocyclic_Ribofuranosylamines/3056665
A synthesis of 5-substituted cyclopentylamine precursors for
5‘-substituted carbocyclic nucleoside analogues was developed. We show that the stereochemistry of the OsO<sub>4</sub>-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 OsO<sub>4</sub> approach from the endo-face, yielding hydroxylation products analogous to carbocyclic lyxosides. A
key intermediate for carbocyclic sugar production, (1<i>S</i>,2<i>S</i>,3<i>R</i>,
4<i>R</i>,5<i>S</i>)-1-(<i>tert</i>-butyloxycarbonyl)amino-5-bromo-2,3-(dimethylmethylene)dioxy-4-hydroxymethylcyclopentane, was synthesized starting from a commercially available enantiomerically pure lactam, (1<i>S</i>)-(+)-2-azabicyclo[2.2.1]hept-5-en-3-one, in seven steps in an overall yield of 21%.