Enzymatic Resolution of Aminocyclopentenols as Precursors to d - and l -Carbocyclic Nucleosides

Racemic cis -4-aminocyclopent-2-en-1-ols were synthesized in three steps utilizing hetero Diels−Alder chemistry. Starting from suitably protected hydroxylamines, oxidization with sodium periodate and trapping with cyclopentadiene afforded cycloadducts (±)- 5a − d . The N−O bond of the cycloadducts was reduced with Mo(CO) 6 to afford (±)- cis -4-aminocyclopent-2-en-1-ols (±)- 6a − d . These compounds, or their corresponding acetates, were kinetically resolved by enzymatic acetylation or hydrolysis, respectively. Enzymatic acetylation of cis - N -(benzylcarbamoyl)-4-aminocyclopent-2-enol [(±)- 6a ] with Candida antarctica B lipase and Pseudomonas species lipase gave the corresponding acetate (−)- 7a in 90% and 92% ee, respectively, after 40% conversion. Enzymatic hydrolysis of cis - N -acetyl-4-aminocyclopent-2-enol 1- O -acetate (±)- 7d with electric eel acetylcholine esterase was successful in providing both cis - N -acetyl-4-aminocyclopent-2-enols (+)- 6d and (+)- 7d in 92% ee (99% ee after a single recrystallization) after 40% conversion. Further synthetic transformations of these resolved synthetic building blocks and derivatives are also reported.