ENZYMATIC RESOLUTION OF AMINOCYCLOPENTENOLS AS PRECURSORS TO D-CARBOCYCLIC AND L-CARBOCYCLIC NUCLEOSIDES

Racemic cis-4-aminocyclopent-2-en-1-ols were synthesized in three step s utilizing hetero Diels-Alder chemistry. Starting from suitably prote cted hydroxylamines, oxidization with sodium periodate and trapping wi th cyclopentadiene afforded cycloadducts (+/-)-5a-d. The N-O bond of t he cycloadducts was reduced with Mo(CO)(6) to afford (+/-)-cis-4-amino cyclopent-2-en-1-ols (+/-)-6a-d. These compounds, or their correspondi ng acetates, were kinetically resolved by enzymatic acetylation or hyd rolysis, 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 i n 90% and 92% ee, respectively, after 40% conversion. Enzymatic hydrol ysis 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 (+)ed and (+)-7d in 92% ee (99% ee after a single recrystallization) after 40% conversion. Further syn thetic transformations of these resolved synthetic building blocks and derivatives are also reported.