The overarching goal of our research program has been the development of synthetic strategies that permit facile, stereocontrolled access to carbocyclic analogues of purine and pyrimidine nucleosides. These compounds are found to exhibit a variety of therapeutically-promising properties which include antitumor, antibacterial, and antiviral activities. Aristeromycin (1) is representative of this intriguing class of naturally occurring compounds and was selected as the centerpiece of this synthetic endeavor. Our enantioselective approach to the target molecule is outlined in retrosynthetic format (Scheme 1). Optically active (+)-cis-4-acetoxy-1-hydroxy-cyclopent-2-ene ((+)-2 was selected as our retrosynthetic starting material for a number of strategic reasons including the preeminent fact that it shares the same absolute configuration found in natural nucleosides.

The search for a high-yield route to (+)-2 led us to the discovery that the enzyme acetyl cholinesterase from Electrophorus electricus (electric eel; EEAC) could enantiotopically differentiate between pro-R and pro-S acetoxy groups on meso-diester 4 to afford chiral 2 with a selectivity of 96% enantiomeric excess (> 99%, i.e. after one recrystallization) and a chemical yield of 94% (equation 1). Since we first published this result, a spinkling of reports involving EEAC with other meso-diester substrates has appeared in the literature. These encouraging findings have prompted us to further investigate the scope and limitations of using EEAC in organic synthesis.