Efficient Enzymatic Routes for the Synthesis of New Eight-membered Cyclic β-Amino Acid and β-Lactam Enantiomers

Abstract

Efficient enzymatic resolutions are reported for the preparation of new eight-membered ring-fused enantiomeric β-amino acids [(1R,2S)-9 and (1S,2R)-9] and β-lactams [(1S,8R)-3, (1R,8S)-3 (1S,8R)-4 and (1R,8S)-7], through asymmetric acylation of (±)-4 (E > 100) or enantioselective hydrolysis (E > 200) of the corresponding inactivated (±)-3 or activated (±)-4 β-lactams, catalyzed by PSIM or CAL-B in an organic solvent. CAL-B-catalyzed ring cleavage of (±)-6 (E > 200) resulted in the unreacted (1S,8R)-6, potential intermediate for the synthesis of enantiomeric anatoxin-a. The best strategies, in view of E, reaction rate and product yields, which underline the importance of substrate engineering, are highlighted.

Alicyclic β- and γ-Amino Acids: Useful Scaffolds for the Stereocontrolled Access to Amino Acid-Based Carbocyclic Nucleoside Analogs

“…Taking into consideration our widespread experiences in selective and controlled functionalization of versatile unsaturated cyclic amino acid derivatives [35,36,37,38], further studies in order to investigate the possible functionalization of the ring olefin bond of product nucleoside analogs are currently being investigated in our laboratory. Furthermore, based on our experiences in enzymatic resolution of various bicyclic β- and γ-lactams [39,40], as well as on enzymatic ester hydrolysis methodologies [41], synthesis of enantiomerically pure substances will be performed.…”

New enzymatic strategies for the preparation of pharmaceutically important enantiomeric β-amino acid derivatives

“…The optical rotation values were determined based on literature data [57,156] and considering that CALB exhibits (S)-selective hydrolysis for cis compounds.…”