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

Efficient enzymatic resolutions are reported for the preparation of new eight-membered ring-fused enantiomeric β-amino acids [(1 R ,2 S )- 9 and (1 S ,2 R )- 9 ] and β-lactams [(1 S ,8 R )- 3 , (1 R ,8 S )- 3 (1 S ,8 R )- 4 and (1 R ,8 S )- 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 (1 S ,8 R )- 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.