Stereomodulating effect of remote groups on the NADH-mimetic reduction of alkyl aroylformates with 1,4-dihydronicotinamide-β-lactam amides

Conformationally restricted NADH peptidomimetics 4a-e, characterized by the presence of a (1,4-dihydronicotinamide)-(beta-lactam) moiety, have been synthesized and used to study the Mg2+ cation-promoted asymmetric reduction of alkyl aroylformates in acetonitrile. Increasing the bulkiness of peripheral substituents at the nitrogen atom of the beta-lactam ring, at the 1,4-dihydronicotinamide moiety, or at the aroylformate ester group, was found to cause weak but clearly detectable variations of the enantiomeric excess of the reaction. A rational for these observations was consistent with a chelated NADH/Mg2+/ArCOCO2R3 ternary complex model, according to DFT calculations computed at a B3LYP/631G(sic) theory level. (C) 2010 Elsevier Ltd. All tights reserved.