1179897-81-4Relevant articles and documents
Stereomodulating effect of remote groups on the NADH-mimetic reduction of alkyl aroylformates with 1,4-dihydronicotinamide-β-lactam amides
Aizpurua, Jesus M.,Palomo, Claudio,Fratila, Raluca M.,Ferrón, Pablo,Miranda, José I.
, p. 3187 - 3194 (2010)
Conformationally restricted NADH peptidomimetics 4a-e, characterized by the presence of a (1,4-dihydronicotinamide)-(β-lactam) moiety, have been synthesized and used to study the Mg2+ cation-promoted asymmetric reduction of alkyl aroylformates
Mechanistic insights on the magnesium(II) ion-activated reduction of methyl benzoylformate with chelated NADH peptide β-lactam models
Aizpurua, Jesus M.,Palomo, Claudio,Fratila, Raluca M.,Ferron, Pablo,Benito, Ana,Gomez-Bengoa, Enrique,Miranda, Jose I.,Santos, Jose I.
supporting information; experimental part, p. 6691 - 6702 (2009/12/30)
(Chemical Equation Presented) Mechanistic details of the Mg2+ ion-activated enantioselective reduction of methyl benzoylformate have been investigated at a B3LYP/6-31G* theory level, using peptide NADH models 1 rigidified with a β-lactam ring. Computation of the reaction pathway revealed important structural differences between the intermediate NADH/Mg 2+/ArCOCO2R ternary complexes 3 and the corresponding transition states leading to enantiomeric methyl mandelates. Thus, ternary complexes showed the dihydronicotinamide moiety placed quasiequatorial to a seven-membered chelation pseudoplane including the two amide carbonyls and the Mg2+ cation, whereas productive transition states were strongly deformed with the dihydronicotinamide group oriented quasiaxial to the chelation pseudoplane. This chelation model was further applied to acyclic nonrigidified NADH models and, based on the fluxional mobility of the peptide chain bonds, experimental enantioselectivities were correctly predicted. Parallel experiments were also conducted in deuterated acetonitrile, using NMR techniques, to study the structure of the binary complexes 2 (NADH/Mg2+) and ternary complexes 3 (NADH/Mg2+/PhCOCO2Me). Finally, owing to the incorporation of two diastereotopic trimethylsilyl NMR-tags in the β-lactam-NADH peptidomimetics, a nonproductive ternary complex predicted by calculations could be observed and its structure characterized on the basis of ROESY experiments and molecular modeling.
