ATROPISOMERIC FLAVOENZYME MODELS WITH A MODIFIED PYRIMIDINE RING - SYNTHESES, PHYSICAL-PROPERTIES, AND STEREOCHEMISTRY IN THE REACTIONS WITH NAD(P)H ANALOGS

Optically active 5-deazaflavin derivatives phenyl)pyrimido[4,5-b]quino line-2,4(3H,10H)-dione) with an axial chirality at the pyrimidine ring have been synthesized, and the kinetics of enantiomerization have bee n measured for some of them. The absolute configurations of these comp ounds have been determined by X-ray crystallographic analysis and chem ical reactions for the first time in atropisomeric flavoenzyme models. Enantioface-differentiating (net) hydride-transfer reactions with 1-b enzyl-1,4-dihydronicotinamide (BNAH) have revealed that the selectivit y of the reacting face. of the 3-[2-(hydroxymethyl)phenyl] derivative 1 changes depending on the presence or absence of Mg2+; the hydroxymet hyl group of 1 exerts steric inhibition in the absence of Mg2+, wherea s it facilitates the approach of BNAH. in the presence of Mg2+ Asymmet ric (net) hydride-transfer reactions with chiral methyl-N-(alpha-methy lbenzyl)-1-propylnicotinamide (Me(2)PNPH) predict that the most favora ble intermolecular arrangement of these two molecules at the transitio n state is the one in which the pyrimidine ring of 1 and the carbamoyl group of Me(2)PNPH tend to face each other and the maximum overlap of their molecular planes is achieved regardless of the presence or abse nce of Mg2+. The arrangement mimics that of FAD and NADPH in the activ e site of a flavoenzyme. The present result indicates an energetically favorable overlap of the molecular planes of a flavin and an NAD(P)H coenzyme, as well. as a significant influence of functional groups fro m an apoenzyme in proximity to a flavin coenzyme on the stereochemistr y of biological redox reactions.