Models of NADH with C2 and D2 Symmetry
Doctoral thesis, 1995
A novel supramolecular approach to the design of NADH models is presented in this dissertation. The models can be divided into two types, C2 symmetric and D2 symmetric macrocyclic structures. The C2 symmetric models are made from a chiral C2 symmetric unit, two dihydronicotinamide units and a phenylene spacer, to form a macrocyclic structure. The use of cyclic models has restricted the number of possible conformations of the NADH models. By this method, H4R and H4S in the dihydropyridine ring have been made distinctly different, as shown by their different 1H-NMR shifts in the C2 symmetric models. Furthermore, zinc tetraphenylporphyrin (ZnTPP) has been used to determine which of the two, H4R or H4S, is the reactive hydrogen. One of the models has been shown, by deuterium marking, to stereospecifically deliver only one of the diastereotopic hydrogens to a reactive carbonyl compound via a boat-like structure of the dihydropyridine ring. By the use of ZnTPP as a shift reagent, it could be determined that zinc coordinates to the carboxamide oxygen of the C2 symmetric NADH model. Furthermore, the enantiomeric excess, when reducing methyl phenyl pyruvate to methyl mandelate, is high. Based on the ordered structure of the NADH model and the knowledge of which hydrogen is the reactive one, a refined mechanistic model has been suggested. The D2 symmetric NADH models are introduced as potential chiral hydride transfer reagents. The models are made from two C2 symmetric chiral units with two pyridinium ions each. By connecting these units with phenylene spacers, a hydrophobic cavity is formed and the pyridinium ions act as ion-pairing devices. It has been shown that these macrocyclic compounds with paraphenylene spacers have the capacity to encapsulate small charged and polar guests. This host also forms a complex with N-benzyldihydronicotinamide in water. In this complex, a hydride ion is transferred from the guest to the host.