NAD/NADH models with axial/central chiralities: Superiority of the quinoline ring system

Precursors of NAD model compounds 1c and 3a,b were successfully resolved in to their atropisomers with respect to carbamoyl rotation. Atropisomers of q uinoline derivatives are much more stable than pyridine derivatives as dete rmined by cyclic voltammetry and X-ray crystallography. The 1,4-reduction o f NAD model compound 4 was successfully achieved, affording novel NADH mode l compound 5. The rotational properties of the side chain of 5 were investi gated by means of dynamic NMR. The rotational rate and syn/anti ratio, whic h indicate the orientation between carbonyl oxygen and hydrogen at the 4-po sition, are significantly affected by addition of magnesium ion. In the rot ational transition state, the double-bond character of the CcarbonylNamide bond is disrupted judging from the activation parameters. The oxidation of chiral 5 with p-benzoquinone in the presence of magnesium ion catalyst gave predominantly one enantiomer of 4. On the other hand, oxidation of 5 with p-chloranil (tetrachloro-p-benzoquinane) in the absence of magnesium ions a ffords the opposite enantiomer of 4 as the major product. The product enant iomer ratio is parallel to the syn/anti ratio in the starting material, ind icating the importance of ground state conformation to stereochemistry of t he reaction.