NAD/NADH Models with Axial/Central Chiralities:  Superiority of the Quinoline Ring System

Abstract

Precursors of NAD model compounds 1c and 3a,b were successfully resolved into their atropisomers with respect to carbamoyl rotation. Atropisomers of quinoline derivatives are much more stable than pyridine derivatives as determined by cyclic voltammetry and X-ray crystallography. The 1,4-reduction of NAD model compound 4 was successfully achieved, affording novel NADH model compound 5. The rotational properties of the side chain of 5 were investigated by means of dynamic NMR. The rotational rate and syn/anti ratio, which indicate the orientation between carbonyl oxygen and hydrogen at the 4-position, are significantly affected by addition of magnesium ion. In the rotational transition state, the double-bond character of the C(carbonyl)-N(amide) 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-benzoquinone) in the absence of magnesium ions affords the opposite enantiomer of 4 as the major product. The product enantiomer ratio is parallel to the syn/anti ratio in the starting material, indicating the importance of ground state conformation to stereochemistry of the reaction.

Redox‐ and Hypoxia‐Responsive MRI Contrast Agents

“…Based on this result, a biocompatible PARACEST redox sensor was developed by mimicking one of the most important biological redox systems, the NADH/NAD + couple. [58] Eu 3+ - 16 , containing two N -methylquinolinium moieties as redox-active functional groups, [59] was nearly MRI silent in its oxidized form, but was turned on after reduction to the dihydroquinoline derivative by NADH (Figure 16). The larger CEST signal upon reduction arose from the slower, more optimal water exchange rate of the reduced form ( τ M = 90 μs).…”

Progress on Chiral NAD(P)H Model Compounds

“…[1][2][3][4][5][6][7] NADPH (Figure 1) plays a vital part in biological chemistry, for example in photosynthesis, glycolysis, citric acid metabolism, and amino acid decomposition. [8][9][10][11][12][13][14] The study of NADPH is crucial because it will help to solve two major scientific problems of biological photochemistry: (1) how carbon dioxide is reduced into sugar using ATP and coenzyme NADPH in the presence of dehydrogenase and other biocatalysts during the dark reactions of photosynthesis; and (2) how water is oxidized and released as oxygen in the complex "Z" pathway and how NAD(P) + serves as terminal electron acceptor in photosystem II (PSII) of photosynthesis.…”

Deracemization of Axially Chiral Nicotinamides by Dynamic Salt Formation with Enantiopure Dibenzoyltartaric Acid (DBTA)

“…Among a series of aromatic amides, nicotinamide is important because it is an essential element of nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP), which are known for their part in biomimetic asymmetric reduction and oxidation in NAD/NADH model systems. The importance of nicotinamides has been demonstrated in both biology and chemistry [22][23][24][25][26]; however, only a few examples of axially chiral nicotinamides have been reported and used for asymmetric synthesis [26][27][28][29][30][31][32][33]. We are interested in the development of convenient methods for preparing axially chiral nicotinamides through dynamic resolution by crystallization.…”