NAD Model Compounds Research Articles

Consideration of molecular arrangements in regio- and enantioselective reduction of an NAD model compound controlled by carbonyl oxygen orientation

The regio- and enantioselectivity of the reduction of an NAD model compound having axial chirality with respect to the C(3)(quinolinium)-C(carbonyl) bond, 3-piperidinylcarbonyl-1,2,4-trimethylquinolinium ion (1), by using several reducing agents is described. Reaction of 1 with sodium hydrosulfite affords the 1,4-reduced product, 3-piperidinylcarbonyl-1,2,4-trimethyl-1,4-dihydroquinoline (), with low enantioselectivity, whereas sodium borohydride promotes 1,2-reduction, affording 3-piperidinylcarbonyl-1,2,4-trimethyl-1,2-dihydroquinoline () as the sole product in a moderate enantioselectivity. When 1 was reduced by the chiral NADH model compound, 2,4-dimethyl-3-(N-alpha-methylbenzylcarbamoyl)-1-propyl-1,4-dihydropyridine (Me(2)PNPH (4)), the regioselectivity and enantioselectivity of the reaction were significantly altered by the stereochemistry of 1 and 4. An achiral NADH model compound, 1-propyl-1,4-dihydronicotinamide (PNAH (5)) exhibited both high regio- and enantioselectivities. The product selectivity reflects the change in molecular arrangement in the transition state of the reaction and reveals the relative importance of the parameters governing the molecular arrangement in the reaction.

Carbonyl orientation determines regio- and enantioselectivity in 1,2-/1,4-reduction of an NAD model compound.

An optically active, axially chiral NAD model compound(1) with a quinoline ring system was reduced by the chiral NADH model compound (4), affording a mixture of 1,2- and 1,4-dihydroquinolines. The carbonyl orientation governs the molecular arrangement in the transition state of the reaction and determines the regio- and enantioselectivity of the product.

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 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.

Highly reactive and stereospecific reaction of quinoline-type NADH model compounds with methyl benzoylformate

NADH model compounds with a dihydroquinoline ring can reduce methyl benzoylformate with very high reactivity and stereospecificity. Chiral column HPLC is effective in the separation and analysis of enantiomers of NADH and NAD model compounds, respectively.

Out-of-Plane Orientation of the Carbamoyl Group in an NAD Model Compound: Preferred 1,3-Diaxial Methyl Configuration

The carbamoyl group in 3-(cis-2,6-dimethylpiperidinylcarbonyl)-1-methylpyridinium iodide, C14H21N2O+.I−, has an out-of-plane orientation in the crystalline state. The planarity of the amide moiety is conserved and the two methyl groups in the piperidine ring are both in axial configurations.

ChemInform Abstract: Redox Reactions with Cyclopeptide‐Like Quinoline Derivatives as Lipophilic NAD Model Compounds.

AbstractThe 14‐membered cyclopeptide analogues (II) are obtained as single diastereomers by dimerization of quinoline derivatives (I).

Redoxreaktionen mit cyclopeptidartigen Chinolinderivaten als lipophil-maskierte NAD-Modellverbindungen / Redox Reactions with Cyclopeptide-Like Quinoline Derivatives as Lipophilic NAD Model Compounds

Quaternary salts of the amides of N-(3-quinolinecarbonyl) amino acids (7) cyclise under the influence of base to give fourteen membered rings (9). This dimerisation is a reaction with high diastereoselectivity. The addition product 9 can be regarded as lipophilic, masked NAD model compound: 9 oxidizes 2-propanol under ZnCl2 catalysis to give in high yield acetone and the 1.4-dihydroquinoline.

1.4]Diazepino[6.5-c]chinoline mit L-Aminosäurebaustein — Darstellung und Reaktionen / [1.4]Diazepino[6.5-c]quinolines with L-Amino Acid Moiety — Preparation and Reactions

Quaternary salts of the amides of N-(3-quinolinecarbonyl)-N-alkyl-amino acids (6) cyclise under the influence of base to the title compounds (7). This intramolecular addition is a reaction with high diastereoselectivity, dependent on the amino acid part. 7 disproportionates to 8 and 9. 7 behaves as lipophilic NAD model compound in the reaction with 2-propanol under ZnCl2 catalysis.