Nicotinamide pyridinium salt

Nicotinic acid and nicotinamide are precursors of the coenzymes NAD+ and NADP+, which play a vital role in oxidation-reduction reactions (see Box 7.6), and are the most important electron carriers in intermediary metabolism (see Section 15.1.1). We shall look further at the chemistry of NAD+ and NADP+ shortly (see Box 11.2), but note that, in these compounds, nicotinamide is bound to the rest of the molecule as an A-pyridinium salt. 

Nicotinamide adenine dinucleotide reduction of a pyridinium salt... 

Cyanide ions attack the 4-position in pyridinium salts. For example, nicotinamide pyr-iV-methiodide (143, R = CHS) and di-phosphopyridine nucleotide give the 4-cyano- 1,4-dihydro derivatives (144) 328,329 3-Acetyl-iV-benzylpyridinium chloride similarly gives the 4-cyano-1,4-dihydro derivative and no attack at C-2 has been reported.330 Hydrosulfite reduction of nicotinamide quaternary salts... 

Electrochemical oxidation of the reduced form (NADH) of nicotinamide adenine dinucleotide and its analogs has been investigated [262] best results are obtained using a carbon felt electrode. The results are consistent with an ECE mechanism yielding the pyridinium salt. Indirect oxidation of NADH (and reduction of NAD" ) is treated in Chapters 27 and 29. 

The easy specific reduction of 3-acylpyridinium salts giving stable 3-acyl-1,4-dihydropyridines using sodium dithionite is often quoted, because of its perceived relevance to nicotinamide coenzyme activity the mechanism involves addition of sulfur at C-4 as its first step, as shown below.1,4-Dihydropyridines are normally air-sensitive, easily rearomatised molecules the stability of 3-acyl-1,4-dihydropyr-idines is related to the conjugation between ring nitrogen and side-chain carbonyl group (see also Hantzsch synthesis, section 5.15.1.2). However, even simple pyridinium salts, provided the A-substituent is larger than propyl, or for example benzyl, can be reduced to 1,4-dihydropyridines with sodium dithionite. ... 

N-Labelled nicotinamide (27) has been obtained in high yield by the reaction of the pyridinium salt (26) with labelled ammonium chloride (Scheme 13). ... 

Nicotinamide adenine dinucleotide 42) in the 1,4-dihydro form is a coenzyme that does tend itself well for use in model systems. The reactive portion is the 1,4-dihydronicotinamide ring 43), which is capable of acting as hydride donor towards many substrates the pyridinium salt 44f) acts in turn as hydride acceptor (eq. 15). The sugar nucleotide tail can be deleted without fatal consequences for the reactivity although the 1,4-dihydropyridine form 44) by itself has little tendency to reduce anything except the most reactive of potential substrates. The problem is not... 

The approach of eq. 18 has been followed by Lehn s group. The tartrate derived [18]crown-6 derivative (22) has been connected via the pyridine nitrogens to four nicotinamide derivatives to form (47). A potential substrate can be attached to an ammonium salt to give, for example, (4S), which complexes in the crown ether (eq. 21). The only reaction so far investigated using this approach is, as can be seen from eq. 21, not a carbonyl group reduction but rather hydride transfer to a pyridinium salt. 

A series of compounds that appear to be derived from nicotinic acid is found in a number of euphorbiaceous plants. Ricinine (49), an alkaloid from Ricinus communis, is derived from nicotinic acid via nicotinamide (50). This alkaloid may occur in quantities as great as 1% of the plant dry weight. A crude enzyme preparation has been isolated that will convert a series of pyridinium salts into ricinine and related compounds (Fig. 28.20) (Fodor and Colasanti, 1985). This alkaloid disappears completely from senescent leaves. Ricinine (49) has an LD50 p.o. of 42 mg/kg in Agelaius (Wink, 1993). 

Intermediates in the sodium dithionite reduction of pyridinium salts have been isolated. Thus l-(p-chlorobenzyl)nicotinamide (X-129) yielded the dihydrosulfmate X-130, which is desulfmated in alkaline media to l-(p-chlorobenzyl)-l,4-dihydronicotinaniide (X-131). The desulHnation of X-130 was confirmed by deuterium exchange experiments. 

The anomeric A-xylofuranosyl-pyridinium salts derived from nicotinamide have been prepared as nucleoside analogues, and equilibration of their dihydro derivatives was shown to favour the /3-form. ... 

Theoretical calculations of charge distribution on the nicotinamide ring by B. Pullman in Paris agree with a hydride attack at position C-4. Experimental evidence comes from reaction with a deuterated alcohol and isolation of the pyridinium salt. Methylation and oxidation take place without loss of deuterium, proving that the labeling occurs only at C-4. 

Before truly reliable criteria for distinguishing between 1,2- and 1,4-dihydropyridines were available, the products of dithionite reduction of many quaternary salts, mainly nicotinamide derivatives, had been examined, notably by Karrer and his co-workers and wrongly formulated as 1,2-dihydropyridines. Whilst each example requires careful examination, it seems to be almost generally true that dithionite reduction of pyridinium salts gives l,4-dihydropyridinesi 1077, 1090-2, 1101 An exception is the... 

Acetates of organic bases Diethylamine acetate Pyridinium salt Tetramethylammonium acetate, Tetraethyl-ammonium-Piperidinium acetate Isoxazolium salts Trialkyloxonium salt Amidinium salts Ketenimines Diazomethane K-methyldiazotate Hexamethylenetetramine Azo compounds Triazenes p-Nitrobenzene-diazonium sulfate Sulfanilic acid, diazotized HCONH2, CHsCONH2 Dimethylacylamines HCON(CHs)2, CHsCON(CHs)2 Dimethylformaldehyde dineopentyl acetate 1-Benzyl-1,4 -dihydro nicotinamide N,N -Diethylnicotin-amide C0(NH2)2, (CHs)2NCON(CHs)2 Phenyl isocyanate Carbodiimides Dicyclohexylcarbodi-imide, Di-p-tolyl-Antipyrine... 

Lessons from Redox-Active Pyridinium Salts in Nature Nicotinamide Adenine Dinucleotide, Dihydropyridines, and Synthesis... 

The utility of the Zincke reaction has been extended to the preparation of various NAD and NADH analogs. Holy and co-workers synthesized a series of NAD analogs containing nucleotide bases as a means to study through-space interaction between the pyridinium and base portions. Nicotinamide-derived Zincke salt 8 was used to link with various adenine derivatives via tethers that contained hydroxyl (105 —> 106, Scheme 8.4.35), phosphonate (107—>108, Scheme 8.4.36), and carboxylate "... 

NAD g-Nicotinamide adenine dinucleotide Pyridinium, 3-carbamoyl-1-6-D-ribofuranosyl hydroxide, 5 - 5 - ester with adenosine 5 —(tr1 hydrogen pyrophosphate), inner salt (8) Adenosine 5 -(trihydrogen diphosphate), 5 - ... 

Adenosine 5 -(trihydrogen diphosphate)-2 (dihydrogen phosphate) (S r5 ) ester with 3-( amino carbonyl)-l-(S-D-ribofuranosyl-pyridinium hydroxide inner salt, 9CI. Nicotinamide adenine dinucleotide phosphate. Codehydrase II. Codehydrogenase II. Na-difosfate. Phosphocozymase. Triphospho-pyridine nucleotide. NADP. TPN. NADP [53-59-8]... 

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