Ammonia reductive half-reaction

The Role of Ammonia in the Reductive Half-Reaction Mechanism of Methanol Dehydrogenase... 

DAAO is one of the most extensively studied flavoprotein oxidases. The homodimeric enzyme catalyzes the strictly stere-ospecihc oxidative deamination of neutral and hydrophobic D-amino acids to give a-keto acids and ammonia (Fig. 3a). In the reductive half-reaction the D-amino acid substrate is converted to the imino acid product via hydride transfer (21). During the oxidative half-reaction, the imino acid is released and hydrolyzed. Mammalian and yeast DAAO share the same catalytic mechanism, but they differ in kinetic mechanism, catalytic efficiency, substrate specificity, and protein stability. The dimeric structures of the mammalian enzymes show a head-to-head mode of monomer-monomer interaction, which is different from the head-to-tail mode of dimerization observed in Rhodotorula gracilis DAAO (20). Benzoate is a potent competitive inhibitor of mammalian DAAO. Binding of this ligand strengthens the apoenzyme-flavin interaction and increases the conformational stability of the porcine enzyme. 

The nitrogenase enzyme complex found in nitrogen-fixing bacteria catalyzes the production of ammonia from molecular nitrogen. The half-reaction of reduction (Figure 23.2a) is... 

A substituted benzoic acid serves as precursor for the nontricyclic antidepressant bipena-mol (175). Selective. saponification of ester 171 afford.s the half-acid 172. Reaction of the acid chloride derived from this intermediate (173) with ammonia gives the amide 174. Reduction of the last by means of lithium aluminum hydride gives bipenamol (175) [44]. 

A solution of 151 grams of 1-(3, 4 -dimethoxyphenyl)-2-propanone oxime in 200 cc of absolute ethanol is treated with 5 grams of Raney nickel catalyst and ammonia in an autoclave at about 25 atm of pressure and at 75 -100°C. The reduction is complete in about one-half hour and the reaction mixture is filtered and fractionated under reduced pressure to recover the a-methylhomoveratrylamine formed by the reduction. a-Methylhomoveratryl-amine thus prepared boiled at 163°-165°C at 18 mm pressure. 

An efficient synthesis of ( )-quebrachamine is based on the construction of a suitable precursor via ring cleavage of an a-diketone monothioketal (810) (80JCS(P1)457). This monothioketal, available from 4-ethoxycarbonylcyclohexanone ethylene ketal, was fragmented to the dithianyl half ester (811) with sodium hydride in the presence of water. Reaction of (811) with tryptamine and DCC provided an amide which was converted to the stereoisomeric lactams (812) on hydrolysis of the dithiane function. Reduction of either the a- or /3-ethyl isomer with lithium aluminum hydride followed by conversion of the derived amino alcohol to its mesylate produced the amorphous quaternary salt (813). On reduction with sodium in liquid ammonia, the isomeric salts provided ( )-quebrachamine (814 Scheme 190). 

An example of a condensation reaction with diastereotopic group selectivity (see appendix) is the lactonization of either of the two racemic, C2-symmetrical 5-hydroxy-2,4,6,8-tetramethylnonanedioic acids. This reaction desymmetrizes a compound with two pairs of equivalent stereocenters (C-5 is achiral ) into a product with five different stereocenters. The trilithium salt is generated by reduction of the 2,4,6,8-tetramethyl-5-oxononanedioic acid with lithium in ammonia and then either acidified to pH 3 followed by rapid extraction of the lactones formed (kinetic control) or equilibrated at pH w 1 to the lactone mixture (thermodynamic control). Depending on the steric interactions in the chair-like transition states and in the half-chair lactone products, either kinetic or thermodynamic control leads with high diastereoselectivity to the lactone with trans-configuration at C-5 and C-6 of the tetra-hydro-2/f-pyran-2-one ring (T. R. Hoye, 1984). 

Classes. Molecular nitrogen, the physiological substrate of N2ase, consumes six electrons and is reduced to 2 NH3 (41). The lack of specific inhibition of N2 reduction by NH4 indicates that ammonia does not complex strongly with N2ase. No enzyme-free intermediates have been detected (42,43,44) and, on the basis of 2-, 4-, 6-, 8-, 10-, 12-, and 14-electron addition products found in other N2ase-catalyzed reactions (Figure 3), enzyme-bound diimide and hydrazine are the obvious, but not yet detected, intermediates. The N2 concentration for half maximal rate is about 0.1 mM (15, 29, 45, 46, 47, 48, 49, 50). 

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