Amino acid oxidative decarboxylation

True alkaloids derive from amino acid and they share a heterocyclic ring with nitrogen. These alkaloids are highly reactive substances with biological activity even in low doses. All true alkaloids have a bitter taste and appear as a white solid, with the exception of nicotine which has a brown liquid. True alkaloids form water-soluble salts. Moreover, most of them are well-defined crystalline substances which unite with acids to form salts. True alkaloids may occur in plants (1) in the free state, (2) as salts and (3) as N-oxides. These alkaloids occur in a limited number of species and families, and are those compounds in which decarboxylated amino acids are condensed with a non-nitrogenous structural moiety. The primary precursors of true alkaloids are such amino acids as L-ornithine, L-lysine, L-phenylalanine/L-tyrosine, L-tryptophan and L-histidine . Examples of true alkaloids include such biologically active alkaloids as cocaine, quinine, dopamine, morphine and usambarensine (Figure 4). A fuller list of examples appears in Table 1. 

Horseradish peroxidase, it has been observed, will oxidatively decarboxylate amino-acids such as (63).21... 

Pyridoxal phosphate is a necessary coenzyme for a number of different biochemical reactions transamination, amino acid oxidation, amino acid decarboxylation, glycogen breakdown, and racemization of d- and L-amino acids. 

The direct oxidation of amino acids (oxidative deamination) is insignificant compared to transamination. Decarboxylation is important only for some special metabolic processes. Serine, e.g., is transformed to ethanolamine, one of the major components of the phosphatides. Similarly, cysteine can become /3-mercaptoethyl-amine, a constituent of coenzyme A. Decarboxylation also plays a role in the formation of certain hormones (cf. Chapt. VIII-5). 

Strecker Degradation (Oxidative Deamination), Mild oxidizing agents such as aqueous sodium hypochlorite or aqueous A-bromosuccinimide, cause decarboxylation and concurrent deamination of amino acids to give aldehydes. 

Van Tamelen (I24a) has reported a useful and specific synthetic method for the production of enamines by the oxidative decarboxylation of N,N-dialkyl a-amino acids with sodium hypochlorite. 

The NAD- and NADP-dependent dehydrogenases catalyze at least six different types of reactions simple hydride transfer, deamination of an amino acid to form an a-keto acid, oxidation of /3-hydroxy acids followed by decarboxylation of the /3-keto acid intermediate, oxidation of aldehydes, reduction of isolated double bonds, and the oxidation of carbon-nitrogen bonds (as with dihydrofolate reductase). 

The first stage of the reaction is a special case of the oxidative decarboxylation of amino acids, for which two general mechanistic hypotheses are under discussion.This is followed by aromatiz-ation. A possible mechanism (241- 242- 243- 245) has been... 

The amino acid leucine is biosynthesized from n-ketoisocaproate, which is itself prepared from -ketoisovalerate by a multistep route that involves (1) reaction with acetyl CoA, (2) hydrolysis, (3) dehydration, (4) hydration. (5) oxidation, and (6) decarboxylation. Show lhe steps in the transformation, and propose a mechanism for each. 

The ring-opening of the cyclopropane nitrosourea 233 with silver trifiate followed by stereospecific [4 + 2] cycloaddition yields 234 [129]. (Scheme 93) Oxovanadium(V) compounds, VO(OR)X2, are revealed to be Lewis acids with one-electron oxidation capability. These properties permit versatile oxidative transformations of carbonyl and organosilicon compounds as exemplified by ring-opening oxygenation of cyclic ketones [130], dehydrogenative aroma-tization of 2-eyclohexen-l-ones [131], allylic oxidation of oc,/ -unsaturated carbonyl compounds [132], decarboxylative oxidation of a-amino acids [133], oxidative desilylation of silyl enol ethers [134], allylic silanes, and benzylic silanes [135]. 

Strecker aldehyde are generated by rearrangement, decarboxylation and hydrolysis. Thus the Strecker degradation is the oxidative de-amination and de-carboxylation of an a-amino acid in the presence of a dicarbonyl compound. An aldehyde with one fewer carbon atoms than the original amino acid is produced. The other class of product is an a-aminoketone. These are important as they are intermediates in the formation of heterocyclic compounds such as pyrazines, oxazoles and thiazoles, which are important in flavours. 

Dopamine synthesis in dopaminergic terminals (Fig. 46-3) requires tyrosine hydroxylase (TH) which, in the presence of iron and tetrahydropteridine, oxidizes tyrosine to 3,4-dihydroxyphenylalanine (levodopa.l-DOPA). Levodopa is decarboxylated to dopamine by aromatic amino acid decarboxylase (AADC), an enzyme which requires pyri-doxyl phosphate as a coenzyme (see also in Ch. 12). 

Under suitable conditions, oxidation of /V-alkyl-a-amino acids, accompanied by decarboxylation, has made it possible to carry out regioselective syntheses of nitrones which were utilized in the synthesis of 1-azabicyclic alkaloids (Scheme 2.6) (48, 49). 

Oxidative decarboxylation of a-amino carboxylic acid The electrochemical oxidation of Al-acyl-a-amino acids (96) in MeOH affords N, O-acetals (98) through acyliminium intermediates (97) (Scheme 36) [121]. 

This use of a weaker oxidant has several consequences. First, the reaction is readily reversible. Indeed, at neutral pH and with average substrate concentrations, the equilibrium tends to lie toward amino acid formation. Second, since the oxidant is not an ubiquitous oxygen, with a discardable product, but costly NAD(P)", forming NADPH, it becomes essential in any production process to find a way to reclaim or recycle the cofactor. Third, the absence of H2O2 among the products largely removes the concern about further reaction of the oxoacid through oxidative decarboxylation. 

Phenylglycines are important components of the vancomycin/teicoplanin antibiotics, and the conforma-tionally restricted amino acids contribute to the unique architecture and biological function of these clinically important NRPs. 4-Hydroxyphenylglycine is produced from L-tyrosine in a pathway that involves three enzymes. In the key step, a nonheme iron oxidase catalyzes the oxidative decarboxylation of the a-keto acid derivative of L-tyrosine resulting in loss of carbon dioxide and generation of the phenylglycine carbon framework. 

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