A-Amino acids decarboxylation

Reaction with ninhydrin Ninhydrin is a strong oxidizing agent. When a solution of amino acid is boiled with ninhydrin, the amino acid is oxidatively deaminated to produce ammonia and a ketoacid. The keto acid is decarboxylated to produce an aldehyde with one carbon atom less than the parent amino acid. The net reaction is that ninhydrin oxidatively deaminates and decarboxylates a-amino acids to C02, NH3 and an aldehyde. The reduced ninhydrin then reacts with the liberated ammonia and another molecule of intact ninhydrin to produce a purple coloured compound known as Ruhemann s purple. 

Oxidative decarboxylation a-Amino acids and a-hydroxy carboxylic acids are degraded, to give nitriles and carbonyl compounds, respectively. 

Figure 11.13 Reactions at a-carbon of a-amino acids catalyzed by pyridoxal enzymes All three substituents at C are subject to labilization in the three types of a-carbon reactions. The hydrogen is labilized in recemization reactions, the amino group is labUized in the transamination and the carboxyl group is labilized in decarboxylation. a-Amino acid condenses with pyridoxal phosphate to yield pyridoxylidene imino acid (an aldimine). The common intermediate, aldimine and distinct ketimines leading to the production of oxo-acid (in transamination), amino acid (in racemization) and amine (in decarboxylation) are shown. The catalytic acid (H-A-) and base (-B ) are symbolic both can be from the same residue such as Lys258 in aspartate aminotransferase.

With active methylene compounds, the carbanion substitutes for the hydroxyl group of aHyl alcohol (17,20). Reaction of aHyl alcohol with acetylacetone at 85°C for 3 h yields 70% monoaHyl compound and 26% diaHyl compound. Malonic acid ester in which the hydrogen atom of its active methylene is substituted by A/-acetyl, undergoes the same substitution reaction with aHyl alcohol and subsequendy yields a-amino acid by decarboxylation (21). 

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 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... 

Implication of the same type of intermediate (342 X = H) allows the rationaUzation of the acid-catalyzed decarboxylation of 1,2,3,4-tetrahydro-j8-carboline-l-carboxylic acids. As is stated in Section III,A,1, a, the tetrahydroisoquinoline-1-carboxylic acids and a-amino acids of analogous structure are converted into the corresponding... 

A more general method for preparation ofa-amino acids is the amidotnalmatesynthesis, a straightforward extension of the malonic ester synthesis (Section 22.7). The reaction begins with conversion of diethyl acetamidomalonate into an eno-late ion by treatment with base, followed by S 2 alkylation with a primary alkyl halide. Hydrolysis of both the amide protecting group and the esters occurs when the alkylated product is warmed with aqueous acid, and decarboxylation then takes place to vield an a-amino acid. For example aspartic acid can be prepared from, ethyl bromoacetate, BrCh CCHEt ... 

More recently Hand et al. (ref. 9) have studied the decomposition reaction of N-chloro-a-amino acid anions in neutral aqueous solution, where the main reaction products are carbon dioxide, chloride ion and imines (which hydrolyze rapidly to amine and carbonyl products). They found that the reaction rate constant of decarboxylation was independent of pH, so they ruled out a proton assisted decarboxylation mechanism, and the one proposed consists of a concerted decarboxylation. For N-bromoamino acids decomposition in the pH interval 9-11 a similar concerted mechanism was proposed by Antelo et al. (ref. 10), where the formation of a nitrenium ion (ref. 11) can be ruled out because it is not consistent with the experimental results. Antelo et al. have also established that when the decomposition reaction takes place at pH < 9, the disproportionation reaction of the N-Br-amino acid becomes important, and the decomposition goes through the N,N-dibromoamino acid. This reaction is also important for N-chloroamino compounds but at more acidic pH values, because the disproportionation reaction... 

By contrast, the cytoplasmic decarboxylation of dopa to dopamine by the enzyme dopa decarboxylase is about 100 times more rapid (Am 4x 10 " M) than its synthesis and indeed it is difficult to detect endogenous dopa in the CNS. This enzyme, which requires pyridoxal phosphate (vitamin B6) as co-factor, can decarboxylate other amino acids (e.g. tryptophan and tyrosine) and in view of its low substrate specificity is known as a general L-aromatic amino-acid decarboxylase. 

Another interesting example is SHMT. This enzyme catalyzes decarboxylation of a-amino-a-methylmalonate with the aid of pyridoxal-5 -phosphate (PLP). This is an unique enzyme in that it promotes various types of reactions of a-amino acids. It promotes aldol/retro-aldol type reactions and transamination reaction in addition to decarboxylation reaction. Although the types of apparent reactions are different, the common point of these reactions is the formation of a complex with PLP. In addition, the initial step of each reaction is the decomposition of the Schiff base formed between the substrate and pyridoxal coenzyme (Fig. 7-3). 

In order to account for the nonvolatility, infusibility, and limited solubility, Leuchs postulated polymerization of the ground type cyclic compound, as indicated by the subscript x in his formula given above. It is now well established that linear polypeptides are produced on decarboxylation of the N-carboxyanhydrides of a-amino acids, and under favorable conditions the chain length may be fairly large. Leuchs favored the view that strained rings, i.e., those of other than five or six... 

The regio- and stereochemical outcome of the intermolecular 1,3-dipolar cycloaddition of an azomethine ylide generated by the decarboxylative condensation of an isatin with an a-amino acid was unambiguously determined by a single-crystal X-ray study of the spirocyclic heterocycle 49 (R1 =4-Br, R2 = H, X = CH2) <1998TL2235>. 

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. 

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). 

Allenic amino acids belong to the classical suicide substrates for the irreversible mechanism-based inhibition of enzymes [5], Among the different types of allenic substrates used for enzyme inhibition [128, 129], the deactivation of vitamin B6 (pyr-idoxal phosphate)-dependent decarboxylases by a-allenic a-amino acids plays an important role (Scheme 18.45). In analogy with the corresponding activity of other /3,y-unsaturated amino acids [102,130], it is assumed that the allenic amino acid 139 reacts with the decarboxylase 138 to furnish the imine 140, which is transformed into a Michael acceptor of type 141 by decarboxylation or deprotonation. Subsequent attack of a suitable nucleophilic group of the active site then leads to inhibition of the decarboxylase by irreversible formation of the adduct 142 [131,132]. 

Scheme 36 Anodic decarboxylation of N-acyl a-amino acids to a N-acycl iminium intermediates.

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]. 

As shown by Sato et al. N-phthaloyl derivatives of C-unprotected amino acids efficiently undergo decarboxylation upon irradiation [248,249]. In this case, the iV-phthaloyl a-amino acid of methionine 310 represents an exception, because the normal decarboxylation route is not followed. Two main products are obtained, the trans-hydroxy acid 313 and the tetracyclic lactone 314 [250, 251]... 

The catecholamines noradrenaline (norepinephrine) and adrenaline (epinephrine) are amines derived via decarboxylation of amino acids. Noradrenaline is a mammalian neurotransmitter, and adrenaline, the... 

In addition to the 20 proteinogenic amino acids (see p. 60), there are also many more compounds of the same type in nature. These arise during metabolic reactions (A) or as a result of enzymatic modifications of amino acid residues in peptides or proteins (B). The biogenic amines (C) are synthesized from a-amino acids by decarboxylation. 

A chemical reaction in which the carboxyl group of an a-amino acid is replaced by an acyl group Le., an acyl-decarboxylation). In this reaction, an a-amino acid is reacted with an anhydride in the presence of pyridine and the resulting product is an A-acylated ketone. In certain instances, A-substituted amino acids will also act as reactants. 

Histamine is synthesized in tissues by decarboxylation of amino acid L-histidine, a process catalyzed by the pyridoxalphosphate-dependent enzyme L-histidinedecarboxylase. Histamine can enter the organism with food it also can be generated by bacteria of the gastrointestinal tract. However, these sources do not create additional reserves of histamine since exogenous histamine is easily catabolized in the organism. 

An analogous method was used by Endo and colleagues in a-amination of unreactive carboxylic acids. Treatment of iV-acylhydroxylamine O-carbamates 92 by KHMDS or LDA followed by [3,3]-sigmatropic rearrangement and decarboxylation provided a-amino acid analogues 93 (equation 29). 

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