Hernâni L. S. Maia

Efficient synthesis of dehydroamino acid derivatives

By using a DMAP catalysed reaction of β-hydroxyamino acid derivatives with tert-butylpyrocarbonate, the corresponding dehydroamino acid derivatives were obtained in high yields.

An improved approach for the synthesis of α,α-dialkyl glycine derivatives by the Ugi–Passerini reaction

A general and simple strategy for routine peptide synthesis with α,α-dialkyl glycines taking advantage of the four-component Ugi–Passerini reaction is presented. The isonitrile required for the reaction can be relatively simple and its selection based on cost, as the group it generates is easily removed under acidic conditions; in addition, this removal is not visibly affected by the bulkiness of the α-alkyl groups. Being a good leaving group from the N-terminal amino group of the amino acid, 4-methoxybenzyl was the choice for the amine component of the reaction. The method is illustrated with the synthesis of a series of acyl derivatives of several α,α-dialkyl glycines. The preparation of the latter compounds is also reported.

High yielding synthesis of heterocyclic β-substituted alanine derivatives

Heterocyclic β-substituted alanine derivatives such as β-(pyrazol-1-yl) and β-(1,2,4-triazol-1-yl)-alanine are synthesized in high yields by a Michael addition of heterocyclic nucleophiles to N,N-bis(tert-butyloxycarbonyl)-dehydroalanine methyl ester, using mild reaction conditions and simple work-up procedures.

High yielding synthesis of dehydroamino acid and dehydropeptide derivatives

By using a 4-dimethylaminopyridine (DMAP) catalysed reaction of β-hydroxyamino acid derivatives with tert- butyl pyrocarbonate [(Boc)2O], dehydroamino acid derivatives are obtained in high yields. The same methodology applied to dipeptides with a β-hydroxyamino acid residue gives the corresponding dipeptides with a dehydroamino acid residue.

Synthesis of N-acyl-N,α,α-trialkyl and N-acyl-α,α-dialkyl glycines by selective cleavage of Ugi–Passerini adducts. Qualitative assessment of the effect of substituents on the path and yield of reaction

Several symmetric N-acyl-N,α,α-trialkyl glycine amides were synthesised by the Ugi–Passerini four-component reaction and subjected to selective cleavage with trifluoroacetic acid. In almost all cases it was possible to obtain the corresponding N-acyl-N,α,α-trialkyl and N-acyl-α,α-dialkyl glycines in fair to good yields directly from the reaction adducts. With some of the bulkier compounds our results show that the selectivity of cleavage is concentration dependent with respect to the acid, which suggests kinetically controlled processes. The isolation of a stable oxazolone as the product of some of the reactions seems to confirm that amide cleavage involves in all cases formation of an oxazolone-type derivative.

Synthesis of 2,3,5-substituted pyrrole derivatives

2,3,5-Substituted pyrrole derivatives are prepared by treatment of 2,3-dihydrofuran derivatives with trifluoroacetic acid. These in turn are obtained by Michael addition of carbon nucleophiles of the β-dicarbonyl type to N-(4-toluenesulfonyl)-N-(tert-butyloxycarbonyl)-dehydroalanine methyl ester.

Novel aziridine esters by the addition of aromatic nitrogen heterocycles to a 2H-azirine-3-carboxylic ester

Abstract Methyl 2-(2,6-dichlorophenyl)-2 H -azirine-3-carboxylate acts as an efficient alkylating agent for a variety of five-membered aromatic heterocycles. The aziridines derived from heterocycles that bear an α-carbonyl substituent react with TFA to give pyrroloimidazoles; 2,6-dichlorobenzaldehyde is also produced.

Synthesis of novel derivatives of 4-amino-3,5-dicyanopyrazole

Diazotisation of substituted arylamines followed by reaction with malononitrile gave substituted arylazomalononitriles. Cyclisation of these intermediates with chloroacetonitrile and triethylamine, as base, gave the corresponding new aminodicyanopyrazoles, in 22–80% yields.

Electrochemical synthesis of diaminodicarboxylic acid derivatives

Diaminoadipic acid derivatives were synthesized in good yields by electrolysis of N,N-diacyldehydroalanines. Cyclic voltammetry measurements on the precursors are presented and interpreted as supporting formation of a nucleophilic intermediate generated by electrochemical reduction.

A temporary marker for biological applications

Abstract Having in mind the development of new colour labelled amino acid derivatives, a carboxyl azo dye was coupled to amino acid esters to give the corresponding orange N -acyl derivatives, which were in turn further acylated at their N-terminus with Boc for investigation of the conditions of possible cleavage of the chromophore by electrolysis or with nucleophiles. While difficulties were met with electrolysis owing to competitive reduction of the azo group, cleavage with N , N -diethylaminoethylamine (DEAEA) gave satisfactory results. This allows the use of the chromophore as a temporary marker.