Luís S. Monteiro

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.

Synthesis Using Suzuki Cross Couplings of Sulfur Analogues of Dehydrotryptophan with a Definite Stereochemistry

Sulfur analogues of dehydrotryptophan (5−7) were prepared in moderate to good yields (40−80%) by Suzuki cross coupling [Pd(PPh3)4, Na2CO3 or NaHCO3, DME/H2O, 90 °C] of several benzo[b]thiophene boronic acids with the methyl esters of N-tert-butyloxycarbonyl-β-bromodehydroalanine [Boc-ΔAla(β-Br)-OMe] or N-tert-butyloxycarbonyl-β-bromodehydroaminobutyric acid [Boc-ΔAbu(β-Br)-OMe]. The β-bromodehydroamino acid precursors 2 were, in turn, synthesized in high yields from the corresponding N,N-diacyldehydroamino acids 1 by treatment with trifluoroacetic acid (TFA) and N-bromosuccinimide (NBS) in two steps or in a one-pot procedure. Both procedures were stereoselective for the E-isomer of Boc-ΔAla(β-Br)-OMe. However, for Boc-ΔAbu(β-Br)-OMe, different ratios of E/Z isomers were obtained in each procedure. The stereoselectivity for the Z-isomer was increased greatly with the one-pot procedure. Pure isomers were used in the coupling reactions and the stereochemistry of the starting material was generally maintained. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)

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.

Reductive cleavage of N-substituted aromatic amides as tert-butyl acylcarbamates

Synthetic and spectroscopic details relating to a set of heteroaromatic N-benzyl carboxamides and in particular the corresponding tert-butyl acylcarbamates are reported. These compounds were required to study the postulated effect of various heterocycles (pyridine and pyrazine with and without condensed benzene rings) on the cleavage of acyl–N bonds by reduction. All compounds were initially characterized by cyclic voltammetry (CV) which indicated various degrees of facilitated reduction, reflecting a direct influence of the heterocyclic component. Selected acylcarbamates were studied with respect to acyl–N bond cleavage by mild reducing agents, and selectively deacylated by activated aluminium and sodium borohydride. Conversion to acylcarbamates followed by reduction might therefore be a mild, efficient two-step procedure to effect cleavage of amides, allowing isolation of carbamates and with sodium borohydride also the corresponding alcohols.

Synthesis of novel β-substituted α,β-dehydroamino acid derivatives

Abstract β-Substituted α,β-dehydroamino acids are synthesised in high yields by a Michael addition of heterocyclic nucleophiles to the methyl esters of N-tert -butyloxycarbonyl, N -(4-toluenesulfonyl)dehydroamino acids, followed by a base-induced elimination of the 4-toluenesulfonyl group with regeneration of the α,β-double bond.

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 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.

Synthesis and electrochemical behaviour of β-halodehydroamino acid derivatives

Several new β,β-dihalo and β-halo-β-substituted dehydroalanines and dehydrodipeptides were synthesized by reacting the corresponding dehydroamino acid derivative with a N-halosuccinimide or in the case of β,β-di-iododehydroalanines with iodine. The results obtained confirmed that the stereochemical outcome of the halogenation reaction with β-substituted dehydroamino acids depends on the substrate. Thus, an increase Z-stereoselectivity was found when the β-phenyldehydroalanines were used as substrates and when these compounds were N-protected with 4-tolylsulfonyl or with carbamates. From this study, it is also possible to conclude that when N-iodosuccinimide was used as reagent a much higher Z-stereoselectivity is found. The electrochemical behaviour of the halogenated dehydroamino acids was studied by cyclic voltammetry. The results show a shift in the reduction peak to higher potentials of the β-halogenated dehydroamino acids when compared with the corresponding non-halogenated derivatives. As expected, the β,β-dihalodehydroalanines exhibit higher peak potentials than β-halo-β-substituted dehydroalanines and the bromo derivatives have lower peak potentials when compared with the corresponding iododehydroamino acids. Controlled potential electrolysis of several β-halo-β-substituted dehydroamino acids afforded the corresponding dehalogenated dehydroamino acids as mixtures of their E and Z-isomers. In all cases, the major isomer isolated results from dehalogenation without isomerization. These new results show that electrochemical reduction constitutes a valuable method for the synthesis of the E-isomer of β-substituted dehydroalanines.

Synthesis of non-proteinogenic amino acids from N-(4-toluenesulfonyl)dehydroamino acid derivatives

By treating N-(4-toluenesulfonyl)-N-(tert-butyloxycarbonyl)-dehydroamino acid derivatives with different reactants under different conditions, a variety of new amino acids are obtained, viz. (i) α-alcoxy-α-amino acids, (ii) α,α-diamino acids and (iii) novel β-substituted dehydroamino acids.

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.