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Synthesis of Dehydrodipeptide and N-ethyl-dehydrodipeptide Derivatives with an α-Aminoisobutyric Acid Residue

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Resumo:Several dipeptides with an N-benzyloxycarbonyl or an N-(tert-butyloxycarbonyl) α-aminoisobutyric acid residue and a β-hydroxyamino acid methyl ester were subjected to dehydration to form dehydrodipeptide derivatives. N-Ethylation of these dipeptides using triethyloxonium tetrafluoroborate with potassium tert-butoxide as auxiliary base led to complex mixtures that failed to render pure products. However, when the 4-nitrophenylsulfonyl protecting group was substituted for the benzyloxycarbonyl or tert-butyloxycarbonyl groups and N,N-diisopropylethylamine was substituted for potassium tert-butoxide, the dehydrodipeptide derivatives were selectively N-alkylated at the amino terminal nitrogen in fair to high yields. Alternatively, N-ethylation can be carried out prior to dehydration. Thus, through a combination of dehydration and N-ethylation procedures, it was possible to obtain dipeptides with α-aminoisobutyric acid and dehydroamino acid residues, which are N-alkylated at the amino terminal nitrogen.
Autores principais:Monteiro, Luís S.
Outros Autores:Pereira-Lima, Sílvia M. M. A.; Pereira, Sofia
Assunto:Alkylation dehydration dehydroamino acids dehydrodipeptide α, α-Dialkylglicines N-Alkyl-dehydrodipeptides N-Alkylamino acids Dehydrodipeptides α α-dialkylglicines
Ano:2014
País:Portugal
Tipo de documento:artigo
Tipo de acesso:acesso aberto
Instituição associada:Universidade do Minho
Idioma:inglês
Origem:RepositóriUM - Universidade do Minho
Descrição
Resumo:Several dipeptides with an N-benzyloxycarbonyl or an N-(tert-butyloxycarbonyl) α-aminoisobutyric acid residue and a β-hydroxyamino acid methyl ester were subjected to dehydration to form dehydrodipeptide derivatives. N-Ethylation of these dipeptides using triethyloxonium tetrafluoroborate with potassium tert-butoxide as auxiliary base led to complex mixtures that failed to render pure products. However, when the 4-nitrophenylsulfonyl protecting group was substituted for the benzyloxycarbonyl or tert-butyloxycarbonyl groups and N,N-diisopropylethylamine was substituted for potassium tert-butoxide, the dehydrodipeptide derivatives were selectively N-alkylated at the amino terminal nitrogen in fair to high yields. Alternatively, N-ethylation can be carried out prior to dehydration. Thus, through a combination of dehydration and N-ethylation procedures, it was possible to obtain dipeptides with α-aminoisobutyric acid and dehydroamino acid residues, which are N-alkylated at the amino terminal nitrogen.