Publicação
Synthesis of catecholic amino acids and peptides or conjugates of catechols with amino acids and peptides
| Resumo: | Oxidative stress is an imbalance between the amount of oxidants and antioxidants in favour of the oxidants. Thus, when there is excessive production of reactive oxygen species (ROS) or antioxidant defence mechanisms are diminished, oxidative stress occurs. In order to maintain normal cellular functioning any excess of ROS must be continuously inactivated through the use of antioxidants.1,2 Phenolic amino acids, such as tyrosine, exhibit a wide range of biological activities and have shown to be effective antioxidants in different in vitro antioxidant activities studies. Phenolic acids coupled with amino acids are involved in suppressing the adverse effects of oxidative stress and have a wide range of biological activities, such as antioxidant,3 anticancer4 and antimicrobial.5 In this work a strategy based on the Ugi reaction was developed for the synthesis of new phenolic amino acids. Hydroxybenzaldehyde derivatives were reacted with 4-methoxybenzylamine, cyclohexyl isocyanide and benzoic acid, phenolic acids or catecholic acids to give Ugi adducts that were treated with trifluoroacetic acid, yielding N-acyl (hydroxyphenyl)glycine amides in good yields. The use of N-benzyloxycarbonylglycine as acid component allowed the preparation of a 3,4-dihydroxyphenylglycyl dipeptide derivative. Radical-scavenging activity studies of the polyphenolic amino acid derivatives showed a sharp increase in activity with the increase in number of hydroxyl or catechol groups present. Several studies suggest that a cocktail of antioxidants, endowed with different mechanisms of action, results more effectively than a single antioxidant because of the synergistic effect of the molecules. To promote possible synergistic mechanisms and to better understand the mechanistic aspects, the use of modified and/or dualistic molecules is a valuable approach.6 Dehydroamino acids constitute an important class of non-proteinogenic amino acids with various biological activities, including antioxidant. N-phenolic and N-catecholic derivatives of dehydrophenylalanine were synthesized using a method which comprises coupling phenolic or catecholic acids and/or phenolic or catecholic amines. |
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| Autores principais: | Machado, Inês Marques |
| Assunto: | Ciências Naturais::Outras Ciências Naturais |
| Ano: | 2018 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade do Minho |
| Idioma: | inglês |
| Origem: | RepositóriUM - Universidade do Minho |
| Resumo: | Oxidative stress is an imbalance between the amount of oxidants and antioxidants in favour of the oxidants. Thus, when there is excessive production of reactive oxygen species (ROS) or antioxidant defence mechanisms are diminished, oxidative stress occurs. In order to maintain normal cellular functioning any excess of ROS must be continuously inactivated through the use of antioxidants.1,2 Phenolic amino acids, such as tyrosine, exhibit a wide range of biological activities and have shown to be effective antioxidants in different in vitro antioxidant activities studies. Phenolic acids coupled with amino acids are involved in suppressing the adverse effects of oxidative stress and have a wide range of biological activities, such as antioxidant,3 anticancer4 and antimicrobial.5 In this work a strategy based on the Ugi reaction was developed for the synthesis of new phenolic amino acids. Hydroxybenzaldehyde derivatives were reacted with 4-methoxybenzylamine, cyclohexyl isocyanide and benzoic acid, phenolic acids or catecholic acids to give Ugi adducts that were treated with trifluoroacetic acid, yielding N-acyl (hydroxyphenyl)glycine amides in good yields. The use of N-benzyloxycarbonylglycine as acid component allowed the preparation of a 3,4-dihydroxyphenylglycyl dipeptide derivative. Radical-scavenging activity studies of the polyphenolic amino acid derivatives showed a sharp increase in activity with the increase in number of hydroxyl or catechol groups present. Several studies suggest that a cocktail of antioxidants, endowed with different mechanisms of action, results more effectively than a single antioxidant because of the synergistic effect of the molecules. To promote possible synergistic mechanisms and to better understand the mechanistic aspects, the use of modified and/or dualistic molecules is a valuable approach.6 Dehydroamino acids constitute an important class of non-proteinogenic amino acids with various biological activities, including antioxidant. N-phenolic and N-catecholic derivatives of dehydrophenylalanine were synthesized using a method which comprises coupling phenolic or catecholic acids and/or phenolic or catecholic amines. |
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