Síntese de derivados de asparaginas não-naturais N4-substituídas e modificação de peptídeos: adição fotoredox de radicais carbamoil à dehidroalanina

Abstract

The development of sustainable methodologies for the synthesis of byologic relevant molecules is of great importance for both, academia (especially in organic synthesis and medicinal chemistry) and pharmaceutical industry. Thus, the use of visible light in synthesis of new compounds and systems with high degree of structural complexity has allowed the design of new methodologies. A special emphasis can be given to the use of photocatalyzed reactions in synthesis of unnatural amino acids and in modification of macromolecules. For these reasons and the efforts of our research group in development of photocatalyses process, was performed in this research project the synthesis of unnatural Asparagine N4-substitued, as well as late-stage peptides modifications through photochemical methodologies metal-free photocatalysts, thus allowing the obtainment of more economical, efficient and environmentally favorable strategies. For this, it was used the unnatural amino acid dehydroalanine (Dha), as a radical acceptor molecule, 4-carbamoyl-dihydropyridines as a source of carbamoyl radicals and the organic photocatalyst 4CzIPN. 22 examples of carbamoyl radicals could be obtained and added to Dha, with yields until 97%. Moreover, one dipeptide that contained the Dha fragment in N-terminal position could be functionalized with yield of 65%. These results were able to demonstrate the robustness of the method and the high potential to be applied to more others peptides, as well as proteins.