Synthesis of α/β dipeptides containing linear or cyclic α-dehydro-β-amino acids as scaffolds for bioactive compounds
| Autor: | Dario Corbisiero, Eleonora Potenza, Roberto Greco, Alessandra Tolomelli, Lucia Ferrazzano, Giulia De Seriis, Andrea Garelli |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Allylic rearrangement Peptidomimetic Clinical Biochemistry Biochemistry Catalysis Acylation 03 medical and health sciences chemistry.chemical_compound Side chain Organic chemistry Methylene Amines Amino Acids Amination chemistry.chemical_classification 030102 biochemistry & molecular biology Molecular Structure Chemistry Organic Chemistry Regioselectivity Stereoisomerism Dipeptides Amino acid 030104 developmental biology Cyclization Peptidomimetics |
| Zdroj: | Amino acids. 51(10-12) |
| ISSN: | 1438-2199 |
| Popis: | The synthesis of α/β dipeptides containing linear or cyclic α-dehydro-β-amino acids has been performed starting from alkylidene acetacetamides, which were obtained from α-amino esters via Ir-catalyzed allylic amination. Differently hindered carbonates were synthesized via a protocol involving chemoselective Luche's reduction, acylation, and allylic amination. Depending on the nature of the selected α-amino acid, we observed strong influence on the product regiochemistry due to the carbonate size and the amino-acid side chain. In particular, complete regioselectivity was observed in the aminic allylation of carbonates deriving from amino acids possessing a methylene unit in β-position. On the contrary, methyl carbonates deriving from β-branched amino acid afforded different results depending on the hindrance of the carbonate. Moreover, spontaneous cyclization was observed for carbamate-containing intermediates, allowing to obtain peptidomimetic polyfunctionalized dihydropyrimidine-2,4-dione. Finally, by inverting the order of reduction/acylation steps on the starting alkylidene acetoacetamides, the formation of polyfunctionalized 1,3-oxazinane-2,4-dione was obtained demonstrating the wide applications of these substrates for the preparation of bioactive peptidomimetics. |
| Databáze: | OpenAIRE |
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