Synthesis of α/β dipeptides containing linear or cyclic α-dehydro-β-amino acids as scaffolds for bioactive compounds

Ferrazzano, Corbisiero, Greco, Potenza, De Seriis, Garelli, Tolomelli (2019) Synthesis of α/β dipeptides containing linear or cyclic α-dehydro-β-amino acids as scaffolds for bioactive compounds Amino Acids (IF: 3.5) 51(10-12) 1475-1483

Abstract

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.

Links

http://www.ncbi.nlm.nih.gov/pubmed/31520287
http://dx.doi.org/10.1007/s00726-019-02782-7

Similar articles

Tools