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

Abstract

The synthesis of  dipeptides containing linear or cyclic -dehydro--amino acids has been performed starting from alkylidene acetacetamides deriving from -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 -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 -position. On the contrary, branched amino acid-deriving methyl carbonates 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 1,3oxazinane-2,4-dione was obtained demonstrating the wide applications of these substrates for the preparation of bioactive peptidomimetics.

Studies on Fluorofunctionalization of Some Functionalized Alkene Scaffolds

“…Thus, the synthetic need for analogues of functionalized cyclic amino acid derivatives and bioactive compounds is unquestionable. As a result, their synthesis has increasingly become the focus of organic transformations in the last two decades [44][45][46][47][48][49].…”

Studies on Fluorofunctionalization of Some Functionalized Alkene Scaffolds

“…Thus, the synthetic need for analogues of functionalized cyclic amino acid derivatives and bioactive compounds is unquestionable. As a result, their synthesis has increasingly become the focus of organic transformations in the last two decades [44][45][46][47][48][49].…”