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

Synthesis of α/β dipeptides containing linear or cyclic α-dehydro-β-amino acids as scaffolds for bioactive compounds.
Amino Acids. 2019 Sep 13;:
Authors: Ferrazzano L, Corbisiero D, Greco R, Potenza E, De Seriis G, Garelli A, Tolomelli A
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 ...

Source: Amino Acids - September 12, 2019 Category: Biochemistry Authors: Ferrazzano L, Corbisiero D, Greco R, Potenza E, De Seriis G, Garelli A, Tolomelli A Tags: Amino Acids Source Type: research