Conformational Control of Absolute Stereospecificity

Abstract

New peptides are prepd. which have D-amino acids placed at key positions, resulting in diastereomeric peptides with enantiomeric selectivity profiles. Protected tetrapeptides Boc-L-His(π-Me)-L-Pro-Aib-Xaa-OMe (I; Boc = Me3CO2C; Aib = α-aminoisobutyric acid; Xaa = L-Phe, D-Phe, L-Val, D-Val, Gly) and Boc-L-His-D-Pro-Aib-Xaa-OMe (II) were prepd. as acyl transfer catalysts for the stereoselective acylation of trans-2-acetamidocyclohexanol. Protected tetrapeptides I and II represent interesting functional group ensembles for this purpose since they possess a catalytically active alkylimidazole substructure within a sequence that is biased toward the adoption of a β-turn conformation. The single L-proline to D-proline enantiomeric stereochem. change within the tetrapeptide sequence conferred a reversal of acyl transfer selectivity. [on SciFinder(R)]