A novel synthesis of ( R)- and ( S)-α-alkylated aspartic and glutamic acids: α-alkylated aspartic succinimides as new type of β-turn type II and II′ mimetics

Abstract

A novel and efficient synthesis of optically pure ( R)- and ( S)-α-methyl glutamic acid ( 1), ( R)- and ( S)-α-methyl aspartic acid ( 2a) and ( R)- and ( S)-α-isobutyl aspartic acid ( 2b) using L-phenylalanine cyclohexylamide 4 as chiral auxiliary is described. Crystal structures show that the ( R)- and ( S)-α-methyl glutamic acid derivatives ( S,S)- 5 and ( R,S)- 6 adopt β-turn type I geometries, whereas the corresponding aspartimide derivatives ( R,S)- 12a,b form a β-turn type II and ( S,S)- 11a a β-turn type II′. These findings suggest, that the succinimide derivatives of ( R)- and ( S)-α-alkyl aspartic acids can serve as building blocks to stabilise β-turns of type II (or II′) in peptides depending on their absolute configuration.