title: Examination of the potential for adaptive chirality of the nitrogen chiral center in aza-aspartame.
abstract: The potential for dynamic chirality of an azapeptide nitrogen was examined by substitution of nitrogen for the α-carbon of the aspartate residue in the sweetener S,S-aspartame. Considering that S,S- and R,S-aspartame possess sweet and bitter tastes, respectively, a bitter-sweet taste of aza-aspartame 9 could be indicative of a low isomerization barrier for nitrogen chirality inter-conversion. Aza-aspartame 9 was synthesized by a combination of hydrazine and peptide chemistry. Crystallization of 9 indicated a R,S-configuration in the solid state; however, the aza-residue chiral center was considerably flattened relative to its natural amino acid counterpart. On tasting, the authors considered aza-aspartame 9 to be slightly bitter or tasteless. The lack of bitter sweet taste of aza-aspartame 9 may be due to flattening from sp2 hybridization in the urea as well as a high barrier for sp3 nitrogen inter-conversion, both of which may interfere with recognition by taste receptors.
authors.affiliation: Département de chimie, Université de Montréal, 2900 Boul. Edouard-Monpetit, Montréal, QC H3T 1J4, Canada. william.lubell@umontreal.ca.
authors.forename: Samir H
authors.initials: SH
authors.lastname: Bouayad-Gervais
authors.forename: William D
authors.initials: WD
authors.lastname: Lubell
mesh_terms: D001218:Aspartame / Q000138:chemical synthesis / Q000737:chemistry*; D018716:Molecular Mimicry; D015394:Molecular Structure; D009584:Nitrogen / Q000737:chemistry*; D013549:Sweetening Agents / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D013549:Sweetening Agents; D009584:Nitrogen; D001218:Aspartame