Examination of the Potential for Adaptive Chirality of the Nitrogen Chiral Center in Aza-Aspartame

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

<i>N</i>-Aminosulfamide Peptide Mimic Synthesis by Alkylation of Aza-sulfurylglycinyl Peptides

<i>N</i>-Aminosulfamides are peptidomimetics in which the C_αH and the carbonyl of an amino acid residue are both respectively replaced by a nitrogen atom and a sulfonyl group. Aza-sulfurylglycinyl tripeptide analogs were effectively synthesized from amino acid building blocks by condensations of <i>N</i>-protected amino hydrazides and <i>p</i>-nitrophenylsulfamidate esters. The installation of <i>N</i>-alkyl chains and access to other aza-sulfuryl amino acid residues were effectively achieved by chemoselective alkylation

<i>N</i>-Aminosulfamide Peptide Mimic Synthesis by Alkylation of Aza-sulfurylglycinyl Peptides

<i>N</i>-Aminosulfamides are peptidomimetics in which the C_αH and the carbonyl of an amino acid residue are both respectively replaced by a nitrogen atom and a sulfonyl group. Aza-sulfurylglycinyl tripeptide analogs were effectively synthesized from amino acid building blocks by condensations of <i>N</i>-protected amino hydrazides and <i>p</i>-nitrophenylsulfamidate esters. The installation of <i>N</i>-alkyl chains and access to other aza-sulfuryl amino acid residues were effectively achieved by chemoselective alkylation