Azapeptide Atropisomers From Late-Stage -Alkylations.

We evaluate peptide sequence compatibility during late-stage azapeptide -alkylation reactions and describe the atropisomeric properties of the azapeptoid and 1,2-dialkylated azapeptide products. Our findings indicate that almost all protected amino acid side chains are compatible with the late-stage alkylation conditions on resin, with the exception of methionine. Using variable temperature NMR and dynamic HPLC, N-N rotational energy barriers of 15-16 and 20-24 kcal/mol are reported for a series of azapeptoids (monoalkylated) and 1,2-dialkylated azapeptides, respectively.