Helton Molly E, Howard Christopher S, Prieto Bruno Keisy, Cartrette Katelyn D, Bowles Maxwell O, Hearne William A, Proulx Caroline
Department of Chemistry, North Carolina State University, Raleigh, North Carolina 27695-8204, United States.
Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
J Org Chem. 2025 Jul 11;90(27):9549-9558. doi: 10.1021/acs.joc.5c01024. Epub 2025 Jun 30.
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.
我们评估了后期氮杂肽 - 烷基化反应过程中的肽序列兼容性，并描述了氮杂拟肽和1,2 - 二烷基化氮杂肽产物的阻转异构性质。我们的研究结果表明，除甲硫氨酸外，几乎所有受保护的氨基酸侧链都与树脂上的后期烷基化条件兼容。使用可变温度核磁共振和动态高效液相色谱法，分别报道了一系列氮杂拟肽（单烷基化）和1,2 - 二烷基化氮杂肽的N - N旋转能垒为15 - 16千卡/摩尔和20 - 24千卡/摩尔。
