Department of Chemistry, University of California, Irvine, Irvine, California 92697-2025, USA.
J Org Chem. 2011 May 6;76(9):3166-73. doi: 10.1021/jo102598n. Epub 2011 Apr 15.
This paper reports the use of natural amino acids, the tripeptide β-strand mimic Hao, and the β-turn mimic δ-linked ornithine to generate water-soluble 54-, 78-, and 102-membered-ring macrolactams. These giant macrocycles were efficiently prepared by synthesis of the corresponding protected linear peptides, followed by solution-phase cyclization and deprotection. The protected linear peptide precursors were synthesized on 2-chlorotrityl chloride resin by conventional Fmoc-based solid-phase peptide synthesis. Macrocyclization was typically performed using HCTU and N,N-diisopropylethylamine in DMF at ca. 0.5 mM concentration. The macrocycles were isolated in 13-45% overall yield after HPLC purification and lyophilization. 1D, 2D TOCSY, and 2D ROESY (1)H NMR studies of the 54- and 78-membered-ring macrolactams establish that these compounds fold to form β-sheet structures in aqueous solutions.
本文报道了使用天然氨基酸、三肽β-折叠模拟物 Hao 和β-转角模拟物 δ-连接的鸟氨酸来合成水溶性 54 元、78 元和 102 元大环内酯。这些大环通过相应保护的线性肽的合成、溶液相环化和脱保护来高效制备。保护的线性肽前体通过常规的 Fmoc 固相肽合成在 2-氯三苯甲基氯树脂上合成。环化通常使用 HCTU 和 N,N-二异丙基乙胺在 DMF 中于约 0.5 mM 浓度下进行。经 HPLC 纯化和冻干后，大环化合物的总收率为 13-45%。对 54 元和 78 元大环内酯的 1D、2D TOCSY 和 2D ROESY (1)H NMR 研究表明，这些化合物在水溶液中折叠形成β-折叠结构。
