Associated date for Macrocylases as synthetic tools for ligand synthesis

Dataset containing additional compound characterisation data to support Brewster RC, Labeaga IC, Soden CE, Jarvis AG. 2021 Macrocylases as synthetic tools for ligand synthesis: enzymatic synthesis of cyclic peptides containing metal-binding amino acids. R. Soc. Open Sci. 8: 211098 Improving the sustainability of synthesis is a major goal in green chemistry, which has been greatly aided by the development of asymmetric transition metal catalysis. Recent advances in asymmetric catalysis show that the ability to control the coordination sphere of substrates can lead to improvements in enantioselectivity and activity, in a manner resembling the operation of enzymes. Peptides can be used to mimic enzyme structures and their secondary interactions and they are easily accessible through solid-phase peptide synthesis. Despite this, cyclic peptides remain underexplored as chiral ligands for catalysis due to synthetic complications upon macrocyclization. Here, we show that the solid-phase synthesis of peptides containing metal-binding amino acids, bipyridylalanine (1), phenyl pyridylalanine (2) and N,N-dimethylhistidine (3), can be combined with peptide macrocylization using peptide cyclase 1 (PCY1) to yield cyclic peptides under mild conditions. High conversions of the linear peptides were observed (approx. 90%) and the Cu-bound cyclo(FSAS(1)SSKP) was shown to be a competent catalyst in the Friedel-Crafts/conjugate addition of indole. This study shows that PCY1 can tolerate peptides containing amino acids with classic inorganic and organometallic ligands as side chains, opening the door to the streamlined and efficient development of cyclic peptides as metal ligands.

本数据集包含补充性化合物表征数据，用于支撑Brewster RC、Labeaga IC、Soden CE、Jarvis AG于2021年发表的研究：《大环化酶（Macrocylases）作为配体合成工具：含金属结合氨基酸的环肽酶促合成》，刊载于《英国皇家学会开放科学》（R. Soc. Open Sci.）8卷：211098。提升合成可持续性是绿色化学的核心目标，不对称过渡金属催化的发展极大推动了这一目标的实现。近期不对称催化领域的研究进展表明，通过调控底物的配位球可改善反应的对映选择性与催化活性，其机制类似酶的催化过程。肽可用于模拟酶的结构及其次级相互作用，且可通过固相肽合成（solid-phase peptide synthesis）便捷获取。尽管如此，由于大环化过程中存在合成难题，环肽作为催化用手性配体的研究仍相对不足。本研究表明，将含金属结合氨基酸（联吡啶丙氨酸（bipyridylalanine）(1)、苯基吡啶丙氨酸（phenyl pyridylalanine）(2)与N,N-二甲基组氨酸(3)）的肽的固相肽合成，与采用肽环化酶1（peptide cyclase 1, PCY1）的肽大环化反应相结合，可在温和条件下生成环肽。线性肽的转化率较高（约90%），且结合铜的cyclo(FSAS(1)SSKP)被证实可作为吲哚的傅-克/共轭加成反应的有效催化剂。本研究证实，PCY1可兼容带有经典无机及有机金属配体侧链的氨基酸肽，为精简高效开发金属配体用环肽开辟了新路径。