School of Chemical Sciences, National Institute of Science Education and Research (NISER)-Bhubaneswar, Jatni campus, Bhubaneswar-752050, Odisha, India.
Homi Bhabha National Institute (HBNI)-Mumbai, Anushaktinagar, Mumbai, 400 094, India.
Org Biomol Chem. 2024 Aug 22;22(33):6822-6832. doi: 10.1039/d4ob00800f.
Aryl oxalamides are constituents of various promising drug-like molecules. Their aryl groups are derived from the benzenoid aromatic moiety. However, non-benzenoid aromatic molecules, troponoids, are found in various bioactive natural products. It would be thought-provoking to explore non-benzenoid aryl oxalamide derivatives. This report describes the synthesis of -troponyl-oxalamide peptides by Pd(II)-catalyzed C(sp)-H functionalization of -troponyl glycinate peptides. This is the first instance of β-hydride elimination at the palladium complex of -troponyl glycinates that generates imine , rendering the synthesis of oxalamides. Importantly, the crystal structures of representative oxalamide derivatives form distinctive foldameric structures, such as β-sheet type structures, owing to the presence of additional troponyl carbonyl groups. Hence, these non-benzenoid oxalamides are potential scaffolds for tuning the structure and function of -troponyl peptides, which could provide innovative avenues of research in the development of emerging structural and functional peptides.
芳基草酰酰胺是各种有前途的药物样分子的组成部分。它们的芳基部分源自苯环芳香部分。然而，非苯环芳香分子，即张力蛋白，存在于各种生物活性天然产物中。探索非苯环芳基草酰酰胺衍生物将是发人深省的。本报告描述了通过 Pd(II)催化的 -张力蛋白甘氨酸肽的 C(sp)-H 功能化合成 -张力蛋白-草酰酰胺肽。这是首例 -张力蛋白甘氨酸酯钯配合物中的 β-氢消除生成亚胺，从而合成草酰酰胺。重要的是，代表性草酰酰胺衍生物的晶体结构形成独特的折叠结构，如β-折叠型结构，这是由于存在额外的张力蛋白羰基。因此，这些非苯环草酰酰胺是调节 -张力蛋白肽结构和功能的潜在支架，这可能为新兴结构和功能肽的开发提供创新性的研究途径。
