PIII‐Directed Late‐Stage Ligation and Macrocyclization of Peptides with Olefins by Rhodium Catalysis. Issue 31 (10th June 2022)

• Record Type: Journal Article
• Authors: Liu, Lei; Fan, Xinlong; Wang, Boning; Deng, Hong; Wang, Tianhang; Zheng, Jie; Chen, Jun; Shi, Zhuangzhi; Wang, Huan
• Is Part Of: Angewandte Chemie international edition. Volume 61:Issue 31(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-06-10
• Subjects: C−H Activation -- Macrocyclization -- Peptide Modification -- Rhodium -- Tryptophan; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.202206177
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: Transition metal‐catalyzed C−H activation is a step‐economical strategy for peptide functionalization. Herein, we report the method of late‐stage peptide ligation and macrocyclization through rhodium‐catalyzed alkylation of tryptophan residues at the C7 position. This method utilizes a N ‐P t Bu2 directing group and tolerates various peptide and alkene substrates. Utilizing internal olefins, this study represents the first example of site‐selective peptide C−H alkylation through deconjugative isomerization. Furthermore, our method provides access to peptide macrocycles with unique Trp(C7)‐alkyl crosslinks and potent cytotoxicity towards cancer cells. Abstract : A method for late‐stage peptide ligation and macrocyclization through rhodium‐catalyzed C7‐selective alkylation of tryptophan residues has been developed. This method is compatible with internal olefins and represents the first example of site‐selective peptide C−H alkylation through deconjugative isomerization.