Journal
NATURE COMMUNICATIONS
Volume 10, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-019-11395-3
Keywords
-
Categories
Funding
- European Research Council under the European Community [307535]
- DFG [SPP 1807]
- Onassis Foundation
Ask authors/readers for more resources
Methods for the late-stage diversification of structurally complex peptides hold enormous potential for advances in drug discovery, agrochemistry and pharmaceutical industries. While C-H arylations emerged for peptide modifications, they are largely limited to highly reactive, expensive and/or toxic reagents, such as silver(I) salts, in superstoichiometric quantities. In sharp contrast, we herein establish the ruthenium(II)-catalyzed C-H alkylation on structurally complex peptides. The additive-free ruthenium(II)carboxylate C-H activation manifold is characterized by ample substrate scope, racemization-free conditions and the chemo-selective tolerance of otherwise reactive functional groups, such as electrophilic ketone, bromo, ester, amide and nitro substituents. Mechanistic studies by experiment and computation feature an acid-enabled C-H ruthenation, along with a notable protodemetalation step. The transformative peptide C-H activation regime sets the stage for peptide ligation in solution and proves viable in a bioorthogonal fashion for C-H alkylations on user-friendly supports by means of solid phase peptide syntheses.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available