Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Site-selective incorporation of deuterium into biologically active compounds is of high interest in pharmaceutical industry. We present a mild and environmentally benign metal-free method for the remote selective radical C-H monodeuteration of aliphatic C-H bonds in various amides with inexpensive heavy water (D O) as the deuterium source. The method uses the easily installed N-allylsulfonyl moiety as an N-radical precursor that generates the remote C-radical via site-selective 1,5- or 1,6-hydrogen atom transfer (HAT). Methyl thioglycolate, that readily exchanges its proton with D O, serves as the radical deuteration reagent and as a chain-carrier. The highly site-selective monodeuteration has been applied to different types of unactivated sp -C-H bonds and also to the deuteration of C-H bonds next to heteroatoms. The potential utility of this method is further demonstrated by the site-selective incorporation of deuterium into natural product derivatives and drugs.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8456965 | PMC |
| http://dx.doi.org/10.1002/anie.202104254 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Photocatalyzed Decarboxylative B-C Couplings for the Synthesis of Carboranyl Amino Acids and Peptides.
J Am Chem Soc
August 2025
Frontiers Science Center for Transformative Molecules, Center for Chemical Glycobiology, Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, State Key Laboratory of Synergistic Chem-Bio Synthesis, School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai 20
Boron neutron capture therapy (BNCT) is a promising and selective strategy for treating aggressive and refractory tumors, but its clinical success depends on the development of effective boron delivery agents. These agents must offer high tumor selectivity, structural stability, and sufficient boron content─criteria that current clinical options fail to fully satisfy. Herein, we report a visible-light-driven decarboxylative B-C cross-coupling between boron-functionalized carborane carboxylic acids and dehydroalanine (Dha)-containing peptides, enabling the first synthesis of boron-vertex-substituted carboranyl peptides under mild conditions.
View Article and Find Full Text PDFFrom Mono--Protected Amino Acids to Pyridones: A Decade of Evolution of Bifunctional Ligands for Pd(II)-Catalyzed C-H Activation.
Acc Chem Res
August 2025
Department of Chemistry, The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, California 92037, United States.
ConspectusFunctionalization of carbon-hydrogen (C-H) bonds has emerged as a powerful strategy in modern organic synthesis, offering efficient routes to build molecular complexity from simple and abundant substrates. Among various transition-metal catalysts, palladium(II) complexes have proven particularly versatile for C-H activation, owing to the diverse reactivity of carbon-palladium bonds. To advance this approach, the discovery of ligands that can accelerate C-H activation as well as subsequent steps in the catalytic cycle is the pivotal driving force.
View Article and Find Full Text PDFLate-Stage Serine Modification Enables Noncanonical Peptide Synthesis.
J Am Chem Soc
August 2025
Department of Chemistry, New York University, 100 Washington Square East, New York, New York 10003, United States.
Noncanonical amino acids play a critical role in enhancing drug efficacy, specificity, pharmacokinetics, and other key therapeutic properties. However, their incorporation into peptides or small molecules often presents significant synthetic challenges. Late-stage modification of natural residues, after the primary structural framework of a molecule is established, offers an efficient strategy for generating analogue libraries.
View Article and Find Full Text PDFPalladium-Catalyzed Late-Stage Maleimidation of Phenylalanine-Containing Peptides.
Org Lett
August 2025
Key Laboratory of Catalytic Conversion and Clean Energy in Universities of Shandong Province, School of Chemistry and Chemical Engineering, Qufu Normal University, Qufu 273165, P. R. China.
The incorporation of bioactive fragments or non-natural covalent linkages has shown to significantly improve the chemical stability and biological activity of peptides. In this study, we have developed a novel methodology for site-selective Pd-catalyzed maleimidation of phenylalanine-containing peptides. This synthetic strategy offers a straightforward and efficient approach for the construction of maleimide-phenylalanine covalent peptide conjugates.
View Article and Find Full Text PDFSamarium(II) Iodide (SmI)-Mediated Reductive Ring-Opening of Cyclopropanecarboxylates for Site-Selective Deuteration.
J Org Chem
August 2025
College of Pharmacy, Nankai University, Tianjin 300353, P. R. China.
Herein, we report a SmI-mediated reductive ring-opening deuteration of cyclopropanes bearing carboxylate ester substituents. This method enables the regioselective synthesis of α,γ-dideuterated esters with high deuterium incorporation efficiency. By increasing the stoichiometry of SmI/EtN/DO, the reaction proceeds through a sequential pathway: initial cyclopropane ring-opening followed by ester reduction, yielding α,α,β,δ-tetradeuterated alcohols as the final products.
View Article and Find Full Text PDF