Year: 2024
Type: article
Abstract: The selective modification of nitrogen heteroaromatics enables the development of new chemical tools and accelerates drug discovery. While methods that focus on expanding or contracting the skeletal structures of heteroaromatics are emerging, methods for the direct exchange of single core atoms remain limited. Here, we present a method for 14N → 15N isotopic exchange for several aromatic nitrogen heterocycles. This nitrogen isotope transmutation occurs through activation of the heteroaromatic substrate by triflylation of a nitrogen atom, followed by a ring-opening/ring-closure sequence mediated by 15N-aspartate to effect isotopic exchange of the nitrogen atom. Key to the success of this transformation is the formation of an isolable 15N-succinyl intermediate, which undergoes elimination to give the isotopically labeled heterocycle. These transformations occur under mild conditions in high chemical and isotopic yields.
DOI: 10.1021/jacs.3c11515
Language: English
Subfield: Pharmaceutical Science
Domain: Life Sciences
Open Access status: green
Awards: Acquisition of a Cryoprobe and Related Accessories for a 600 MHz NMR Spectrometer to Support Health Research Activities at the University of California, Berkeley, G1373954501, G271676902, G3215714589, NSF Center for Computer-Assisted Synthesis, High Performance Computing Cluster for Public Health Driven Molecular Science - Core Facility, G5350220339, G5766157962, Renewal: Strategies and Methods for Complex Molecule Synthesis, G993257700
OpenAlex ID: W4391360165