Use of Aldehyde-Alkyne-Amine Couplings to Generate Medicinal Chemistry-Relevant Linkers.

ABSTRACT: Copper catalyzed aldehyde-alkyne-amine (A³) couplings lead to multifunctional, racemic, propargylic amines, many on a multigram scale. As part of an industrial collaboration, a selection of linkers was purified by chiral HPLC to afford single enantiomers, the absolute configuration of which was determined by vibrational circular dichroism (vCD). To show medicinal chemistry applications, selected linkers were further derivatized into potential cellular probes and (+)-JQ1 containing PROTACs (proteolysis targeting chimeras), which degraded their target protein BRD4.

SUBMITTER: McGown A 

PROVIDER: S-EPMC11831382 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature