Modular Assembly of Heterotrifunctional Molecules Enabled by Iodosulfonylation of Allenes and Subsequent Amination

J Med Chem. 2024 Nov 20. doi: 10.1021/acs.jmedchem.4c02114. Online ahead of print.

Abstract

Beyond the rapid achievements of therapeutic heterobifunctional molecules, some recent efforts have focused on constructing heterotrifunctional molecules, aiming at developing more potent and selective therapeutic agents or emerging additional functions to heterobifunctional molecules. However, the synthesis of these complex molecules requires a specific design and lengthy steps. We have developed a two-step strategy for the modular construction of heterotrifunctional molecules, enabled by the sustainable and convenient iodosulfonylation of allenes followed by SN2'-selective amination. This strategy successfully incorporates a broad range of biologically active molecules, labeling them with a fluorescent group. The applications of the obtained compounds in selective protein labeling, subcellular imaging, and targeted inhibition of tumor cells make this strategy highly appealing.