Hetero‐Selective Cross‐Linking of Primary and Secondary Alkyl Amines with CS <sub>2</sub> Under Ambient Aerobic Oxidation for Bioconjugation
Abstract
Abstract Umpolung of primary amines via isothiocyanation presents an attractive approach for cross‐linking biorelevant molecules through two nucleophilic handles. However, conventional isothiocyanation reactions typically require highly electrophilic reagents or strongly oxidative conditions, rendering them unsuitable for complex molecular systems. Herein, we present a robust and nonchemist‐friendly protocol for the isothiocyanation of primary alkyl amines using CS 2 under ambient aerobic oxidation conditions, eliminating the need for additional promoters. These mild conditions not only ensure broad compatibility with endogenous functional groups in biorelevant molecules but also unlock a powerful new capability: selective differentiation between primary and secondary alkyl amines. Notably, the unique suppression of homo‐linking for both primary and secondary amines under these conditions enables near‐perfect hetero‐selectivity in cross‐linking two different biorelevant molecules via their abundant amino handles in a one‐pot operation, offering a streamlined, thiol‐independent, and small‐footprint approach to biocompatible conjugation.
Article Details
Authors (10)
Shuai Jiang
State Key Laboratory of Chemical Reaction Dynamics and Dalian Coherent Light Source, Dalian Institute of Chemical Physics
Xin Chu
State Key Laboratory and Institute of Elemento-Organic Chemistry, College of Chemistry
Xiangmei Kong
Children’s Medical Center Research Institute, Department of Pediatrics, University of Texas Southwestern Medical Center
Xintao Miao
State Key Laboratory and Institute of Elemento-Organic Chemistry, College of Chemistry
Xiaoxi Xu
State Key Laboratory and Institute of Elemento-Organic Chemistry, College of Chemistry
Weimin Xuan
State Key Laboratory of Advanced Fiber Materials & College of Chemistry and Chemical Engineering
Chuanzheng Zhou
State Key Laboratory of Elemento-Organic Chemistry, Frontiers Science Center for New Organic Matter, Department of Chemical Biology, College of Chemistry
Gang He
Tianfei Liu
Frontiers Science Center for New Organic Matter, State Key Laboratory of Advanced Chemical Power Sources, Key Laboratory of Advanced Energy Materials Chemistry (Ministry of Education), State Key Laboratory of Elemonto-organic Chemistry, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Academy of Advanced Interdisciplinary Studies, College of Chemistry
Gong Chen
State Key Laboratory and Institute of Elemento-Organic Chemistry, College of Chemistry