β-alkoxy enones for biocompatible primary amine conjugation.

In this study, we present an innovative and efficient approach to amine conjugation that offers many advantages over existing methods. Our method employs an easily prepared β-alkoxy enone as the core reagent, achieving unparalleled specificity to primary amines. It operates effectively under neutral pH conditions and at room temperature. This eliminates the need for metal catalysts or additives, thereby simplifying the process and reducing potential contaminants. A key attribute of our method is its remarkable cleanliness, with ethanol as the sole by-product, ensuring minimal environmental and biological impact. The conjugation products exhibit exceptional stability, even in the presence of diverse biomolecules, making this method highly suitable for intricate biological systems. Our approach demonstrates a broad substrate scope, effectively conjugating a range of compounds from lysine derivatives to complex protein and drug conjugates as well as amino-sugar conjugates. Its ability to selectively target different amine types while remaining unreactive toward anilines and secondary amines such as proline underscores its potential for advancing drug development and biologic synthesis. This method marks a significant breakthrough, offering promising avenues for exploration in biochemical and pharmaceutical research.