In Situ Synthesis of Alkenyl Tetrazines for Highly Fluorogenic Bioorthogonal Live‐Cell Imaging Probes1. (24th April 2014)

• Record Type: Journal Article
• Authors: Wu, Haoxing; Yang, Jun; Šečkutė, Jolita; Devaraj, Neal K.
• Is Part Of: Angewandte Chemie. Volume 126:Number 23(2014)
• Page Start: 5915
• Page End: 5919
• Publication Date: 2014-04-24
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.201400135
• Languages: English
• ISSNs: 0044-8249

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>In spite of the wide application potential of 1, 2, 4, 5‐tetrazines, particularly in live‐cell and in vivo imaging, a major limitation has been the lack of practical synthetic methods. Here we report the in situ synthesis of (<italic>E</italic>)‐3‐substituted 6‐alkenyl‐1, 2, 4, 5‐tetrazine derivatives through an elimination–Heck cascade reaction. By using this strategy, we provide 24 examples of π‐conjugated tetrazine derivatives that can be conveniently prepared from tetrazine building blocks and related halides. These include tetrazine analogs of biological small molecules, highly conjugated buta‐1, 3‐diene‐substituted tetrazines, and a diverse array of fluorescent probes suitable for live‐cell imaging. These highly conjugated probes show very strong fluorescence turn‐on (up to 400‐fold) when reacted with dienophiles such as cyclopropenes and trans‐cyclooctenes, and we demonstrate their application for live‐cell imaging. This work provides an efficient and practical synthetic methodology for tetrazine derivatives and will facilitate the application of conjugated tetrazines, particularly as fluorogenic probes for live‐cell imaging.</p> </abstract>