Very unusual method of turning Tryptophan into click-reactive handle

 

This research comes to us from very reputable group of Dr. Yiyi Weng at Zhejiang University of Technology.
This paper shows how to turn any Tryptophan into strange tertiary azide heterocycle with about 87% efficiency.
Could be useful if no other functionalization methods are available.
I am not sure how reactive this azide will be (because it is tertiary), but nevertheless, somebody might find it useful.
Please enjoy here: https://onlinelibrary.wiley.com/doi/abs/10.1002/anie.202206308
Abstract:
As the aromatic tryptophan (Trp) side chain plays a pivotal role in influencing the structure and function of peptides and proteins, it has become an attractive target for the late-stage modification of these important biomolecules. Herein, we report an electrochemical approach for late-stage functionalization of peptides containing a Trp side chain through manganese-catalyzed tandem radical azidation/heterocyclization. This electrochemical oxidative strategy provides access to azide-substituted tetrazolo[1,5-a]indole-containing peptides with broad functional group tolerance, high site selectivity, and good yields of products (up to 87 %) under mild buffer conditions. Moreover, the modified Trp-containing peptides bearing an azide functionality are promising building blocks, paving the way for the construction of various derivatives, such as “click” chemistry products.

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