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Updated: Nov 2, 2025

Chemoselective Modification of Viral Surfaces via Bioorthogonal Click Chemistry
Published on: August 19, 2012
Synthetic methodology towards allylic trans-cyclooctene-ethers enables modification of carbohydrates: bioorthogonal
Mark A R de Geus1, G J Mirjam Groenewold1, Elmer Maurits1
1Leiden Institute of Chemistry, The Institute for Chemical Immunology, Leiden University Einsteinweg 55 2333 CC Leiden The Netherlands m.c.araman@lic.leidenuniv.nl s.i.van.kasteren@lic.leidenuniv.nl.
Abstract:
The inverse electron-demand Diels-Alder (IEDDA) pyridazine elimination is one of the key bioorthogonal bond-breaking reactions. In this reaction trans-cyclooctene (TCO) serves as a tetrazine responsive caging moiety for amines, carboxylic acids and alcohols. One issue to date has been the lack of synthetic methods towards TCO ethers from functionalized (aliphatic) alcohols, thereby restricting bioorthogonal utilization. Two novel reagents were developed to enable controlled formation of cis-cyclooctene (CCO) ethers, followed by optimized photochemical isomerization to obtain TCO ethers. The method was exemplified by the controlled bioorthogonal activation of the lac operon system in E. coli using a TCO-ether-modified carbohydrate inducer.
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