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Readily Accessible Ambiphilic Cyclopentadienes for Bioorthogonal Labeling
Brian J Levandowski1, Raymond F Gamache1, Jennifer M Murphy2
1Department of Chemistry and Biochemistry , University of California , Los Angeles , California 90095 , United States.
Abstract:
A new class of bioorthogonal reagents based on the cyclopentadiene scaffold is described. The diene 6,7,8,9-tetrachloro-1,4-dioxospiro[4,4]nona-6,8-diene (a tetrachlorocyclopentadiene ketal, TCK) is ambiphilic and self-orthogonal with remarkable stability. The diene reacts rapidly with a trans-cyclooctene and an endo-bicyclononyne, but slowly with dibenzoazacyclooctyne (DIBAC), allowing for tandem labeling studies with mutually orthogonal azides that react rapidly with DIBAC. TCK analogues are synthesized in three steps from inexpensive, commercially available starting materials.
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