Of course, it is from Bertozzi's group in Berkeley.
Improving Cu-free click chemistry...
- Mechanistic Curiosities
- Host/guest chemistry: cyclodextrin - harnessing highly reactive small-molecule components
- Bioorthogonal Chemistries
It is exciting. But, far beyond what I can understand :-(
All I got is that, now, we have a better compound to use for copper free click labeling.
J Am Chem Soc. 2010 Jul 28. [Epub ahead of print]
DOI: 10.1021/ja105005tDifluorobenzocyclooctyne: Synthesis, Reactivity, and Stabilization by beta-Cyclodextrin.
Sletten EM, Nakamura H, Jewett JC, Bertozzi CR.Departments of Chemistry and Molecular and Cell Biology and Howard Hughes Medical Institute, University of California, Berkeley, California 94720, and The Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, California 94720.
Highly reactive cyclooctynes have been sought as substrates for Cu-free cycloaddition reactions with azides in biological systems. To elevate the reactivities of cyclooctynes, two strategies, LUMO lowering through propargylic fluorination and strain enhancement through fused aryl rings, have been explored. Here we report the facile synthesis of a difluorobenzocyclooctyne (DIFBO) that combines these modifications. DIFBO was so reactive that it spontaneously trimerized to form two asymmetric products that we characterized by X-ray crystallography. However, we were able to trap DIFBO by forming a stable inclusion complex with beta-cyclodextrin in aqueous media. This complex could be stored as a lyophilized powder and then dissociated in organic solvents to produce free DIFBO for in situ kinetic and spectroscopic analysis. Using this procedure, we found that the rate constant for the cycloaddition reaction of DIFBO with an azide exceeds those for difluorinated cyclooctyne (DIFO) and dibenzocyclooctyne (DIBO). Cyclodextrin complexation is therefore a promising approach for stabilizing compounds that possess the high intrinsic reactivities desired for Cu-free click chemistry.
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