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45503-G4
Photoactivated 1,3-Dipolar Cycloaddition: Scope and Applications

Qing Lin, State University of New York at Buffalo

During the first funding year, we have developed a very mild, photoactivated 1,3-dipolar cycloaddition procedure, and successfully employed it in the synthesis of polysubstituted pyrazolines. This procedure involved the in situ generation of the reactive nitrileimine dipoles using a hand-held UV lamp at 302 nm, followed by spontaneous cycloaddition with a broad range of 1,3-dipolarophiles with excellent solvent compatibility, functional group tolerance, regioselectivity, and yield. A publication detailing the scope and utility of this new procedure appeared recently in the web release of Organic Letters journal.

We have begun to apply this extremely mild, photoinducible 1,3-dipolar cycloaddition to the selective modification of proteins containing the diphenyltetrazole moietyin the biological media. We found the labeling reaction is extremely fast and tolerant of proteinaceous groups. Moreover, green fluorescent adducts are formed, providing an additional tool for the reaction monitoring. A manuscript disclosing this robust bioorthogonal reaction has been submitted, and is currently under review.

We are currently working on the optimization of the photoreactivity of the diaryltetrazoles with an aim to shift the photoactivation wavelength to the long wavelength region (>405 nm). Furthermore, we are working on the use of this chemistry for the protein target-guided in situ synthesis of potential tetrasubstituted pyrazoline/pyrazole MDM2 inhibitors.

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