NOVEL FAMILY OF AROMATIC DIAZIRINES FOR PHOTOAFFINITY-LABELING

A series Of simple methods for modifying diazirines bearing an aromatic ring has been accomplished. This first versatile approach involving direct substitution on the aromatic ring of diazirines has been achieved by means of the aromatic thallation of (alkoxyphenyl)diazirines. Introduction of the thallium moiety was successfully followed by nitration, iodination, or palladium-catalyzed carbonylation to give a family of substituted aryldiazirines useful for photolabeling. For instance, diazirines labeled with a nitro group can be detected by spectrophotometric methods, and those labeled with an iodo group can be useful in tracer experiments. The (methoxyphenyl)diazirines were also found to be stable under certain demethylation conditions, thus providing a potential source of diazirines with modifiable phenol hydroxyl groups. By means of this approach, a spacer arm to link diazirines with ligands was readily introduced. Radioactive diazirines labeled with carbon-14 or tritium were also prepared using this method. All the new diazirines were derived from a pair of simple (methoxyphenyl)diazirines. The ease of derivatization of the (alkoxyphenyl)diazirines described here may offer a practical approach to simplify the time-consuming methods currently used for diazirine synthesis.