Synthetic routes to trifluoromethylphenyl diazirine photolabeling reagents containing an alkyne substituent (TPDYNE) for chemical biology applications

Abstract

The trifluoromethylphenyl diazirine (TPD) group is widely used in photoaffinity labeling studies. The TPDYNE group (TPD with an additional alkyne substituent on the phenyl ring) enables the use of click chemistry in conjunction with photoaffinity labeling and expands the utility of the TPD group. New methods for preparing previously known as well as new TPDYNE reagents are reported. Additional methods for preparation of a TPDYNE precursor from which the TPDYNE group can be generated once the precursor is attached to the molecule of interest are also described. Procedures for attaching the TPDYNE or TPDYNE precursor to carboxyl, amino, hydroxyl and alkyne groups are demonstrated using steroids as examples.