PHOTOCHEMICAL METHODS FOR NUCLEOPHILIC SUBSTITUTION REACTIONS AND INHIBITION OF CYSTEINE PROTEASES.

We hereby report the development of the novel photochemical approach to the induction of nucleophilic substitution reactions. This strategy employs a light-activated leaving group based on the 9-aryl-9-fluorene system. 9-fluorenol undergoes efficient photolysis of the C–O bond to generate a fluorenyl cation that is highly reactive. It rapidly undergoes cyclization, activating the leaving group and increasing the electrophilicity of the substrate. Irradiation of 9-aryl-9-fluorenyl derivatives at 300 nm in dichloromethane in the presence of a nucleophile afforded efficient photolysis. The method was applied to form a glycosidic bond between mannosyl sugar and methanol. o-naphthoquinone methides (o-NQMP) are reactive electrophilic intermediates. Their ability to undergo rapid Michael addition with thiols has developed an interest in protein labeling and modification. Upon irradiation at 350 nm, PEG4-NQMP and Biotin-NQMP efficiently inhibited cysteine protease papain. In addition, the binding of Biotin-NQMP with papain was confirmed via western blot.