SYNTHESIS OF PHOTOREACTIVE DIAZIRINYL SALICIN DERIVATIVE TO ELUCIDATE FUNCTIONAL ANALYSIS OF THE BITTER TASTE RECEPTOR (Dedicated to Professor Isao Kuwajima on the occasion of his 77th birthday)

Salicin (salicyl alcohol glucoside) is a substance well known for its bitter taste. A photoreactive diazirinyl derivative of salicin will be utilized for the functional analysis of interactions between the bitter taste receptor and salicin. Glucosides of salicyl derivatives are more difficult than phenol derivatives that are unsubstituted at the ortho-position. A diazirinyl salicin derivative was synthesized at moderate yields by glucosidation of 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl bromide and 2-hydroxy-4-[3-(trifluoromethyl)-3H-diazirin-3-yl]-benzaldehyde in the presence of a phase-transfer catalyst, nBuEt3NBr, followed by reduction and deprotection. Salicin is long known as one of the major components of phenyl glycosides in the family Salicaceae and is a bitter anti-inflammatory compound. Elucidation of the functions of its gustatory receptor on the basis of structure–activity relationships may reveal the mechanism of homeostatic functions, which is of great interest to scientists. Photoaffinity labeling is one of the most common techniques used in the analysis of chemical biology. To the best of our knowledge, there are no reports on the preparation of photoreactive salicin derivatives for the analysis of bitter taste receptors. Two modifications of phenyl glucoside derivatives using diazirine have been reported. The derivatives are not substituted at the o-position of phenol. One modification is glucosidation of p-diazirinyl phenol to synthesize α-glucoside and the other This paper is dedicated to Prof. Dr. Isao Kuwajima on the occasion of his 77th birthday. is construction of the diazirine moiety in the precursor of the phenyl glucoside derivative. However, glucosides of salicyl alcohol derivatives are more complicated than glucosides of the o-position unsubstituted phenol derivatives. Optimization of glucosidation of salicyl alcohol or salicyl aldehyde derivatives is essential to the synthesis of target diazirinyl derivatives of salicin. In this study, we report the synthesis of diazirinyl derivative and preliminary screening of glucosidations for salicyl alcohol and salicyl aldehyde derivatives. O OH HO HO OH O F3C N N OH O OAc AcO AcO AcO OAc F3C N N