Selective Nitroalkane alkene 1,3 dipolar cycloaddition : a new stategy for peptide conjugation

Abstract

Chemoselective 1,3-dipolar cycloaddition reaction between the nitroalkane functionalized peptides and alkenes is reported. The reactive nitrile oxide can be generated in situ through dehydration reaction using phenyl isocyanate. The in situ generated nitrile oxide was trapped with alkenes to give isoxazolines on peptides. The nitrile oxide-alkene 1,3-dipolar cycloaddition reaction was found to be compatible with solution as well as solid phase peptide synthesis. In a sharp contrast to the copper catalyzed 1,3-dipolar cycloaddition of azides, the nitrile oxides can undergo cycloaddition with both alkynes and alkenes. More importantly, alkenes are easy to synthesize compared to alkynes and also a variety of alkenes are commercially available. The selective and mild nitro-alkene cycloaddition reaction reported in this project can be utilized to functionalize peptides and other small molecules. Though the reaction is mild and compatible for broad substrates, however still there is a need to improve the efficiency of the reaction and also finding alternative to phenyl isocyanate to activate the nitro group is important.