Serendipitous discovery of an efficient method for the synthesis of dimeric-RGD analogues using DMAP-photoirradiation

Abstract

We describe a novel disulfide reaction via UV/N,N-dimethylaminopyridine (DMAP) methodology for efficient construction of alkyl and aryl symmetrical disulfides. Compared with other chemical strategies, our methodology is distinguished in that the dimerization reaction can proceed efficiently without metal catalysts, expensive reagents or forcing conditions. This methodology was successfully applied to the preparation of complex dimeric biological peptide-based molecules, and the dimeric RGD peptides produced by this methodology had better binding affinity than the commercially available E-[RGDfK]₂. Our methodology will greatly extend the method to the construction of a complex disulfide bond under mild conditions.