Design, Synthesis and Late-Stage Modification of Indane-Based Peptides via [2+2+2] Cyclotrimerization

Abstract

Here, we prepared several dipeptides containing 2-aminoindane-2-carboxylic acid (Aic) and carried out further synthetic transformations. Synthesis and purification of modified peptides by using [2+2+2] cyclotrimerization is a challenging task. We are able to modify the unusual amino acids and peptide derivatives by late-stage incorporation of benzylhalo functionality. To incorporate benzylhalo moiety we used [2+2+2] cyclotrimerization in the presence of Mo(CO)₆ . These halo derivatives are potential substrates for further modification by Sonogashira reaction, Suzuki-Miyaura cross-coupling, sultine formation, and the Diels-Alder reaction sequence.

Keywords: Diels-Alder reaction; Indane-based dipepeptide; Sonogashira Coupling; Suzuki Coupling; [2+2+2] cyclotrimerization.