Catalytic N-modification of α-amino acids and small peptides with phenol under bio-compatible conditions

Abstract

The functionalization of α-amino acids and peptides provides the opportunity to tailor the properties of these biomolecules for diverse applications in chemistry and biology. Previous methods for N-modification involve the use of aliphatic alcohols, aldehydes, or halides. Alternatively, phenolic compounds are more desirable alkylating reagents as they constitute the backbone of lignin, making them an attractive bio-renewable resource. Here we report a method to N-modify 17 out of the 20 amino acids with phenol or derivatives, with water as the sole by-product. N-arylation is achieved using 2-cyclohexen-1-one and cyclohexanone as the coupling partners. Notably, phenol is successfully used to N-cyclohexylate α-amino acids and small peptides in excellent yields under bio-compatible conditions without racemization.