Protocol for efficient solid-phase synthesis of peptides containing 1-hydroxypyridine-2-one (1,2-HOPO)

Abstract

•Metal chelation has found many applications that directly affect human's life.•Natural siderophores are one of the most potent chelators for Fe (III)•1-Hydroxypyridine-2-one (1,2-HOPO) (Fig.1a), which is shown in 4-carboxy-1-hydroxypyridin-2-one (1,2-HOPO-4-COOH) (Fig.1b), is a moiety that electronically resembles the hydroxamate group found in natural siderophores (Fig.1c). Of note, 1,2-HOPO moiety is present in the natural siderophore cepabactin [1]•Synthesis of 1,2-HOPO containing chelators has been carried in solid phase using carboxylic acid derivatives of 1,2-HOPO and required the protection of the reactive hydroxyl group usually with benzyl group (Bzl). After the peptide elongation, the Bzl group has been removed on the same solid phase using a bit harsh conditions: 0.1 M BBr3 in DCM for 60 min [2], 10% HBr in AcOH for 14 h [3]; in solution: 1 M BCl3 in DCM for 2 d [4], 50% HCl in AcOH for 4 d [5], H2-Pd/C, AcOH-MeOH [6].•First of all, a method for the incorporation of the 1,2-HOPO-4-COOH through its carboxyl group into the peptide backbone without protecting the N-OH is proposed (the presence of the carboxyl group facilitates the attachment).•Furthermore, in the cases that Bzl protection is required for the N-OH, a friendlier method for removing the Bzl is described. The removal of the Bzl is done concomitantly to the global deprotection and cleavage of the peptide from the resin using TFA- TFMSA-H2O (8:3:1).