Synthesis of allose-templated hydroxyornithine and hydroxyarginine analogs

Abstract

Conformationally constrained amino acid analogs are widely used to probe the bioactive conformation of peptides. In this paper we report on the synthesis of hexafunctional allose-templated l- and d-hydroxyornithine and l- and d-hydroxyarginine analogs in which the allose-based polyol scaffold constrains the side chain of hydroxyornithine and hydroxyarginine in an extended conformation. The partially protected building blocks were selected for future use in solid-phase peptide synthesis using the Fmoc-strategy. The synthesis starts from a previously prepared C-glucosyl glycine analog. Multiple chemical protection–deprotection steps and an oxidation are used to prepare 3-keto- C-glucosyl analogs that serve as a precursor to install an amino function via reductive amination. Guanidinylation of the amino group provides access to allose-templated hydroxyarginine analogs. Both hexafunctional building blocks are further chemically modified to provide suitable protection for solid-phase peptide synthesis using the Fmoc-strategy.