Sodium borohydride surprisingly cleaves the Threonine2 (Thr2) peptide bond in N-protected Polymyxin B. Occurring at 20 ºC, the mild reductive cleavage is novel; and it facilitates the synthesis of PMB-derived antibiotics. The reaction fails when both Threonine2,10 hydroxyls are protected. The reaction can be performed on all therapeutic peptides containing Threonine.
Supporting Information - Selective Reductive Cleavage of the Threonine2 Peptide Bond of Penta-N-Boc-Polymyxin B with Sodium Borohydride