Preparation of the β3‐Homoselenocysteine Derivatives Fmoc‐β3hSec(PMB)‐OH and Boc‐β3hSec(PMB)‐OH for Solution and Solid‐Phase‐Peptide Synthesis and Selenoligation

Abstract

AbstractThe title compounds, 4 and 7, have been prepared from the corresponding α‐amino acid derivative selenocystine (1) by the following sequence of steps: cleavage of the SeSe bond with NaBH4, p‐methoxybenzyl (PMB) protection of the SeH group, Fmoc or Boc protection at the N‐atom and Arndt–Eistert homologation (Schemes 1 and 2). A β3‐heptapeptide 8 with an N‐terminal β3‐hSec(PMB) residue was synthesized on Rink amide AM resin and deprotected (‘in air’) to give the corresponding diselenide 9, which, in turn, was coupled with a β3‐tetrapeptide thiol ester 10 by a seleno‐ligation. The product β3‐undecapeptide was identified as its diselenide and its mixed selenosulfide with thiophenol (Scheme 3). The differences between α‐ and β‐Sec derivatives are discussed.