Preparation of the β3-homoselenocysteine derivatives Fmoc-β3hSec(PMB)-OH and Boc-β3hSec(PMB)-OH for solution and solid-phase-peptide synthesis and selenoligation

Article abstract of DOI:10.1002/hlca.200790171

The 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.