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

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 NaBH 4 , 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 β 3 ‐heptapeptide 8 with an N‐terminal β 3 ‐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 β 3 ‐tetrapeptide thiol ester 10 by a seleno‐ligation. The product β 3 ‐undecapeptide was identified as its diselenide and its mixed selenosulfide with thiophenol ( Scheme 3 ). The differences between α ‐ and β ‐Sec derivatives are discussed.