PREPARATION OF PHOSPHOAMINO ACID-DERIVATIVES WITH ACID STABLE O-PHOSPHONO-PROTECTION FOR THE BOC-MODE SOLID-PHASE SYNTHESIS OF PHOSPHOPEPTIDES

Boc-phosphoamino acid derivatives with O-[di(4-nitrobenzyl)- or dicycl ohexylphosphono]-protection were prepared for application to the Boc-m ode solid-phase synthesis of phosphopeptides. These protecting groups are both stable to TFA, but removable with a combination of trifluorom ethanesulfonic acid and methylthiobenzene in TFA. Of these derivatives , N-alpha-Boc-O-(dicyclohexylphosphono)serine and N-alpha-Boc-O(dicycl ohexylphosphono)threonine were obtained as crystalline compounds to be favorably utilized as starting materials for solid-phase synthesis us ing an automated peptide synthesizer. On the other hand, N-alpha-Boc-O -(dicyclohexylphosphono)tyrosine and all of the O-[di(4-nitrobenzyl)]p hosphono derivatives were prepared as crystalline cyclohexylammonium o r dicyclohexylammonium salts.