Synthesis of peptide-cellulose conjugate mediated by a soluble cellulose derivative having β-Ala esters (II): conjugates with O-phospho-l-serine-containing peptides

A synthetic route is described here for novel peptide-cellulose conjugates containing O-phospho-l-serine. First, Boc-Ser(PO₃Ph₂) and the related dipeptides, Boc-Ser(PO₃Ph₂)-Asp(OBzl) and Boc-Asp(OBzl)-Ser(PO₃Ph₂), were synthesized by adopting the phosphoryl-protection strategy. The condensation reaction between the α-carboxyl group of the protected Boc-Ser(PO₃Ph₂) and the β-amino groups of β-Ala-Cellulose using isobutyl chloroformate and N-methylmorpholine yielded the product conjugate, N ^β-[Boc-Ser(PO₃Ph₂)]-β-Ala-Cellulose. The degree of substitution of Boc-Ser(PO₃Ph₂) towards the β-amino groups of β-Ala-Cellulose was estimated as DS ^N = 0.75 (maximum, 1.0). Similar reactions between β-Ala-Cellulose and two kinds of protected dipeptides, Boc-Asp(OBzl)-Ser(PO₃Ph₂) and Boc-Ser(PO₃Ph₂)-Asp(OBzl), gave the corresponding conjugates, and the DS ^N was estimated to be 0.95 and 0.69, respectively. The phenyl, benzyl, and Boc groups were removed in one-pot using the Pt₂O catalyst in 50 % trifluoroacetic acid/acetic acid. The ³¹P-NMR and UV-Visible spectra indicated the complete deprotection without any observable elimination of the phosphorylated peptides.