Synthesis of a N-Fmoc dibenzyl pyrazolyl phosphonate protected τ-phosphohistidine building block for Fmoc SPPS

Stable phosphohistidine (pHis) analogues which can be incorporated into peptides are valuable tools for the study of pHis in a biological context. The phosphopyrazolyl side chain has proved useful in the generation of selective τ-pHis antibodies. To allow potential incorporation of the phosphopyrazolyl side chain to peptides a N-Fmoc dibenzyl pyrazole phosphonate building block 3 was synthesized. N-Fmoc dibenzyl pyrazole phosphonate 3 was accessible in four synthetic steps using the Hirao cross coupling reaction via a P-aryl bond formation, and Vederas Boc-β-lactone 11 opening reaction to give the protected amino acid.