Fmoc/solid‐phase synthesis of Tyr(P)‐containing peptides through t‐butyl phosphate protection

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Abstract
The synthesis is of Tyr(P)‐containing peptides by the use of Fmoc‐Tyr(PO3Me2)‐OH in Fmoc/solid phase synthesis is complicated since, firstly, piperidine causes cleavage of the methyl group from the ‐Tyr(PO3 Me2)‐residue during peptide synthesis and, secondly, harsh conditions are needed for its final cleavage. A very simple method for the synthesis of Tyr(P)‐containing peptides using t‐butyl phosphate protection is described. The protected phosphotyrosine derivative, Fmoc‐Tyr(PO3tBu2)‐OH was prepared in high yield from Fmoc‐Tyr‐OH by a one‐step procedure which employed di‐t‐butyl N,N‐diethyl‐phosphoramidite as the phosphorylation reagent. The use of this derivative in Fmoc/solid phase peptide synthesis is demonstrated by the preparation of the Tyr(P)‐containing peptides, Ala‐Glu‐Tyr(P)‐Ser‐Ala and Ser‐Ser‐Ser‐Tyr(P)‐Tyr(P).