Efficient Fmoc/solid-phase synthesis of Abu(P)-containing peptides using Fmoc-Abu(PO3Me2)-OH

Abstract

The synthesis of the two 4-phosphono-2-aminobutanoyl-containing peptides, Leu-Arg-Arg-Val-Abu(P)-Leu-Gly-OH.CF3CO2H and Ile-Val-Pro-Asn-Abu(P)-Val-Glu-Glu-OH.CF3CO2H was accomplished by the use of Fmoc-Abu(PO3Me2)-OH in Fmoc/solid-phase peptide synthesis. The protected phosphoamino acid, Fmoc-Abu(PO3Me2)-OH, was prepared from Boc-Asp-OtBu in seven steps, the formation of the C-P linkage being effected by the treatment of Boc-Asa-OtBu with dimethyl trimethylsilyl phosphite. Peptide synthesis was performed using Wang Resin as the polymer support with both peptides assembled by the use of PyBOP for the coupling of Fmoc amino acids and 20% piperidine for cleavage of the Fmoc group from the Fmoc-peptide after each coupling cycle. Cleavage of the peptide from the resin and peptide deprotection was accomplished by the treatment of the peptide-resin with 5% thioanisole/TFA followed by cleavage of the methyl phosphonate group by 1 M bromotrimethylsilane/1 M thioanisole in TFA.