Synthesis of N(1)-Phosphorylated Tryptophan Derivatives

Article abstract of DOI:10.1021/jo00268a031

The first synthesis of the N(1)-(dimethylphosphono)tryptophan derivatives Z-Trp(PO3Me2)-OBzl and Boc-Trp(PO3Me2)-ONBzl by reaction of the lithium indolate of protected tryptophan derivatives Z-Trp-OBzl and Boc-Trp-ONBzl with dimethyl phosphorochloridate is described.The N(1)-(dimethylphosphono)tryptophan or Trp(Dmop) derivatives are stable to hydrogenation, and to TFA and high HF treatment, and can be fully deprotected with TFMSA/TFA/m-cresol/dimethyl sulfide or TFMSA/TFA/m-cresol/thioanisole to yield the novel hydrophilic amino acid N(1)-phosphonotryptophan quantitatively.Weak base treatment of Trp(Dmop) compounds yields N(1)-(methylphosphono)tryptophan derivatives.