Phthalyl (Pht) is an acyl amino protecting group. In peptide synthesis, when Pht is selected as an amino protecting group, the carboxyl end of the peptide chain cannot be protected with methyl or ethyl esters, but must be protected with benzyl or tert-butyl esters to avoid the step of saponification removal in the future.
Introduction of Pht
The first method to introduce Pht group was to melt phthalic anhydride with amino acids at 145-150 °C, but this method would cause partial racemization of some amino acids. So some improvements were made on this basis, that is, Pht was introduced by reacting phthalic anhydride in CHCl3 at 70 °C. In addition, N-carbethoxyphthalimide is also a commonly used reagent for the introduction of Pht.
Removal of Pht
Pht is stable to catalytic hydrogenolysis, HBr/HOAc treatment, and Na/NH3 (liquid) reduction, but it is easily removed by hydrazine treatment. Generally, the Pht group can be completely removed by refluxing the alcohol solution of hydrazine hydrate for 2 hours or leaving it at room temperature for 1-2 days. Under this condition, Cbz, Boc, Trt, Tos, etc. are not affected. In the case of poor hydrazine effect, the Pht group can be removed by reacting NaBH4/i-PrOH-H2O (6:1) and AcOH at 80 ℃ for 5-8 hours. In addition, the Pht group can also be easily removed by refluxing concentrated HCl.
