Abstract
The synthetic strategy for the suppression of α to β rearrangement of aspartyl peptides during anhydrous hydrogen fluoride treatment was designed in which the carboxyl protecting groups stable to hydrogen fluoride, such as β-phenancyl or β-p-nitrobenzyl ester, were used and the protected peptides were treated with hydrogen fluoride-anisole mixture to remove protecting groups other than β-phenancyl or β-p-nitrobenzyl ester group followed by deprotection of the β-carboxyl protecting group under the mild conditions. Thus, the model dipeptide derivative, Z (OMe)-Asp (ONb)-Ser (Bzl)-OBzl, was treated with hydrogen fluoride-anisole mixture. The product was submitted to hydrogenolysis to remove the p-nitrobenzyl ester group. Under such a strategy, no product due to the rearrangement was detected on paper chromatograms. Similarly, the treatment of Boc-Asp (OPac)-Ser (Bzl)-OBzl gave a satisfactory result. H-Asp-Ser-Asp-Pro-Arg-OH, which is a fragment of immunogloblin E and is reported to be biologically active, has been synthesized from Boc-Asp (ONb)-Ser (Bzl)-Asp (ONb)-Pro-Arg (NO2)-resin as an application of this strategy. Chemical and physical properties of the pentapeptide were in fair agreement with those of the pentapeptide which was synthesized under the mild conditions from Boc-Asp (OBzl)-Ser (Bzl)-Asp (OBzl)-Pro-Arg (NO2)-ONb.
