| Abstract: | In building up large polypeptides, it has become the established practice to use acide-labile protecting groups of the t-butyl type. Up to now, only one step of selectivity under acidic conditions has been used, consisting in the cleavage of Trt, Bpoc or Ppoc from N(α) without attacking the t-butyl protecting groups. We have found that the use of 90% trifluoroethanol as solvent permits the selective cleavage of Trt in the presence of Bpoc or Ppoc under controlled acidolytic conditions. This additional selectivity-step may be utilized when two-chained polypeptides are to be constructed. The procedure consists in acidolytic cleavage with hydrochloric acid at a constant potential as measured by the glass electrode (pH-stat). The automatic protonation of the freshly deprotected amino groups permits the evaluation of kinetic and quantitative data of the cleavage reaction. The selectivity ratios and cleavage conditions of Trt, Bpoc and Ppoc in N(α) are demonstrated here by reference to a series of model dipeptides. The successful application of this technique in the total synthesis of human insulin, a polypeptide with two peptida chains, has recently been described 8]. |
