Patent ID: 6346601
Filing Date: 2002-02-12
Classification: C07K

Abstract:
A procedure for obtaining octreotide and its pharmaceutical acceptable salts comprising the steps of:a) providing a linear peptide having the first sequence Boc-D-Phe-Cys(Trt)-Phe-D-Trp-Lys(Boc)-Thr(tBu)-Cys(Trt)-2Cl-trityl-R, wherein R is a polymer insoluble in dichloromethane or dimethylformamide; b) treating the first sequence with an acid to obtain Boc-D-Phe-Cys(Trt)-Phe-D-Trp-Lys(Boc)-Thr(tBu)-Cys(Trt)OH; c) obtaining (2,7 cyclic) Boc-D-Phe-Cys(Trt)-Phe-D-Trp-Lys(Boc)-Thr(tBu)-Cys(Trt)-Throl disulfide by: 1) oxidizing Boc-D-Phe-Cys(Trt)-Phe-D-Trp-Lys(Boc)-Thr(tBu)-Cys(Trt)OH in the presence of iodine to obtain(2,7 cyclic) Boc-D-Phe-Cys(Trt)-Phe-D-Trp-Lys(Boc)-Thr(tBu)-Cys(Trt)OH disulfide and contacting the latter with a threoninol residue, or 2) contacting Boc-D-Phe-Cys(Trt)-Phe-D-Tip-Lys(Boc)-Thr(tBu)-Cys(Trt)OH with a threoninol residue to obtain Boc-D-Phe-Cys(Trt)-Phe-D-Trp-Lys(Boc)-Thr(tBu)-Cys(Trt)-Throl and oxidizing Boc-D-Phe-Cys(Trt)-Phe-D-Trp-Lys(Boc)-Thr(tBu)-Cys(Trt)-Throl in the presence of iodine; and d) deprotecting side chains of (2,7 cyclic) Boc-D-Phe-Cys(Trt)-Phe-D-Trp-Lys(Boc)-Thr(tBu)-Cys(Trt)-Throl disulfide with 70-95% trifluoroacetic acid in the presence of scavengers to obtain (2,7 cyclic) D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Throl disulfide.