IMPROVED PROCESS FOR PREPARATION OF OCTREOTIDE BY SOLUTION PHASE PEPTIDE SYNTHESIS

摘要

The present invention relates to a novel processes for commercial production of pharmaceutical grade octreotide using classical solution phase peptide synthesis in high yield and purity and using inexpensive amino acid derivatives. Thus the protected octapeptide alcohol Boc -D- Phe - Cys (Trt)-Phe -D - Trp - Lys (Boc) - Thr - Cys (Trt) - Thr - OL is prepared by condensation of hexapeptide acid Boc -D - Phe - Cys (Trt)-Phe -D - Trp - Lys (Boc) - Thr - OH with dipeptide alcohol H- Cys (Trt) - Thr - OL. The hexapeptide Boc -D- Phe - Cys (Trt)-Phe -D - Trp - Lys (Boc) - Thr - OMe is prepared by condensing Boc - D - Phe - Cys (Trt) - OH with tetrapeptide H-Phe -D - Trp - Lys (Boc) - Thr - OMe followed by hydrolysis. The linear octapeptide alcohol is treated with cocktail mixture TFA /water/ TIS (9.0:0.5:0.25), in one step removes the Trt and Boc groups, followed by oxidation with hydrogen peroxide to affords octreotide.