This invention relates a process for preparing octreotide and derivatives thereof. The starting material, Cys(Trt)-2-Chlorotrityl resin is coupled with various amino acids to obtain a protected heptapeptide of formula 2: Boc-D-Phe-Cys(Trt)-Phe-D-Trp-Lys(Boc)-Thr(OBut)-Cys(Trt)-2-Chlorotrityl resin. The linear protected peptide of formula 2 is cleaved from the support using TFA,TIS and water to yield linear protected peptide of formula 3 Boc-D-Phe-Cys(Trt)-Phe-D-Trp-Lys(Boc)-Thr(OBut)-Cys(Trt)-OH Linear protected heptapeptide of formula 3 is deprotected to yield heptapeptide of formula 6: D-Phe-Cys-Phe-D-Trp- Lys-Thr-Cys-OH SH SH which is cyclized using hydrogen peroxide and to the cyclic peptide of formula 7 D-Phe-Cys-Phe-D-Trp- Lys-Thr-Cys-OH threoninol is coupled at C terminal to yield octreotide. Alternatively threoninol is coupled to the heptapeptide of formula 3 to yield protected octapeptide of formula 4 Boc-D-Phe-Cys(Trt)-Phe-D-Trp-Lys(Boc)-Thr(OBut)-Cys(Trt)-Thr-OL which is subsequently deprotected to yield linear octapeptide of formula 5 D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-OL SH SH and cyclized with hydrogen peroxide to yield cyclic octreotide with a yield of > 95%. - 7 NOV 2008
