SYNTHESIS OF SOMATOSTATIN AND [D-TRP8]- SOMATOSTATIN

Experimental details for practical syntheses of somatostatin and D‐Trp8‐somatostatin are described. The peptides were assembled from three fragments which permit further syntheses of analogs with modifications at positions 1, 2 or 8. Nα‐Bpoc protecting groups were used for the two major fragments and these were selectively removed in the presence of the tert‐butyl derived amino acid side chain functionalities. The two cysteine residues were protected by acetamidomethyl groups. All the peptide intermediates were fully characterized and a 10‐g synthesis of the protected tetradecapeptide is reported. Major fragments were coupled by the azide method in good yield. Dihydrosomatostatin and D‐Trp8‐dihydrosomatostatin were isolated, purified, characterized and cyclized. Polymeric side‐product was successfully recycled (by reduction with dithiothreitol and reoxidation) to give an overall yield for the oxidation of 52%. Somatostatin and D‐Trp8‐somatostatin were purified by gel filtration or countercurrent distribution and the final products were fully characterized and determined to be>97% pure by reversed phase high performance liquid chromatography.