H.-D. Jakubke

SYNTHESIS OF CYCLO-(DES(1,2-L-ALANYL-GLYCINE, 14-L-CYSTEIN)-3-S-CARBOXYMETHYL-L-HOMOCYSTEINAMIDE, 8-D-TRYPTOPHAN)SOMATOSTATIN

The authors describe the synthesis of a shorter-chained somatostatin analogue in which the ring size of the native molecule is largely preserved by incorporation of S-carboxymethyl-L-homocysteinamid and ring closure via its side-chain function. This synthesis involves the linkage of Boc-Phe-D-Trp-Lys[Z(pCl)]-Thr-Phe-Thr-Ser-OH to H-Hcy(CH2-CO-Lys[Z(oCl)]-Asn-Phe-OMe)-NH2 and subsequent azide cyclization. In contrast to somatostatin, the somatostatin analogue thus obtained produces, when applied intracerebroventricularly to rats, a decrease in the dopamine content of the striatum.

A NEW SYNTHESIS OF SOMATOSTATIN

The synthesis of somatostatin by linking together Boc-Ala-Gly-Cys(Bzl)-Lys(Z)-Asn-Phe-NHNH2 and H-Phe-Trp-Lys[Z(pCl)]-Thr-Phe-Thr-Ser-Cys(Bzl)-OBzl is described. The two partial sequences were obtained from segments which in general are also used in preparing somatostatin analogues. The synthesis of the partial sequences was optimized. The intracerebroventricular application of the somatostatin thus obtained to rats produced an increase of the dopamine and serotonin contents in the striatum. The results achieved were identical with those realized with standard somatostatin (Serono).