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Summary.A detailed account is given of the total synthesis of human calcitonin M, the hypocalcaemic hormone possessing the dotriacontapeptide sequence I. I n the build up of I, the protected sequences 1-10 and 11-32 served as intermediates for the preparation of the protected precursor dotriacontapeptide 1-32 (11). While the synthesis of the fragment 1-10 has been reported previously [l], the present account includes a detailed description of the build up of the intermediate 11-32. Racemisation encountered in the synthesis of this fragment is discussed and conditions indicated in which it is minimized.From the final coupling step using dicyclohexylcarbodiimide-N-hydroxysuccinimide 131, the protected dotriacontapeptide I1 was obtained pure in a yield of 65% after counter-current distribution.In the removal by acidolysis of the protecting groups from I1 even under optimal conditions two side reactions occur: alkylation of the 8-methionine side chain and N to 0 acyl migration at the serine or threonine residues. By-products from these reactions were removed by countercurrent distribution giving very pure I free of diastereoisomers and possessing the biological activity of highly purified natural calcitonin M. In the routine assay [4] after repeated testing its activity was evaluated a t 100 -J= 5 U/mg (calculated on content of free peptide).In

Assays of 8 synthetic analogues of human calcitonin in rats showed that their hypocalcaemic activity was drastically reduced by deletion of the C-terminal amide group, chain-shortening or opening of the disulphide ring, but unaffected or enhanced by modification of the N-terminal amino group.

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Summary. The total synthesis of the hypocalcaemic hormone a-thyrocalcitonin (I) isolatcd froin porcine thyroid glands is reported in detail. By the fragment condensation approach, using coupling procedures known to avoid racemisation, the fully protected dotriacontapeptide sequence I1 was synthesised. In the build up of I1 the disulfide ring bridge connecting the cysteine residues 1 and 7 was preformed in the protected nonapeptide fragment 1-9. Simultaneous removal by acidolysis of the nine protecting groups present in I1 yielded synthetic a-thyrocalcitonin (I) in a state of high purity and possessing full biological activity; the disulfide bond remained intact during the de-protection step. On repeated biological assay the synthetic preparation I in the test system of 2)Inzwischen haben auch GUTTMANN und Mitarbeiter [8] in einer Kurzniitteilung eine Synthese von I beschrieben.