SYNTHESIS OF N-ALPHA-(6-HYDRAZINONICOTINOYL)-OCTREOTIDE - A PRECURSOROF A [TC-99M] COMPLEX

The synthesis of the title compound 12 via [3 + 4] and [7 + 2] segment condensation, respectively using minimal protection of amino acid sid e chains is presented. The need to include the 6-hydrazinonicotinic ac id into a complete peptide synthesis originates from the juxtaposition of two factors, namely from the poor regioselectivity of Boc(2)O towa rds the amino groups of octreotide 1 and secondly from the distinct ch emical properties of N-hydroxysuccinimide eaters of 6-hydrazinonicotin ic acid derivatives in general. The structure of the ligated octreotid e derivative 12 suitable for the preparation of a [Tc-99m]-labelled me tal complex was established by spectroscopic methods. The study is com plemented by conformational considerations on the pharmacophore of 12 and the parent octapeptide 1, being based on circular dichroism spectr oscopy and 2D-NMR techniques.