Synthesis of N‐α‐(6‐Hydrazinonicotinoyl)‐Octreotide: A Precursor of a [99mTc] Complex

Abstract

AbstractThe synthesis of the title compound 12 via [3 + 4] and [7 + 2] segment condensation, respectively, using minimal protection of amino acid side chains is presented. The need to include the 6‐hydrazinonicotinic acid into a complete peptide synthesis originates from the juxtaposition of two factors, namely from the poor regioselectivity of Boc2O towards the amino groups of octreotide 1 and secondly from the distinct chemical properties of N‐hydroxysuccinimide esters of 6‐hydrazinonicotinic acid derivatives in general. The structure of the ligated octreotide derivative 12 suitable for the preparation of a [99mTc]‐labelled metal complex was established by spectroscopic methods. The study is complemented by conformational considerations on the pharmacophore of 12 and the parent octapeptide 1, being based on circular dichroism spectroscopy and 2D‐NMR techniques.