Synthesis of leuprorelin using segment condensation approach

Leuprorelin was synthesized by segment condensation strategy (2+7). The protected dipeptide, Fmoc-Arg(Pbf)-Pro-NHEt, was synthesized in solution phase and its yield reached 84.8%, when DIC was used as the coupling reagent, THF as the solvent, and the molar ratio of Pro-NHEṫHCl and Fmoc-Arg(Pbf)-OH was 1 : 1.25. The protected pentapeptide synthesized in solid phase yielded 81.3%. The protected leuprorelin was synthesized by segment condensation using DMF : DMSO (V : V=1 : 1) as the solvent and HATU/HOBt/DIEA as the coupling reagent. The target product of leuprorelin was achieved after cutting the side-chain.