Abstract: In a step-wise synthesis of degarelix comprising 0.3% by weight or less of 4-([2-(5-hydantoyl)]acetylamino)-phenylalanine analog on (solid support)-NH2 a step comprises providing a solution of an amino acid or peptide of which the ?-amino group is protected by Fmoc; contacting the support with the solution in the presence of reagent for forming a peptide bond between a carboxyl group of the amino acid or peptide and (solid support)-NH2; removing Fmoc by contacting the support with an organic base, in particular piperidine, in an organic solvent. Also disclosed is degarelix of high purity prepared by the method of the invention and the use of Fmoc in the synthesis of degarelix.

Abstract: The peptides Ac-D-2Nal-D-4ClPhe-D-3Pal-OH and Boc-D-2Nal-D-4ClPhe-D-3Pal-OH are intermediates useful in the synthesis of LHRH analogs by coupling with suitable heptapeptides, in particular with the heptapeptides P1-Ser(P2)-MMeTry(P3)-D-Lys(Nic)-Leu-Lys(iPr,P4)-Pro-D-AlaNH2 and P1-Ser(P2)-NMeTry(P3)-D-Asn-Leu-Lys(iPr,P4)-Pro-D-AlaNH2.

Abstract: In a step-wise synthesis of degarelix comprising 0.3% by weight or less of 4-([2(5-hydantoyl)]acetylamino)-phenylalanine analog on (solid support)-NH2 a step comprises providing a solution of an amino acid or peptide of which the ?-amino group is protected by Fmoc; contacting the support with the solution in the presence of reagent for forming a peptide bond between a carboxyl group of the amino acid or peptide and (solid support)-NH2; removing Fmoc by contacting the support with an organic base, in particular piperidine, in an organic solvent. Also disclosed is degarelix of high purity prepared by the method of the invention and the use of Fmoc in the synthesis of degarelix.

Abstract: The peptides Ac-D-2Nal-D-4ClPhe-D-3Pal-OH and Boc-D-2Nal-D-4ClPhe-D-3Pal-OH are intermediates useful in the synthesis of LHRH analogs by coupling with suitable heptapeptides, in particular with the heptapeptides P1-Ser(P2)-MMeTry(P3)-D-Lys(Nic)-Leu-Lys(iPr,P4)-Pro-D-AlaNH2 and P1-Ser(P2)-NMeTry(P3)-D-Asn-Leu-Lys(iPr,P4)-Pro-D-AlaNH2.

Abstract: A nona- or decapeptide is purified from residual organic solvent by dissolving in a solvent comprising water and at least one C1–C3 alcohol followed by precipitation into a vigorously stirred solvent consisting of an alkyl ester of a carboxylic acid, the ester comprising from 3 to 6 carbon atoms, and one or several non-polar compounds selected from hexane, heptane, octane, cyclohexane, methylcyclohexane, and, optionally, of up to 5% of acetic or propionic acid, isolating the precipitated nona- or decapeptide, followed by washing with a mixture of C3–C5 esters and drying, with the provisio that the water content of the solvent comprising water and the at least one alcohol is below 8% (v/v), and that the volume ratio of the dissolution solvent mixture and the precipitation solvent mixture is 1:10 or higher. Also described is the monoacetate of Ac-D-2Nal-D-4ClPhe-D-3Pal-Ser-MeTyr-D-Asn-Leu-Lys(iPr)-Pro-D-Ala-NH2.