Abstract: The present invention relates to an improved process for the preparation of N6-(aminoiminomethyl)-N2-(3-mercapto-1-oxopropyl-L-lysylglycyl-L-?-aspartyl-L-tryptophyl-L-prolyl-L-cysteinamide, cyclic(1?6)-disulfide of formula (1), which involves assembling amino acid residues and a thioalkyl carboxylic acid with appropriate protecting groups on a solid phase resin, cleaving the peptide thus obtained from the resin with concomitant removal of side chain protecting groups except Acm protecting group of thiol moiety to obtain peptide amide of formula (3), converting lysine residue of peptide amide of formula (3) having protected thiol group to homoarginine residue by guanylation to obtain peptide of formula (4), preparing silver peptide of formula (5), followed by simultaneous deprotection, obtaining silver peptide of formula (5) and oxidation of silver peptide to obtain crude peptide amide comprising compound of formula (1) and finally subjecting to chromatographic purification.

Abstract: The present invention relates to an improved process for the preparation of N6-(aminoiminomethyl)-N2-(3-mercapto-1-oxopropyl)-L-lysylglycyl-L-?-aspartyl-L-tryptophyl-L-prolyl-L-cysteinamide, cyclic(16)-disulfide of formula (1), which involves assembling a peptide chain comprising of six amino acids and a thioalkyl carboxylic acid in a required sequence on a solid support to obtain a peptide bound resin of formula (2), capping the free amino groups after each coupling, cleaving Dde group in the peptide of formula (2) from the solid support to obtain peptide-solid support of formula (3), guanylating the peptide of formula (3) at ?-lysine-NH2 in an organic solvent to obtain peptide-solid support of formula (4), cleaving and deprotecting all groups in the peptide of formula (4) from the solid support to obtain peptide-amide formula (5), oxidizing the SH-peptide of formula (5) with an appropriate oxidizing agent to obtain the crude peptide-amide of formula (1) and purifying the crude peptide-amide of formula (1) b