Process for the preparation of plecanatide

A process for the preparation of Plecanatide of Formula I (SEQ ID NO 1):

• which comprises the following steps:
• a) preparing peptide Fragment A (SEQ ID NO 2), Fragment B and Fragment D (SEQ ID NO 4) separately:
• b) coupling of Fragment A (SEQ ID NO 2) with Fragment B in presence of coupling agent and solvent, followed by amino deprotection to provide Fragment C (SEQ ID NO 3);
• Wherein, X represents carboxyl or hydroxy protecting group;
• Y represents amino protecting group;
• and
• Z represents thiol protecting group,
• c) coupling of the Fragment C (SEQ ID NO 3) with Fragment D (SEQ ID NO 4);
• (SEQ ID NO 4)
• Y-Asn(Y)-Asp(X)-Glu(X)-Cys(Z)-Glu(X)-Lue-OH
• Faragment D
• in presence of coupling agent and solvent to provide protected linear peptide of SEQ ID NO 5:
• (SEQ ID NO 5)
• H-Asn(Y)-Asp(X)-Glu(X)-Cys(Z)-Glu(X)-Lue-Cys(Z)-
• Val-Asn(Y)-Val-Ala-Cys(Z)-Thr(X)-Gly-Cys(Z)-
• Lue(X)
• Protected linear peptide
• d) deprotecting the protected linear peptide of SEQ ID NO. 5 using deblocking cocktail mixture to obtain linear 1-16 peptide (SEQ ID NO 6);
• and
• (SEQ ID NO 6)
• H-Asn-Asp-Glu-Cys-Glu-Lue-Cys(Z)-Val-Asn-Val-Ala-
• Cys-Thr-Gly-Cys(Z)-Lue-OH
• 1-16 linear peptide
• e) oxidizing the linear 1-16 peptide using oxidizing agent to obtain crude Plecanatide;
• and
• f) purification of crude plecanatide using preparative HPLC using Tris hydrochloride or Triethylammonium phosphate to obtain pure plecanatide of formula I (SEQ ID NO 1).