Method for preparation of peptides with psWang linker

A method for the preparation of a peptide (PEP) which comprises a coupling in liquid phase of two peptide fragments, an N-terminal fragment (FRAG1) of peptide (PEP) and a C-terminal fragment (FRAG2) of peptide (PEP);

• wherein the C-terminal COOH of the C-terminal fragment (FRAG2) is protected by a psWang residue;
• the psWang residue is a residue of formula (psWang);
• wherein (*) denotes the covalent bond to the C atom of the CO residue of the C-terminal COOH of the C-terminal fragment (FRAG2);
• R1, R2, R3 and R4 are identical or different and independently from each other selected from the group consisting of H, C1-4 alkyl, C1-4 alkoxy, CN, F, Cl and Br;
• R5 and R6 are identical or different and are, independent from each other, H or C1-4 alkyl;
• m is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
• wherein the C-terminal fragment (FRAG2) is prepared by a solid phase peptide synthesis (SPPS);
• wherein the psWang linker or the psWang residue respectively is connected to a first resin used for the solid phase peptide synthesis (SPPS) by an ether bond (ETHBOND2);
• wherein the ether bond (ETHBOND2) is cleavable under weakly acidic conditions using trifluoroacetic acid (TFA), trifluoroethanol (TFE), or hexafluoroisopropanol (HFIP);
• and
• wherein the first resin is selected from the group consisting of a chlorotritykhloride
• (CTC) resin, a Rink acid resin a SASRIN resin
• a resin modified with 5-(4-hydroxymethyl-3,5-dimethoxyphenoxy)valeric acid (HAL), and a resin modified with 4-(4-hydroxymethyl-3-methoxyphenoxy)butyric acid (HMPB);
• wherein the Rink acid resin, the SASRIN resin, the resin modified with HAL, and the resin modified with HMPB are used in the chlorinated form.