Method for synthesizing etelcalcetide or salts thereof

A method for synthesizing etelcalcetide (of the following formula (I)) or salts thereof, comprising the steps of:

• (a) using a solid support as a starting material in solid phase peptide synthesis and sequentially synthesizing a D-form amino acid of formula (I) by Fmoc chemistry;
• deprotecting Fmoc group and acetylating the amino group to obtain a sequence A comprising protecting groups (abbreviated as PG) in the side chain of D-Cys and D-Arg:
• (A);
• Ac-D-Cys(PG)-D-Ala-D-Arg(PG)-D-Arg(PG)-D-Arg-(PG)-
• D-Ala-D-Arg(PG)-solid support
• (b) removing the protecting group in the side chain of D-Cys of the sequence A to obtain a sequence B:
• (B);
• Ac-D-Cys-D-Ala-D-Arg(PG)-D-Arg(PG)-D-Arg-(PG)-D-
• Ala-D-Arg(PG)-solid support
• (c) disulfide formation at D-Cys of the sequence B by (PG)-L-Cys-OH to obtain a sequence C:
• (C);
• Ac-D-Cys-D-Ala-D-Arg(PG)-D-Arg(PG)-D-Arg-(PG)-D-Ala-D-Arg(PG)-solid support
• |
• (PG)-L-Cys-OH
• and
• (d) using a cleavage solution to remove the protecting groups of the sequence C to give etelcalcetide as formula (I):