Renin substrates. Part 2. Rapid solid phase synthesis of the ratine sequence tetradecapeptide using BOP reagent

Abstract

A successful synthesis of Asp¹-Arg²-Val³-Tyr⁴-IIe⁵-His⁶-Pro⁷-Phe⁶-His⁹-Leu¹⁰-Leu¹¹-Tyr¹²-Tyr¹³-Ser¹⁴ has been achieved by the classical stepwise solid-phase method using 1% crosslinked Merrifield resin and benzotriazolyloxytris(dimethylamino)phosphonium hexafluorophosphate (BOP reagent) respectively as solid support and coupling reagent. The coupling protocol included in situ neutralization of the amino partners after Boc-deprotection and the coupling times seldom exceeded 30 min. For His⁶ and His⁹, Boc-His(Boc). DCHA was neutralized in situ and allowed to couple. The peptide, purified by reparative h.p.l.c., was obtained in 29% overall yield based on the first residue attached to the solid support.