Novel immonium type peptide coupling reagent: 5-(1H-benzotriazol-1-yloxy)-3,4-dihydro-1-methyl 2H-pyrrolium hexachloroantimonate (BDMP (R))

A novel immonium type coupling reagent, 5-(1H-benzotriazol-1-yloxy)-3, 4-di hydro-methyl 2H-pyrroliun hexachloroantimonate (BDMP) has been designed, sy nthesized and utilized to synthesize oligopeptides and biologically active peptide both in solution and solid phase with satisfactory yield, low racem ization and fast reaction rate. The estimation of racemization and the infl uence of several reaction parameters were studied by HPLC method using the model reaction: Z-Gly-Phe-OH + Val-OMe . HCl --> Z-Gly-D/L-Phe-Val-OMe. It was shown that the reactivity of BDMP was much higher and the racemization was much lower than those of HOBt-based 'onium' reagents, even though its a nalogues BOMI. To further verified the effectiveness of BDMP, Leu-enkephali n was synthesized both in solution and solid phase using BDMP as coupling r eagent. The proposed mechanism was also speculated.