A p-methylbenzhydrylamine resin for improved solid-phase synthesis of peptide amides

A p-methylbenzhydrylamine-resin, alpha-(p-tolyl)-amino-aminomethyl-functionalized copoly(styrene-1%-dvinylbenzene), was prepared for the improved solid-phase synthesis of peptide alpha-carboxamides. Following a Friedel-Crafts acylation of polymer beads, the resulting ketone resin was reductively aminated via the Leuckart reaction. A comparison of the relative acid stability of the p-methylbenzhydrylamine-(MBHA)-, benzhydrylamine (BHA)- and alpha-phenyethylamine-resins indicated that the p-methylbenzhydrylamine-resin provided the best yields of the model peptide carboxamides.