New Useful Reagents for Peptide Synthesis. Insoluble Active Esters of Polystyrene-Bound 1-Hydroxybenzotriazole

Abstract

Insoluble 1-hydroxybenzotriazole-bound polystyrene was prepared through a series of chemical modifications of commercially available polystyrene. Reaction of 3-nitro-4-chlorobenzyl alcohol or of 3-nitro-4-chlorobenzyl bromide with polystyrene in the presence of aluminium trichloride yielded (3-nitro-4-chloro)benzylated polystyrene. Upon reaction with hydrazine it was converted to (3-nitro-4-hydrazine)benzylated polystyrene which was cyclized, by acidolysis, to yield 1-hydroxybenzotriazole-bound polystyrene. This was coupled, using N,N'-dicyclohexylcarbodiimide as the coupling agent, to many N-blocked amino acid derivatives, yielding polymeric polystyrene-bound active esters. Such derivatives are highly reactive and their efficacy in the synthesis of several peptides, including that of the tetrapeptide Boc-l-Leu-l-Leu-l-Val-OBzl-l-Tyr-OBzl and of thyrotropin-releasing hormone was demonstrated.