The solid-phase intramolecular N-acyliminium Pictet-Spengler reaction as a crossroad to a plethora of novel heterocyclic peptides

摘要

In the search for new drugs,peptide isosters and peptidomimetics incorporating heterocyclic motifs have received considerable attention among academic and industrial research groups.Towards this objective,the conversion of short peptide strands into heterocycles has emerged as a successful approach.Efforts aimed at obtaining solid-supported compounds with heterocyclic core structures have successfully adapted many classical reactions from the field of heterocyclic organic chemistry to solid-phase synthesis,e.g.the Fischer indole synthesis,the Huisgen 1,3-dipolar cycloaddition and the Pictet-Spengler reaction.In general,the establishment of novel routes towards heterocycles continues to be the most important and intensely investigated area of research in solid-phase synthesis.The aim of the present investigation is to device highly effective routes to pharmacologically interesting heterocyclic ring systems.To this end,a novel solid-phase application of the classical Pictet-Spengler reaction has recently been developed,which allows quantitative and highly diastereoselective formation of carbon-carbon bonds and heterocycles attached to peptides.