Fully Automated Synthesis of DNA-Binding Py-Im Polyamides Using a Triphosgene Coupling Strategy

The fully automated solid-phase synthetic strategy of hairpin pyrrole–imidazole polyamides is described. A key advance is the development of methodology for the application of triphosgene as a coupling agent in the automated synthesis of hairpin polyamides without racemization. This automated methodology is compatible with all the typical building blocks, enabling the facile synthesis of polyamide libraries in good yield (9–15%) and crude purity