The Encore Technique: A Novel Approach to Directed Split-and-Pool Combinatorial Synthesis

Abstract

Publisher Summary This chapter discusses the Encore technique that is useful for the directed split-and-pool combinatorial synthesis. The Encore method is based on one-dimensional spatial encoding of the synthesis chemical history, referred to as necklace coding, and applied for the synthesis on SynPhase Crowns and Lanterns. The Encore technique combines three different coding methods: (1) sequential position on a necklace for the first combinatorial step, (2) color coding of individual necklaces for the second combinatorial step, and (3) reaction vessel coding to identify the last building block. The Encore synthesizer represents a simple and efficient personal chemistry tool that allows the execution of directed split-and-pool combinatorial synthesis. The current version of the Encore synthesizer is designed for solid-phase synthesis on SynPhase Lanterns; however, it can be modified for the synthesis on alternative solid supports such as resin plugs from Polymer Laboratories (like StratoSpheres Plugs). The split-and-pool synthesis not only simplifies the complexity of the combinatorial synthetic process, but also offers additional important benefits. Parallel synthesis of a thousand compounds requires handling of a thousand reaction vessels. The timely addition of sensitive reagents at low temperature (–78°C) under inert atmosphere during parallel synthesis is not a trivial task. It can be done if sophisticated automated synthesizer equipment is designed to handle and tolerate such reaction conditions. Such a synthesis can alternatively be performed easily in a manual fashion using a split-and-pool method that requires only a limited number of reaction vessels.