Microchip Encoded Combinatorial Libraries: Generation of a Spatially Encoded Library from a Pool Synthesis The Solid-Phase Synthesis of Complex Small Molecules

Abstract

An encoding method which provides ready access to the structure of individual compounds in a combinatorial library of small organic molecules has been developed. Glass-encased microchips each of which contain a unique binary encoded ID which can be scanned and recorded using radiofrequency (RF) were added to indi vidual tea bags containing polystyrene polymer functionalized with a Wang linker. The tea bags were subjected to a three-step synthesis. At each stage of the synthesis, the microchips were RF-scanned and the unique ID's were recorded. After the synthesis was complete, each tea bag was introduced to individual wells of a microtiter plate and the products were deblocked from the polymer. The histogram of the ID for each well was then used to assign the structure of every product in the library. A library of 64 compounds was thus synthesized using a pooled compound strategy, affording a positionally encoded discrete library.