Hitting the SPOT: small-molecule macroarrays advance combinatorial synthesis

The small-molecule macroarray represents a new tool to accelerate combinational library synthesis and screening. This array platform originates from the SPOT-synthesis technique, or the spatially addressed synthesis of peptides on cellulose supports. Recent advances in the field have expanded this technique beyond peptidic systems into the realm of complex small-molecule synthesis. Small-molecule macroarrays offer some significant advantages over traditional combinatorial synthesis platforms — these focused, 50–200 compound arrays are straightforward to synthesize, inexpensive, and amenable to numerous screening applications where the array compounds are either bound to or cleaved from the planar support. Critical advances in the small-molecule macroarray technique are highlighted herein, including the use of microwave-assisted organic reactions, multicomponent reactions, and automated spotting methods to further accelerate and broaden macroarray technology.