Multiwell MAOS

GRAZ, Austria—The high processing speed of microwave-assisted organic synthesis (MAOS) has made the technique very popular in drug discovery, allowing researchers to identify and optimize many reaction parameters almost on the fly. For library synthesis, however, the technique has suffered from the thermal instability and uneven heating of typical multiwell plates and the difficulty of performing reactions under pressure. Researchers at Karl-Franzens-University and Anton Paar GmbH may have a solution.

As they report in the Journal of Combinatorial Chemistry, the researchers solved the thermal property problems by developing a 48-well plate comprised of sintered silicon carbide, which is very temperature resistant and offers homogeneous plate heating (<0.3 °C variance) by absorbing the microwave energy and radiating it to the wells. They similarly developed a sealing system that allows them to perform reactions at pressures approaching 25 bars, expanding the range of chemical syntheses.

The researchers tested their system, constructing a 30-member library of 2-aminopyrimidines, confirming the results by LC/MS. All but one reaction cleanly generated the expected products, most at yields similar to those achieved in single-mode reactions.