High resolution magic angle spinning NMR in combinatorial chemistry

Solid phase organic chemistry coupled with combinatorial methods promises t o increase dramatically the diversity and number of small molecules availab le for medical and biological applications. However, optimizing the reactio n conditions can be a time consuming step, especially since analytical tool s to monitor reaction progress and detect impurities for solid phase chemis try are less developed than for solution chemistry. The use of high resolut ion magic angle spinning (HRMAS) NMR is described here as such an analytica l tool. Whereas initial applications of molecular identification using deut erated organic solvents to swell the resins presented a significant gain in time over the cleave-and-analysis methods, the introduction of a different ial diffusion filter has made immediate recording of spectra possible witho ut any sample treatment. The applications of HRMAS NMR to different solid s upports that are used in combinatorial chemistry will be described in terms of rapidity, robustness and sensitivity.