Dynamic combinatorial resolution nitroaldol

Vongvilai P, Angelin M, Larsson R, Ramstrom O (2007) Dynamic combinatorial resolution direct asymmetric lipase-mediated screening of a dynamic nitroaldol library. Angew Chem Int... 

Lipases are a family of enzymes that, in addition to their hydrolytic activity on triglycerides, also catalyze (trans)esterification reactions. They recognize a broad range of unnatural substrates in either aqueous or nonaqueous phase, have a high commercial availability, do not require expensive cofactors, and are easily recoverable. These factors make lipases especially interesting and they have been used extensively in, for example, asymmetric synthesis. The lipase from Pseudomonas cepacia was also targeted in a dynamic combinatorial resolution-type protocol [36]. Based on the efficient nitroaldol (Henry) reaction, DCLs of aldehydes, nitroal-kanes, and P-nitroalcohols could be easily generated (Scheme 5.9). 

Scheme 5.9 Dynamic combinatorial resolution of nitroaldol DCL (ee, enantiomeric excess).

Dynamic combinatorial nitroaldol libraries were also used to illustrate iDCR [5,6], In this case, one of the library components was selected for its possibility to undergo an irreversible tandem cyctizafion reaction following equilibrium formation. This provided an internal kinetic selection pressure on the library, subsequently forcing the library to complete amplification of this novel reaction product. Furthermore, interesting crystalline properties were observed for one of the diastereoisomers of this isoindolinone-type product, providing a route to demonstrate consecutive resolution processes resolving coupled DCLs in a one-pot experiment. 

---