High-Throughput Purification in Drug Discovery: Scaling New Heights of Productivity.

With the "low hanging fruit" of early drug discovery gone, pharmaceutical companies are increasingly turning to developing high-throughput synthetic platforms capable of greatly shortening the design-make-test cycle of new drugs. Purification has long been considered the bottleneck of this procedure; however, new technologies and systems are now being integrated into these high-throughput synthetic workflows, providing compounds of high purity capable of being used directly in biological screening.

Recent developments in enantio- and diastereoselective hydrogenation of N-heteroaromatic compounds.

The enantioselective and diastereoselective hydrogenation of N-heteroaromatic compounds is an efficient strategy to access chirally enriched cyclic heterocycles, which often possess highly bio-active properties. This strategy, however, has only been established in recent times. This is in part due to the challenges of the high stability of the aromatic compounds and the presence of heteroatoms that have the potential to poison the chiral catalysts.

Formal synthesis of (+)-lactacystin from l-serine.

A formal, stereocontrolled synthesis of lactacystin has been completed from -Bul-serine, providing the key intermediate 13, also useful for the generation of a range of C-9 analogues.

Asymmetric Oxidation of Enol Derivatives to α-Alkoxy Carbonyls Using Iminium Salt Catalysts: A Synthetic and Computational Study.

We report herein the first examples of asymmetric oxidation of enol ether and ester substrates using iminium salt organocatalysis, affording moderate to excellent enantioselectivities of up to 98% ee for tetralone-derived substrates in the α-hydroxyketone products. A comprehensive density functional theory study was undertaken to interpret the competing diastereoisomeric transition states in this example in order to identify the origins of enantioselectivity. The calculations, performed at the B3LYP/6-31G(D) level of theory, gave good agreement with the experimental results, in terms of the magnitude of the effects under the specified reaction conditions, and in terms of the preferential formation of the ( R)-enantiomer.