Design of a highly selective quenched activity-based probe and its application in dual color imaging studies of cathepsin S activity localization.

The cysteine cathepsins are a group of 11 proteases whose function was originally believed to be the degradation of endocytosed material with a high degree of redundancy. However, it has become clear that these enzymes are also important regulators of both health and disease. Thus, selective tools that can discriminate between members of this highly related class of enzymes will be critical to further delineate the unique biological functions of individual cathepsins.

Racemization free protocol for the synthesis of N-tert-butanesulfinyl ketimines.

A general and robust racemization-free protocol for the synthesis of a variety of N-tert-butanesulfinyl ketimines is reported. Reaction progress was monitored by (1)H NMR using the nonperturbing internal standard diglyme, and ketimines were formed in good to high yields in either THF or CPME (cyclopentyl methyl ether) as solvent with heating to reflux.

High stereoselectivity in chelation-controlled intermolecular Heck reactions with aryl chlorides, vinyl chlorides and vinyl triflates.

Highly stereoselective chelation-controlled Pd(0)-catalyzed beta-arylations and beta-vinylations of a five-membered chiral, pyrrolidine-based vinyl ether were achieved using aryl- and vinyl chlorides as substrates, yielding quaternary 2-aryl/vinyl-2-methyl cyclopentanones in 89-96% ee under neutral reaction conditions.

Selective terminal heck arylation of vinyl ethers with aryl chlorides: a combined experimental-computational approach including synthesis of betaxolol.

Reaction conditions have been developed for palladium-catalyzed terminal (beta-) arylation of acyclic vinyl ethers with high regioselectivity using inexpensive aryl chlorides as starting materials and the P(t-Bu)3 releasing preligand [(t-Bu3)PH]BF4 as the key additive. This swift and straightforward protocol exploits non-inert conditions and controlled microwave heating to minimize handling and processing times and uses aqueous DMF or environmentally friendly PEG-200 as the reaction medium. The selectivity for linear beta-product in PEG-200 is slightly higher than in aqueous DMF.

A rapid microwave protocol for Heck vinylation of aryl chlorides under air.

In modern high-throughput chemistry, the overall workflow is a crucial factor and much work is devoted to speeding up the process of chemistry development. Since automated microwave-based synthesizers are known to streamline the compound production and to accelerate slow organic transformations, this technology was implemented for Heck reactions with sluggish aryl chlorides. Furthermore, homogeneous palladium-catalyzed Heck vinylations of aryl chlorides can be performed under air under optimized conditions.