A general approach to high-throughput screening of enantiomeric excess (ee) and concentration was developed by using indicator displacement assays (IDAs), and the protocol was then applied to the vicinal diol hydrobenzoin. The method involves the sequential utilization of what we define herein as screening, training, and analysis plates. Several enantioselective boronic acid-based receptors were screened by using 96-well plates, both for their ability to discriminate the enantiomers of hydrobenzoin and to find their optimal pairing with indicators resulting in the largest optical responses. The best receptor/indicator combination was then used to train an artificial neural network to determine concentration and ee. To prove the practicality of the developed protocol, analysis plates were created containing true unknown samples of hydrobenzoin generated by established Sharpless asymmetric dihydroxylation reactions, and the best ligand was correctly identified.artificial neural networks ͉ catalyst discovery ͉ enantioselective indicator displacement assay ͉ supramolecular chemistry T he unique role of chiral bioactive therapeutic substances is a source of inspiration for the design of efficient asymmetric catalytic processes (1). To this end, combinatorial synthesis and stockpiles of chiral ligands can afford large libraries of molecules as a potential source of new and improved catalysts (2, 3). Traditionally, the search for asymmetric catalysts has relied on iterative approaches wherein a single catalyst is designed, synthesized, tested, and optimized. This cycle is repeated until a catalytically active system is obtained with the desired level of enantioselectivity. In contrast, if a high-throughput screening (HTS) strategy for ee determination existed, it would enable one to rapidly identify effective asymmetric catalysts, thus allowing for a much broader range of catalyst candidates and experimental conditions to be evaluated (4, 5). However, most of these methods require prior derivatization of the analyte or require expensive instrumentation, and many are still quite slow. Herein, we report a colorimetric strategy based on indicator displacement assays (IDAs) for creating HTS protocols that can be used for the rapid determination of molecular chirality as well as the yield of a reaction.An indicator displacement assay relies on a colorimetric or fluorescent indicator that changes optical or electrochemical properties when bound to a host relative to being free in the bulk medium (6). The most commonly used indicators are pH indicators (7). The competition between an indicator and the guest of interest for the binding site of the host allows the determination of total guest (or analyte) concentration [G] t [Scheme 1 (Eq.1)]. An IDA both eliminates the need to incorporate the chromophore or fluorophore into the structure of the host, thus simplifying the synthesis of the host molecule, and allows one to tune the sensitivity of the assay because of the ability to change the identity and concentration of the ind...

Mechanistic studies of a general reaction that decages a wide range of substrates on exposure to visible light are described. The reaction involves a photochemically initiated reduction of a quinone mediated by an appended thioether. After reduction, a trimethyl lock system incorporated into the quinone leads to thermal decaging. The reaction could be viewed as an electron-transfer initiated reduction of the quinone or as a hydrogen abstraction -Norrish Type II -reaction. Product analysis, kinetic isotope effects, stereochemical labeling, radical clock, and transient absorption studies support the electron transfer mechanism. The differing reactivities of the singlet and triplet states are determined, and the ways in which this process deviates from typical quinone photochemistry are discussed. The mechanism suggests strategies for extending the reaction to longer wavelengths that would be of interest for applications in chemical biology and in a therapeutic setting.

The first enantioselective total synthesis of the epipolythiodiketopiperazine (ETP) natural product (−)-acetylapoaranotin (3) is reported. The concise synthesis was enabled by an eight-step synthesis of a key cyclohexadienol-containing amino ester building block. The absolute stereochemistry of both amino ester building blocks used in the synthesis is set through catalytic asymmetric (1,3)-dipolar cycloaddition reactions. The formal syntheses of (−)-emethallicin E and (−)-haemotocin are also achieved through the preparation of a symmetric cyclohexadienol-containing diketopiperazine.

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