Isocyanides are important chemicals, with limited availability, thus reducing their general use. Our highly improved isocyanide synthesis performed on mole to μ-mole scale, individually or in a 96-well parallel fashion enables unprecedented exploration of novel chemistries.

Miniaturization and acceleration of synthetic chemistry are critically important for rapid property optimization in pharmaceutical, agrochemical, and materials research and development. However, in most laboratories organic synthesis is still performed on a slow, sequential, and material-consuming scale and not validated for multiple substrate combinations. Herein, we introduce fast and touchless acoustic droplet ejection (ADE) technology into small-molecule chemistry to transfer building blocks by nL droplets and to scout a newly designed isoquinoline synthesis. With each compound in a discrete well, 384 random derivatives were synthesized in an automated fashion, and their quality was monitored by SFC-MS and TLC-UV-MS analysis. We exemplify a pipeline of fast and efficient nmol scouting to mmol- and mol-scale synthesis for the discovery of a useful novel reaction with great scope.

Miniaturized and automated nanomole synthesis using acoustic dispensing technology dramatically accelerated the production of diverse libraries of three small molecule scaffolds.

The compatibility of free boronic acid building blocks in multicomponent reactions to readily create large libraries of diverse and complex small molecules was investigated. Traditionally, boronic acid synthesis is sequential, synthetically demanding, and time-consuming, which leads to high target synthesis times and low coverage of the boronic acid chemical space. We have performed the synthesis of large libraries of boronic acid derivatives based on multiple chemistries and building blocks using acoustic dispensing technology. The synthesis was performed on a nanomole scale with high synthesis success rates. The discovery of a protease inhibitor underscores the usefulness of the approach. Our acoustic dispensing–enabled chemistry paves the way to highly accelerated synthesis and miniaturized reaction scouting, allowing access to unprecedented boronic acid libraries.

Acoustic dispensing was used to synthesize 1536 compounds on a nano scale, screened by differential scanning fluorimetry, cross-validated by microscale thermophoresis against the protein interaction menin–MLL to discover binders, one co-crystallized.

Screening of large and diverse libraries is the 'bread and butter' in the first phase of the discovery of novel drugs. However, maintenance and periodic renewal of high-quality large compound...

A reliable method is disclosed to introduce a fused methylene tetrahydrofuran ring into carbohydrates. The resulting bicyclic saccharides can be used as scaffolds in medicinal chemistry and drug design. In addition, the enol ether functionality serves as a handle that enables modification in biological systems via photoclick chemistry. The approach is based on the regioselec-tive oxidation of the C-3 hydroxy group in gluco-configured pyranosides, followed by stereoselective indium-mediated allylation. The ring formation is induced by an iodocyclization reaction with a neighboring hydroxy group. Subsequent dehydrohalogenation affords the desired methylene-tetrahydrofuran-containing carbohydrates.

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