Kaiman A. Cheung

High-throughput experimentation (HTE) has become an increasingly important approach for reaction discovery, optimization, and AI-ready data generation in synthetic chemistry. However, despite rapid adoption, many practical limitations associated with implementing HTE workflows remain underreported, particularly outside industrial settings. In practice, experimental reliability is frequently constrained by factors such as solvent compatibility, evaporation, sealing performance, plate geometry, liquid handling limitations, and the physical constraints introduced through miniaturization. These effects can strongly influence reproducibility and data quality, yet are often treated as secondary implementation details rather than core considerations. Alongside these operational challenges, digital HTE workflows remain fragmented, with limited interoperability between software, hardware, analytical systems, and data structures. In this perspective, we discuss a range of practical and digital bottlenecks encountered during plate-based HTE, drawing on direct experimental experience, supporting experimental data, and recent developments across the field. In particular, we present new observations relating to solvent evaporation and sealing performance in common HTE formats, highlighting how seemingly minor physical effects can substantially influence experimental reliability and downstream interpretation. By making these practical considerations more explicit, we aim to support the development of more reproducible, interoperable, and scalable HTE workflows across academic and industrial chemistry.

Azo dyes constitute one of the largest and most commercially important classes of synthetic colorants, widely applied in textiles, plastics, inks, and food. However, their manufacture through traditional batch processes is often constrained by safe-ty risks, poor heat and mass transfer, and inconsistent product quality. To address these challenges, we present a continuous telescopic strategy for the synthesis of the azo dye Sudan Yellow-3G. The workflow integrates Amar-made MicroFLO™ reactors for coupler and diazonium salt preparation, followed by azo coupling in a SlurryFLO™ reactor. This continuous approach mitigates hazards associated with exothermic and potentially runaway reactions while enabling tighter process con-trol. Optimization is further enhanced through the ReactWise© software platform, which applies machine learning to guide reaction conditions, minimizes experimental effort, and provides in-depth analytics. Together, this hardware-software integra-tion demonstrates a scalable, safer, and more resource-efficient alternative to conventional batch synthesis. Beyond the case of Sudan Yellow-3G, this work illustrates a transferable framework for modernizing azo dye manufacturing and highlights the broader potential of combining continuous flow chemistry with AI-driven optimization in industrial colorant production.

Azo dyes constitute one of the largest and most commercially important classes of synthetic colorants, widely applied in textiles, plastics, inks, and food. However, their manufacture through traditional batch processes is often constrained by safe-ty risks, poor heat and mass transfer, and inconsistent product quality. To address these challenges, we present a continuous telescopic strategy for the synthesis of the azo dye Sudan Yellow-3G. The workflow integrates Amar-made MicroFLO™ reactors for coupler and diazonium salt preparation, followed by azo coupling in a SlurryFLO™ reactor. This continuous approach mitigates hazards associated with exothermic and potentially runaway reactions while enabling tighter process con-trol. Optimization is further enhanced through the ReactWise© software platform, which applies machine learning to guide reaction conditions, minimizes experimental effort, and provides in-depth analytics. Together, this hardware-software integra-tion demonstrates a scalable, safer, and more resource-efficient alternative to conventional batch synthesis. Beyond the case of Sudan Yellow-3G, this work illustrates a transferable framework for modernizing azo dye manufacturing and highlights the broader potential of combining continuous flow chemistry with AI-driven optimization in industrial colorant production.

A biocatalytic Diels–Alder reaction creates trans-decalin I with four new stereocenters in the synthesis of the antibiotic (−)-13-deoxytetrodecamycin. X-ray crystallography and modelling provide insights into the biocatalytic [4 + 2]-cycloaddition.

The abyssomicins are a structurally intriguing family of bioactive natural products that include compounds with potent antibacterial, antitumour and antiviral activities. The biosynthesis of the characteristic abyssomicin spirotetronate core occurs via an enzyme-catalysed intramolecular Diels–Alder reaction, which proceeds via one of two distinct stereochemical pathways to generate products differing in configuration at the C15 spirocentre. Using the purified spirotetronate cyclases AbyU (from abyssomicin C/atrop-abyssomicin C biosynthesis) and AbmU (from abyssomicin 2/neoabyssomicin biosynthesis), in combination with synthetic substrate analogues, here we show that stereoselectivity in the spirotetronate-forming [4 + 2]-cycloaddition is controlled by a combination of factors attributable to both the enzyme and substrate. Furthermore, an achiral substrate was enzymatically cyclised to a single enantiomer of a spirocyclic product. X-ray crystal structures, molecular dynamics simulations, and assessment of substrate binding affinity and reactivity in both AbyU and AbmU establish the molecular determinants of stereochemical control in this important class of biocatalysts.