Search for: All records

Isatins are extensively researched compounds with diverse applications, particularly as synthetic precursors in pharmaceutical developments. However, their use as optical probes for enantioselective sensing of chiral amines has not been explored to date. Herein, we present a novel chiroptical assay with an optimized isatin that generates strong, red‐shifted circular dichroism (CD) signals at approximately 380 nm upon ketimine formation with chiral amines. The intensity of the induced CD signal increases linearly with the enantiomeric excess of the analyte and thus allows quantitative chirality analysis. The general usefulness of this approach is demonstrated with a broad range of aliphatic and aromatic chiral amines, and by accurate determination of the enantiomeric composition of 10 samples. 

Abstract Asymmetric reaction development often involves optimization of several mutually dependent parameters that affect the product yield and enantiomeric excess. Widely available high-throughput experimentation equipment and optical sensing assays can drastically streamline comprehensive optimization efforts and speed up the discovery process at reduced cost, workload, and waste production. A variety of chiroptical assays that utilize fluorescence, UV, and circular dichroism measurements to determine reaction yields and ee values are now available, enabling the screening of numerous small-scale reaction samples in parallel with multi-well plate technology. Many of these optical methods considerably shorten work-up protocols typically required for traditional asymmetric reaction analysis and some can be directly applied to crude mixtures thus eliminating cumbersome separation and purification steps altogether. 1 Introduction 2 Fluorescence Assays 3 UV Sensing Methods 4 Sensing with Circular Dichroism Probes 5 Hybrid Approaches 6 Optical Analysis with Intrinsically CD-Active Reaction Products 7 Conclusion 

A chromophoric bifunctional probe design that allows selective chiroptical sensing of cysteine in aqueous solution is introduced. The common need for chiral HPLC separation is eliminated which expedites and simplifies the sample analysis while reducing solvent waste. Screening of the reaction between six phenacyl bromides and the enantiomers of cysteine showed that cyclization to an unsaturated thiomorpholine scaffold coincides with characteristic UV and CD effects, in particular when the reagent carries a proximate auxochromic nitro group. The UV changes and CD inductions were successfully used for determination of the absolute configuration, enantiomeric composition and total concentration of 18 test samples. This assay is highly selective for free cysteine while other amino acids, cysteine derived small peptides and biothiols do not interfere with the chiroptical signal generation.