Bepotastine salicylate

Herein, we report a scalable and mild strategy for the monofluoroalkylation of a wide array of Giese acceptors via visible-light-mediated photoredox catalysis in continuous flow. The use of flow technology significantly enhances productivity and scalability, whereas mildness of conditions and functional group tolerance are ensured by leveraging 4CzIPN, a transition-metal-free organic photocatalyst. Structurally diverse secondary and tertiary monofluoroalkyl radicals can thus be accessed from readily available α-monofluorocarboxylic acids. Given the mild reaction conditions, this protocol is also amenable to the late-stage functionalization of biologically relevant molecules such as menthol, amantadine, bepotastine, and estrone derivatives, rendering it suitable for application to drug discovery programs, for which the introduction of fluorinated fragments is highly sought after. This method was also extended to enable a reductive multicomponent radical-polar crossover transformation to rapidly increase the complexity of the assembled fluorinated architectures in a single synthetic operation.

Bepotastine (BPT), a second-generation antihistamine used for treating allergic rhinitis and pruritus, requires precise dosage calculation and accurate measurement in aqueous humor to ensure therapeutic efficacy and avoid adverse effects. This study presents a highly sensitive, cost-effective, readily-implementable, and ecologically sustainable method to detect BPT by enhancing its weak native fluorescence. This has been achieved by switching off the intramolecular photoinduced electron transfer (PET) process through phosphoric acid-induced protonation of the nitrogen in the piperidinyl ring. Further fluorescence enhancement was achieved by incorporating a solution of sodium dodecyl sulfate (SDS) surfactant thus increasing the quantum yield of BPT up to 10 folds. Fluorescence intensity was measured at 425 nm following excitation at 265 nm. The method, validated according to ICH guidelines, demonstrated linearity over the range of 0.70-6.0 µg/mL with a correlation coefficient of 0.9972 and a low detection limit of 0.046 µg/mL. It was successfully applied to measure BPT in aqueous humor and eye drops with % recoveries between 97.59 % and 102.62 %. Finally, sustainability was assessed using various tools, confirming the method's practicality for routine clinical and pharmaceutical quality control analyses.