Synthesis and fluorescent properties of alkynyl- and alkenyl-fused benzotriazole-derived α-amino acids

Riley, L., Mclay, T. N. and Sutherland, A. (2023) Synthesis and fluorescent properties of alkynyl- and alkenyl-fused benzotriazole-derived α-amino acids. Journal of Organic Chemistry, 88(4), pp. 2453-2463. (doi: 10.1021/acs.joc.2c02886) (PMID:36749161) (PMCID:PMC9942204)

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Fluorescent unnatural α-amino acids are widely used as probes in chemical biology and medicinal chemistry. While a variety of structural classes have been developed, there is still a requirement for new environmentally sensitive analogues that can closely mimic proteinogenic α-amino acids. Here, we report the synthesis and fluorescent properties of highly conjugated, benzotriazole-derived α-amino acids designed to mimic l-tryptophan. Alkynyl-substituted analogues were prepared using three key steps, nucleophilic aromatic substitution with a 3-aminoalanine derivative, benzotriazole formation via a one-pot diazotization and cyclization process, and a Sonogashira cross-coupling reaction. E-Alkenyl-substituted benzotriazoles were accessed by stereoselective partial hydrogenation of the alkynes using zinc iodide and palladium catalysis. The alkynyl analogues were found to possess higher quantum yields and stronger brightness and, a solvatochromic study with the most fluorogenic α-amino acids demonstrated sensitivity to polarity.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Sutherland, Professor Andrew and Riley, Leanne
Authors: Riley, L., Mclay, T. N., and Sutherland, A.
College/School:College of Science and Engineering > School of Chemistry
Journal Name:Journal of Organic Chemistry
Publisher:American Chemical Society
ISSN (Online):1520-6904
Published Online:07 February 2023
Copyright Holders:Copyright © 2023 The Authors
First Published:First published in Journal of Organic Chemistry 88(4): 2453-2463
Publisher Policy:Reproduced under a Creative Commons licence

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
172865EPSRC DTP 16/17 and 17/18Mary Beth KneafseyEngineering and Physical Sciences Research Council (EPSRC)EP/N509668/1Research and Innovation Services