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)

Abstract

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
• Status: Published
• Refereed: Yes
• 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: 0022-3263
• 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

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
172865		EPSRC DTP 16/17 and 17/18	Mary Beth Kneafsey	Engineering and Physical Sciences Research Council (EPSRC)	EP/N509668/1	Research and Innovation Services