Synthesis and Biological Evaluation of a Library of AGE‐Related Amino Acid Triazole Crosslinkers

Three N‐Boc‐protected amino acids, l‐serine, l‐aspartic, and l‐glutamic acid, were either converted into their methyl azidoalkanoates or various alkynes via Bestmann‐Ohira strategy or via reaction with propargylamine and propargyl bromide, respectively. The Cu‐catalyzed click reaction provided a lib...

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Bibliographic Details
Published in:European journal of organic chemistry 2020-09, Vol.2020 (33), p.5368-5379
Main Authors: Icik, Esra, Jolly, Anthony, Löffler, Paul, Agelidis, Nektarios, Bugdayci, Bakiye, Altevogt, Luca, Bilitewski, Ursula, Baro, Angelika, Laschat, Sabine
Format: Article
Language:English
Subjects:
Alkynes
Amino acids
Biological activity
Biological properties
Chemical reactions
Click chemistry
Crosslinking
E coli
Fibroblasts
Glutamic acid
Iodides
Libraries
Microorganisms
Toxicity
Triazoles
Triazolium
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Summary:Three N‐Boc‐protected amino acids, l‐serine, l‐aspartic, and l‐glutamic acid, were either converted into their methyl azidoalkanoates or various alkynes via Bestmann‐Ohira strategy or via reaction with propargylamine and propargyl bromide, respectively. The Cu‐catalyzed click reaction provided a library of amino acid based triazoles, which were further N‐methylated to triazolium iodides or deprotected and precipitated as free amino acid triazole dihydrochlorides. The biological properties of all derivatives were investigated by cytotoxicity assay (against L929 mouse fibroblasts) and broth microdilution method (E. coli ΔTolC and S. aureus). First results reveal complete inactivity for triazolium iodides with cell viabilities and microbial growths nearly 100 %, indicating them as possible analogs of advanced glycation endproducts (AGEs). Click reaction between l‐amino acid derived azides and alkynes gave amino acid functionalized triazoles, which were further derivatized to charged triazolium iodides and free amino acid hydrochlorides. The products reveal high cell viabilities in a standard cytotoxicity assay making them attractive as AGE analogs.
ISSN:1434-193X
1099-0690
DOI:10.1002/ejoc.202000811