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Divalent Triazole‐Linked Carbohydrate Mimetics: Synthesis by Click Chemistry and Evaluation as Selectin Ligands
Author(s) -
Salta Joana,
Reissig HansUlrich
Publication year - 2020
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.202000618
Subject(s) - chemistry , click chemistry , divalent , cycloaddition , linker , triazole , combinatorial chemistry , azide , diazo , pyran , stereochemistry , organic chemistry , catalysis , computer science , operating system
Starting from an enantiopure 3‐amino‐substituted pyran derivative, the synthesis of a series of divalent 1,2,3‐triazole‐linked carbohydrate mimetics is described. The preparation of the required 3‐azido‐substituted pyran proceeds smoothly by copper‐catalyzed diazo transfer. Using different conditions for the Huisgen‐Meldal‐Sharpless cycloaddition, this azide reacts with several diynes to furnish the desired divalent carbohydrate mimetics bearing rigid or flexible linker units. The in situ generation of the 3‐azidopyran in the presence of Cu/C as catalyst followed by the reaction with the alkyne allows a direct one‐pot transformation from the 3‐aminopyran to the desired click products. We also examined the Sakai‐Westermann method that transfers primary amines with the aid of α,α‐dichlorotosylhydrazones into 1,2,3‐triazoles. These copper‐free click conditions were applied for the first time to the preparation of a divalent compound. The O ‐sulfation of the carbohydrate mimetics was achieved using the SO 3 ‐DMF complex under careful 1 H‐NMR control. Five polysulfated compounds could be obtained in pure form and these were tested by surface plasmon resonance spectroscopy as inhibitors of L‐selectin giving IC 50 values between 45 n m and 50 µ m .