Multivalent 1,2,3‐Triazole‐Linked Carbohydrate Mimetics by Huisgen–Meldal‐Sharpless Cycloadditions of an Azidopyran

• Published in: European journal of organic chemistry Vol. 2020; no. 47; pp. 7333 - 7342
• Main Authors: Salta, Joana, Arp, Fabian F., Kühne, Christian, Reissig, Hans‐Ulrich
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 20.12.2020; Wiley Subscription Services, Inc
• Subjects: Alkynes; Azides; Buckminsterfullerene; Carbohydrate mimetics; Carbohydrates; Chemical synthesis; Chemistry; Chemistry, Organic; Click chemistry; Complex compounds; Copper; Cycloaddition; Fullerenes; Ligands; Physical Sciences; Science & Technology; Triazoles; Triethylamine; RECOGNITION; BUILDING-BLOCKS; ONE-POT; AZIDE; SELECTIN BINDING; Azides; GLYCOSIDASE INHIBITION; Fullerenes; CHEMISTRY; Click chemistry; SCAFFOLDS; DERIVATIVES; Carbohydrate mimetics; GLYCOMIMETICS; Alkynes
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.202001389

Starting from an enantiopure 3‐azido‐substituted pyran derivative and various oligo‐alkynes a series of multivalent 1,2,3‐triazole‐linked carbohydrate mimetics was synthesized. The copper‐catalyzed Huisgen–Meldal‐Sharpless cycloaddition (CuAAC) served as key coupling reaction. Cu/C in the presence of triethylamine proved to be a good catalytic system in most cases. Tri‐, tetra‐, hexa‐, and octavalent compounds with typical rigid or flexible core units were prepared. The most complex compound contains a C60‐fullerene center leading to a dodecavalent carbohydrate mimetic. Only a few of the multivalent target compounds could be converted into pure O‐sulfated derivatives that are required for their evaluation as L‐ and P‐selectin ligands. Nevertheless, preliminary experiments suggest that the dodecavalent C60‐derived compound may be a promising ligand of these biologically important proteins with IC50 values in the low nanomolar range. An azidopyran was coupled through a CuAAC reaction with oligoalkynes to provide multivalent carbohydrate mimetics with flexible or rigid core elements. Preliminary SPR measurements indicate that an O‐sulfated C60‐derived dodecavalent compound may be an excellent ligand of L‐ and P‐selectins (IC50 values in low nM range).