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

Abstract

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.

Multivalent glycosystems for human lectins

“…These results indicate that a higher valency achieved by preparing nanoparticles lead to more active compounds if they are compared with the derivatives of lower valence prepared by the group of Reissig. 193–195 In brief, the 5–10 nm sized multivalent nanoparticles inhibited leukocyte migration and supported the importance of the application of nanocarriers in the design of systems with improved selectin-binding properties.…”

“…Among the O-sulphated derivatives tested, they observed inhibitory activity towards L-and P-selectins also in the micromolar range (IC 50 = 0.6-100 mM for L-selectin and IC 50 = 1.1-30 mM for P-selectin). 194,195 Aminopyrans have also been recently employed by Tavernaro et al 196 in the development of gold, silver and iron oxide nanospheres and quantum dots for selectin targeting. Competitive SPR experiments pointed out that Au-based nanospheres containing sulphated aminopyrans behaved as L-selectin inhibitors in the low nanomolar range (IC 50 = 0.35-1.9 nM).…”

“Copper catalyzed azide alkyne cycloaddition” based synthesis and applications of oligo-1, 2, 3-triazoles connected by suitable building blocks and “N-(CH)n-C” linked triazole oligomers

“…Although synthesized and tested, the purity of an O-sulfated C60-fullerene based dodecavalent similar system could not be established (Scheme 2.33). 50…”

Multivalent Aminoseptanose Mimetics by Copper‐Catalyzed (3+2) Cycloadditions of Azidomethyl‐Substituted Bicyclic 1,2‐Oxazines

“…[1,2] Easily available aminopyran derivatives A were connected by amide bonds to give different multivalent carbohydrate mimetics B. [3,4] Furthermore, the related azidopyran C and suitable alkynes could be converted into di-and trivalent systems D [5][6][7] by applying the well-established coppercatalyzed (3 + 2) cycloaddition (CuAAC) approach. [8][9][10] As alternative, we also studied the Sakai-Westermann reaction [11,12] which directly converted aminopyrans A into triazoles D. [6] Moreover, the azidooxepanes E were transferred by the CuAAC method into multivalent triazole derivatives F. [13] The multivalent compounds B, D and F bear the connecting functional groups directly at the heterocyclic core, which results in restricted conformational flexibility of the synthesized systems.…”