Divalent Triazole‐Linked Carbohydrate Mimetics: Synthesis by Click Chemistry and Evaluation as Selectin Ligands

Abstract

Dedicated to Professor Bernd Giese on the occasion of this 80th birthday.

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

“…In order to test the Sakai–Westermann method of triazole synthesis [ 17 ] – a valuable metal‐free alternative to the CuAAC – we converted 3‐aminopyran 9 into triazole derivative 10 (Scheme 3). [ 5 ] The three hydroxy groups of this compound were alkylated with propargyl bromide under established conditions and the resulting trisalkyne 11 was subsequently treated with 3‐azidopyran 1 in the presence of Cu/C to furnish the unsymmetrical trivalent carbohydrate mimetic 12 in 69 % yield.…”

“…[4] In preceding publications, we reported the synthesis of divalent compounds F and G employing 3-azidopyran 1 and 4azidooxepane 2 which were prepared from the corresponding amino compounds by an efficient diazo transfer reaction. [5] The copper-catalyzed azide-alkyne (3+2) cycloaddition (Huisgen-complex compound contains a C 60 -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.…”

“…[ 4 ] In preceding publications, we reported the synthesis of divalent compounds F and G employing 3‐azidopyran 1 and 4‐azidooxepane 2 which were prepared from the corresponding amino compounds by an efficient diazo transfer reaction. [ 5 ] The copper‐catalyzed azide‐alkyne (3+2) cycloaddition (Huisgen–Meldal‐Sharpless cycloaddition, CuAAC) [ 6 ] was optimized with respect to the catalyst system applied, and most of the divalent products F and G were obtained in good yields. The synthesis of a few trivalent compounds derived from azidooxepane 2 was also reported.…”

“…-H, 7′′-H),8.03 (s, 8 H, 5′-H) ppm;13 C NMR (176 MHz, CD 3 OD): δ = 23 5,. 26.8 (2 q, Me), 43.5 (s, C-6′′), 49.6 (d, C-5), 61.7 (t, 2-CH 2 ), 62.3 (t, 5-CH 2 ), 64.4 (t, C-7′′), 65.2 (t, C-1′′), 70.4 (d, C-3), 71.1 (t, C-4′′), 71.6 (t, C-2′′), 71.9 (d, C-2), 72.7 (t, C-5′′), 73.1 (d, C-3), 77.6 (s, C-6), 78.7 (d, C-3′′), 125.7 (d, C-5′), 146.1 (d, C-4′) ppm; IR (ATR): ν = 3350 (OH), 2930 (C-H), 1450 (C=C), 1060 (C-O-C) cm -1 ; HRMS (ESI-TOF): m/z [M + Na + H] 2+ calcd.…”

Cu(I)-Catalyzed Click Chemistry in Glycoscience and Their Diverse Applications

“…Salta and Reissig developed divalent triazolyl glycomimetics ( 1215 – 1219 ) (Figure ) from 3-amino-substituted pyran via diazo-transfer reaction followed by CuAAC coupling . During the reaction, in situ generation of 3-azidopyran followed by coupling with the alkyne resulted in the direct one-pot synthesis of desired click products.…”