Cyclodextrin-Scaffolded Glycoclusters

Abstract

Mono-and hepta-antennated C-6 branched glycosylthioureido-cyclomaltoheptaose derivatives have been prepared efficiently by reaction, at ambient temperature, of b-d-glycopyranosyl isothiocyanates in the glucopyranose, cellobiose, and lactose series with either 6 I -amino-6 I -deoxycyclomaltoheptaose in pyridine or heptakis(6-amino-6-deoxy)cyclomaltoheptaose in water ± acetone at pH 8. The reverse strategy, which involves the corresponding glycosylamines as nucleophiles in reaction with cyclomaltoheptaose isothiocyanates, proved less satisfactory resulting in a number of by-products which hampered the purification step. The synthetic scheme was extended to alkyl and aryl isothiocyanate, electrophiles which as functional groups are of interest for the elaboration of dendritic wedges and the modification of the interaction and inclusion properties of cyclodextrins.

Dendritic Galactosides Based on aβ-Cyclodextrin Core for the Construction of Site-Specific Molecular Delivery Systems: Synthesis and Molecular Recognition Studies

“…8 Hz,1 H;4.45 (m,1 H;4.13 (m,3 H;6',6'),4.06 (d,2 J 15.5 Hz,1 H;CHCl), 4.00 (d, 2 J 15. 5 Hz,1 H;CHCl),3.88 (m,1 H;, 3.78 (m,2 H;5),2.16,2.13,2.07,2.06,2.05,2.04,1.97 (7 s,21 H;7 Ac); 13 C NMR (75.5 MHz,CDCl 3 ): d 171.0 ± 166.0 (CO), 100.9 (C-1'), 78.4 (C-1), 75.9 (C-4), 74.7 (C-5), 72.2 (C-3), 71.0, 70.8, 70.6 (C-3',5',2), 69.0 (C-2'), 66.7 (C-4'), 61.9 (C-6), 60.9 (C-6'), 42.3 (CH 2 Cl), 20.9 ± 20.5 (CH 3 CO);IR (KBr): n Ä 3350, 1749, 1705, 1532, 1369, 1229 ; elemental analysis calcd (%) for C 28 H 38 ClNO 18 (712): C 47.23,H 5.38,N 1.96;found: C 47.50,H 5.50,N 1.86. 2,3,3',4',: Thiourea (2.14 g, 28.1 mmol) was added to a solution of 3 (2.00 g, 2.81 mmol) in anhydrous acetone (30 mL).…”

“…The resulting precipitate was filtered and compound 7 was obtained (586 mg, 79 % 99.4 (C-1''), 96.7 (C-1), 82.5 (C-1'), 77.9 (C-4), 75.7, 74.9 (C-4',5'), 73.2 (C-3' or C-3''), 70. 6, 70.1, 69.6, 69.4 (C-2,3,5,2',3' or 3'',5''), 68.9 (C-2''), 66.8 (C-4''), 61.6 (C-6'), 60.3 (C-6''), 31.5 (C-6), 19.8 ± 19.4 Heptakis{2,3-di-O-acetyl-6-amino-6-deoxy-6-N- [2',3',6'-tri-O-acetyl-4-O-(2'',3'',4'',6''-tetra-O-acetyl- (8) 3.25 (m,140 H;2',2'',3,3',3'',4,4',4'',5,5',5'',6,6',6'',6,6',6'',CH 2 8, 72.2, 69.9 (C-2,3,5), 77.7, 76.3, 75.0, 71.4 (C-2',3',4',5'), 75.2, 72.4, 70.8, 68.4 (C-2'',3'',4'',5''), 60.9, 59.8 (C-6',6'') Bis (3-chloroacetamidopropyl)-N-tert-butoxycarbonylamine (17): A suspension of compound 16 (8.05 g, 16.11 mmol) and Pd/C (822 mg) in MeOH (100 mL) was stirred under H 2 atmosphere (2.5 atm) for 1 h at room temperature. The mixture was filtered and the Pd/C washed twice with MeOH.…”

“…In this context, we have reported [4] the synthesis of a variety of persubstituted b-CD derivatives branched with O-, S-glycosides and glycopyranosylamines with, in some cases, enhanced lectin binding affinity. Other groups have recently reported alternative strategies for the synthesis of glyco-b-CDs persubstituted onto the primary face, [5] secondary face and both primary and secondary faces simultaneously. [6] Working on the same concept, other research groups have reported the synthesis of cluster glycosides based on different cores such as calixarenes [7] and calix [4]resorcarenes.…”

“…Reaction of compounds 26 ± 28 with per-6-deoxy-6-iodo-b-CD (5) was carried out at 60 8C in dry DMF under Ar atmosphere using Cs 2 CO 3 in order to generate in situ the cesium thiolate derivatives (Schemes 3 and 4). After seven days, acetic anhydride, pyridine and DMAP were added.…”

Synthesis of cyclodextrin derivatives with monosaccharides and their binding with ampicillin and selected lectins

“…1 Cyclodextrins (CDs) offer unique features towards the formation of glycoclusters for biological applications, since they are biocompatible and can be easily modified in their primary side with carbohydrate moieties. Per-carbohydrate modified CD derivatives have been reported [6][7][8][9][10][11][12][13][14][15] demonstrating the advantages of multivalency and clustering effect in homo-and heterogeneously decorated cyclodextrin scaffolds. Herein, the synthesis of a series of new cyclodextrin-based glycoclusters with seven and eight monosaccharide units connected to the CD core via optimally sized linkers, as well as the corresponding monosubstituted derivatives, is reported.…”