Synthesis of Carbohydrate-Centered Oligosaccharide Mimetics Equipped with a Functionalized Tether

Abstract

Synthetic glycoclusters have gained substantial attention as mimetics of multivalent glycoconjugates. For their proposed glycobiological applications, it is advantageous to incorporate a functionalized tether into the clusters, which allows coupling to solid supports and other molecules such as reporter groups or even bioactive molecules. We herein report the use of carbohydrates as oligofunctional scaffolds for the synthesis of tethered cluster mannosides. Glycocluster 11 was prepared following two different pathways, starting either from glucose or the nonreducing disaccharide trehalose. The oligo alcohols 5 and 14 served as acceptors in the subsequent oligo-mannosylation reaction, in which three main problems were overcome: (i) incomplete glycosylation, (ii) cleavage of the core-glycoside, and (iii) ortho ester formation. Optimum conditions for the glycosylation were identified utilizing an advanced MALDI-TOF protocol.

Synthesis of Functionalized Amphiphilic Glycoconjugates and Glycoclusters

“…A quick indication of ester hydrolysis can be obtained from the disappearance in the NMR spectrum of the singlet signals corresponding to the methyl ester groups at about 3.67 ppm. A third synthetic sequence was dedicated to functionalization of the carbohydrate-centered cluster mannoside 24 [23] to give amphiphilic neoglycoconjugates (Scheme 4). HATU-mediated peptide coupling with lauric acid with this complex molecule was tried first, providing the alkyl oligosaccharide mimetic 25 in high yield.…”

Towards synthetic vaccines built on carbohydrate cores

“…Tetra-allylation of compound l a using sodium hydride and allyl bromide in DMF [9] gave the tetraether l b in 67% yield. Regioselective hydroboration of the tetraether l b using 9-BBN in THE followed by oxidative workup [10], gave the tetraol lc in 70% yield. Conversion of the hydroxyl groups of compound le to their corresponding phthaloyl-protected amines was achieved in 94% yield using Mitsunobu conditions (phthalimide, DEAD, PPh3) [11], giving ld.…”

Octopus glycosides: multivalent molecular platforms for testing carbohydrate recognition and bacterial adhesion

“…According to the concept outlined in Figure 2, the AB 4 -type b-Dglucoside 18 could be prepared from glucose pentaacetate in three steps. 25 Our early work on oligo-a-mannosylation revealed that using Schmidt's O-acetylated mannosyl trichloroacetimidate as the glycosyl donor was complicated by orthoester formation. This turned out to be a severe problem, as isomerization of the orthoesters to the respective glycosides was not always successful and in addition, structural analysis of carbohydrate-centred cluster glycosides with partial orthoester impurities is very difficult.…”

“…4, 23 and 27), trehalose (24), melibiose (25), and raffinose (26) cores, respectively. 26 For their synthesis, the same chemistry as described above (cf.…”