Glycoclusters

Konig et al. have achieved thioether functionalization of T8[CH = CH2]8 via the radical addition of thiols such as thiophenol, cyclohexylthiol, and 2-mercaptopyridine in the presence of azobisisobutyronitrile (AIBN) as a radical initiator (Table 13), while Gao et al. have also used this method to prepare very highly functionalized POSS by reacting T8[CH = CH2]8 with thiol-terminated glycosides giving glycoclusters in 70% yield (Figure 22). 

Fig. 2. Common scaffolds used in the design of glycoclusters and glycodendrimers.

By virtue of promising preliminary biological results indicating that tri- and tetravalent glycoclusters constitute potent inhibitors of bacterial binding, which fitted particularly well into the CRD of bacterial lectins (especially for mannose-specific adhesion) straightforward syntheses of low-valency glycoclusters were initiated. 

Binding affinities of the new flexible synthetic glycocluster toward type-1-piliated E. coli were evaluated by HAI and bladder-binding assay (BBA). The results indicated that, with an inhibition of bacterial bladder-cell binding at 12 nM ( 6000- and 64-fold lower than mannose and 59, respectively), the tetravalent compound 60 is currently one of the most promising antiadhesive drugs under development for the treatment of urinary tract infections. 

Through the years, the development of transition metal-catalyzed methodologies, notably involving cyclotrimerization and Sonogashira or Heck cross coupling, has paved the way for rapid and efficient access to aryl glycoclusters with desired and controlled valency. 

Fig. 6. Early (1962) glycoclusters used in quantititative immunoprecipitation of anticarbohydrate antibodies.89...

However, these elegant glycosylated nanostructures displayed only weak biological activity relative to their native glucan elicitor counterparts. Nevertheless, such glycoclusters provided unique environments for host-guest chemistry of amphi-pathic molecules owing to their lipophilic core surrounded by a hydrophilic periphery. 

Scheme 12. Pd(0)-catalyzed Sonogashira and Heck cross-coupling reactions leading to glycoclusters.100...

SCHEME 13. Persulfurated glycoclusters bearing 18 a-D-mannopyranoside residues.103... 

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