Fullerene hexakis-adducts bearing 12 peripheral carbohydrate moieties have been prepared by grafting sugar derivatives onto the fullerene core through the copper mediated Huisgen 1,3-dipolar cycloaddition of azides and alkynes.

Fullerene hexakis-adducts bearing 12 peripheral mannose moieties have been prepared by grafting sugar derivatives onto the fullerene core and assayed as inhibitors of FimH, a bacterial adhesin, using isothermal titration calorimetry, surface plasmon resonance and hemagglutination assays.

L,D-Heptosides (L-glycero-D-manno-heptopyranoses) are found in important bacterial glycolipids such as lipopolysaccharide (LPS), the biosynthesis of which is targeted for the development of novel antibacterial agents. This work describes the synthesis of a series of fullerene hexa-adducts bearing 12 copies of peripheral sugars displaying the mannopyranose core structure of bacterial L,D-heptoside. The multimers were assembled through an efficient copper-catalyzed alkyne-azide cycloaddition reaction as the final step. The final fullerene sugar balls were assayed as inhibitors of heptosyltransferase WaaC, the glycosyltransferase catalyzing the incorporation of the first L-heptose into LPS. Interestingly, the inhibition of the final molecules was found in the low micromolar range (IC(50) =7-45 μM), whereas the corresponding monomeric glycosides displayed high micromolar to low millimolar inhibition levels (IC(50) always above 400 μM). When evaluated on a "per-sugar" basis, these inhibition data showed that, in each case, the average affinity of a single glycoside of the fullerenes towards WaaC was significantly enhanced when displayed as a multimer, thus demonstrating an unexpected multivalent effect. To date, such a multivalent mode of inhibition had never been evidenced with glycosyltransferases.

Heptosides are found in important bacterial glycolipids such as lipopolysaccharide (LPS), the biosynthesis of which is targeted for the development of novel antibacterial agents. This work describes the synthesis of a fluorinated analogue of ADP‐L‐glycero‐β‐D‐manno‐heptopyranose, the donor substrate of the heptosyl transferase WaaC, which catalyzes the incorporation of this carbohydrate into LPS. Synthetically, the key step for the preparation of ADP‐2F‐heptose is the simultaneous and stereoselective installation of both the fluorine atom at C‐2 and the phosphoryl group at C‐1 through a selectfluor‐mediated (selectfluor=1‐chloromethyl‐4‐fluorodiazoniabicyclo[2.2.2]octane bis(triflate)) electrophilic addition/nucleophilic substitution involving a heptosylglycal. Therefore, we detail in this article 1) the stereoselective preparation of the key intermediates heptosylglycals, 2) the development of a new fluorophosphorylation procedure allowing an excellent β‐gluco stereoselectivity with “all‐equatorial” glycals, 3) the synthesis of the target ADP‐2F‐heptose, and 4) some comments on the contacts observed between the fluorine atom of the final molecule and the protein in the crystallographic structure of heptosyltransferase WaaC.

Abstract. Long-lasting insecticidal nets and indoor residual spraying have contributed to a decline in malaria over the last decade, but progress is threatened by the development of physiological and behavioral resistance of mosquitoes against insecticides. Acknowledging the need for alternative vector control tools, we quantified the effects of eave screening in combination with a push-pull system based on the simultaneous use of a repellent (push) and attractant-baited traps (pull). Field experiments in western Kenya showed that eave screening, whether used in combination with an attractant-baited trap or not, was highly effective in reducing house entry by malaria mosquitoes. The magnitude of the effect varied for different mosquito species and between two experiments, but the reduction in house entry was always considerable (between 61% and 99%). The use of outdoor, attractant-baited traps alone did not have a significant impact on mosquito house entry but the high number of mosquitoes trapped outdoors indicates that attractant-baited traps could be used for removal trapping, which would enhance outdoor as well as indoor protection against mosquito bites. As eave screening was effective by itself, addition of a repellent was of limited value. Nevertheless, repellents may play a role in reducing outdoor malaria transmission in the peridomestic area.