Amphiphilic Calix[4arene Nanostructures

Guided by the need to prepare well-defined clusters having good binding properties in solid phase enzyme immunosorbent assays (ELISA) while having readily exposed carbohydrate ligands, we became interested in synthesizing glycosylated calix [ra]arene derivatives. In many ways, glycocalix[ra]arenes, which possess guest-host capabilities that can be used as drug vectors, are structurally related to cyclodextrins. Additionally, they have advantages unsurpassed by the cyclodextrins because they can be readily modified at either ''upper'' or ''lower'' rim [65]. Commercially available p-ferf-butylcalix[4]arene (37) is already equipped with a hydrophobic tail that has been useful in coating polystyrene microtiter plates [66].

Thus, by freezing 37 in the cone conformation upon treatment with ethyl bro-moacetate, ester hydrolysis, and acid chloride formation, known [67] tetraacid chloride 38 was readily made available [68] (Scheme 7). Treatment of 38 with a slight excess of mono-Boc-protected 1,4-butanediamine gave 39 in 62%. Trifluoroaceto-lysis of the Boc protecting groups resulted in tetramine 40 quantitatively. N-Chlo-roacetylation ((ClC^CO^O, Et3N, CH2Q2) gave 41 in 63% yield which, when treated with peracetylated thiosialoside 7 (Et3N, CH3CN, N2, 16 h, room temperature) and protecting group hydrolysis (NaOMe, then NaOH) gave 42 in 65% yield. In spite of having high hydrophobic content, tetrameric thiosialoside 42 was fairly water soluble (4.8 mM, 13 mg/mL). It showed strong binding affinity to the plant lectin wheat germ agglutinin (WGA) in a microtiter plate assay. Moreover, it formed insoluble cross-linked lattices with WGA as demonstrated by turbidimetric experiments. The insoluble complex could be inhibited by monomeric phenylthio a-sia-loside 11 (free OH), thus demonstrating the specificity of the binding interaction.

Following several observations leading to the easy formation of well-organized cross-linked lattices with simple clusters [59,68], including dimers [69], we became

intrigued by the possibility of generating "sugar rods.'' Several of these molecules could be synthesized via olefin self-metathesis reactions catalyzed by Grubb's catalyst [(PCy3)2Cl2Ru=CHPh] [70]. Additionally, they can be prepared from a-alkynyl sialosides (Z. Gan, R. Roy, unpublished data) by using palladium(0)-catalyzed cross-coupling chemistry (Sonogashira reaction) (71). These novel derivatives fall outside the scope of this chapter, so their synthesis will be described in due course.

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