Dendritic, 1,1′-Binaphthalene-Derived Cleft-Type Receptors (Dendroclefts) for the Molecular Recognition of Pyranosides

Abstract

Two series of optically active, cleft-type dendritic receptors (dendroclefts) for carbohydrate recognition were prepared by attaching Fréchet-type dendrons via ethynediyl linkers to a core consisting of one or two 1,1′-binaphthalene-2,2′-diyl phosphate moieties. Sugar substrates were expected to bind via bidentate ionic H-bonding of two OH groups to the phosphodiester core and, additionally, to undergo van der Waals and CH⋅⋅⋅π interactions with the aromatic rings of the surrounding dendritic wedges. The synthesis of the dendritic receptors G-1-(S)-1, G-2-(S)-2, and G-3-(S)-3 (Fig. 1; G-x=dendritic generation) with a single binaphthalene core started from 3,3′-diethynylated MOM-protected (MOM=methoxymethyl) 1,1′-binaphthalene-2,2′-diol (S)-13 to which the Fréchet-type dendrons of generations 1 – 3 were attached via Sonogashira cross-coupling (Scheme 3). MOM-Ether deprotection followed by phosphodiester formation and ion exchange provided the targeted receptors. By a similar route, receptor G-1-(S)-23 with dendritic wedges capped with oligoether groups was obtained (Scheme 4). In receptor G-1-(S)-26, the ethynediyl linker was omitted, and, in its synthesis, the dendritic wedges were attached to MOM-protected 3,3′-diiodo-1,1′-binaphthalene-2,2′-diol by Suzuki cross-coupling (Scheme 5). The synthesis of the dendritic receptors G-2-(S,S)-42 and G-1-(S,S)-43 with two binaphthalene moieties at the core (Fig. 3) started from diethynylated (S,S)-39 and (S,S)-33, which contain two MOM-protected 1,1′-binaphthalene-2,2′-diol moieties bridged by p-phenylene or buta-1,3-diynediyl linkers, respectively, and was completed by attachment of the dendritic wedges by Sonogashira coupling, MOM-ether deprotection, phosphodiester formation, and ion exchange (Schemes 9 and 10). By an alternative route, the C-frame of receptor G-2-(S,S)-41 was prepared by coupling the dendron to dialkynylated 1,1′-binaphthalene (S)-44, followed by oxidative Glaser-Hay coupling (Scheme 8). For control studies, the non-dendritic reference receptors (S)-4 and (S)-5 (Fig. 1) with one and (S,S)-31 and (S,S)-32 (Fig. 2) with two 1,1′-binaphthalene-2,2′-diyl phosphate moieties were also prepared. 1H-NMR Complexation studies with the dendritic receptors containing one binaphthalene core and octyl glycosides 53 – 55 in CD3CN and CDCl3 (Tables 2 – 4) revealed that ionic H-bonding between the phosphodiester core in the dendritic receptors and the sugar OH groups provides the major driving force for stoichiometric 1 : 1 host-guest association. A smaller, yet significant contribution to the binding free enthalpy was also provided by interactions between the sugar guests and the dendritic wedges. Binding selectivity was weak in all cases, and only small changes in association strength were observed as a function of dendritic generation. In studies with the dendritic receptors, which contain two binaphthalene moieties at the core, higher-order complex stoichiometries prevented the determination of quantitative binding data. As a result of unfavorable steric interactions between the dendritic wedges, these flexible receptor systems apparently avoid adopting the `syn'-conformation with convergent phosphodiester sites that is required for efficient 1 : 1 host-guest complexation.