ACHIRAL CYCLODEXTRIN ANALOGS

The synthesis of a new family of cyclodextrin (CD) analogues is descri bed, This family consists of novel cyclic oligosaccharides built from monosaccharides that possess the same relative but opposite absolute ( D- and L-) configurations. The alternation of such D- and L-residues-s pecifically, D- and L-rhamnose or D- and L-mannose-in a macrocyclic st ructure results in S-n-type symmetry and, consequently, optical inacti vity. The synthesis of these cyclic oligosaccharides was achieved by a n economical polycondensation/cycloglycosylation approach that relies on an appropriately-derivatized disaccharide monomer and that avoids t he time-consuming, and often low-yielding, stepwise growth of long lin ear oligosaccharide precursors. In the cases reported, the key precurs ors are the disaccharide monomers 1-RR and 1-MM, which bear both a gly cosyl donor (cyanoethylidene function) and a glycosyl acceptor (trityl oxy group). These compounds are able to undergo Tr+-catalyzed polycond ensation which, under appropriate dilution conditions, can be terminat ed by cycloglycosylation. Thus, compound 1-RR was converted into a ran ge of protected cyclic rhamnooligosaccharides 15-19 in 64% overall yie ld. All these products, including the unique cyclic dodeca- and tetrad ecasaccharides 18 and 19, have been isolated by preparative HPLC. Unex pectedly, treatment of the manno analogue of the disaccharide 1-RR (co mpound 1-MM) under the same conditions produced only the cyclic hexasa ccharide 28 and numerous apparently linear oligomers. Removal of the p rotecting groups from 16-19 afforded the free cyclic oligosaccharides 21-24, which exhibited the predicted zero optical rotation and very si mple NMR spectra, indicating highly symmetrical structures. X-ray crys tallography reveals that in the solid stale the cyclooctaoside 21 poss esses a C-2 symmetric structure, on account of a slight deformation of its cylindrical shape, The channel-type crystal packing of molecules of 21 forms nanotubes with an internal diameter of around 1 nm. Conver sely, the cyclic hexa saccharide 29 possesses a C-i symmetric solid-st ate structure and its molecules pack to form a parquet-like superstruc ture.