Three-in-One: Miniature Models of Natural Acyl-Transfer Systems Enable Vector-Selective Reaction on the Primary Side of Cyclodextrins.

Miniature models of acyl-transfer systems in cells, which were composed by replacing the protein, coenzyme, and substrate with CD, functional group, and CD, respectively, and combining them all together in one, displayed definite role-sharing and exact cooperation of the functional groups and hydrophobic cavity, and thus enabled the regio-specific reaction.

A one-pot synthetic method for the hetero-bifunctionalization of α-cyclodextrin at the secondary hydroxyl side with high clockwise-counterclockwise selectivity.

α-Cyclodextrin and 3,3'-benzophenonedisulfonylimidazole in a unimolecular ratio were stirred at 40 °C for 1 h in the presence of a catalytic amount of Cs2CO3 in DMF, and then treated with sodium hydroxide to give 2A,3A-mannoepoxy-2B-sulfonyl-α-cyclodextrin in 14% isolated yield. The isomer with the reversed saccharide sequence was not detected.

A vector-selective reaction enables efficient construction of specific topology upon the primary side of beta-cyclodextrin.

N-dansylcysteines attached on the primary side of beta-cyclodextrin reacted with the saccharide hydroxyl groups in a vector-selective manner, affording the corresponding lactones. The desired topology of the lactones can be efficiently constructed simply by the selection of the proper enantiomer of D/L-cysteines. In comparison with the exo-lactone, the endo-lactone displayed 4 times stronger fluorescence intensity, stronger binding affinity to sodium adamantanecarboxylate, and 15 times larger signal changes in fluorescence intensity upon binding.

Selective modification of beta-cyclodextrin: an unexpected tandem reaction enables the cross-linking of C2(A) and C2(B) via a sulfur atom.

2(A),3(A)-Alloepithio-2(B)-sulfonyl-beta-cyclodextrin undergoes a tandem reaction to generate an unprecedented C2(A)-S-C2(B)-bridged glucosyl-3(A),6(A)-anhydroglucoside segment.

The first topologically controlled synthesis of doubly bridged beta-cyclodextrin dimers.

Reaction 6(A),6(B)-di(O-tosyl)-beta-cyclodextrin with Na(2)S in DMF gave the cis-dimer of beta-cyclodextrin in 21% isolated yield while the trans-dimer was not detected.

Clockwise-counterclockwise differentiation on the upper rim of a monofunctional gamma-cyclodextrin: efficient topological control in the syntheses of capped cyclodextrins.

Intramolecular condensation of 6(A)-(N-dansyl-l-cysteine)-gamma-cyclodextrin occurred only at 6(B)-OH of the many OH groups to afford the corresponding lactone with an exo-topology.

Shortcut synthesis of beta-cyclomannin from beta-cyclodextrin.

Beta-cyclomannin, a cyclic oligosaccharide consisting of seven alpha-D-mannosides connected together by the (1-->4) glycoside linkage, has been efficiently synthesized by the OsO4 oxidation of heptakis(2,3-didehydroxy)-beta-cyclodextrin which was prepared from beta-cyclodextrin by a five-step transformation. The novel cyclooligosaccharide not only showed water solubility high enough to meet the requirement for drug formulation but also demonstrated strong binding ability toward guest molecules. [reaction: see text]

The first hetero-bifunctionalization of the secondary face of beta-cyclodextrin: selective and efficient conversion of the A-ring of a 2A,2B-disulfonate to 2A,3A-epoxymannoside.

The A-ring of 2(A),2(B)-O,O-di(mesitylenesulfonyl)-beta-cyclodextrin was converted to 2(A),3(A)-epoxymannoside without affecting the other sulfonylated residue, which affords the first approach to hetero-bifunctionalization at the secondary hydroxyl side of cyclodextrins.

Functionalization of cyclodextrins via reactions of 2,3-anhydrocyclodextrins.

Three types of reactions of 2,3-anhydro-beta-cyclodextrins, namely nucleophilic ring-opening, reduction to 2-enopyranose, and reduction to 3-deoxypyranose, have been investigated to regio- and stereoselectively functionalize the secondary face of beta-cyclodextrin. Upon treatment with various nucleophiles, both 2,3-mannoepoxy and 2,3-alloepoxy-beta-cyclodextrins are found to undergo nucleophilic ring-opening reaction generating 3- and 2-modified cyclodextrin derivatives. In each case, the 3-position is more easily accessible than the 2-position. By using these ring-opening reactions, imidazolyl, iodo, azido, and benzylmercapto groups are selectively introduced to the secondary face of beta-cyclodextrin in place of the 2- or 3-hydroxyl groups. The functionalized cyclodextrins have either modified glucosidic subunits or modified altrosidic subunits that make the hydrophobic cavity slightly distorted from that of native beta-cyclodextrin. Thiourea also reacts with the cyclodextrin epoxides. In this case, thiirane and olefin species are generated instead of any ring-opening products. By ameliorating the reaction condition, cyclodextrin olefin, diene, and triene derivatives are prepared in moderate to good yields. Reduction of per[6-(tert-butyldimethyl)silyl]-beta-cyclodextrin permannoepoxide with lithium aluminum hydride produces the per(3-deoxy)-beta-cyclomannin. All these chemically modified cyclodextrins are structurally well characterized and most of them are expected to serve as versatile scaffolds for diverse purposes such as the construction of catalysts and development of synthetic receptors and molecular containers.