Functionalization of Cyclodextrins via Reactions of 2,3-Anhydrocyclodextrins

Abstract

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.

Diisobutylaluminium Hydride (DIBAL‐H) Promoted Secondary Rim Regioselective Demethylations of Permethylated β‐Cyclodextrin: A Mechanistic Proposal

“…Note, CDs 5, 6 and 7 are modified on the secondary rim in a regioselective manner, a rather difficult task to achieve. [9][10][11] The optimized results are summarized in Scheme 2 and Table 1.…”

Monosubstituted Cyclodextrins as Precursors for Further Use

“…[117,118] Both can be synthesised regioselectively. [117,120,121] Opening of 2 A ,3 A -allo-epoxy--CD with NaN 3 afforded 2 A -azido-2 A -deoxy-altro--CD, whereas opening of 2 A ,3 A -manno-epoxy--CD afforded the "real" 2 A -azido-2 A -deoxy--CD, but in a very low yield of 3.6 % (Scheme 7). 3 A -O-(Naphthalene-2-sulfonyl)--CD gives rise to 2 A ,3 A -allo-epoxy--CD under basic conditions (Scheme 7).…”

Convenient Preparation of Mono-2 or Mono-3-O-benzoyl-β-cyclodextrin Dependent the Solvent Equilibrium

“…However only very few examples are known of the introduction of a single benzoyl group at the secondary face of CDs, because of the competitive reaction of the primary face and purification of the synthesized cyclodextrin derivatives 16 . Hao et al monobenzoylated β-CD on the secondary face with acyl chloride in alkaline acetonitrile solution, a method which used a toxic solvent and a highly reactive reagent.…”