Chemical clockwise tridifferentiation of alpha- and beta-cyclodextrins: bascule-bridge or deoxy-sugars strategies

Chemistry. 2007;13(35):9757-74. doi: 10.1002/chem.200700971.

Abstract

The selective and efficient functionalisation of large concave molecules is a chemical challenge opening the door to various applications, such as artificial enzymes. We propose here a method, based on deprotection of benzylated cyclodextrins, to selectively access a variety of complex structures with two or three new different functionalities on the primary platform. Our strategy is based on a mechanistic hypothesis involving the approach of an aluminium reagent between the primary oxygen atom and the endocyclic one of the same sugar unit. Due to its cyclic directionality, a change in steric hindrance on a given position of the cyclodextrin has a different effect on the clockwise or the counterclockwise directions. This concept is illustrated and exploited in two complementary ways: deoxygenation of the primary position of two diametrically opposed sugars induces a debenzylation reaction on the neighbouring clockwise sugars of alpha- and beta-cyclodextrins. Reversible capping, or bascule-bridging, of the same pair of sugars has the same effect on the debenzylation of alpha-cyclodextrin, but induces an important change of the geometry of beta-cyclodextrin, hence allowing the selective access to yet another functionalisation pattern. A combined use of deoxygenation and bascule-bridging allows the access to an alpha-cyclodextrin with its three pairs of primary functions differentiated and ready for further modifications. Bascule-bridge or deoxy-sugars are two complementary means to operate steric decompression and induce selective reactions to efficiently access a number of new patterns of functionalities on concave molecules.

MeSH terms

  • Benzene / chemistry
  • Cross-Linking Reagents / chemistry*
  • Deoxy Sugars / chemistry*
  • Hydrogen / chemistry
  • Magnetic Resonance Spectroscopy
  • Molecular Structure
  • Oxygen / chemistry
  • Stereoisomerism
  • alpha-Cyclodextrins / chemistry*
  • beta-Cyclodextrins / chemistry*

Substances

  • Cross-Linking Reagents
  • Deoxy Sugars
  • alpha-Cyclodextrins
  • beta-Cyclodextrins
  • Hydrogen
  • Benzene
  • Oxygen