Rapid synthesis of carbohydrate derivatives, including mimetics of C-linked disaccharides and C-linked aza disaccharides, using the hetero-Diels-Alder reaction

J Org Chem. 2010 Nov 5;75(21):7210-8. doi: 10.1021/jo101219w.

Abstract

In this work we demonstrate the value of performing a hetero-Diels-Alder reaction (HDAR) between Danishefsky's diene and a range of aldehydes or imines, under microwave irradiation. By using a range of aldehydes and imines, including those derived from carbohydrates, access to functionalized 2,3-dihydro-4H-pyran-4-ones or 2,3-dihydro-4-pyridinones in good to excellent synthetic yields is possible. A particular strength of the methodology is its ability to access mimetics of C-linked disaccharides and C-linked aza disaccharides, targets of current therapeutic interest, in a rapid, convenient, and diastereoselective manner. The effect of high pressure on the HDARs involving carbohydrate-derived aldehydes and imines is also explored, with enhancement in yields occurring for the aldehyde substrates. Finally, HDARs using carbohydrate derived ketones, enones, and enals are described under a range of conditions. Optimum results were obtained under high-pressure conditions, with highly functionalized carbohydrate derivatives being afforded, in good yields, in this way.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehydes / chemistry
  • Aza Compounds / chemistry*
  • Biomimetic Materials / chemical synthesis*
  • Biomimetic Materials / chemistry*
  • Carbon / chemistry*
  • Disaccharides / chemical synthesis*
  • Disaccharides / chemistry*
  • Imines / chemistry
  • Ketones / chemistry
  • Kinetics
  • Oxidation-Reduction
  • Pyridines / chemistry
  • Pyrones / chemistry

Substances

  • Aldehydes
  • Aza Compounds
  • Disaccharides
  • Imines
  • Ketones
  • Pyridines
  • Pyrones
  • Carbon
  • pyridine