Novel Method for Direct Synthesis of C-Glycosides from Unprotected 2-N-Acyl-Aldohexoses for Multiple Therapeutic Purposes (No. 0080)

 
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Summary

C-glycosides are highly stable bioactive molecules, widely known for their therapeutic activity. These molecules are found in nature and can be synthesized synthetically for multiple purposes: probes, building blocks and most importantly – for numerous therapeutic applications, such as anti-cancerous anti-diabetes, antiviral and anti-bacterial treatments. Despite the importance of these molecules, current methods for c-glycosides synthesis are relatively limited and do not provide access to important compounds with desired bioactive functions. Researchers led by Prof. Fujie Tanaka have developed a novel method for C-glycosides synthesis from unprotected carbohydrates and inactivated ketones via the C–C bond formation at the anomeric carbon of the carbohydrate. This method can provide C-glycoside derivatives that cannot be synthesized through previously reported methods. It is atom-economical, requires mild conditions, and results with products expressing high stereo-selectivity.

 

Lead Researcher:
Fujie Tanaka

Faculty of Chemistry and Chemical Bioengineering Unit

Applications

Generation of bioactive compounds for multiple purposes:

  • C-glycosides, glycoconjugates, carbon-chain elongated carbohydrates and related compounds
  • Molecules used as therapeutics, bioactive candidates, probes, synthons, and building blocks

 

Advantages

  • Excellent stereoselectivity (>10:1)
  • Mild reaction conditions (25 degC)
  • Atom- and step-economical reactions
  • Enables to generate products that were not demonstrated through other known methods

Figure 1. C-C bond formation at the anomeric carbon of unmodified aldopyranoses to generate C-glycosides. (a). Catalyst system (used in the novel invention). (b). Transition state at the non-catalytic method.

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Technology's Essence

This novel strategy enables generation of C-glycosides from unprotected 2-N-acyl-aldohexoses through C–C bond formations at the anomeric centers of unprotected carbohydrates. In the first step, reactions are performed with 1,3-diketones via Knoevenagel condensation, followed by the elimination of the acyl group. Generation of the C-glycosides in the last step, involves aldol condensations of unprotected carbohydrates with simple ketones such as acetone, followed by oxa-Michael cyclization. This reaction utilizes amine-based catalysts to generate enamines from the ketones, and simultaneously provides interactions that allow the opening of the cyclic hemiacetals carbohydrates to form the aldehyde groups, by mimicking enzyme strategies.

 

Media Coverage and Presentations

 

CONTACT FOR MORE INFORMATION

  Graham Garner
Technology Licensing Section

  tls@oist.jp
  +81(0)98-966-8937