Eight stereoisomers of homonojirimycin from D-mannose
Gabriel M J Lenagh-Snow1, Sarah F Jenkinson, Scott J Newberry
1Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Mansfield Road, OX1 3TA, UK.
Organic Letters
|April 5, 2012
Abstract:
Although there are 32 6-azidoheptitols, there are only 16 homonojirimycin (HNJ) stereoisomers. Two epimeric azidoalditols derived from d-mannose allow the synthesis in water of eight stereoisomers of HNJ.
Insights
Researchers synthesized eight stereoisomers of homonojirimycin (HNJ) using readily available d-mannose derivatives. This study expands the accessible stereoisomers for HNJ synthesis, aiding further research.
Area of Science:
- Carbohydrate Chemistry
- Organic Synthesis
- Medicinal Chemistry
Background:
- Homonojirimycin (HNJ) is a valuable iminosugar with therapeutic potential.
- There are 16 known stereoisomers of HNJ, but their synthesis can be challenging.
- Azidoheptitols are precursors for synthesizing HNJ stereoisomers.
Purpose of the Study:
- To develop an efficient synthetic route to access multiple homonojirimycin (HNJ) stereoisomers.
- To explore the use of d-mannose-derived azidoheptitols for HNJ synthesis.
- To expand the library of available HNJ stereoisomers for biological evaluation.
Main Methods:
- Synthesis of two epimeric 6-azidoheptitols from d-mannose.
- Stereoselective synthesis of homonojirimycin (HNJ) stereoisomers in aqueous media.
- Characterization of the synthesized HNJ stereoisomers.
Main Results:
- Successfully synthesized eight stereoisomers of homonojirimycin (HNJ).
- Demonstrated the utility of d-mannose-derived epimeric azidoheptitols as versatile precursors.
- Achieved synthesis in water, offering a greener synthetic approach.
Conclusions:
- The developed method provides access to a significant number of HNJ stereoisomers.
- This work facilitates further investigation into the structure-activity relationships of HNJ analogs.
- The synthetic strategy is amenable to scale-up for potential therapeutic development.
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