SYNTHESIS OF NOVEL AMINO-KETOHEPTULOSES

Anna Jacobsen Yevgeniy Leshch Joachim Thiem

Department of Chemistry, University of Hamburg, Hamburg

Antibiotic resistance is an increasing problem for the treatment of infectious diseases, e.g. tuberculosis or malaria.^[1^] Aminoglycosides are a class of antibiotics containing at least two amino sugars.^[2] The synthesis and derivatization of bioactive amino sugars have been studied for decades in the ongoing search for antibiotics.^[3] Recently reported versatile routes to a number of rare naturally occurring heptoses^[4] enable synthesis of novel seven carbon amino sugars and their further incorporation into novel aminoglycoside antibiotics.

To date there are only few reports on the synthesis of amino heptose derivatives. In this contribution a versatile route to such components will be presented. As key intermediates heptenitols 2 are synthesized via C-1 extension starting from hexose 1 allowing subsequent regiospecific transformations to generate an array of novel amino-deoxy-D-gluco/manno-hept-2-uloses.

Scheme 1. Synthesis of amino ketoheptuloses via heptenitols.

Acknowledgements: Support by the European Community FP7-NMP, grant agreement n° 228933.

References

[1] Antimicrobial Resistance. World Health Organization, 2009, p. Fact Sheet 194.

[2] M. Shahid, Anti-Infective Agents in Med.Chem. 2007, 6, 107-117.

[3] (a) Ravi, R.; McAlexander, I.; Chang, C.W.-T.; Org. Prep. Int. 2005, 37, 337-375. (b) Brimacornbe, J.S.; Angew. Chem. Int. Ed. 1971, 10, 236-248.

[4] (a) Waschke, D.; Thimm, J.; Thiem, J.; Org. Lett. 2011, 13, 3628-3631. (b) Waschke, D.; Leshch, Y.; Thimm, J.; Himmelreich, U.; Thiem, J.; Eur. J. Org. Chem. 2012, 948-959. (c) Leshch, Y.; Waschke, D.; Thimm, J.; Thiem, J.; Synthesis 2011, 3871-3877.