Structural studies of phenylhydrazine integration in carbohydrate derivatives

Today the aminoglycosides are still the most commonly used antibiotics worldwide thanks to the combination of their high efficacy with low cost. The interest of aminoglycoside antibiotics is due to their use in treatment of wide variety infections. These compounds act on gram-positive and gram-negative bacteria as protein synthesis inhibitors.[1] However, they are nephrotoxic and ototoxic in some cases, thus limiting its use. Kanamycin is an aminoglycoside antibiotic with multiple therapeutic applications. A previous step of their synthesis is the formation of 3-amino-3-deoxy-D-glucose from commercial available products. Integration of phenylhydrazine with a sugar derived dialdehyde (2) in water, as a key step, has been used[2] as an elegant and easy strategy synthesis. However, a low reproducibility of this method makes synthetic chemists reluctant to its use, in such a way that other routes of synthesis of 3-amino-3-deoxy-D-glucose are preferred.[3] All this, despite the fact that the above mentioned integration reaction can be considered as a representative example of green chemistry.[4] We have revisited this process and we report herein new NMR and IR data of compounds 2 and 3 that they confirm the structures proposed in literature. In addition, we describe novel different conditions for their synthesis that reduce the time of reactions, especially in case of dialdehyde 2. We thank the AECID (Projects A/023577/09 and A/040322/10) and the \'Junta de Andalucía\' (FQM 142 and Project P09-AGR-4597) for financial support. [1] a) Li, J.; Chang. T., Anti-Infec. Agents in Med. Chem. 2006, 5, 255.; b) Corey, E. J.; Czakó, B.; Kürti, L., Molecules and Medicine. John Wiley & Sons, New Jersey, 2007 [2] Patroni, J.; Stick, R. Aust. J. Chem, 1985, 38, 947 and reference therein. [3] Faghih, R.; Cabrera-Escribano, F. et al, J. Org. Chem. 1986, 51, 4558 [4] Anastas, Y.; Warner, J.C. Green Chemistry: theory and practice.Oxford University Press, New York, 1998