A convenient synthesis of orthogonally protected 2-deoxystreptamine (2-DOS) as an aminocyclitol scaffold for the development of novel aminoglycoside antibiotic derivatives against bacterial resistance.
The development of new aminoglycoside analogues to reduce the emergence of bacterial resistance has become a topic of high interest. We describe here a rapid and facile access to orthogonally protected 2-deoxystreptamine (2-DOS), a meso-diaminocyclitol known to be a pivotal component of most active aminoglycosides. Our synthetic approach started from highly protected methyl alpha-D-glucopyranoside which in turn was converted by a Ferrier rearrangement into an enantiopure polyfunctionalized cyclohexane ring. Finally, two different N-protected groups were successively introduced. The first one was inserted as an oximino benzylether followed by a diastereofacial hydride reduction, working with Me(4)NBH(OAc)(3) only in TFA at low temperature rather than in AcOH as usual. The second group was introduced by displacement of a hydroxyl group through a Mitsunobu reaction using a DPPA-DIAD-Ph(3)P system for azide transfer.
Bauder
Claude
C
Institut de Chimie, UMR 7177 associé au CNRS-Université de Strasbourg, 1 rue Blaise Pascal, BP 296 R8, 67008, Strasbourg Cedex, France. cbauder@chimie.u-strasbg.fr
D000617:Aminoglycosides / Q000737:chemistry*; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry; D054812:Cyclitols / Q000737:chemistry*; D004352:Drug Resistance, Microbial; D006595:Hexosamines / Q000138:chemical synthesis / Q000737:chemistry; D015394:Molecular Structure; D010084:Oxidation-Reduction; D013237:Stereoisomerism
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D054812:Cyclitols; D006595:Hexosamines; C007265:2-deoxystreptamine