A general strategy for the practical synthesis of nojirimycin C-glycosides and analogues. Extension to the first reported example of an iminosugar 1-phosphonate.
An efficient and versatile strategy for the synthesis of nojirimycin C-glycosides and related compounds with full stereocontrol is reported. The key steps of the process are the addition of organometallic reagents onto an L-sorbose-derived imine (13) followed by an internal reductive amination. The addition step, which controls the alpha- vs beta-configuration at the pseudoanomeric center in the final product, is highly diastereoselective (re-face addition), and the stereoselectivity can be effectively inverted by adding an external monodentate Lewis acid (si-face addition). The complete synthesis could be achieved in 10 steps only from commercially available 2,3;4,6-di-O-isopropylidene-alpha-L-sorbofuranose and provided alpha- or beta-1-C-substituted 1-deoxynojirimycin derivatives in 27-52% overall yield. The strategy was successfully extended to the first example of an iminosugar 1-phosphonate. The methodology provides access to a wide range of biologically relevant glycoconjugate mimetics in which the glycosidic function is replaced by an imino-C-glycosidic linkage.
D017485:1-Deoxynojirimycin / Q000031:analogs & derivatives; D020650:Combinatorial Chemistry Techniques; D005944:Glucosamine / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D006027:Glycosides / Q000138:chemical synthesis*; D007097:Imines / Q000138:chemical synthesis; D018716:Molecular Mimicry; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D009942:Organometallic Compounds / Q000737:chemistry*; D010084:Oxidation-Reduction; D013237:Stereoisomerism
D006027:Glycosides; D007097:Imines; D009942:Organometallic Compounds; D017485:1-Deoxynojirimycin; D005944:Glucosamine; C013626:nojirimycin