302788-36-9Relevant academic research and scientific papers
α-1-C-Alkyl-1-deoxynojirimycin derivatives as potent and selective inhibitors of intestinal isomaltase: Remarkable effect of the alkyl chain length on glycosidase inhibitory profile
Godin, Guillaume,Compain, Philippe,Martin, Olivier R.,Ikeda, Kyoko,Yu, Liang,Asano, Naoki
, p. 5991 - 5995 (2007/10/03)
A series of α- and β-1-C-alkyl-1-deoxynojirimycin derivatives was prepared and evaluated as glycosidase inhibitors. Biological assays showed a marked dependence of the selectivity and potency of the inhibitors upon the position of the alkyl chain (α-1-C-, β-1-C- or N-alkyl derivatives). In addition, the efficiency of α-1-C-alkyl-1-deoxynojirimycin derivatives as intestinal isomaltase inhibitors increases with the length of the alkyl chain. The strongest inhibition was found for α-1-C -nonyl-1- deoxynojirimycin with an IC50 = 3.5 nM (25x more potent inhibitor than the shorter chain homologue carrying a C8 chain). These results demonstrate that subtle changes in the aglycon fragment may result in remarkable enzyme specificity.
A general strategy for the practical synthesis of nojirimycin C-glycosides and analogues. Extension to the first reported example of an iminosugar 1-phosphonate
Godin, Guillaume,Compain, Philippe,Masson, Geraldine,Martin, Olivier R.
, p. 6960 - 6970 (2007/10/03)
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 α vs β-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-C-L-sorbofuranose and provided α or β-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.
A new, stereocontrolled approach to iminosugar C-glycosides from L-sorbose
Masson, Géraldine,Compain, Philippe,Martin, Olivier R.
, p. 2971 - 2974 (2007/10/03)
The efficient synthesis of the iminoalditols derivatives 1 and 2 (nojirimycin α-C-glycosides) has been achieved in 10 steps from commercially available 2,3;4,6-di-O-isopropylidene-α-L-sorbofuranose in an overall yield of 23-27%.
