864442-63-7Relevant academic research and scientific papers
Synthesis and comparative glycosidase inhibitory properties of reducing castanospermine analogues
Perez, Paula Diaz,Garcia-Moreno, M. Isabel,Mellet, Carmen Ortiz,Garcia Fernandez, Jose M.
, p. 2903 - 2913 (2005)
The feasibility of the intramolecular nucleophilic addition of the nitrogen atom in cyclic (thio)carbamates with a pseudo-C-nucleoside structure to the masked carbonyl group in aldose precursors in the synthesis of reducing (i.e., 5-hydroxy)-6-oxaindolizidine frameworks is illustrated by the preparation of the 6-epi, 7-epi, 8-epi and 6,8a-di-epi diastereomers of the potent glycosidase inhibitor (+)-castanospermine. In all cases, the increased anomeric effect caused by the high sp2 character of the pseudoamide-type nitrogen atom resulted in the pseudoanomeric hydroxy group being anchored in an axial orientation in aqueous solution, as in the aglycons in α-glycosides. These analogs of the natural alkaloid showed a higher selectivity in the inhibition of α-glucosidases. Structure/glycosidase inhibitory activity studies indicated that inversion of any hydroxy group resulted in a dramatic decrease in the inhibition potency, confirming the critical importance of a correct hydroxylation profile. In the case of (+)-8-epi-6-oxacastanospermine derivatives, with a hydroxylation profile with a structural complementarity to that of D-galactose, a moderate but very selective inhibition of α-galactosidase was observed, supporting the importance of a defined configuration at pseudoanomeric centres for anomeric specificity. Wiley-VCH Verlag GmbH & Co. KGaA, 2005.
