Herrera-Gonzalez, Irene , GONZALEZ CUESTA, MANUEL, Isabel Garcia-Moreno, M. , Garcia Fernandez, Jose Manuel , Ortiz Mellet, Carmen
No
ACS Omega
Article
Científica
2
1
4.1
0.694
16/06/2022
000821759200001
A simple and efficient method for the stereoselective synthesis of nojirimycin alpha-C-glycoside derivatives has been developed using a bicyclic carbamate-type sp2-iminosugar, whose preparation on a gram scale has been optimized, as the starting material. sp2-iminosugar O-glycosides or anomeric esters serve as excellent precursors of acyliminium cations, which can add nucleophiles, including C-nucleophiles. The stereochemical outcome of the reaction is governed by stereoelectronic effects, affording the target alpha-anomer with total stereoselectivity. Thus, the judicious combination of C-allylation, carbamate hydrolysis, cross-metathesis, and hydrogenation reactions provides a very convenient entry to iminosugar alpha-C-glycosides, which have been transformed into N,C-biantennary derivatives by reductive amination or thioureaforming reactions. The thiourea adducts undergo intramolecular cyclization to bicyclic iminooxazolidine iminosugar alpha-C-glycosides upon acid treatment, broadening the opportunities for molecular diversity. A preliminary evaluation against a panel of commercial glycosidases validates the approach for finely tuning the inhibitory profile of glycomimetics.