Preparation of 1,6-di-deoxy-d-galacto and 1,6-di-deoxy-l-altro nojirimycin derivatives by aminocyclization of a 1,5-dicarbonyl derivative

Abstract

Iminosugars are known glycosidase inhibitors which are the subject of drug development efforts against several diseases. The access to structurally-related families of iminosugars is of primary importance for running structure-activity relationship studies. In this work, the double reductive amination (aminocyclization) reaction of a dicarbonyl derivative of the l-arabino series, in turn obtained from lactose, is reported. Different ratios of 1,6-di-deoxy-d-galacto and 1,6-di-deoxy-l-altro nojirimycin derivatives were obtained depending on the amine employed in this transformation which provided an insight into the effects of their structure on the outcome of the reaction. Of particular interest were the results obtained when two enantiomeric amino acids (d-Phe-OMe and l-Phe-OMe) were used, which resulted in the inversion of the reaction stereoselectivity.