The intramolecular reverse-Cope elimination gives 3-methylindolizidines

Iminosugars are sugar analogues in which the endocyclic oxygen atom is replaced by nitrogen. This substitution not only originates several synthetical challenges but also offers the possibility of obtaining compounds with interesting biological activity. In this context, iminosugars are one of the most studied classes of glycomimetics, exhibiting their biological activity as antibiotic, antiviral, antitumoral, and therapeutic agents The biological activity of polyhydroxylated indolizidines has already been reported, as well as of pyrrolizidines bearing a methyl substituent adjacent to the bridge-head nitrogen1. However, the synthesis of polyhydroxylated 3-methylindolizidines has not been accomplished yet, and their bioactivity remains unknown. We report the synthesis of 3-methylindolizidines 4-7 analogous to Castanospermine, starting from inexpensive sugar-based nitrones and using the Cope-House reaction as a key step within domino processes. Biological assays on final indolizidines are under evaluation.