Background: The inherent glycosidase inhibitory activity and potentially
therapeutic value of the polyhydroxylated pyrrolizidine alkaloids containing a
hydroxymethyl substituent at the C-3 position have been well documented. Belonging to
this class, the naturally occurring hyacinthacine C-type alkaloids are of general interest
among iminosugar researchers. Their selective micromolar α -glycosidase inhibitory
ranges (10 – 100 μM) suggest that these azasugars are potential leads for treating type II
diabetes. However, the structures of hyacinthacine C1, C3 and C4 are insecure with
hyacinthacine C5 being recently corrected.
Objective: This review presents the hyacinthacine C-type alkaloids: their first discovery to
the most recent advancements on the structures, biological activities and total synthesis.
Conclusion: The hyacinthacine C-type alkaloids are of exponentially increasing interest and will undoubtedly
continue to be reported as synthetic targets. They represent a challenging but rewarding synthetic feat for the
community of those interested in accessing biologically active iminosugars. Since 2009, ten total syntheses
have been employed towards accessing similarly related products but only three have assessed the glycosidase
inhibitory activity of the final products. This suggests the need for an accessible and universal glycosidase
inhibitory assay so to accurately determine the structure-activity relationship of how the hyacinthacine C-type
alkaloids inhibit specific glycosidases. Confirming the correct structures of the hyacinthacine C-type alkaloids
as well as accessing various analogues continues to strengthen the foundation towards a marketable treatment
for type II diabetes and other glycosidase related illnesses.