Corrected Structure of Natural Hyacinthacine C via Total Synthesis.

Hyacinthacines C and C are natural products that were isolated from Hyacinthoides non-scripta and Scilla socialis in 1999 and 2007, respectively. Despite their different H NMR and C NMR spectroscopic data, these compounds have been assigned the same structures, including absolute configurations. This work details the total synthesis of natural (+)-hyacinthacine C, whose structure is confirmed as being the C-6 epimer of that reported. The synthetic strategy focused on inverting the configuration at C-1 of the final hyacinthacines via operating the inversion at the corresponding carbon atom in three previously synthesized intermediates. To do this, the advanced intermediates were subjected to Swern oxidation, followed by a stereoselective reduction with L-Selectride. This approach led to the synthesis of (+)-5 -epi-hyacinthacine C (15), the corrected structure for (+)-hyacinthacine C (19), (+)-6,7-di- epi-hyacinthacine C (23), and (+)-7- epi-hyacinthacine C (29). Glycosidase inhibition assays revealed that (+)-hyacinthacine C (19) proved the most active, with IC values of 33.7, 55.5, and 78.2 μM, against the α-glucosidase of rice, human lysosome, and rat intestinal maltase, respectively.