10.1021/acs.joc.8b00585.s003 Anthony W. Carroll Anthony W. Carroll Kongdech Savaspun Kongdech Savaspun Anthony C. Willis Anthony C. Willis Masako Hoshino Masako Hoshino Atsushi Kato Atsushi Kato Stephen G. Pyne Stephen G. Pyne Total Synthesis of Natural Hyacinthacine C<sub>5</sub> and Six Related Hyacinthacine C<sub>5</sub> Epimers American Chemical Society 2018 Related Hyacinthacine C 5 Epimers future antidiabetic drug development Petasis borono Mannich reaction hyacinthacine C-type products hyacinthacine C-type compounds 9.9 μ M Natural Hyacinthacine C 5 IC 50 S N 2 ring-opening hyacinthacine C 5 130 μ M 2018-04-27 00:00:00 Dataset https://acs.figshare.com/articles/dataset/Total_Synthesis_of_Natural_Hyacinthacine_C_sub_5_sub_and_Six_Related_Hyacinthacine_C_sub_5_sub_Epimers/6216800 The total synthesis of natural (+)-hyacinthacine C<sub>5</sub> was achieved, which allowed correction of its initially proposed structure, as well as six additional hyacinthacine C-type compounds. These compounds were readily accessible from two epimeric <i>anti</i>-1,2-amino alcohols. Keeping a common A-ring configuration, chemical manipulation occurred selectively on the B-ring of the hyacinthacine C-type products through methods of <i>syn</i>-dihydroxylation, S<sub>N</sub>2 ring-opening of a cyclic sulfate, and also employing either (<i>R</i>)- or (<i>R</i>,<i>S</i>)-α-methylallyl amine for the Petasis borono Mannich reaction. Our small analogue library was then assessed for its glycosidase inhibitory potency against a panel of glycosidases. (−)-6-<i>Epi</i>-hyacinthacine C<sub>5</sub> and (+)-7-<i>epi</i>-hyacinthacine C<sub>5</sub> (compound names are based on the corrected structure of hyacinthacine C<sub>5</sub>) proved most active, with inhibitory activities ranging between weak (IC<sub>50</sub> = 130 μM) and moderate (IC<sub>50</sub> = 9.9 μM) against the α-glucosidases of rat intestinal maltase, isomaltase, and sucrase, thus identifying potential new leads for future antidiabetic drug development.