Carroll, Anthony W. Savaspun, Kongdech Willis, Anthony C. Hoshino, Masako Kato, Atsushi Pyne, Stephen G. Total Synthesis of Natural Hyacinthacine C<sub>5</sub> and Six Related Hyacinthacine C<sub>5</sub> Epimers 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. 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
    https://acs.figshare.com/articles/journal_contribution/Total_Synthesis_of_Natural_Hyacinthacine_C_sub_5_sub_and_Six_Related_Hyacinthacine_C_sub_5_sub_Epimers/6216806
10.1021/acs.joc.8b00585.s001