%0 Journal Article %A Carroll, Anthony W. %A Savaspun, Kongdech %A Willis, Anthony C. %A Hoshino, Masako %A Kato, Atsushi %A Pyne, Stephen G. %D 2018 %T Total Synthesis of Natural Hyacinthacine C5 and Six Related Hyacinthacine C5 Epimers %U 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 %R 10.1021/acs.joc.8b00585.s001 %2 https://acs.figshare.com/ndownloader/files/11307848 %K Related Hyacinthacine C 5 Epimers %K future antidiabetic drug development %K Petasis borono Mannich reaction %K hyacinthacine C-type products %K hyacinthacine C-type compounds %K 9.9 μ M %K Natural Hyacinthacine C 5 %K IC 50 %K S N 2 ring-opening %K hyacinthacine C 5 %K 130 μ M %X The total synthesis of natural (+)-hyacinthacine C5 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 anti-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 syn-dihydroxylation, SN2 ring-opening of a cyclic sulfate, and also employing either (R)- or (R,S)-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-Epi-hyacinthacine C5 and (+)-7-epi-hyacinthacine C5 (compound names are based on the corrected structure of hyacinthacine C5) proved most active, with inhibitory activities ranging between weak (IC50 = 130 μM) and moderate (IC50 = 9.9 μM) against the α-glucosidases of rat intestinal maltase, isomaltase, and sucrase, thus identifying potential new leads for future antidiabetic drug development. %I ACS Publications