%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