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.