jo8b00585_si_003.cif (43.62 kB)
Total Synthesis of Natural Hyacinthacine C5 and Six Related Hyacinthacine C5 Epimers
dataset
posted on 2018-04-27, 00:00 authored by Anthony
W. Carroll, Kongdech Savaspun, Anthony C. Willis, Masako Hoshino, Atsushi Kato, Stephen G. PyneThe 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.