ja8b03729_si_001.pdf (4.7 MB)
Substrate Conformation Correlates with the Outcome of Hyoscyamine 6β-Hydroxylase Catalyzed Oxidation Reactions
journal contribution
posted on 2018-06-05, 00:00 authored by Richiro Ushimaru, Mark W. Ruszczycky, Wei-chen Chang, Feng Yan, Yung-nan Liu, Hung-wen LiuHyoscyamine 6β-hydroxylase
(H6H) is an α-ketoglutarate
dependent mononuclear nonheme iron enzyme that catalyzes C6-hydroxylation
of hyoscyamine and oxidative cyclization of the resulting product
to give the oxirane natural product scopolamine. Herein, the chemistry
of H6H is investigated using hyoscyamine derivatives with modifications
at the C6 or C7 position as well as substrate analogues possessing
a 9-azabicyclo[3.3.1]nonane core. Results indicate that hydroxyl rebound
is unlikely to take place during the cyclization reaction and that
the hydroxylase versus oxidative cyclase activity of H6H is correlated
with the presence of an exo-hydroxy group having syn-periplanar geometry with respect to the adjacent H atom
to be abstracted.