Substrate Conformation Correlates with the Outcome of Hyoscyamine 6β-Hydroxylase Catalyzed Oxidation Reactions Richiro Ushimaru Mark W. Ruszczycky Wei-chen Chang Feng Yan Yung-nan Liu Hung-wen Liu 10.1021/jacs.8b03729.s001 https://acs.figshare.com/articles/journal_contribution/Substrate_Conformation_Correlates_with_the_Outcome_of_Hyoscyamine_6_-Hydroxylase_Catalyzed_Oxidation_Reactions/6480557 Hyoscyamine 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 <i>exo</i>-hydroxy group having <i>syn</i>-periplanar geometry with respect to the adjacent H atom to be abstracted. 2018-06-05 00:00:00 oxidative cyclase activity cyclization Substrate Conformation Correlates catalyzes C 6-hydroxylation H 6H C 7 position nonheme iron enzyme Hyoscyamine 6β- Hydroxylase Catalyzed Oxidation Reactions Hyoscyamine 6β- hydroxylase hyoscyamine