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Substrate Conformation Correlates with the Outcome of Hyoscyamine 6?-Hydroxylase Catalyzed Oxidation Reactions.

ABSTRACT: Hyoscyamine 6?-hydroxylase (H6H) is an ?-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.

SUBMITTER: Ushimaru R

PROVIDER: S-EPMC6488034 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Substrate Conformation Correlates with the Outcome of Hyoscyamine 6β-Hydroxylase Catalyzed Oxidation Reactions.

Ushimaru Richiro R Ruszczycky Mark W MW Chang Wei-Chen WC Yan Feng F Liu Yung-Nan YN Liu Hung-Wen HW

Journal of the American Chemical Society 20180611 24

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 pl ...[more]

PMID: 29870653

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Changes in Regioselectivity of H Atom Abstraction during the Hydroxylation and Cyclization Reactions Catalyzed by Hyoscyamine 6β-Hydroxylase.

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