55869-99-3Relevant articles and documents
Changes in Regioselectivity of H Atom Abstraction during the Hydroxylation and Cyclization Reactions Catalyzed by Hyoscyamine 6β-Hydroxylase
Ushimaru, Richiro,Ruszczycky, Mark W.,Liu, Hung-Wen
, p. 1062 - 1066 (2019/01/23)
Hyoscyamine 6β-hydroxylase (H6H) is an αKG-dependent nonheme iron oxidase that catalyzes the oxidation of hyoscyamine to scopolamine via two separate reactions: hydroxylation followed by oxidative cyclization. Both of these reactions are expected to involve H atom abstraction from each of two adjacent carbon centers (C6 vs C7) in the substrate. During hydroxylation, there is a roughly 85:1 preference for H atom abstraction from C6 versus C7; however, this inverts to a 1:16 preference during cyclization. Furthermore, 18O incorporation experiments in the presence of deuterated substrate are consistent with the catalytic iron(IV)-oxo complex being able to support the coordination of an additional ligand during hydroxylation. These observations suggest that subtle differences in the substrate binding configuration can have significant consequences for the catalytic cycle of H6H.
Preparative separation of four isomers of synthetic anisodamine by HPLC and diastereomer crystallization
Wu, Tong,Zhu, Jiu-Xin,Wei, Qian,Li, Ping,Wang, Li-Bo,Huang, Jian,Wang, Jin-Hui,Tang, Li-Ke,Wu, Li-Jun,Li, Chang,Han, Wei-Na
, p. 11 - 20 (2018/11/23)
Anisodamine (654-1), a well-known cholinergic antagonist, is marketed as synthetic anisodamine (mixture of four isomers, 654-2) in China. To preparative resolution and comparison of the bioactivities of the four isomers of synthetic anisodamine, current work explores an economic and effective separation method by using preparative high performance liquid chromatography (HPLC) and diastereomer crystallization. Their absolute configurations were established by single-crystal X-ray diffraction and circular dichroism method. The purities of each isomer were more than 95%. Among them, 654-2-A2 (6R, 2′S configuration) exhibited better effect on cabachol preconditioned small intestine tension more than 654-2 and other isomers. The direct separation method without using HPLC was tried as well, which was still on progress. This is the first report of the method for preparative separation of four isomers of synthetic anisodamine which could be used for large-scale production in industry.
Absolute configuration of natural diastereoisomers of 6β- hydroxyhyoscyamine by vibrational circular dichroism
Munoz, Marcelo A.,Munoz, Orlando,Joseph-Nathan, Pedro
, p. 1335 - 1340 (2008/12/20)
The absolute configuration of the two natural diastereoisomers of 6β-hydroxyhyoscyamine has been determined using vibrational circular dichroism (VCD) spectroscopy. The predicted VCD and IR spectra of (3R,6R,2′S)-6β-hydroxyhyoscyamine (1) and (3S,6S,2′S)-6β- hydroxyhyoscyamine (2) were calculated using density functional theory (DFT) with the B3LYP functional and 6-31G(d) basis set and considering the eight lower energy conformations of each diastereoisomer. In both cases, the first four conformers showed the N-Me group in the syn orientation, permitting the formation of a hydrogen bond between the hydroxy group at the tropane ring and the tertiary nitrogen atom. In addition the eight conformers showed an intramolecular hydrogen bond between the hydroxy and carbonyl groups of the tropic ester moiety. The calculated IR spectra of both molecules showed good agreement with the experimental spectra, while comparison of the experimental and calculated VCD spectra showed that the absolute configuration of dextrorotatory 6β-hydroxyhyoscyamine is (3R,6R,2′S), while the levorotatory isomer is (3S,6S,2′S).