138-12-5Relevant academic research and scientific papers
The Assignment of the Absolute Configuration of β-Chiral Primary Alcohols with Axially Chiral Trifluoromethylbenzimidazolylbenzoic Acid
Kriegelstein, Michal,Profous, David,P?ibylka, Adam,Canka?, Petr
, p. 12912 - 12921 (2020/11/23)
Axially chiral trifluoromethylbenzimidazolylbenzoic acid (TBBA) was used as a chiral derivatization agent for the assignment of the absolute configuration of β-chiral primary alcohols. The structures varied from simple aliphatic alcohols to complex cyclic systems and highly substituted sugar derivatives. The NMR-based method was successfully implemented to evaluate 17 compounds and displayed ΔδPM values higher than 0.1 ppm in most cases, which makes TBBA superior to MTPA and MPA and comparable to 9-AMA.
Buscopan labeled with carbon-14 and deuterium
Latli, Bachir,Stiasni, Michael,Hrapchak, Matt,Li, Zhibin,Grinberg, Nelu,Lee, Heewon,Busacca, Carl A.,Senanayake, Chris H.
, p. 557 - 564 (2016/11/23)
Hyosine butyl bromide, the active ingredient in Buscopan, is an anticholinergic and antimuscarinic drug used to treat pain and discomfort caused by abdominal cramps. A straightforward synthesis of carbon-14– and deuterium-labeled Buscopan was developed using scopolamine, n-butyl-1-14C bromide, and n-butyl-2H9 bromide, respectively. In a second carbon-14 synthesis, the radioactive carbon was incorporated in the tropic acid moiety to follow its metabolism. Herein, we describe the detailed preparations of carbon-14– and deuterium-labeled Buscopan.
Contra-thermodynamic Hydrogen Atom Abstraction in the Selective C-H Functionalization of Trialkylamine N-CH3 Groups
Barham, Joshua P.,John, Matthew P.,Murphy, John A.
supporting information, p. 15482 - 15487 (2016/12/09)
We report a simple one-pot protocol that affords functionalization of N-CH3 groups in N-methyl-N,N-dialkylamines with high selectivity over N-CH2R or N-CHR2 groups. The radical cation DABCO+?, prepared in situ by oxidation of DABCO with a triarylaminium salt, effects highly selective and contra-thermodynamic C-H abstraction from N-CH3 groups. The intermediates that result react in situ with organometallic nucleophiles in a single pot, affording novel and highly selective homologation of N-CH3 groups. Chemoselectivity, scalability, and recyclability of reagents are demonstrated, and a mechanistic proposal is corroborated by computational and experimental results. The utility of the transformation is demonstrated in the late-stage site-selective functionalization of natural products and pharmaceuticals, allowing rapid derivatization for investigation of structure-activity relationships.
Total Synthesis of (±)-Scopolamine: Challenges of the Tropane Ring
Nocquet, Pierre-Antoine,Opatz, Till
, p. 1156 - 1164 (2016/03/05)
Scopolamine was synthesized using 6,7-dehydrotropine as a key intermediate. Rhodium-catalyzed [4 + 3] cycloaddition chemistry and a modified Robinson-Sch?pf reaction were each independently evaluated for their utility in constructing the tropane core. Both synthetic approaches gave comparable overall yields.
Functional characterization of recombinant hyoscyamine 6β-hydroxylase from Atropa belladonna
Li, Jing,Van Belkum, Marco J.,Vederas, John C.
experimental part, p. 4356 - 4363 (2012/08/28)
(-)-Hyoscyamine, the enantiomerically pure form of atropine, and its derivative scopolamine are tropane alkaloids that are extensively used in medicine. Hyoscyamine 6β-hydroxylase (H6H, EC 1.14.11.11), a monomeric α-ketoglutarate dependent dioxygenase, converts (-)-hyoscyamine to its 6,7-epoxy derivative, scopolamine, in two sequential steps. In this study, H6H of Atropa belladonna (AbH6H) was cloned, heterologously expressed in Escherichia coli, purified and characterized. The catalytic efficiency of AbH6H, especially for the second oxidation, was found to be low, and this may be one of the reasons why Atropa belladonna produces less scopolamine than other species in the same family. 6,7-Dehydrohyoscyamine, a potential precursor for the last step of epoxidation, was shown not to be an obligatory intermediate in the biosynthesis of scopolamine using purified AbH6H with an in vitro 18O labeling experiment. Moreover, the nitrogen atom in the tropane ring of (-)-hyoscyamine was found to play an important role in substrate recognition.
The thermosalient phenomenon. jumping crystals and crystal chemistry of the anticholinergic agent oxitropium bromide
Skoko, Zeljko,Zamir, Sharona,Naumov, Pance,Bernstein, Joel
scheme or table, p. 14191 - 14202 (2010/12/24)
The anticholinergic agent oxitropium bromide possesses rich crystal chemistry, most remarkably exhibiting a strong thermosalient effect ( jumping crystal effect), a mechanical property with potential applications in organic-based actuators. The thermosalient effect, manifested in forceful jumps of up to several centimeters, was investigated by a combination of structural, microscopic, spectroscopic, and thermoanalytical techniques, providing data on which to base a proposed mechanism for the phenomenon. Direct observation of the effect in a single crystal and structure determination of both phases revealed that the jumping of the crystals is a macroscopic manifestation of a highly anisotropic change in the cell volume. The cell distortion is accompanied by a conformational change of the oxitropium cation, which triggers increased separation between the ion pairs in the lattice at nearly identical separation between the cation and the anion within each ion pair. At the molecular level, the cation acts as a molecular shuttle composed of two rigid parts (epoxy-aza-tricyclic-nonyl portion and phenyl ring) that are bridged by a flexible ester linkage. The structure of the rigid, inert aza-tricyclic portion remains practically unaffected by the temperature, suggesting a mechanism in which the large, thermally accumulated strain is transferred over the ester bridge to the phenyl ring, which rotates to trigger the phase transition. Mechanistic details of the higher temperature solid-state phenomena are also presented. The high-temperature phase can also be obtained by grinding or UV irradiation of the room-temperature phase. In addition, if it is irradiated with UV light in the presence of KBr, the high-temperature phase undergoes intramolecular photochemical rearrangement. Heating the high-temperature phase to slightly below the melting temperature results in an additional solid-state reaction that results in the conversion of the salt to a mixture of neutral compounds.
Molecular cloning, expression and characterization of hyoscyamine 6β-hydroxylase from hairy roots of Anisodus tanguticus
Liu, Tao,Zhu, Ping,Cheng, Ke-Di,Meng, Chao,He, Hui-Xia
, p. 249 - 253 (2007/10/03)
Anisodus tanguticus, one of the indigenous Chinese ethnological medicinal plants of the Solanaceae, produces anticholinergic alkaloids such as hyoscyamine, 6β-hydroxyhyoscyamine and scopolamine. Hyoscyamine 6β-hydroxylase (H6H), a key enzyme in the biosynthetic pathway of scopolamine, catalyzes the hydroxylation of hyoscyamine and epoxide formation from 6β-hydroxyhyoscyamine to generate scopolamine. A full-length cDNA of H6H has been isolated from A. tanguticus hairy roots. Nucleotide sequence analysis of the cloned cDNA revealed an open reading frame of 1035 bp encoding 344 amino acids with high homology to other known H6Hs. The equivalent amino acid sequence shows a typical motif of 2-oxoglutarate-dependent dioxygenase. The A. tanguticus H6H was expressed in Escherichia coli and purified for enzyme function analysis. This study characterized the recombinant AtH6H and showed it could generate scopolamine from hyoscyamine.
Method for preventing crystal formation in a dispersion of a liquid in a matrix
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, (2008/06/13)
An improved method for the manufacture of transdermal drug delivery devices comprising liquid dispersions of a liquid in an aqueous or nonaqueous matrix is disclosed. More particularly, the invention relates to preventing the formation of a crystalline structure in such liquid dispersions by annealing films and laminates in-line immediately following film formation and/or lamination during the manufacture of these devices.
A method for preventing the formation of a crystalline hydrate in a dispersion of a liquid in a nonaqueous matrix
-
, (2008/06/13)
A method for preventing the formation of crystalline hydrates in a dispersion of a hydratable liquid in a nonaqueous matrix is disclosed. The method is particularly useful in the manufacture of laminated items formed from such dispersions and comprises forming individual subunits from such dispersions, heating the subunits, preferably after they have been packed in sealed containers, to a temperature high enough to melt the crystalline hydrate, maintaining said subunits at such temperature for a time sufficient to melt all the crystalline hydrate present and to prevent the occurrence of crystals for an extended period of time after cooling and cooling subunits to ambient conditions. The use of the method in the manufacture of transdermal delivery devices for the delivery of scopolamine base is described.
