Potencies of Four Stereoisomers of Anisodamine on Muscarinic Receptor

用[3~H]-QNB配体受体结合实验,抗Ach对豚鼠回肠纵肌条收缩效应,抗毛果芸香碱流涎及扩瞳效应为指标,比较山莨菪碱四个立体异构体(A.6S,2′S;B.6S,2′R;C.6R,2′R;D.6R,2′S)与M受体相互作用的构效关系,结果A,B,C,D四个异构体效应分别为:(1)受体结合实验K_i(M)2.69×10^(-7),1.43×10^(-7),1.63×10^(-5),2.15×10^(-6);(2)抗Ach豚鼠回肠纵条收缩:K_6(M)2.98×10^(-8);1.38×10^(-8);1.52×10~5;1.0l×10^(-7);(3)扩瞳:ED_4(mol/kg)1.6×10^(-6),1.9×10^(-6),5.1×10^(-5),3.6×10^(-5);(4)抗毛果芸香碱流涎:ED_(50)(mol/kg)1.5×10^(-6);1.3×10^(-6);2.6×10^(-5);3.1×10^(-5)。以上结果表明四个异构体效应强度为6S,2′R≌6S,2′S>>6R,2′S>6R,2′R。

Determination of Stereoisomers of Epalrestat by Liquid Chromatography

An isocratic reversed-phase liquid chromatographic (LC) method is described for the determination of epalrestat and its three stereoisomers (degradation impurities) in drug substance. The LC separation system consisted of a Hypersil C18 column (250 mm×4.6 mm, 5 μm) with a mobile phase comprising methanol, acetonitrile and water (volume ratio 60∶1∶50, pH 4.5) delivered at a flow rate of 1.6 mL/min and UV detection at 280 nm. The proposed LC method is simple and selective for the determination of the stereoisomers of epalrestat in the drug substance with a limit of detection and quantification of 3.9 μg/mL and 4.9 μg/mL, respectively. The stereoisomers were identified by liquid chromatography-mass spectrometry (LC-MS).

Assessment and Comparison of in vitro Immunoregulatory Activity of Three Astaxanthin Stereoisomers

In recent years,the immune-modulatory role of all-trans astaxanthin from different pigment sources has been studied.It was reported that all-trans astaxanthin might exist as three stereoisomers,and the composition of all-trans stereoisomers in natural materials differs from that of synthetic products.However,the different biological effects of various all-trans stereoisomers still remain unclear.In the present study,we evaluated the bioactivity of three astaxanthin stereoisomers,(3S,3'S)-trans-,(3R,3'R)-transand meso-trans-astaxanthin,in regulating cell-mediated immune response using mice lymphocytes and peritoneal exudates cells(PECs) systems.After the treatment with three astaxanthin stereoisomers(20 μmol L-1),the lymphocyte proliferation capacity,neutral red phagocytosis of PECs and natural killer(NK) cell cytotoxic activity were comparatively assessed.The results showed that all three astaxanthin stereoisomers significantly promoted lymphocyte proliferation,phagocytic capacity of PECs,and cytotoxic activity of NK cells.Moreover,the(3S,3'S)-trans-astaxanthin exhibited a much higher response than others.

Enumeration of Stereoisomers of Chiral and Achiral Derivatives of Monocyclic Cycloalkanes Having Heteromorphous Alkyl Substituents with Distinct Length <i>k</i>

A combinatorial method based on the determination of the averaged weight of permutations controlling the chirality/achirality fittingness of 2n substitution sites of the monocyclic cycloalkane allows to obtain generalized functional equations for direct enumeration of enantiomers pairs and achiral skeletons of any derivatives of monocyclic cycloalkanes having heteromorphic alkyl substituents with the distinct length k with the empirical formula , wherein at least two alkyl groups??of the distinct size ?each. ?is the number of alkyl radicals ?of the system??verifying the relation . The integer sequences of enantiomer pairs and achiral skeletons are given for substituted derivatives of monocyclic cycloalkane for n = 3, 4 and k = 3, 4, 5. The composite stereoisomerism of this particular compound is also highlighted.

First synthesis and characterization of key stereoisomers related to Ezetimibe

uring the laboratory optimization and the late phase manufacturing studies of the cholesterol absorption inhibitor Ezetimibe 1, the formation of several stereoisomers was observed. To study the complete stereoisomer profile of Ezetimibe 1, we have synthesized and completely characterized several key stereoisomers of Ezetimibe 1 for the first time. This study will provide an access to the reference standard of these stereoisomers and may have some implications in the development of new medicines.

A highly efficient way to recycle inactive stereoisomers of Bedaquiline into two previous intermediates via base-catalyzed C_(sp3)–C_(sp3) bond cleavage

Bedaquiline is a new medicine for pulmonary multi-drug resistant tuberculosis （MDR-TB）, which is a pure enantiomer with two chiral centers. The current industrial preparation process requires the separation of active Bedaquiline from a mixture of four isomers. Obviously, direct dispose of the other three undesired stereoisomers will cause significant waste and increase the unnecessary cost of production. Here, we developed an efficient, facile and scalable process for recycling the inactive stereoisomers of Bedaquiline. All these inactive stereoisomers could be recycled by their conversion to two important intermediates in the Bedaquiline synthesis via a base-catalyzed Csp3-Csp3 bond cleavage of a benzyl alcohol intermediate. And the precise conditions and mechanism of the base-catalyzed cleavage reaction were discussed.

A set of interesting sequoiatones stereoisomers from a wetland soil-derived fungus Talaromyces flavus

Four interesting sequoiatones stereoisomers(1-4) were isolated from a wetland soil-derived fungus Talaromyces flavus by chiral HPLC.On the basis of comprehensive NMR and mass analyses,their planar structures were elucidated as the same as that of sequoiatone B.Among them,1 and 3(or 2 and 4)were a pair of enantiomers,and 1 and 2(or 3 and 4) were a pair of stereoisomers with epimerization at C-12,which indicated that sequoiatione-type metabolites exist as enantiomers rather than as optically pure compounds in some strains.With the quantum chemical ECD calculations,the absolute configurations of C-8 in 1-4 were determined,which is the first report to establish the absolute configuration of C-8 in sequoiatones.However,the absolute configurations of C-12 in sequoiatones are still unsolved.

STUDY ON CONFIGURATION OF STEREOISOMERS OF ISOHARRINGTONINE

The synthesis of isoharringtonine has been reported previously. In the synthetic process, two new chiral centres, C2′ and C3′, were built, then the product should be a mixture of four stereoisomers. Because the starting material is optically active cephalotaxine whose absolute configuration is 3S, 4S, 5R, the absolute configuration of the four stereoisomers of isoharringtonine could be ascertained by confirming the absolute configuration of their side chain.

^(59)Co-NMR MEDIUM EFFECT, ISOTOPE EFFECT AND CHELATE COMPLEX STEREOISOMERS

The ^(59)Co-NMR spectra of several cobalt (Ⅲ) complexes have been directly recorded bypulsed Fourier transform nuclear magnetic resonance (FT-NMR) technique. The influences ofsolvents, concentration and temperature on ^(59)Co spectra have been investigated. Optical andgeometric isomers of the chelate complexes have been distinguished by ^(59)Co-NMR spectra. ForCo(±pn)_3Cl_3, the resonances of Δ(λλλ) and Δ(δδδ) appeared at the lower field, the δ_(mer) beinggreater than δ_(fac), followed by the peaks of Δ(λλδ) and Δ(δδλ). For Co(en)_3Cl_3-D_n, all the13 isotopic isomers, from D_0 to D_(12), have been resolved in their ^(59)Co spectra. Each H/Dexchange causes ^(59)Co peaks to move upfield 5.4 ppm. The factors affecting the direction andmagnitude of isotopic shift and its additivity have been discussed. Chemical equilibrium isotopiceffect has also been studied.

Antiviral stereoisomers of 3,5-bis(2-hydroxybut-3-en-1-yl)-1,2,4-thiadiazole from the roots of Isatis indigotica

Four stereoisomers of 3,5-bis（2-hydroxybut-3-en-1-yl）-l,2,4-thiadiazole, named insatindigothiadia- zoles A-D （1a-1d）, were isolated from the roots oflsatis indigotica. Their structures were determined by spectroscopic analysis; specifically, the absolute configurations were assigned by using the MPA determination rule based on △δrs values of MPA esters, and supported by electronic CD （ECD） calculations. Proposed biosynthetic pathways and preliminary investigations of the biological activities of la-1d against influenza virus A （H3N2）, Coxsackie virus B3, and/or HSV-1 are also discussed.

First Synthesis and Characterization of Stereoisomers of Choleretic Drug Dihydroxydibutylether

Dihydroxydibutylether （DHBE） is a choleretic drug used for the treatment of gallstone and hepatic disorders due to its choleretic activity and hepatoprotective action. The drug is a mixture of three regioisomers. The main re- gioisomer 3-（3-hydroxylbutoxy）-1-butanol （III） contains four stereoisomers, including （R）-3-（（R）-3-hydroxyl- butoxy）-1-butanol （IIIa）, （R）-3-（（S）-3-hydroxylbutoxy）-1-butanol （IIIh）, （S）-3-（（R）-3-hydroxylbutoxy）-1-butanol （Ille） and （S）-3-（（S）-3-hydroxylbutoxy）-1-butanol （IIId）. In this paper, the four stereoisomers are synthesized separately for the first time.

Formation of RRR-a-tocopherol in rumen and intestinal digestibility of tocopherols in dairy cows

Tocopherol sources in diets are often a combination of all-rac-a-tocopheryl acetate(synthetic a-tocopherol)from vitamin supplements and natural tocopherols and 2R-(4’R,8’R)-5,7,8-trimethyltocotrienol(a-tocotrienols)from the feed sources.Synthetic a-tocopherol consists of 8 different stereoisomers including 2R-(4’R,8’R)-5,7,8-trimethyltocol(RRR-a-tocopherol),2R-(4’S,8’R)-5,7,8-trimethyltocol(RSR-a-tocopherol),2R-(4’R,8’S)-5,7,8-trimethyltocol(RRS-a-tocopherol),2R-(4’S,8’S)-5,7,8-trimethyltocol(RSS-a-tocopherol),2S-(4’S,8’S)-5,7,8-trimethyltocol(SSS-a-tocopherol),2S-(4’R,8’S)-5,7,8-trimethyltocol(SRS-a-tocopherol),2S-(4’S,8’R)-5,7,8-trimethyltocol(SSR-a-tocopherol),and2S-(4’R,8’R)-5,7,8-trimethyltocol(SRR-a-tocopherol).The pre-absorption metabolism of tocopherols and tocotrienols in ruminants differs from monogastric animals due to the extensive microbial fermentation in the anaerobic rumen.The current study investigated the impact of toasting and decortication of oats on metabolism in the digestive tract(synthesis,digestion),and intestinal digestibility of tocopherols in dairy cows by using 4 ruminal and intestinal cannulated Danish Holstein cows in a 4×4 Latin square design for 4 periods.Cows were fed a total mixed ration ad libitum containing different forms of oats:whole oat,decorticated oat,toasted oat,and decorticated toasted oat,all rolled before mixed ration.Overall means across 4 treatments were statistically analyzed,testing whether overall means were different from zero.Decortication or toasting did not affect the balance or digestibility of a-tocopherols in rumen.Average across treatments showed the ruminal degradation of synthetic a-tocopherol(279 mg/d,P=0.02;P-value shows that average across treatments is different from zero),synthetic 2R-a-tocopherol(133 mg/d,P<0.01;summation of RRS-,RSR-and RSS-a-tocopherol),and 2S-a-tocopherol(190 mg/d;P<0.01,summation of SSS-,SRS-,SSR,and SRR-a-tocopherol),while RRR-a-tocopherol was formed in the rumen(221 mg/d,P=0.10).The average across treatments showed that small intestinal digestibility of tocopherols ranked in the following order:a-tocotrienol>natural a-tocopherol>synthetic a-tocopherols>2R-(4’R,8’R)-,7,8-dimethyltocol(γ-tocopherol).The average across treatments for small intestinal and feed-ileum digestibility ranked in the following order:RRR-a-tocopherol>synthetic 2R-a-tocopherol>2S-a-tocopherol.Results showed the first evidence for RRR-a-tocopherol formation under anaerobic conditions in the rumen.In addition,synthetic a-tocopherol stereoisomers,γ-tocopherol and a-tocotrienol were degraded in the rumen.There was a discrimination against absorption of synthetic 2R-and 2S-a-tocopherol in the small intestine.

Activated Anilide in Heterocyclic Synthesis： Synthesis of New Dihydropyridines, Dihydropyridazines and Thiourea Derivatives

A series of new dihydropyridines, butanamide, dihydropyridazines and thiourea derivatives have been prepared through the reactions of 3-aminopyridine （1） and N-（pyridin-3-yl）-3-（pyridin-3-ylimino）butanamide 3 with some electrophilic reagents, aryl diazonium salts and isothiocyanates. Elementary analysis, MS, IR, and 1H NMR spectra confirmed the identity of the products.

Nanoporous Vesicular Membranes of Amphiphilic Polymers Containing Trans/Cis Isomers

Nanoporous membranes and vesicles are interesting systems with potential in applications offering channels for material exchange.Herein,nanoporous membranes and polymersomes are developed by self-assembly of trans-and cis-stereoisomers of amphiphilic polymers.Two polymers,PEG550-TPEChol and PEG550-SS-TPE-SS-Chol,containing a central tetraphenylethene(TPE),a cholesterol(Chol),and a poly(ethylene glycol)(PEG550)are studied.

A quadruple helicene with a rubicene core: synthesis, structural analyses and properties

We report the synthesis of a quadruple helicene with a rubicene core R1 by a Scholl reaction.Among the 10 stereoisomers including 4 pairs of enantiomers and 2 meso isomers,only 2 pairs of enantiomers and 1 meso isomer have been isolated.The sample structures were unambiguously determined by X-ray crystallography to be(P,P)_(6)-(P,P)_(5)/(M,M)_(6)-(M,M)_(5)-R1-A,which has a propeller-shaped structure,and(M,M)_(6)-(P,P)_(5)/(P,P)_(6)-(M,M)_(5)-R1-B and(M,P)_(6)-(P,M)_(5)-R1-C,which have saddle-shaped structures.The chiral resolutions of R1 were carried out by chiral HPLC,revealing two pairs of chiral stereoisomers(P,P)_(6)-(P,P)_(5)/(P,P)_(6)-(M,M)_(5),(M,M)_(6)-(P,P)_(5)/(M,M)_(6)-(M,M)_(5) as well as a meso isomer(M,P)_(6)-(P,M)_(5),which were further characterized by CD spectroscopy and time-dependent density functional theory(TD-DFT)calculations.Surprisingly,the UV-vis absorption and emission spectra of these resolved stereoisomers and unresolved R1 were almost identical.In addition,the chemical oxidation of R1 led to the formation of radical cations and dications at room temperature.

Synthesis of proline fullerene derivative

THE unique spherical nature and potential application of fullerene have attracted great attention. Their functionalization is in particular an active research field. Many methods are now available for the preparation of fullerene derivatives. The 1, 3-dipole cycloaddition of ylide to fullerene is one of the best known methods. We have recently reported that aminoacid esters can be added to C60 to form fulleropyrrolidine derivatives under photolysis. Our in-