- Pentazocine prodrug as well as preparation method and application thereof
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The invention discloses a pentazocine prodrug shown as a formula (I), a preparation method thereof and medical application of a pharmaceutical preparation containing the pentazocine prodrug, wherein Ris hydrogen or deuterium. The water solubility of the prodrug compound is improved by 20 times or above at room temperature, the prodrug compound is chemically stable, the onset time is delayed, thedrug effect is prolonged, meanwhile, the same parent drug blood concentration is generated at a low dosage, and the prodrug compound has a wide clinical application prospect.
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Paragraph 0040; 0056-0057
(2020/07/15)
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- Preparation and purification method of diltiazem chiral isomer impurity
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The invention provides a method for preparing and purifying a diltiazem chiral isomer. The method comprises the steps of taking p-methoxybenzaldehyde as a starting raw material, carrying out Darzens condensation, a reaction with o-aminobenzenethiol and a cyclization reaction to prepare an intermediate, carrying out chiral column separation on the intermediate, then carrying out an alkylation and acetylation reaction separately to obtain a diltiazem chiral isomer impurity I. The method is simple to operate and short in period, and the purity of the obtained diltiazem chiral isomer impurity is high, so that a reference substance is provided for quality research and drug synthesis process research of diltiazem drugs, and the method has important significance in control and checking of the chiral purity in the pharmaceutical research of diltiazem.
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Paragraph 0017-0018
(2019/11/20)
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- Efficient Preparation of Alkaloids Polycarpine and Polycarpaurines A and C
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An efficient method for the preparation of alkaloids polycarpine and polycarpaurines A and C via microwave-assisted three-step one-pot reaction as the key step has been developed. This is the first report about the synthesis of polycarpaurines A and C. Starting from commercially available p-methoxybenzaldehyde, polycarpine and polycarpaurine A were obtained over seven steps with 40 and 24 % overall yield, respectively. Polycarpine could convert to polycarpaurine C in 72% yield in the presence of NaHSO3. The structure of polycarpine and polycarpaurines A and C was confirmed by1H NMR,13C NMR, and HRMS.
- Guo, Pengbin,Yan, Shuang,Hu, Zeliang,Zhuang, Weihui,Xiong, Yan,Zhang, Lanya,Wang, Ziwen,Wang, Qingmin
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p. 121 - 124
(2017/02/05)
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- Synthesis of 3-Arylpyridines via Palladium/Copper-Catalyzed Annulation of Allylamine/1,3-Propanediamine and Aldehydes
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A novel and efficient method for the synthesis of 3-arylpyridines from allylamine/propanediamine and aldehydes by palladium/copper-catalyzed oxidative tandem cyclization has been developed. With this reaction, a series of desired 3-arylpyridines was synthesized in moderate yields via C-C/C-N bond formation and 6-endo/exo-trig cyclization.
- Yang, Xiaodong,Yang, Shenghua,Xiang, Likui,Pang, Xiaobo,Chen, Baohua,Huang, Guosheng,Yan, Rulong
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supporting information
p. 3732 - 3736
(2016/01/25)
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- Bioresolution production of (2R,3S)-Ethyl-3-phenylglycidate for chemoenzymatic synthesis of the taxol C-13 side chain by galactomyces geotrichum ZJUTZQ200, a new epoxide-hydrolase-producing strain
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A newly isolated Galactomyces geotrichum ZJUTZQ200 strain containing an epoxide hydrolase was used to resolve racemic ethyl 3-phenylglycidate (rac-EPG) for producing (2R,3S)-ethyl-3-phenylglycidate ((2R,3S)-EPG). G. geotrichum ZJUTZQ200 was verified to be able to afford high enantioselectivity in whole cell catalyzed synthesis of this chiral phenylglycidate synthon. After the optimization of the enzymatic production and bioresolution conditions, (2R,3S)-EPG was afforded with high enantioselectivity (e.e.S > 99%, E > 49) after a 8 h reaction. The co-solvents, pH buffer solutions and substrate/cell ratio were found to have significant influences on the bioresolution properties of G. geotrichum ZJUTZQ200. Based on the bioresolution product (2R,3S)-EPG, taxol's side chain ethyl (2R,3S)-3-benzoylamino-2-hydroxy- 3-phenylpropionate was successfully synthesized by a chemoenzymatic route with high enantioselectivity (e.e.S > 95%).
- Wei, Chun,Ling, Jinlong,Shen, Honglei,Zhu, Qing
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p. 8067 - 8079
(2014/07/08)
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- Sc(OTf)3-catalyzed diastereoselective Friedel-Crafts reactions of arenes and hetarenes with 3-phenylglycidates
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Five different para-substituted 3-phenylglycidates (3-phenyloxirane-2- carboxylates) were prepared and subjected to reactions with arenes and hetarenes under Lewis acid catalysis. Sc(OTf)3 was found to effectively (5 mol%) promote a Friedel-Crafts reaction in nitromethane as the solvent. The reaction was shown to proceed stereoconvergently, which makes the intermediacy of a benzylic cation likely. The diastereoselectivities varied depending on the choice of the nucleophile and 3-arylglycidate. Best results were obtained with tert-butyl 3-anisylglycidate, which delivered the respective products with high syn-preference in diastereomeric ratios (d.r.) between 82:18 and >95:5. The observed selectivity can be explained by a model, according to which the intermediate benzylic cations adopt a preferred conformation, which allows for diastereoface-differentiation by the adjacent stereogenic center.
- Wilcke, David,Bach, Thorsten
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supporting information; experimental part
p. 6498 - 6503
(2012/09/08)
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- Transformation of α,β-epoxyesters into 2,3-dideuterioesters promoted by samarium diiodide
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An easy and general sequenced elimination/reduction process by means of samarium diiodide, in the presence of D2O, provides an efficient method for synthesizing 2,3-dideuterioesters 2. The reaction can be also carried out in the presence of H2O instead of D2O, yielding the corresponding saturated esters 4. Other deuterated esters have been also obtained. A mechanism to explain this synthesis has been proposed.
- Concellon, Jose M.,Bardales, Eva,Llavona, Ricardo
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p. 1585 - 1588
(2007/10/03)
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- Synthesis of (E)-α,β-unsaturated esters with total or high diastereoselectivity from α,β-epoxyesters
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Chemical equation presented High stereoselective β-elimination in 2,3-epoxyesters 1 was achieved using samarium diiodide, yielding α,β-unsaturated esters 2, in which the C=C bond is di-, tri- or tetrasubstituted. The starting compounds 1 are easily prepared by reaction of the corresponding lithium enolates of a-chloroesters with aldehydes or ketones at -78 °C. The influence of the reaction conditions and the structure of the starting compounds in the stereoselectivity of the β-elimination reaction is also discussed.
- Concellon, Jose M.,Bardales, Eva
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p. 189 - 191
(2007/10/03)
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- Molecular structure of methyl phenylpyruvates studied by 1H NMR and IR spectroscopies and quantum mechanical calculations
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Molecular structure of methyl phenylpyruvate (MPP) and its p-substituted derivatives has been investigated by 1H NMR and IR spectroscopies. The spectral data point out that MPPs take the enol form both in solution and in the solid state. The ab initio calculations were carried out in order to get information on the configurational and conformational preferences in the enol form. It is suggested from the calculation that the inter- and intra-molecular hydrogen bondings between the enol OH group and the ester C = O group are important for stabilization of the conformer.
- Lee,Takai,Senda,Kuwae,Hanai
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- An improved procedure for the epoxidation of methyl cinnamate derivatives and production of acid sensitive epoxides
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By using a biphasic epoxidation system, unreactive methyl cinnamate derivatives were epoxidized at higher rates, and epoxides that decomposed in the presence of m-chlorobenzoic acid (mCBA) to diol ester opening products under standard conditions were obtained in fair to excellent yields.
- Moyna, Guillermo,Williams, Howard J.,Scott
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p. 2235 - 2239
(2007/10/03)
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- Reactions of Methyl threo-2-Acetoxy-3-chloro-3-(4-methoxyphenyl)propanoate and Methyl cis-2,3-Epoxy-3-(4-methoxyphenyl)propanoate with 3,5-Dimethoxyphenol: Potential Routes to Flavan-3-ols
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Attempted syntheses of flavan-3-ols by reaction of either methyl threo-2-acetoxy-3-chloro-3-(4-methoxyphenyl)propanoate (3) or methyl cis-2,3-epoxy-3-(4-methoxyphenyl)propanoate (14) with 3,5-dimethoxyphenol failed to give the required aryl ethers.Products usually were derived from C-alkylation of the electron-rich phenol although reaction of the chloro acetate (3) with the phenoxide ion gave the furanone (5).The single-crystal X-ray structures of methyl 4-hydroxy-3-(4-methoxyphenyl)-2-(4-methoxyphenylmethyl)-5-oxo-2,5-dihydrofuran-2-carboxylate and cis-3-hydroxy-5,7-dimethoxy-4-(4-methoxyphenyl)-3,4-dihydro-2H-1-benzopyran-2-one have been determined.
- Brown, Roger. F. C.,Jackson, W. Roy,McCarthy, Tom D.,Fallon, Gary D.
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p. 1833 - 1843
(2007/10/02)
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- REACTION OF 4-SUBSTITUTED BENZALDEHYDES AND ACETOPHENONES WITH CHLOROACETONITRILE
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Under conditions of phase-transfer catalysis or in homogeneous solution of potassium tert-butoxide the title compounds give stereoisomeric mixtures of substituted 2,3-epoxy nitriles III and IV.Alkaline hydrolysis of epoxy nitriles IV afforded the corresponding 2-arylpropanals in low yields.On treatment with methanol and potassium carbonate, epoxy nitriles III and IV were converted into epoxy esters in good yields.
- Svoboda, Jiri,Kocfeldova, Zuzana,Palecek, Jaroslav
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p. 822 - 832
(2007/10/02)
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- Catalyst and method for isomerization
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A catalyst for isomerization consisting essentially of a salt or complex salt represented by the formula: where M is a metal of Group IB, IIA, IIB or VIII of the periodic table, L is a ligand, Y is a conjugated base of a Bronsted acid, m is 0, 1, 2, 3 or 4 and n is 1, 2 or 3.
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- Ring-Opening Reactions of cis- and trans-2,3-Bis(4-methoxybenzyl)oxirane: Competition between Assistance by and Migration of an Aryl Group
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The study of the aryl participation in the oxirane ring-opening reactions in acidic conditions was extended to (p-methoxybenzyl)oxiranes cis-2b and trans-3b analogous to the ones unsubstituted on the phenyl ring, 2a and 3a, previously studied.The introduction of the p-methoxy group causes in the trans epoxide 3 the appearance of the syn adduct in the methanolysis reactions and a large increase in the same adduct in the hydrolysis, acetolysis, and trichloroacetolysis reactions.For the cis epoxide 2, the presence of the para substituent causes the loss of complete anti stereoselectivity: in all the reactions but acetolysis, significant amounts of syn adduct are formed.Furthermore some reactions (see methanolysis) of the p-methoxy-substituted compounds 2b and 3b reveal the presence of significant amounts of rearranged 1,3-addition products of the type 31 and 29, respectively, contrary to the corresponding reactions of the epoxides 2a and 3a.Except for the trichloroacetolysis in CH2Cl2, all the reactions of the trans epoxide 3b show a higher syn stereoselectivity than do the corresponding reactions of the cis epoxide 2b.The results obtained for the reactions of p-methoxy-substituted epoxides 2b and 3b further confirm the mechanism previously proposed in order to rationalize the reactions of the unsubstituted epoxides 2a and 3a, which involves the neighboring participation of the phenyl.However the presence of rearranged 1,3-addition compounds among the reaction products led us to insert into the mechanistic scheme the necessary modifications which imply competition between assistance by and migration of the aryl group.
- Crotti, Paolo,Ferretti, Maria,Macchia, Franco,Stoppioni, Annalisa
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p. 2759 - 2766
(2007/10/02)
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- Reaction of 3-Phenylglycidic Esters. Part 1. Stereoselective Opening of the Oxirane Ring of trans-3-Phenylglycidic Esters with 2-nitrothiophenols and the Effects of Various Catalysts Thereon
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In the reaction of 2-nitrothiophenol (2) with trans-3-phenylglycidic esters carrying various substituents on the benzene ring, both reactivity and stereoselectivity of the oxirane ring-opening of the glycidates were markedly influenced by the electronic nature of the substituents.The presence of electron-donating groups was favourable for both reactivity and the preferential formation of cis-opening products, while the reverse was true for electron-withdrawing groups.As a result of our investigation on the catalytic effect of various Lewis acids in the reaction of the 4-methoxy derivative (1) with (2), tin compounds were found to be effective catalysts for cis-opening and readily produced the threo-nitro ester (3a), a key intermediate for the synthesis of diltiazem (5).Isolation of the crystalline complex (adduct A) from the reaction of (2) with SnCl4 and its efficient catalytic activity similar to that of SnCl4 suggest that the transition state involves co-ordination of tin derivatives both with (2) and the epoxy oxygen of (1) to cause highly specific cis-opening.
- Hashiyama, Tomiki,Inoue, Hirozumi,Konda, Mikihiko,Takeda, Mikio
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p. 1725 - 1732
(2007/10/02)
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- Synthesis of the Alkaloids, 3',4'-Dimethoxy-2-82-piperidyl)acetophenone, Julandine, and Cryptopleurine
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Condensation of (3,4-dimethoxybenzoyl)acetic acid (2) with enzyme-generated 3,4,5,6-tetrahydropyridine (3) gives 3',4'-dimethoxy-2-(2-piperidyl)acetophenone (4) which, by reaction with p-methoxyphenylacetaldehyde followed by titanium(IV) chloride- or silicon(IV) chloride-catalysed cyclisation of the resulting enamine (6), leads to julandine (7); thallium(III) trifluoroacetate oxidation of (7) gives cryptopleurine (8) and, as a very minor product, the isomer (9).
- Cragg, John E.,Herbert, Richard B.
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p. 2487 - 2490
(2007/10/02)
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