- Three-component, one-pot sequential synthesis of N-Aryl, N′-alkyl barbiturates
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(Chemical Equation Presented) Condensation between N-alkyl, N′-aryl carbodiimides and malonic acid monoesters leads to a high-yield formation of N-acyl urea derivatives that could be cyclized to C-monosubstituted barbiturates by addition of a suitable bas
- Volonterio, Alessandro,Zanda, Matteo
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Read Online
- Preparation of mono-substituted malonic acid half oxyesters (SMAHOs)
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The use of mono-substituted malonic acid half oxyesters (SMAHOs) has been hampered by the sporadic references describing their preparation. An evaluation of different approaches has been achieved, allowing to define the best strategies to introduce diversity on both the malonic position and the ester function. A classical alkylation step of a malonate by an alkyl halide followed by a monosaponification gave access to reagents bearing different substituents at the malonic position, including functionalized derivatives. On the other hand, the development of a monoesterification step of a substituted malonic acid derivative proved to be the best entry for diversity at the ester function, rather than the use of an intermediate Meldrum acid. Both these transformations are characterized by their simplicity and efficiency, allowing a straightforward access to SMAHOs from cheap starting materials.
- Condon, Sylvie,Le Gall, Erwan,Pichon, Christophe,Presset, Marc,Xavier, Tania
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supporting information
p. 2085 - 2094
(2021/09/02)
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- Hydrogen-Bonding Assisted Catalytic Kinetic Resolution of Acyclic β-Hydroxy Amides
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Enantioenriched acyclic α-substituted β-hydroxy amides are valuable compounds in chemical, material and medicinal sciences, but their enantioselective synthesis remains challenging. A catalytic kinetic resolution (KR) of such amides with selectivity factor(s) up to >200 is developed via enantioselective acylation of primary alcohol with N-heterocyclic carbene. An enhanced selectivity for the catalytic KR process is realized using cyclic tertiary amine as base additive. Diastereomeric transition state models for the process are proposed to rationalize the origin of enantioselectivity.
- Porey, Arka,Mondal, Bhaskar Deb,Guin, Joyram
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supporting information
p. 8786 - 8791
(2021/03/17)
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- Double decarboxylative route to 3-substituted pyrrolidines: Reaction of monoalkyl malonates and related carboxylic acids with sarcosine and formaldehyde
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Three-component reactions of monoalkyl malonates, cyanoacetic acids or 2-ketocarboxylic acids, N-methylglycine, and formaldehyde were developed to rapidly access 3-substituted pyrrolidines in 17–97% yield. These reactions represent a double decarboxylative domino-sequence promoted by pyrrolidine and involve N-methylazomethine ylide as the reactive intermediate.
- Buev, Evgeny M.,Smorodina, Anastasia A.,Moshkin, Vladimir S.,Sosnovskikh, Vyacheslav Y.
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supporting information
(2020/02/22)
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- Synthetic access to 3,4-disubstituted pyroglutamates from tetramate derivatives from serine, allo-threonine and cysteine
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A route allowing the conversion of substituted tetramates to 3,4-disubstituted pyroglutamates, making use of Suzuki coupling on an enol mesylate, followed by reduction, is both general and fully stereoselective.
- Bagum, Halima,Christensen, Kirsten E.,Genov, Miroslav,Pretsch, Alexander,Pretsch, Dagmar,Moloney, Mark G.
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- Synthetic method of tropicamide
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The invention relates to a production method of chemical medicines and particularly relates to a synthetic method of tropicamide. The synthetic method comprises the steps of carrying out hydrolysis and acylation on the raw material, namely diethyl phenylmalonate, condensing diethyl phenylmalonate with N-ethyl-4-methylpyridine amine, and generating reduction reaction with hydroboron, so as to obtain tropicamide. The synthetic method has the beneficial effects that the raw material cost is low, the properties of an intermediate product are stable, impurities are few, the operation steps such aspurification are reduced, and the process is simplified; reaction conditions are safe and mild, extremely toxic substances are not introduced, and the industrial amplified production is promoted; andby optimizing the raw material ratio, the total yield of the reaction is increased to be 65% and is greatly increased, and the production cost is lowered.
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Paragraph 0059; 0064; 0069; 0073; 0074; 0079
(2018/03/24)
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- Novel arylalkenylpropargylamines as neuroprotective, potent, and selective monoamine oxidase B inhibitors for the treatment of Parkinson's disease
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To develop novel neuroprotective agents, a library of novel arylalkenylpropargylamines was synthesized and tested for inhibitory activities against monoamine oxidases. From this, a number of highly potent and selective monoamine oxidase B inhibitors were identified. Selected compounds were also tested for neuroprotection in in vitro studies with PC-12 cells treated with 6-OHDA and rotenone, respectively. It was observed that some of the compounds tested yielded a marked increase in survival in PC-12 cells treated with the neurotoxins. This indicates that these propargylamines are able to confer protection against the effects of the toxins and may also be considered as novel disease-modifying anti-Parkinsonian agents, which are much needed for the therapy of Parkinson's disease.
- Huleatt, Paul B.,Khoo, Mui Ling,Chua, Yi Yuan,Tan, Tiong Wei,Liew, Rou Shen,Balogh, Balázs,Deme, Ruth,G?l?ncsér, Flóra,Magyar, Kalman,Sheela, David P.,Ho, Han Kiat,Sperlágh, Beáta,Mátyus, Péter,Chai, Christina L. L.
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supporting information
p. 1400 - 1419
(2015/03/04)
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- NEW ARYLALKENYLPROPARGYLAMINE DERIVATIVES EXHIBITING NEUROPROTECTIVE ACTION FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES
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The invention relates to novel arylalkenylpropargylamine derivatives of general formula (I) or enantiomers or diastereomers thereof or salts, optionally pharmaceutically acceptable salts, or solvates of any of these. The compounds can be used in treating or preventing a disease or condition in a mammal related to monoamine oxidase dysfunction, especially in neurodegenerative diseases, e.g. Parkinson's disease, Alzheimer's disease or Huntington's disease.
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Page/Page column 96
(2015/06/25)
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- Substrate specificity of an esterase from the archaeon Sulfolobus tokodaii bearing a GGG(A)X motif
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A GGG(A)X-type esterase (Est0071) from an archaeon catalyzes asymmetric hydrolysis of prochiral bulky malonic diesters in good enantioselectivity. The selectivity of Est0071 was for the opposite enantiomer to that previously shown for pig liver esterase, and the resulting enantiomeric excess of the products was higher. Est0071 could also catalyze the hydrolysis of various acetates of secondary alcohols, and showed moderate enantioselectivity in these reactions.
- Wada, Reina,Ozaki, Masanaru,Kumon, Takashi,Ohta, Hiromichi,Miyamoto, Kenji
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p. 188 - 190
(2015/11/09)
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- Neutral nazarov-type cyclization catalyzed by palladium(0)
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Joining the circle: The first Pd0 catalyzed Nazarov-type cyclization of diketoesters (see scheme) proceeds in 70 % to 95 % yield under strictly neutral pH conditions. Aryl substitution of the diketoesters is not required, so the reaction shows great versatility and can also proceed with aliphatic substrates. Copyright
- Shimada, Naoyuki,Stewart, Craig,Bow, William F.,Jolit, Anais,Wong, Kahoano,Zhou, Zhe,Tius, Marcus A.
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supporting information; scheme or table
p. 5727 - 5729
(2012/08/07)
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- MIXTURES OF MESOIONIC PESTICIDES
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Disclosed are compositions comprising (a) at least one compound selected from compounds of Formula (1), N-oxides, and salt thereof, wherein R1 is phenyl optionally substituted with up to 5 substituents independently selected from R3,
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Page/Page column 32
(2011/02/24)
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- Highly enantioselective synthesis of α,α-dialkylmalonates by phase-transfer catalytic desymmetrization
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A novel enantioselective synthetic method for the construction of a quaternary carbon center from malonates via phase-transfer catalytic (PTC) alkylation has been developed. The asymmetric α-alkylation of diphenylmethyl tert-butyl α-alkylmalonates with alkylating agents under phase-transfer catalysis conditions (aq 50% KOH, toluene, 0°C) in the presence of (S,S)-3,4,5-trifluorophenyl-NAS bromide (8) as PTC catalyst afforded the corresponding α,α-dialkylmalonates in high chemical (up to 99%) and optical yields (up to 97% ee) which could be readily converted to versatile chiral intermediates. Notably, the direct double α-alkylations of diphenylmethyl tert-butyl malonate also provided the corresponding α,α-dialkylmalonates without loss of enantioselectivity. The synthetic potential of this method has been demonstrated by the preparation of α,α-dialkylamino acid and oxindole systems.
- Hong, Suckchang,Lee, Jihye,Kim, Minsik,Park, Yohan,Park, Cheonhyoung,Kim, Mi-Hyun,Jew, Sang-Sup,Park, Hyeung-Geun
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supporting information; experimental part
p. 4924 - 4929
(2011/06/10)
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- DERIVATIVES OF 1-PHENYL-1,5-DIHYDRO-BENZO[B] [1.4]DIAZEPINE-2.4-DIONE AS INHIBITORS OF HIV REPLICATION
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Compounds of formula (I) wherein m, R1, R2, R3, X and Y are defined herein, are useful as inhibitors of HIV replication.
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Page/Page column 30
(2011/09/19)
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- Multicomponent, one-pot sequential synthesis of 1,3,5- and 1,3,5,5-substituted barbiturates
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(Chemical Equation Presented) Carbodiimides and malonic acid monoethylesters readily react to afford N-acylurea derivatives that could be cyclized in situ by addition of a suitable base. This process represents a general and straightforward one-pot sequential synthesis of 1,3,5-trisubstituted barbiturates in very mild conditions (organic solvent/2 N NaOH aqueous solution, 20°C). Performing the reaction in the presence of an electrophile resulted in the formation of fully substituted (namely, 1,3,5,5- tetrasubstituted) barbiturates through a three-component one-pot sequential process. The latter, however, occurred only with highly reactive electrophiles, such as benzyl and, in some instances, allyl halides. In order to expand the scope of the process, we sought to develop a general method for the C-alkylation of 1,3,5-trisubstituted barbiturates. We found that C-alkylation occurred upon treatment of 1,3,5-trisubstituted barbiturates with an alkyl halide in CH 3CN at 120°C in the presence of anhydrous K2CO 3 affording the target 1,3,5,5-tetrasubstituted barbiturates in good yields. The multicomponent process was accomplished by combining the three steps in a one-pot sequential fashion, i.e., the condensation of carbodiimides with malonic acid monoethylesters, the cyclization of the resulting N-acylureas, and the C-alkylation of the resulting 1,3,5-substituted barbiturates. A detailed study of the influence of the structure of the reactants on the reaction outcome and mechanism is presented. By selective N′-deprotection of 1,3,5,5-tetrasubstituted barbiturates, the corresponding 1,5,5-trisubstituted barbiturates were also prepared.
- Volonterio, Alessandro,Zanda, Matteo
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p. 7486 - 7497
(2008/12/22)
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- Highly efficient selective monohydrolysis of dialkyl malonates and their derivatives
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The highly efficient selective monohydrolysis of symmetric diesters has been applied to monohydrolysis of several dialkyl malonates and their derivatives. The best conditions apply 0.8-1.2 equiv of aqueous KOH with a co-solvent, THF or acetonitrile, at 0 °C. The procedure is highly practical, yielding the corresponding half-esters in high yields in a straightforward manner, without inducing decarboxylation. It was found that the selectivity tends to become higher with increased hydrophobicity.
- Niwayama, Satomi,Cho, Hanjoung,Lin, Chunlei
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p. 4434 - 4436
(2008/12/21)
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- SYNTHESIS OF HALF ESTERS
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A method for hydrolyzing an ester is provided. In accordance with the method, a compound A is provided which has first and second ester moieties. The compound is reacted in a liquid medium with a base having the formula MaXb,such that the first ester moiety is converted to a carboxyl moiety and the second ester moiety remains, wherein the ratio [Xk-]:[A] in the liquid medium is no greater than 1.6, and wherein k > 0.
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Page/Page column 17-21; 25
(2009/01/24)
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- Palladium-catalyzed asymmetric decarboxylative lactamization of γ-methylidene-δ-valerolactones with isocyanates: Conversion of racemic lactones to enantioenriched lactams
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A palladium-catalyzed asymmetric decarboxylative reaction of racemic γ-methylidene-δ-valerolactones with aryl isocyanates has been developed to give enantioenriched 3,3-disubstituted 2-piperidones. High enantioselectivity has been achieved by tuning the e
- Shintani, Ryo,Park, Soyoung,Shirozu, Fumitaka,Murakami, Masataka,Hayashi, Tamio
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supporting information; experimental part
p. 16174 - 16175
(2009/05/09)
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- Anticholinergic compounds, composititons and methods of treatment
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Compounds of the formula STR1 wherein the variables are defined in the specification. The compounds and their salts are soft anticholinergic/antisecretory agents especially useful as mydriatics and as antiperspirants.
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- Dealkoxycarbonylations of GEM diesters and β-ketoesters via an enzyme catalyzed hydrolysis
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A new method for the dealkoxycarbonylation of malonate esters and β-ketoesters, involving an enzyme catalyzed hydrolysis followed by a high temperature Kugelrohr distillation, is described.
- Ahmar,Bloch,Bortolussi
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p. 1071 - 1074
(2007/10/02)
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- Preparation, hydrolysis, and oral absorption of alpha-carboxy esters of carbenicillin.
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Twelve alpha-carboxy esters of carbenicillin, a parenteral broad spectrum semisynthetic penicillin, were synthesized and examined as potential oral carbenicillin derivatives. The rates at which the esters were hydrolyzed in vitro to carbenicillin by animal and human tissues were compared and the carbenicillin serum levels arising after oral administration of the esters were measured in squirrel monkeys and human volunteer subjects. The alpha-carboxyphenyl ester of carbenicillin [carfecillin (British Pharmacopoeia approved name), BRL 3475] WAS SELECTED FOR FURTHER STUDY AND IS PRESENTLY UNDERGOING CLInical trial.
- Clayton,Cole,Elson,Hardy,Mizen,Sutherland
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p. 172 - 177
(2007/10/06)
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