Synthesis of enantiomerically pure 4-aryl-3,4-dihydropyrimidin-2(1 H )-ones via enzymatic resolution: preparation of the antihypertensive agent ( R )-SQ 32926 †Synthesis and reactions of Biginelli compounds, part 20; for part 19, see: Kappe, C. O.; Shishkin, O. V.; Uray, G.; Verdino, P. Tetrahedron 2000, 56, 1859–1862. †

Schnell, Barbara; Strauss, Ulrike; Verdino, Petra; Faber, Kurt; Kappe, C. Oliver

doi:10.1016/s0957-4166(00)00081-1

Cited by 56 publications

(25 citation statements)

References 17 publications

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“…Chemical resolution and enzymatic strategies are traditional methods to prepare optically pure DHPMs [14,15]. Nevertheless, the catalytic asymmetric Biginelli reaction has rarely been reported.…”

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confidence: 99%

Theoretical investigation on enantioselective Biginelli reaction catalyzed by natural tartaric acid

Lu¹,

Chen²,

Zhang³

et al. 2011

Int J of Quantum Chemistry

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In this study, enantioselective Biginelli reaction of aldehyde, b-ketoester, and urea catalyzed by natural (2R, 3R)-tartaric acid has been investigated using density functional theory calculations. The results indicate that the most favorable pathway involves a protonated imine from aldehyde and urea in the first step. Tartaric acid forms H-bonds network with substrates enhancing the electrophilicity of protonated imine and the nucleophilicity of b-ketoester. (R)-3,4-Dihydropyrimidin-2-(1H)-ones is preferable for the reaction. The solvent effect is discussed in the prediction of enantiomeric excess (ee) values in ethanol and water.

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confidence: 99%

Theoretical investigation on enantioselective Biginelli reaction catalyzed by natural tartaric acid

Lu¹,

Chen²,

Zhang³

et al. 2011

Int J of Quantum Chemistry

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“…In the absence of any known general asymmetric synthesis for this heterocyclic target system, resolution strategies have so far been the method of choice to rapidly obtain enantiomerically pure DHPMs. These methods include fractional crystallization techniques involving diastereomeric a-methylbenzylammonium salts [60] or covalently linked derivatives [12,56,61], or rely on biocatalytic resolution [62]. Analytically, separation of DHPM derivatives can be readily achieved by enantioselective HPLC using a variety of different chiral stationary phases (CSPs) [63], including ™designer-made∫ CSPs that are based on the principle of ™reciprocal∫ recognition of chirality using the immobilized DHPM derivative 38 (Scheme 11) [24].…”

Section: Chirality and Biological Activitymentioning

confidence: 99%

The Generation of Dihydropyrimidine Libraries Utilizing Biginelli Multicomponent Chemistry

Kappe

2003

QSAR Comb. Sci.

156

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With the emergence of high-throughput screening in the pharmaceutical industry over a decade ago, synthetic chemists were faced with the challenge of preparing large collections of molecules to satisfy the demand for new screening compounds. The unique exploratory power of multicomponent reactions such as the Ugi four-component reaction was soon recognized to be extremely valuable to produce compound libraries in a time-and cost effective manner. The present review article summarizes strategies for the construction of libraries through another multicomponent reaction, the Biginelli dihydropyrimidine synthesis. In this three-component condensation dating back to 1893, CH-acidic carbonyl compounds, aldehydes and urea-type building blocks combine to assemble a multifunctionalized dihydropyrimidine scaffold. Due to the interesting pharmacological properties associated with the privileged DHPM structures, the Biginelli reaction and related procedures have received increasing attention in recent years. This review details synthetic advances for the construction of Biginelli libraries via solution phase and solid-phase strategies that are amenable to a highthroughput or combinatorial format.

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“…benzene: ethyl acetate (9:1), benzene: ethyl acetate: Methanol (8.5:1.4:0.1). IR spectra were recorded in KBr on a Perkin Elmer Infrared RXI FTIR spectrophotometer and 1 H NMR spectra were recorded on Bruker Avance II 400 NMR Spectrometer using DMSO-d 6 and CDCl 3 as solvent and tetramethylsilane (TMS) as internal reference standard. All the compounds (4a-m) were synthesized by both the methods and it was observed that yield of the compound obtained by Method B is high as compared to that obtained by Method A (Table 1 c h l o r o p h e n y l ) -1 , 2 , 3 , 4 1 , 2 , 3 E t h y l -6 -m e t h y l -2 -o x o -4 -( 3 , 4 -d i m e t h o x y p h e n y l ) -1 , 2 , 3 , 4 -tetrahydropyrimidin-5-carboxylate (4i) -6 -m e t h y l -2 -o x o -4 -( 2 -h y d r o x y p h e n y l ) -1 , 2 , 3 , 4 c h l o r o p h e n y l ) -1 , 2 , 3 …”

Section: Methodsmentioning

confidence: 99%

“…The 3,4-dihydropyrimidin-2-(1H)-ones (DHPM's) have recently emerged as important target molecules due to their therapeutic and pharmacological properties 2 such as antiviral 3 , antimitotic 4 , anticarcinogenic 5 , antihypertensive 6 and noteworthy, as calcium channel modulators. 7 Owing to the immense therapeutic and medicinal significance of DHPM's, exploring convenient and efficient methods for their synthesis with readily available reagents is of prime importance.…”

Section: Introductionmentioning

confidence: 99%

Comparative Studies of Lewis Acidity of Alkyl-Tin Chlorides in Multicomponent Biginelli Condensation Using Grindstone Chemistry Technique

Sachdeva

Saroj

Khaturia

et al. 2012

J. Chil. Chem. Soc.

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A simple and efficient procedure for the one pot Biginelli Condensation Reaction of aldehydes, β-ketoester and urea employing SnCl 4 .5H 2 O /mono/di/tributyl-tin chloride as a novel catalyst is described. Compared to classical Biginelli reaction conditions, the present method has the advantages of good yields, short reaction times and experimental simplicity. Further, comparative efficiency of alkyl-tin chlorides in multicomponent Biginelli Condensation Reaction is also studied under solvent free conditions.

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Cited by 56 publications

References 17 publications

Theoretical investigation on enantioselective Biginelli reaction catalyzed by natural tartaric acid

Theoretical investigation on enantioselective Biginelli reaction catalyzed by natural tartaric acid

The Generation of Dihydropyrimidine Libraries Utilizing Biginelli Multicomponent Chemistry

Comparative Studies of Lewis Acidity of Alkyl-Tin Chlorides in Multicomponent Biginelli Condensation Using Grindstone Chemistry Technique

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