Showing papers in "Molecules in 1998"

4-Aryldihydropyrimidines via the Biginelli Condensation: Aza-Analogs of Nifedipine-Type Calcium Channel Modulators

Abstract: Recent results from the author's laboratory in the area of dihydropyrimidine chemistry are summarized.

Glutathione Peroxidase-like Activities of Oxygen-Containing Diselenides

Abstract: Various diselenides 1 – 8 have been examined with respect to their glutathione peroxidase-like activities (GPx-activities) as an index of their antioxidant properties. The glutathione oxidase activities of these compounds have also been reviewed reflecting the pro-oxidant properties (GOx-activities) and could be used as an index of cell toxicity. Based on a qualitative structure-activity relationship some trends are suggested.

A New Convenient Synthesis of 5-Acyl-1,2,3,4-tetrahydropyrimidine-2-thiones/ones

Abstract: Anatoly D. Shutalev*, Ekaterina A. Kishko, Natalie V. Sivova and Aleksei Yu. KuznetsovDepartment of Organic Chemistry, State Academy of Fine Chemical Technology, Vernadsky Ave. 86, Moscow 117571,Russian Federation, FAX +7-095-431-6332 (shutalev@orc.ru)Received: 28 January 1998 / Accepted: 18 February 1998 / Published: 9 March 1998Abstract: An efficient one-pot synthesis of 5-acyl-1,2,3,4-tetrahydropyrimidine-2-thiones/ones is described.The synthesis is based on the reaction of readily available α-tosyl substituted thioureas or ureas with enolatesof β-oxoesters or 1,3-dicarbonyl compounds followed by acid-catalyzed dehydration of the obtained 5-acyl-4-hydroxyhexahydropyrimidine-2-thiones/ones.Keywords: α -Tosyl substituted (thio)ureas, 5-acyl-1,2,3,4-tetrahydropyrimidine-2-thiones/ones.IntroductionIn recent years 5-acyl-1,2,3,4-tetrahydropyrimidine-2-thiones/ones (“Biginelli compounds”, i.e., 5a-h ) receivedsignificant attention owing to their diverse range ofbiological properties. For example, some of thesecompounds are very potent calcium channel blockers [1].The presence of several interacting functional groups inBiginelli compounds also determines their great syntheticpotential [2].At the present time there are a few general methods forthe synthesis of 5-acyl-1,2,3,4-tetrahydropyrimidine-2-thiones/ones. One of them is the Biginelli reaction [2,3].This very simple method involves acid-catalyzed three-component condensation of (thio)ureas, aldehydes and β-oxoesters or 1,3-dicarbonyl compounds. The maindisadvantage of this synthesis is quite often low yields ofthe desired pyrimidines because various side reactionsoccur. For instance, the reaction of urea and ethylacetoacetate with aliphatic aldehydes gives ethyl 4-alkyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylates in yieldsless than 30-40 % [4]. A very attractive approach to thesynthesis of Biginelli compounds has been developed byAtwal and co-workers [5]. This approach is based on thereaction of α-arylidene- β -oxoesters with S-(4-methoxybenzyl)isothiourea or O-methylisourea in thepresence of sodium bicarbonate followed bytransformation of the obtained 2-(4-methoxybenzylthio)-or 2-methoxy-1,4-dihydropyrimidine-5-carboxylates into2-thioxo- or 2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylates.Recently we have demonstrated [6,7] that Biginellicompounds can be easily prepared by reaction of α-azidoor α-tosyl substituted thioureas and ureas with sodiumenolates of β-oxoesters or 1,3-dicarbonyl compoundsfollowed by acid-catalyzed dehydration of the obtained 5-acyl-4-hydroxyhexahydropyrimidine-2-thiones/ones. Boththese stages of synthesis proceed under mild conditionsand usually in high yields. This method is very flexible andmakes it possible to prepare a large number of 1,2,3,4-tetrahydropyrimidine-2-thiones/ones bearing varioussubstituents in the pyrimidine ring.

A Straightforward Route to Enantiopure Pyrrolizidines and Indolizidines by Cycloaddition to Pyrroline N-Oxides Derived from the Chiral Pool

Abstract: Enantiomerically pure, five membered cyclic nitrones, easily obtained in large amounts from protected hydroxyacids and aminoacids such as D- and L-tartaric, L-malic, and L-aspartic acids, give cycloaddition reactions with a good diastereocontrol. The adducts of L-malic and L-aspartic acids derived from addition of nitrones to dimethyl maleate and g-crotonolactone were easily converted into enantiopure pyrrolizidinones, which can be transformed into polyhydroxypyrrolidines or polyhydroxypyrrolizidines, both interesting compounds as potential glycosidase inhibitors. The method is suitable for natural products synthesis as exemplified by a straightforward and convenient access to the pyrrolizidine alkaloid necine base (–)-hastanecine, as well as to indolizidine alkaloids, i.e. (+)- lentiginosine.

Enantiodivergent Synthesis of (R)- and (S)-Rolipram

Abstract: : Both enantiomers of rolipram ( 1 ) have been prepared in large quantity from a commonintermediate rac- 3-(3’-cyclopentyloxy-4’-methoxy)phenyl-4-nitro butyric acid ( 6 ), which was resolved byway of the two readily separable diastereoisomeric amides obtained with ( S )-(−)-phenylethylamine. Reductionof the nitro group and intramolecular transamidation gave ( R )-(−)- 1 and ( S )-(+)- 1 , respectively. CD spectraof both enantiomers of rolipram are reported and discussed. Both enantiomers of rolipram presented the samepotency of inhibitory activity against recombinant cyclic-AMP-selective phosphodiesterase (PDE4) subtypes. Keywords: Rolipram, phosphodiesterase, circular dichroism (CD) spectra, enantiodivergent synthesis. Introduction Rolipram ( 1 ) is a compound with varied biologicalactivity. In particular, attention has been drawn to theemetic [1], antiinflammatory [2], immunosupressant [3],antidepressive [4,5], putative antiparkinsonian [6], andneuroprotective [7] effects. The best characterisedbiochemical activity of

Application of Microwave in Organic Synthesis. Dry Synthesis of 2-Arylmethylene-3(2)-naphthofuranones

Abstract: Didier Villemin*, Benoit Martin and Nathalie BarEcole Nationale Superieure d'Ingenieurs de Caen (ISMRA) Universite de Caen,UMR 6507,6 Boulevard du Marechal Juin F-14050 Caen Cedex, FranceTel (33) 2 31 45 28 40, Fax (33) 2 31 45 28 77, E-mail: Didier.Villemin@ismra.frReceived: 19 February 1998 / Accepted: 3 March 1998 / Published: 5 March 1998Abstract: 3(2)-Naphthofuranone ( 1) was condensed in the presence of Al 2O3-KF with aromatic aldehydes(4) to give arylidenenaphthofuranones ( 5a-f ) without solvent under focused microwave irradiation.Keywords : Microwaves, organic synthesis, catalysis, dry reaction, furanone, aurone.IntroductionAurones (aurone, sulfuretol, maritimetol, leptosidol,etc.) are natural yellow pigments of plants related toflavonoids [1]. Aurones have a limited occurrence − thefirst aurone was discovered only in 1943 and, because ofthe limited methods of synthesis [1,3], aurones havereceived very limited attention. Analogy with flavonoidssuggests that aurones could have interesting biologicalproperties [2].We have already reported that five-membered ringcompounds with a carbonyl group, like tetronic acid [3a],pyrazolone [3b], thiohydanthoin [3c] or indanone [3d],exhibit a high carbon acidity due to the pseudo-planarstructure. These compounds consequently can becondensed easily with aldehydes in the presence of a solidcatalyst (alumina, clay, Al2O3-KF) without solvent (drycondensation).We report herein the extension of this reaction to thesynthesis of 2-arylmethylene-3(2)-naphthofuranones.Naphthofuranone (1), the homologue of 2-coumaranone(2), can be derived from 2-naphthoxyacetic acid (3), anuseful auxin hormone [4]. We are also interested instudying the biological properties of such 3(2)-naphthofuranones described in older literature [5] butpoorly studied to date.

Efficient Polymer-Supported Sharpless Alkene Epoxidation Catalyst

Abstract: Homogeneous linear poly(tartrate ester) ligands provide high chemical yields and enantiomeric excesses in the epoxidation of trans-hex-2-en-1-ol using Ti(OPri)4-tert-butyl hydroperoxide. Branched poly(tartrate ester) can be use as heterogeneous ligands in the epoxidation of trans-hex-2-en-1-ol using Ti(OPri)4-tert-butyl hydroperoxide. Removal and recovery of the polymer catalyst is a simple filtration at the end of reactions.

Synthesis of Novel Fused Heterocycles Based on Pyrano[2,3-c]pyrazole

Abstract: 3-Substituted 1,2,4-triazole derivatives (5, 9, 13, 16b, 19), pyrimidinium salts (21), triazines (24), and aryl methylene hydrazono pyrazolopyrano-pyrimidine (27a,b) which are rearranged in basic medium to 30a,b, were afforded via the reaction of 6-amino 1,4,5,6-tetrahydro-5-imino-3-methyl-1-phenyl-4 (pchlorophenyl) pyrazolo [4', 3' : 5,6]-pyrano [2,3-d] pyrimidine (3) with different reagents.

2-a, 3-b-Dihydroxyolean-12-en-28-oic Acid (Maslinic Acid)

Abstract: An industrial procedure has been established for the isolation of 2-alpha,3-beta-dihydroxyolean- 12-en- 28-oic acid (maslinic acid) starting from olive fruits (Olea europaea).[...]

Synthesis and Reactions of New 4-Oxo-4H-benzopyran-3-carboxaldehydes Containing Hydroxy Groups or 2-Oxopyran Cycles

Abstract: The synthesis of eight hydroxy- and 2-oxopyranochromone-3-carboxaldehydes 3, 5 and their reactions with 2-hydroxyaniline, 2,4-dinitrophenylhydrazine and 2-benzothiazolylhydrazine were investigated. Products were confirmed by IR, NMR spectral and elemental analysis data. The semi-empirical AM1 quantum-chemical method has been used to study optimal geometries and heats of formation of synthesized 3-formylchromones.

Synthesis of 2-(6-Acetamidobenzothiazolethio)acetic Acid Esters as Photosynthesis Inhibitors

Abstract: The synthesis and photosynthesis-inhibiting activity of 13 new 2-(6-acetamidobenzothiazolethio)acetic acid esters are reported. The new compounds were prepared by acetylation of 2-(alkoxycarbonylmethylthio)-6-aminobenzothiazoles with acetic anhydride. The structure of the compounds was verified by 1H NMR spectra. The compounds inhibit photosynthetic electron transfer in spinach chloroplasts. The structure - activity relation was studied. Lipophilicity was found to influence substantially photosynthetic electron transfer.

Syntheses of 1,5-Benzothiazepines. Part 20. Syntheses of 8-Substituted-2,5-dihydro-2-(4-N-dimethylaminophenyl)-4-(4-methoxyphenyl)-1,5-benzothiazepines

Abstract: Seema Pant, Babita Singhal, Mani Upreti and Umesh C. Pant*Department of Chemistry, University of Rajasthan, Jaipur-302004 IndiaTel. 0091 141 651969Received: 13 January / Accepted: 6 March 1998 / Published: 15 May 1998Abstract : 8-Substituted-2,5-dihydro-2-(4-N-dimethylaminophenyl)-4-(4-methoxyphenyl)-1,5-benzothiaze-pines (5a-e) have been synthesized by reacting 5-substituted-2-aminobenzene-thiols (1a-e) with 4-N-dimethylaminobenzal-4-methoxy acetophenone ( 2) in dry ethanol saturated with hydrogen chloride gas. Theproducts were tested for purity by tlc and characterized by elemental analysis for carbon, hydrogen andnitrogen and IR,

An Improved Synthesis of Homocitrate

Abstract: Monoethyl malonate (1) and tert-butyl alcohol are esterified by catalysis with dicyclohexylcarbodiimide and 4-dimethylaminopyridine to yield ethyl t-butyl malonate (2). The ethoxymagnesio derivative (3) of the ester is condensed with b-carbomethoxypropionyl chloride to give the triester (4), which is decomposed by heating under vacuum in the presence of b-naphthalensulfonic acid to give ethyl methyl β-ketoadipate (5). Compound 5 is reacted with hydrogen cyanide,followed by hydrolysis of the cyanohydrin to give the free acid (6). Compound 6 is converted to homocitrate (7) by the use of an improved procedure.

Evaluation of Effect of Microwave Irradiation on Syntheses and Reactions of Some New 3-Acyl-methylchromones

Abstract: The 3-Acyl-2-R-methylchromones (R = H, ArO, C6H4(CO)2N) were prepared in good yields by different methods from 2-hydroxyaroylacetone derivatives. Some subsequent reactions of these compounds with hydroxylamine and 3-formylchromones are described. The effect of microwave irradation on some condensation reactions was studied.

Elemental and Molecular Heritage: An Internet-based Display

Abstract: The background to a Web page describing elemental and molecular heritage at Imperial College chemistry department is described. Photographs are shown of the original samples of elemental bromine and crystalline silicon, and molecular ferrocene and mauveine. 3D "Hyperactive" models of these systems are shown, together with a recently discovered heterocyclic systems scorpionine, which like mauveine is made by a deceptively simple chemical synthesis.

3-b-Hydroxyolean-12-en-28-oic Acid (Oleanolic Acid)

Abstract: An industrial procedure has been established for the isolation of 3-beta-hydroxyolean-12-en-28-oic acid (oleanolic acid) starting from olive fruits (Olea europaea).[...]

A New Isoflavone from Smilax glabra

Abstract: A new isoflavone, 7,6’-dihydroxy-3’-methoxyisoflavone, has been isolated from the roots of Smilax glabra. The structure was determined by 2D-NMR techniques.

Synthesis of (2R,5R)-2-Amino-5-Hydroxyhexanoic Acid by Intramolecular Cycloaddition*

Abstract: The title compound was synthesized from sorbic acid by an eight step sequence. The key step was the stereospecific intramolecular Diels-Alder reaction of the acylnitroso derivative of N-sorbyl-L-proline (5). L-Proline served as a temporary tether which directed both the stereochemistry and the regiochemistry of the cycloaddition.

Nucleophilic Additions of 2-Furyllithium to Carbonyl Derivatives of L-Serine. Formal Synthesis of (2R,3R)-β-Hydroxy Aspartic Acid

Abstract: The nucleophilic addition of 2-furyllithium to esters derived from L-serine is described. The obtained furyl ketone 5 is stereoselectively reduced (ds≥95%) with sodium borohydride to afford the corresponding syn aminoalcohol 12 in enantiomerically pure form. Compound 12 was further converted into valuable α-hydroxy-β-amino acids by means of the furan-to-acid equivalence.

(+)-8-Hydroxy-labdan-17-oic Acid

Abstract: Hanson [1,2] reported a compound with [a]D = -7° and identical IR and NMR spectral data to our compound.[...]

An Expedient Synthesis of the Sugarcane Borer Pheromone Components

Abstract: A practical synthesis of the title compounds has been developed. The salient features of the synthesis were i) use of easily accessible starting materials viz. aleuritic acid, 10-undecenoic acid, cyclohexanone etc. and ii) fixation of the required olefinic geometry via Wittig and acetylenic routes.

Synthesis and Biological Evaluation of 14 -Methoxy Digitalis Derivatives

Abstract: M. Gobbini,** N. Almirante, A. Cerri, G. Padoani and P. MelloniPrassis Istituto di Ricerche Sigma-Tau, Via Forlanini, 3, 20019 Settimo Milanese (MI), Italy. Tel +39 2 33500388, Fax +392 33500408, Email: MC3405@mclink.itReceived: 11 November 1997 / Accepted: 15 January 1998 / Published: 25 January 1998Abstract: The synthesis and biological evaluation of 14 β-methoxy derivatives of digitoxigenin and of otherdigitalis-like compounds are reported. These compounds have a 14β-oxygen, which can be a hydrogenbonding acceptor, as is the case of 14 β,15 β -epoxide derivatives, but not a hydrogen bonding donor as is thecase of 14 β-hydroxy derivatives. All the new 14 β-methoxy derivatives show a considerable reduced bindingaffinity on Na

An Asymmetric Synthetic Approach to the A-ring of the Taxol Family of Anti-Cancer Compounds*

Abstract: A synthetic route developed for the preparation of the A-ring of Taxol family of molecules is reported. By means of an intramolecular Diels-Alder reaction an asymmetric approach to this ring has been accomplished. Also, initial studies to prepare the A ring using an intramolecular Diels-Alder reaction have been successful.

1-Methyl-3-nitro-5-methoxycarbonyl Pyrazole

Abstract: The nitroester 2 was prepared by the addition of meta-chloro-perbenzoic acid (m-CPBA) to 1 [1] according to the reported procedure [2,3][]

Cycloartan-2b-2-methyl ButanoateIsolated from Genus Espeletia (Asteraceae)

Abstract: We describe the isolation and characterization of a new cycloartane-type triterpenes, cycloartan- 2b-2-methyl butanoate.[...]

(6-Methoxy-2-naphthyl)-6-aminobenzodioxane

Abstract: The general part of the experimental section [1] on organometallic substitution on arylamines has been described elsewhere.[...]

2(S,R),3(R,S)-2,3-Dibromo-3-methyl-5-phenyl-2-pentanoic Acid

Abstract: The general part of the experimental section [1] has been presented elsewhere. To a stirred solution of (E)-3-methyl-5-phenyl-2-pentenoic acid (2.26 g, 12 mmol) in dry chloroform (50 ml) was added a solution of bromine (0.75 ml, 15 mmol) in dry chloroform (5 ml) dropwise. The mixture was stirred at room temperature for 16 hours and evaporated under reduced pressure to yield 2(S,R),3(R,S)-2,3-dibromo3-methyl-5-phenyl-2-pentenoic acid (4.18 g, 100%) as yellow plates from chloroform/light petroleum.

A Short and Efficient Synthesis of (R)-Phoracantholide I

Abstract: A short and efficient chemoenzymatic synthesis of the title compound has been developed. The salient features of the synthesis were i) preparation of the required chiron via a porcine pancreatic lipase (PPL) catalyzed esterification of a ω-functionalized 2-alkanol and ii) use of easily accessible and inexpensive materials/ reagents.

Tributyl-[(Z)-5-phenyl-2-penten-2-yl]stannane

Abstract: The general part of the experimental section [1] has been presented elsewhere. The Grignard solution prepared from magnesium turnings (0.11 g, 4.4 mmol) and (Z)-2-bromo-5-phenyl-2-pentene (0.90 g, 4 mmol) in dry tetrahydrofuran (15 ml) was decanted via double-ended needle from the excess magnesium, and titrated with tributyltin chloride until the solution decolourised. The resulting solution was stirred at room temperature for 1 hour and the solvent was removed under reduced pressure. The residue was partitioned between ether (30 ml) and water (30 ml). The ether extract was washed with brine (50 ml), dried (Na2SO4), filtered and evaporated under reduced pressure. The crude product was Kugelrohr distilled to yield tributyl-[(Z)-5-phenyl-2-penten-2-yl]stannane (1.13 g, 59%) as a colourless oil.

Synthesis and Intramolecular [4+2] Cycloaddition Reactions of 4-Pyridazinecarbonitriles with Alkyne Side Chains

Abstract: The preparation of a series of new 3-(alkynyl-X)-substituted 4-pyridazinecarbonitriles 2-5 (X = O, NH) is described. The compounds are shown to undergo thermally induced intramolecular Diels-Alder reactions with inverse electron demand, affording the fused benzonitriles 6-8. Incorporation of a 1,2-phenylene unit into the side chain, as in the case of compounds 10 and 13, results in a more favorable conformation of the dienophilic substructure and thus to a pronounced acceleration of the [4+2] cycloaddition reaction.