Saturated heterocycles. 242. Synthesis of 2-substituted-6-(6′,7′-dimethoxy-3′,4′-dihydro-1′-isoquinolyl)-5,6,7,8-tetrahydro- quinazolin-4(3H)-one Derivatives

In the reactions of the recently synthesized β-ketoesters 1-[(3′-methoxycarbonyl- and 1-[(3′-ethoxycarbonyl-4′-oxo)-1′-cyclohexyl]-3,4-dihydroisoquinoline 4, 5 with amidines or cyclic guanidines, a number of 2-substituted-6-(6′,7′-dimethoxy-3′,4′-dihydro-1′-isoquinolyl)-5,6,7,8-tetrahydroquinazolin-4(3H)-one derivatives 6–8 were prepared. The new compounds possess various pharmacological actions.     

Synthesis of some new spiroindoline derivatives incorporated with pyrazoloheterocycles

Indole-2,3-dione ( 1 ) was treated with malonic acid ( 2 ) in a mixture of ethanol/pyridine to afford 1-[3-(2-oxoindolinylidene)]acetic acid ( 3 ). Compound 3 reacted with thionyl chloride to give the corresponding acid chloride ( 4 ). The acid chloride 4 reacted with arenes in the presence of AlCl₃ to yield 3-(2-oxoindolinylidene)acetophenones 5a–c . Compounds 5a–c reacted with 3-methylpyrazolin-5-one derivatives 6a , b to give 3-aracyl-3-[4′-(3′-methylpyrazolin-5-onyl)]-indoline-2-one derivatives 7a–f . Compounds 7a–f were treated with phosphorus pentoxide in phosphoric acid, with ammonium acetate or methanolic methylamine and with phosphorus pentasulfide to give spiro[indoline-3,4′-(pyrazolo[4,5-b]pyran)]-2-ones 8a–f , spiro[indoline-3,4′-(pyrazolo[4,5-b]-dihydropyridine)]-2-ones 9a–f , 10a–f and spiro[indoline-3,4′-(pyrazolo[4,5-b]thiopyran)]-2-ones 10a–f , respectively. All of the synthesized spiroheterocycle derivatives were identified by conventional spectroscopic methods (IR, ¹H NMR) and elemental analyses. © John Wiley & Sons, Inc.     

Studies on the constituents of Broussonetia species X. Six new alkaloids from Broussonetia kazinoki Sieb.

Six new alkaloids, broussonetines W, X, M1, U1, J3, and J2 (1-6) were isolated from the branches of Broussonetia kazinoki SIEB. (Moraceae) as minor constituents. They were formulated as (2R,3R,4R,5R)-2-hydroxy-methyl-3,4-dihydroxy-5-17-(cyclohexy-2-on-1(6)-enyl)heptyllpyrrolidine (1), (2R,3S,4R,5R)-2-hydroxymethyl-3,4-dihydroxy-5-17-(cyclohexy-2-on-1(6)-enyl)heptyl]pyrrolidine-4-O-beta-D-glucopyranoside (2), (2R,3R,4R,5R)-2-hydroxymethyl-3,4-dihydroxy-5-[(9R)-9,13-dihydroxytridecyl]- pyrrolidine (3), (2S,3S,4S)-2-hydroxymethyl-3,4-dihydroxy-5-(10-oxo-13-hydroxytridecyl)-5- pyrroline (4), (2R)-2-[(IS,2S)-1,2-dihydroxy-8-1(2R,3R,4R,5R)-5-(2-hydroxymethyl-3,4-dihydroxy-1-acetylpyrrolidinyl)loctyl]piperidine (5), (2R)-2-[(1S,2S)-1,2-dihydroxy-8-[(2R,3R, 4R,5R)-5-(2-hydroxymethy]-3,4-dihydroxypyrrolidinyl)]octyl]piperidine (6).     

Preparation of new nitrogen-bridged heterocycles. 53. Syntheses of 3-(benzylthio)thieno[3,4-b]indolizine derivatives and their intramolecular arene-arene interactions

Various ethyl 1-arylcarbonyl-3-[(un)substituted methylthio]thieno[3,4-b]indolizine-9-carboxylates were synthesized in good yields by a novel methodology in which the S-alkylation of 5-arylcarbonyl-4-ethoxycarbonylmethyl-3-(1-pyridinio)thiophene-2-thiolates with alkyl or benzyl halides, the 1,5-dipolar cyclization of the resulting pyridinium salts in the presence of a base, and the aromatization were performed. In the X-ray analyses of some 3-(benzylthio)thieno[3,4-b]indolizine-9-carboxylates, a gauche and two anti conformers in relation to the exocyclic sulfide linkage were found. Interestingly, all of the 3-(benzylthio)thieno[3,4-b]indolizine derivatives showed significant high-field shifts (delta up to 0.3 ppm) for the 5- and 6-proton signals compared with those of the 3-methylthio derivatives in the (1)H-NMR spectra and exhibited a definite absorption band near 425 nm in their UV spectra, indicating an intramolecular arene-arene interaction between the thieno[3,4-b]indolizine and the phenyl ring.     

Studies on the constituents of Broussonetia species VIII. Four new pyrrolidine alkaloids, broussonetines R, S, T, and V and a new pyrroline alkaloid, broussonetine U, from Broussonetia kazinoki Sieb

Four new pyrrolidine alkaloids, broussonetines R, S, T, and V and a new pyrroline alkaloid, broussonetine U were isolated from the branches of Broussonetia kazinoki SIEB. (Moraceae) in low yield. Broussonetines R, S and T were formulated as (2R,3R,4R,5R)-2-hydroxymethyl-3,4-dihydroxy-5-[(1R)-1-hydroxy-3-[6-(4-hydroxybutyl)-cyclohexy-2-on-1(6)-enyllpropyl] pyrrolidine (1), (2R,3R,4R,5R)-2-hydroxymethyl-3,4-dihydroxy-5-[(1R,10S)-1,10,13-trihydroxytridecyl] pyrrolidine (2), (2R,3R,4R,5R)-2-hydroxymethyl-3,4-dihydroxy-5-[(1R,5S)-1,5, 13-trihydroxy-10-oxo-tridecyl] pyrrolidine (3). And broussonetines U and V were proposed to be (2S,3S,4S)-2-hydroxymethyl-3, 4-dihydroxy-5-(9-oxo-13-hydroxytridecyl)-5-pyrroline (4), (2R,3S,4R,5R)-2-hydroxymethyl-3,4-dihydroxy-5-[(E)-9-oxo-13-hydroxy-3-tridecenyl] pyrrolidine (5), respectively, by spectroscopic and chemical methods.     

Studies on the constituents of Broussonetia species. VII. Four new pyrrolidine alkaloids, broussonetines M, O, P, and Q, as inhibitors of glycosidase, from Broussonetia kazinoki SIEB

Four new pyrrolidine alkaloids, broussonetines M, O, P, and Q, were isolated from the branches of Broussonetia kazinoki SIEB, (Moraceae). Broussonetines M, O, P, and Q were formulated as (2R,3R,4R,5R)-2-hydroxymethyl-3,4-dihydroxy-5-[(10S)-10,13-dihydroxy-tri decyl]pyrrolidine (1), (2R,3R,4R,5R)-2-hydroxymethyl-3,4-dihydroxy-5-[(E)9-oxo-13-hydroxy-3- tridecenyl]pyrrolidine (2), (2R,3R,4R,5R)-2-hydroxymethyl-3,4-dihydroxy-5-[(E)10-oxo-13-hydroxy-3-++ +tridecenyl]pyrrolidine (3), and (2R,3S,4R,5R)-2-hydroxymethyl-3-hydroxy-4-(beta-D-glucopyranosyloxy++ +)-5-[10-oxo-13-(beta-D-glucopyranosyloxy)tridecyl]pyrrolidine (4) respectively, by spectroscopic and chemical methods. 1-4 inhibited beta-glucosidase, beta-galactosidase and beta-mannosidase.     

Photochemistry of host-guest complexes. VIII. The photoreaction of pyrazinedicarbonitrile derivatives having a crown ether moiety in the presence of an ω-diethylamino-1-alkanaminium salt

Irradiation of 5-[(benzo-18-crown-6)-4′-yl]pyrazine-2,3-dicarbonitrile and 5-(3,4-dimethoxyphenyl)pyrazine-2,3-dicarbonitrile in the presence of ω-diethylamino-l-alkanaminium ion caused the reductive decyanation to give pyrazinemonocarbonitrile derivatives. The reaction is initiated by a single electron transfer from the tertiary amino group of the diamine. The complex formation between the crown ether moiety and the ω- diethylamino-l-alkanaminium ion enhances the photoreaction.     

Synthesis of chiral hydroxyl phospholanes from D-mannitol and their use in asymmetric catalytic reactions

Chiral hydroxyl monophosphane 3 [(2S,3S,4S,5S)-3,4-dihydroxy-2, 5-dimethyl-1-phenylphospholane] and bisphospholanes 5a [1,2-bis[(2S, 3S,4S,5S)-3,4-dihydroxy-2,5-dimethylphospholanyl]benzene] and 5b [1, 2-bis[(2S,3S,4S,5S)-2,5-diethyl-3,4-dihydroxyphospholanyl]benzene] were synthesized from readily available D-mannitol in high yields. Strategies for protection and deprotection of OH-groups in the presence of phosphines have been explored. Rate acceleration in the Baylis-Hillman reaction was observed when a hydroxyl phosphine was used as the catalyst. Rhodium complexes with chiral bisphospholanes are highly enantioselective catalysts for the asymmetric hydrogenation of various kinds of functionalized olefins such as dehydroamino acid derivatives, itaconic acid derivatives, and enamides. An interesting feature of the hydroxyl phospholane system is that hydrogenation of some substrates can be carried out in water with >99% ee and 100% conversion (e.g., itaconic acid).     

Synthesis and properties of ethyl 1-aryl-5-methyl-4-[1-(phenylhydrazinylidene)ethyl]-1<Emphasis Type="Italic">H</Emphasis>-pyrazole-3-carboxylates

Ethyl 1-aryl-4-acetyl-5-methyl-1H-pyrazole-3-carboxylates reacted with phenylhydrazine to give the corresponding hydrazones, ethyl 1-aryl-5-methyl-4-[1-(phenylhydrazinylidene)ethyl]-1H-pyrazole-3-carboxylates, which were converted to ethyl 1′-aryl-4-formyl-5′-methyl-1-phenyl-1H,1′H-3,4′-bipyrazole-3′-carboxylates by treatment with the Vilsmeier–Haack reagent. No indole derivatives were formed from the same hydrazones under the Fischer reaction conditions, but cyclization to 2-aryl-3,4-dimethyl-6-phenyl-2,6-dihydro-7H-pyrazolo[3,4-d]pyridazin-7-ones was observed.     

1,1-Disubstituted-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indolecarboxylic acid esters and ketones. The base catalyzed transformation of 1-(2′,3′,4′,9′-tetrahydrospiro[cyclohexane-1,1′-[1H]pyrido[3,4-b]indol]-2-yl)alkanones into 2-(4,9-dihydro-3H-pyrido[3,4-b]indol-1-yl)-1 -alkylcyclohexanols

Condensation of 1H-indole-3-ethanamines 1 with cyclic β-keto esters 2 under azeotropic conditions followed by acid-catalyzed ring closure of the resulting enamines 3 gave 2′,3′,4′,9′-tetrahydrospiro[piperidine-3,1′,-[1H]pyrido[3,4-b]indole] -4-carboxylic acid alkyl esters 4 . Condensation of 1 with 2-acylcycloalkanones 8 gave two types of enamines, 10 and 11 , respectively. Enamines 10 on treatment with acid gave 1-(2′,3′,4′,9′-tetrahydro-3H-pyrido[3,4-b]indol-1-yl)-1-alkylcyclohexanols 17 . Compounds 17 were further dehydrated to give cycloalkane derivatives 19.     

Reactions of 4-Methoxy-3-quinolinyl and 1,4-Dihydro-4-oxo-3-quino-linyl Sulfides Aiming at the Synthesis of 4-Chloro-3-Quinolinyl Sulfides

The preparation of 1,4-dihydro-4-oxo-3′-alkylthio-3,4′-diquinolinyl sulfides 3 or 1,4-dihydro-4-oxo-3-(alkylthio)quinolines 4 by acid catalysed hydrolysis of 4-methoxy-3′-alkylthio-3,4′-diquinolinyl sulfides 1 or 4-methoxy-3-(alkylthio)-quinolines 2 is described. The reactions of 4-methoxy-3′-alkylthio-3,4′-diquinolinyl sulfides 1 or 1,4-dihydro-4-oxo-3′-alkylthio-3,4′-diquinolinyl sulfides 3 with phosphoryl chloride in DMF afforded 4-chloro-3′-alkylthio-3,4′-diquinolinyl sulfides 5 . Treatment of the title compounds 1 or 3 with boiling phosphoryl chloride systems:leads to 4-chloro-3-(alkylthio)quinolines 6 and thioquinanthrene but those of alkoxy- or oxo-quinolines 2 or 4 lead to 4-chloro-3-(alkylthio)quinolines 6 . The reactions of N-methyl-4(1H)-quinolinones 3n and 4n with phosphoryl chloride directed to 4-chloro-3-(alkylthio)quinolines 6 were studied as well.     

A Versatile Synthesis,PM3‐Semiempirical,Antibacterial, and Antitumor Evaluation of Some Bioactive Pyrazoles

This research work describes the synthesis and biological properties of some novel isolated or fused heterocyclic ring systems with pyrazole, for example; enaminones containing pyrazolone ring photochromic functional unit, 4‐[(4‐chlorophenylamino)methylene]‐3‐methyl‐1‐phenyl‐1H‐pyrazol‐5(4H)‐one (3) and some analogous derivatives 4, 9, and 10, also as pyrazolo[3,4‐b]pyridine, pyrazolo[3,4‐b]quinoline, pyrazolo[3′,4′:4,5]thieno[2,3‐c]pyrazoline and pyrazolo[3,4‐c]pyrazole were synthesized and characterized. Newly synthesized compounds were characterized by IR, ¹H NMR, ¹³C NMR, mass spectral data and quantum mechanical calculations. Selected products were tested for their antibacterial and antitumor agents.     

Novel tetracyclic spiropiperidines. II. Synthesis of 2-aryl-2,3-dihydrospiro[benzofuran-3,4′-piperidines]

A series of 2-aryl-2,3-dihydropsiro[benzofuran-3,4′-piperidines] has been synthesized as potential psychotropic agents via an efficient intramolecular fluorine displacement reaction. Treatment of a key intermediate, 4-cyano-4-(2-fluorophenyl)-1-methylpiperidine ( 2 ), with a large excess of phenylmagnesium bromide in refluxing tetrahydrofuran led to some 2-arylspiro[3H-indole-3,4′-piperidine] derivatives, 10 and 11 , whose structures are elucidated on the basis of chemical and spectral evidence.     

Enolethers. XXI. Synthesis of 5,5′-disubstituted 4,4′-bipyrimidines

1,6-Dialkoxy-3,4-diones 3 are easily accessible by acylation of enol ethers 1 with oxalyl chloride and subsequent elimination of hydrogen chloride using triethylamine. The open-chain 2,5-dimethyl derivative 3b is converted with amidines 4a-c and S-methylisothiourea (4d) , respectively, to give 2,2′-disubstituted 5,5′-dimethyl-4,4′-bipyrimidines 5a-d . The dihydrofuran and dihydropyran derivatives 3c and 3d , however, react with benzamidine (4c) in dimethylformamide only in the presence of calcium hydride as condensation agent yielding 5,5′-bis(2-hydroxyethyl)- and 5,5′-bis(3-hydroxypropyl)-2,2′-diphenyl-4,4′-bipyrimidine 6a and b.     

Studies on the synthesis of heterocyclic compounds. Part IV. Further investigation of the pschorr reaction with some pyrazole derivatives

Thermal decomposition of the diazonium sulfate derived from N-methyl-(1-phenyl-3-methylpyrazol-5-yl)-2-aminobenzamide afforded products formulated as 1-phenyl-3-methyl[2]benzopyrano[4,3-c]pyrazol-5-one (yield 10%), 1,4-dimethyl-3-phenylpyrazolo[3,4-c]isoquinolin-5-one (yield 10%), N-methyl-(1-phenyl-3-methylpyrazol-5-yl)-2-hydroxybenzamide (yield 8%) and 4′-hydroxy-2,3′-dimethyl-1′-phenylspiro[isoindoline-1,5′-[2]-pyrazolin]-3-one (yield 20%). Decomposition of the diazonium sulfate derived from N-methyl-(1,3-diphenylpyrazol-5-yl)-2-aminobenzamide gave products formulated as 7,9-dimethyldibenzo[e,g]pyrazolo[1,5-a][1,3]-diazocin-10-(9H)one (yield 8%), 4-methyl-1,3-diphenylpyrazolo[3,4-c]isoquinolin-5-one (yield 7%) and 4′-hydroxy-2-methyl-1′,3′-diphenylspiro[isoindoline-1,5′-[2]pyrazolin]3-one (yield 10%). The spiro compounds 6a,b underwent thermal and acid-catalysed conversion into the hitherto unknown 2-benzopyrano[4,3-c]pyrazole ring system 7a,b in good yield. Analytical and spectral data are presented which supported the structures proposed.     

Synthesis and characterization of some heterocyclic derivatives from 1,2:3,4-Di-o-isopropylidene-α-d-galacto-1,6-hexadialdo-1,5-pyranose oxime

We report the synthesis of 5-[5′-(1′,2′:3′,4′-di-O-isopropylidene-β-L-arabinopyranosyl)]tetrazole, from 1,2:3,4-di-O-isopropylidene-α-D-galacto-1,6-hexodialdo-1,5-pyranose oxime via 1,2:3,4-di-O-isopropylidene-α-D-galcturononitrile as intermediate by 1,3-dipolar cycloaddition. We also report the synthesis of 5-methyl- and 5-phenyl-2-[5′-(1′,2′:3′,4′-di-O-isopropylidene-β-L-arabinopyranosyl)]-1,3,4-oxadiazole from the tetrazole derivative. The physical and spectroscopic characterizations of the heterocyclic derivatives as well as the intermedi ate nitrile and the principal by product are described and we discuss its possible formation pathway. We present the preferential conformation in solution using computational calculation and spectroscopic data.     

Two new benzopyran derivatives from Gouania leptostachya DC. var. tonkinensis Pitard.

Two new benzopyran derivatives,1-[(rel 2S,3R)-3,5,7-trihydroxy-3,4-dihydro-2H-chromen-2-yl]ethanone(1),and 1-[(rel 25,35)-3,5,7-trihydroxy-3,4-dihydro-2H-chromen-2-yl]ethanone(2),along with four known flavonoids,prodelphinidin C,prodelphinidin B3,(-)-epi-gallocatechin and(+)-gallocatechin,were isolated from the stems of Gouania leptostachya DC.var. tonkinensis Pitard.Their structures were determined on the basis of spectroscopic methods including HR-ESI-MS,1D and 2D NMR.Prodelphinidin C exhibited significant inhibitory activity forα-glucosidase.     

Heterotricyclic systems. Part I. Synthesis of new dipyridopyrazines

Pursuing our previous research on azaquinoxalinones (1,2-dihydropyrido[2,3-b]/[3,4-b]pyrazinones) we prepared, through a reductive cyclization of N-(3′-nitropyridin-2′-yl)piperidine-2-carboxylic acids 3a-c , a set of derivatives of a new tricyclic structure, 7,8,9,10-tetrahydro-5H-dipyrido[1,2-a:3′,2′-e]pyrazin-6(6aH)-ones 4a-c. Starting from these compounds we obtained substituted amides 5a-c and, from 4a , the amidines 6a-c. In the synthesis of 6 , a dehydrogenation reaction occurred giving rise to 7. The compounds 9 and 10 , characterized by a different ring-fusion between the pyridine and pyrazine rings, were synthesized in a similar manner.     

Studies in spiroheterocycles. Part XVII. synthesis of novel fluorine containing spiro[indole-pyranobenzopyran] and spiro[indenopyran-indole] derivatives

An elegant one-step synthesis of two novel spiro ring systems viz: spiro[3H-indole-3,4′-(2′-amino-3′-carbonitrile-[4′H]-pyrano[3,2-c]benzopyran)]-2,5′(1H)-dione8 and spiro[(2-amino-3-carbonitrile-indeno[1,2-b]pyran)-4(5H)>3′-[3H]indole]-2′,5(1′H)-diones in 80–85% yields is described. The spiro heterocycles were prepared by the reactions of fluorine containing 3-dicyanomethylene-2H-indol-2-ones with 4-hydroxy-2H-1-benzopyran-2-one and 1H-indene-1,3(2H)-dione respectively. The synthesized compounds have been characterized on the basis of elemental analyses, ir, pmr, ¹⁹F nmr and mass spectral data.