Darstellung von 2′,3′-Dideoxy-2′-hydroxymethyl-nucleosiden

Zusammenfassung Die Synthese von geschützten 2,3-Dideoxy-2-hydroxymethyl-nucleosiden wird beschrieben. Die durch ein Mehrstufenverfahren aus Isopropylidenglycerol erhaltenen Nucleoside können als Bausteine zur Darstellung von Oligonucleotiden verwendet werden, deren 2- und 5-Positionen über eine Etherbrücke verbunden sind.

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Synthesis of 2,3-dideoxy-2-hydroxymethyl nucleosides

Summary The synthesis of protected 2,3-dideoxy-2-hydroxymethyl nucleosides is presented. The nucleosides, obtained in a multi-step procedure starting from isopropylideneglycerol, may be used as building blocks for the synthesis of 2,5-ether linked oligonucleotides.

     

Cyclization reactions of nitriles. 28. Synthesis and reactions of 3β-acetoxy-2′-methyl-5′-cyanoandrost-5-eno[17,16-c]pyridine-6′ (1′H)-thione

3-Acetoxy-2-methyl-5-cyanoandrost-5-eno[17,16-c]pyridine-6(1H)-thione was obtained by thiylation of 16-dicyanomethyl-3-hydroxypregn-5-en-20-one acetate, and its alkylation by chloroacetonitrile and phenacyl bromide was studied. The same thione was also synthesized by treating the corresponding 6-bromo-2-methyl-5-cyanoandrost-5-eno[17,16-c]pyridine with urea.Communication 27, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 943–946, July, 1988.     

New route for the synthesis of 2-thiouracil analogues of 3′-azido-2′,3′-dideoxy nucleosides

Summary Reaction of 3-azido-5-O-tert-butyldiphenylsilyl-2,3-dideoxy-D-erythro-pentofuranoside (5) with silylated 2-thiouracil and 5-alkoxy-2-thiouracils in the presence of trimethylsilyl trifluoromethanesulfonate afforded an anomeric mixture of the corresponding 3-azido-2,3-dideoxy-2-thiouridine derivatives with the -anomer as the main product. Deprotected nucleosides were obtained by treatment with tetrabutylammonium fluoride.

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Ein neuer Weg zur Synthese von 2-Thiouracil-Analogen von 3-Azido-2,3-dideoxy-Nucleosiden

Zusammenfassung Die Reaktion von 3-Azido-5-O-tert-butyldiphenylsilyl-2,3-dideoxy-D-erythro-pentofuranosid (5) mit silyliertem 2-Thiouracil und 5-Alkoxy-2-thiouracil in Gegenwart von Trimethylsilyltrifluormethansulfonat ergab eine anomere Mischung der entsprechenden 3-Azido-2,3-dideoxy-2-thiouridin-Derivate, wobei das -Anomer das Hauptprodukt darstellte. Die ungeschützten Nucleoside wurden mittels Behandlung mit Tetrabutylammoniumfluorid erhalten.

     

Nitration,amination, and halogenation of Di-O-methylphloracetophenone

Chlorination of the title compound gave 5- and 3-chloro-2-hydroxy-4,6-dimethoxyacetophenone. The nitration of its acetate, followed successively by reduction, diazotization, and reaction with cuprous chloride, gave the 3-substituted series, 2-acetoxy-4,6-dimethoxy-3-nitroacetophenone, 3-amino-2-hydroxy-4,6-dimethoxyacetophenone, and 3-chloro-2-hydroxy-4,6-methoxyacetophenone, respectively. The orientation of substituents in the products was proved. The amino and chloro members of the isomeric 5-substituted series were availablevia 2-hydroxy-4,6-dimethoxy-5-phenylazoacetophenone, the product of the reaction of the title compound with benzenediazonium chloride.

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Nitrierung, Aminierung und Halogenierung von Di-O-methylphloracetophenon

Zusammenfassung Chlorierung der Titelverbindung gab 5- und 3-Chlor-2-hydroxy-4,6-dimethoxyacetophenon. Die Nitrierung des Acetats, gefolgt von Reduktion, Diazotierung und Reaktion mit CuCl ergab die 3-substituierte Reihe: 2-Acetoxy-4,6-dimethoxy-3-nitroacetophenon, 3-Amino-2-hydroxy-4,6-dimethoxyacetophenon und 3-Chlor-2-hydroxy-4,6-dimethoxyacetophenon. Die Orientierung der Substituenten wird diskutiert. Die Amino- und Chlorderivate der isomeren 5-substituierten Reihe sind über 2-Hydroxy-4,6-dimethoxy-5-phenylacetophenon zugängig, dem Produkt der Reaktion der Titelverbindung mit Phenyldiazoniumchlorid.

     

Über Inhaltstoffe der Iris germanica (Schwertlilie)

Acetovanillon and the known flavonoids irisolidone, irigenin, irisolone, tectorigenin and dihydroquercetin-7.3-dimethylether were detected in the rhizomes of Iris germanica. Also a few unknown compounds could be isolated and their structure elucidated; 9-methoxy-7-(3.4.5-trimethoxyphenyl)-8H-1.3-dioxolo[4.5-g] [1]-benzopyran-8-on (=5.3.4.5-tetramethoxy-6.7-methylenedioxyisoflavone (III A); 9-methoxy-7-(3.4-dimethoxyphenyl)-8H-1.3-dioxolo[4.5-g] [1]-benzopyran-8-on (=5.3.4-trimethoxy-6.7-methylenedioxyisoflavone(III B); 9-hydroxy-7-(p-hydroxyphenyl)-8H-1.3-dioxolo[4.5-g] [1]-benzopyran-8-on (=5.4-dihydroxy-6.7-methylenedioxyiosoflavone (IX); 5.7-dihydroxy-3-(3-hydroxy-4-methoxyphenyl)-6-methoxy-4H-1-benzopyran-4-on (=5.7.3-trihydroxy-6.4-dimethoxyisoflavone (XI B); 5.7-dihydroxy-3-(4-hydroxy-3-methoxyphenyl)-6-methoxy-4H-1-benzopyran-4-on (=5.7.4-trihydroxy-6.3-dimethoxyisoflavone (XI C).The structure determination was effected by combined spectroscopical and chemical methods.

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Herrn Prof. Dr.F. Hecht mit den besten Wünschen zum 70. Geburtstag gewidmet.     

Reaction of π-deficient aromatic heterocycles with ammonium polyhalides III. Halogenation of phenothiazin-5-oxide with benzyltriethylammonium polyhalides

Summary Halogenation of phenothiazin-5-oxide with benzyltriethylammonium polyhalides (BTEA) under mild conditions afforded chloro- and bromophenothiazines as well as a few unexpected products e.g. 1,3,7,9-tetrachloro-phenothiazin-5-oxide, 7,3-dibromo-3, 10-diphenothiazinyl tribromide, and 7,3-dichloro-3,10-diphenothiazinyl tetrachloroiodate. A new charge-transfer complex of phenothiazine-5-oxide with bromine is reported.

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Reaktion elektronenarmer aromatischer Heterocyclen mit Ammoniumpolyhalogenverbindungen, 3. Mitt. Halogenierung von Phenothiazin-5-oxid mit Benzyltriethylammoniumpolyhalogeniden

Zusammenfassung Halogenierung von Phenothiazin-5-oxid mit Benzyltriethylammoniumhalogeniden (BTEA) unter milden Bedingungen ergab neben Chlor- und Bromphenothiazinen einige unerwartete Reaktionsprodukte wir z.B. 1,3,7,9-Tetrachlorphenothiazin-5-oxid, 7,3-Dibrom-3,10-diphenothiazinylbromid und 7,3-Dichlor-3,10-diphenothiazinyltetrachloriodat. Außerdem wird über einencharge-transfer-Komplex von Phenothiazin-5-oxid mit Brom berichtet.

     

Zur Mannich-Reaktion von Dihydro-6-methyl-2(1H)-pyrimidinonen

Zusammenfassung Dihydro-4,4,6-trimethyl-2(1H)-pyrimidinone reagieren mit Formaldehyd und sekundären bzw. primären Aminen zu 6-Dialkylaminoäthylidentetrahydro-2(1H)-pyrimidinonen bzw. Hexahydro-2(1H)-pyrido[4,3-d]Pyrimidinonen. Mit Succindialdehyd bzw. Glutardialdehyd und primären Aminen entstehen 5,7-Äthanohexahydro-2(1H)-pyrido[4,3-d]pyrimidinone bzw. Tetrahydro-6,8-propano-6H-pyrimido[1,6-c]pyrimidin-1(2H)-one. Die 6-Dialkylaminoäthylidentetrahydro-2(1H)-pyrimidinone geben mit Phenolen Tetrahydrospiro([1]benzopyran-2,4(1H)-pyrimidin)-2(3H)-one, mit cycl. -Dicarbonylverbindungen Hexahydrospiro([1]benzopyran-2,4(1H)-pyrimidin)-2,5(3H, 6H)-dione bzw. Tetrahydrospiro(2H,5H-pyrano[3,2-c][1]benzopyran-2,4(1H)-pyrimidin)-2(3H),5-dione bzw. mit Malonestern -(Tetrahydro-4,4-dimethyl-2-oxo-6-pyrimidyl)-äthylmalonester.Zusammenfassung Dihydro-4.4.6-trimethyl-2(1H)-pyrimidinones react with formaldehyde and sec. and prim. amines resp. to 6-dialkylaminoethylidentetrahydro-2(1H)-pyrimidinones and hexahydro-2(1H)-pyrido[4.3-d]pyrimidinones, resp. succindialdehyde and glutaraldehyde with primary amines give 5.7-ethanohexahydro-2(1H)-pyrido[4.3-d]pyrimidinones and tetrahydro6.8-propano-6H-pyrimido[1.6-c]pyrimidin-1(2H)-ones, resp. 6-Dialkylaminoethylidentetrahydro-2(1H)-pyrimidinones react with phenols to tetrahydrospiro([1]benzopyran-2.4(1H)-pyrimidin)-2(3H)-ones, with cyclic -dicarbonyl compounds to hexahydrospiro([1]benzopyran-2.4 (1H)-pyrimidin)-2,5 (3H), 6H)-diones and tetrahydrospiro(2H,5H-pyrano[3.2-c][1]benzopyran-2.4(1H)-pyrimidin)-2(3H),5-diones, resp., with malonates -(tetrahydro-4.4-dimethyl-2-oxopyrimidyl-6)-ethylmalonates.

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Mannich reaction with dihydro-6-methyl-2(1H)-pyrimidinones

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Herrn Prof. Dr.F. Kuffner zum 65. Geburtstag gewidmet.     

Synthesis of some 5′-O-amino acid derivatives of uridine as potential inhibitors ofUDP-glucuronosyltransferase

Summary In an attempt to develop potential inhibitors ofUDP-glucuronosyltransferase, some 5-O-amino acid derivatives of uridine were synthesized. N-protectedL-amino acids were coupled at the 5-O-position of 2,3-O-isopropylideneuridine by esterification employing the method of symmetrical anhydrides in presence of 4-dimethylaminopyridine, 5-O-(N-benzyloxycarbonyl-O-tert.butyl-L-threonl)-23-O-isopropylideneuridine (1), 5-O-(N-tert.butyloxycarbonyl-O-benzyl-L-seryl)-2,3-O-isopropylideneuridine and (2), 5-O-(N-tert.butyloxycarbonyl-L-valyl)-2,3-O-isopropylideneuridine (3), and 5-O-(N-tert.butyloxycarbonyl-L-valyl)-2,3-O-isopropylideneuridine (4) were obtained in good yield after column chromatography on silica gel. The treatment of2 withTFA/CH₂Cl₂ (6:1) at room temperature for 30 min led to a selective removal of theBoc group without deblocking of the 2,3-O-isopropylidene group of uridine. Treatment of2 withTFA/H₂O (5:1) at room temperature for 1 h, however, released bothBoc and 2,3-isopropylidene groups. TheZ group of1 was deprotected by catalytic hydrogenolysis over 10% Pd/C/ammonium formate.

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Synthese von 5-O-Aminosäurederivaten des Uridins als potentielle Inhibitoren derUDP-Glukuronosyl-Transferase

Zusammenfassung In einem Versuch, potentielle Inhibitoren derUDP-Glukuronosyl-Transferase zu entwickeln, wurden einige 5-O-Aminosäurederivate des Uridins synthetisiert. N-GeschützteL-Aminosäuren wurden durch Veresterung mit der 5-O-Position des 2,3-isopropylidenuridins gekuppelt (Methode der symmetrischen Anhydride in der Gegenwart von 5-Dimethylaminopyridin). Solcherweise wurden 5-O-(N-Benzyloxycarbonyl-O-tert.butyl-L-threonly)-2,3-O-isopropylidenuridin (1), 5-O-(N-tert.Butyloxycarbonyl-O-benzyl-L-seryl)-2,3-O-isopropylidenuridin (2), 5-O-(N-tert.Butyloxycarbonyl-L-leucyl)-2,3-O-isopropylidenuridin (3) und 5-O-(N-tert.Butyloxycarbonyl-L-valyl)-2,3-O-isopropylidenuridine (4) nach Säulenchromatographie (Kieselgel) in guter Ausbeute hergestellt. Die Behandlung von2 mitTFA/CH₂Cl₂ (6:1) bei Zimmertemperatur (30 min) führte zu einer selektiven Abspaltung derBoc-Gruppe ohne Deblockierung der 2,3-O-Isopropylidengruppe des Uridins. Eine Behandlung von2 mitTFA/H₂O (5:1) bei Zimmertemperatur für 1 Stunde führte hingegen zur Abspaltung sowohl derBoc als auch der 2,3-O-Isopropylidengruppe. DieZ-Gruppe von1 wurde durch katalytische Hydrogenolyse auf 10% Pd/C/Ammoniumformiat abgespalten.

     

Spaltungen mittels Diazoniumverbindungen und Chinonimidchlorid, 6. Mitt.: Über Hydroxychalkone

Zusammenfassung Es wird über die Reaktion verschieden methylsubstituierter 4-Hydroxychalkone mittels Chinonimidchlorid berichtet und gezeigt, daß die Ausbeute an 2,6-Dimethylphenol-indophenol bei der Spaltung von 4,4-Dihydroxy-3,5,3-trimethylchalkon (VII) am RingB dreimal so groß ist als beim 4,4-Dihydroxy-3,3,5-trimethylchalkon (III) am RingA.

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The reaction between several methyl-4-hydroxy-chalkones and p-benzoquinone-monochloroimine has been studied. It has been shown that the yield of 2.6-dimethylphenol-indophenol from the cleavage of 4.4-dihydroxy-3.5.3-trimethyl-chalkon (VII) at ringB is three times the yield resulting from the cleavage of 4.4-dihydroxy-3.3.5-trimethylchalkon (III) at ringA.

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Herrn Prof. Dr.H. Bretschneider zum 60. Geburtstag gewidmet.     

Thiazolobenzo-1, 2, 3-thiadiazoles and derived cyanine dyes

The following tricyclic heterocyclic compounds are synthesized: 2-methylthiazolov (5, 4-e) benzo-1, 2, 3thiadiazole, 2-methylthiazolo (4, 5-e) benzo-1, 2, 3-thiadiazole, 2-methylthiazolo (4, 5-g) benzo-1, 2, 3-thiadiazole, and 2-methylthiazolo (5, 4-g) benzo-1, 2, 3-thiadiazole. The quaternary salts of these bases are used to prepare symmetrical and unsymmetrical trimethinecyanines and dimethinemercocyanines containing N-ethylrhodanine residues. The absorption maxima of these dyes are shifted toward the long-wave region as compared with the corresponding thiacyanines.     

Electronic structure and models of receptor of monooxygenase inductors from a number of polychlorinated polycyclic compounds. IV. MNDO calculations of halogen-substituted azobenzenes

The electron and geometric structures of the cis and trans isomers of 3,3,4,4-tetrachloroazobenzene (3,3,4,4-TCAB) and the trans isomers of 3,3,5,5-TCAB and 3,3-dichloro-4,4-difluoroazobenzene were calculated by the MNDO method. It was established that the trans isomer, which has a planar structure, is most stable for 3,3,4,4-TCAB. Change in the position of the Cl atoms in the azobenzene, i.e., the transition from 3,3,4,4-TCAB to 3,3,5,5-TCAB, does not lead to appreciable change in the formation energy, the position of the electronic levels, the nature of the frontier orbitals, or the charge distribution in the molecules. This gives reason to suggest that the biological activity of 3,3,4,4-TCAB is due to the metabolism products and not to the action of the substrates themselves.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 8, pp. 1797–1801, August, 1990.     

Selektive Synthesen zu 1′-aryl-, 1′-hetaryl-und 1′-alkylsubstituierten 3-Vinylindolen

Selective methods for deriving 1-aryl-, 1-indolyl-, 1-pyrrolyl- and 1-methyl-substituted 3-vinylindoles2 are described. In all cases the precursors were 3-acylindoles. The new compounds are synthetically useful synthons for annelation of the indole skeleton.

     

Soluble polysaccharides of Rhodotorula flava

Conclusions 1. Xanthalin has been shown to have the structure of 2, 2-dimethyl-3, 4,-diangeloyloxy-3, 4-dihydropyrano-5, 6:6, 7-coumarin on the basis of the preparation of a number of derivatives and cleavage products.2. The following products of the alkaline hydrolysis of xanthalin have been isolated and characterized for the first time: (±)-3, 4-dihydroxy-3, 4-dihydroxanthyletin (isokhellactone), C₁₄H₁₄O₅, with mp 213–215° C and (–)-trans-3-hydroxy-4-methoxy-3, 4-dihydroxanthyletin (isomethylkhellactone, C₁₅H₁₆O₅, with mp 136.5–138° C and [] _D ²⁰ –47.7 (ethanol).Khimiya Prirodnykh Soedinenii, Vol. 6, No. 1, pp. 14–19, 1970     

Podand-porphyrins with peripheral chelates

Alkylation of 5-(3-nitro-4-hydroxyphenyl)-10,15,20-triphenylporphyrin with chloropyridines[2,6-dichloromethyl-and 2-chloromethyl-6-(2-nitrophenoxymethylpyridine)] as well as condensation by a mixed-aldehyde method starting with formylpyridines [2-(2-nitro-4-formylphenoxymethyl)-6-(2-nitrophenoxy-methyl-) or 2,6-di(2-nitro-4-formylphenoxymethyl)pyridine], benzaldehyde, and pyrrole are used to synthesize previously unknown podand-porphyrins containing from one to four peripheral chelates.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 475–481, April, 1991.     

Preparation and stereochemical characterization of some N-acyl-[1]benzopyrano[3,4-c]pyrazole derivatives from rotenoids

Summary Several new N-acyl derivatives of 1-(4-hydroxy-2,3-dihydrobenzofuran-5-yl)-7,8-di methoxy-1,9 b,2,3,3 a,4-hexahydro-[1]benzopyrano[3,4-c]pyrazole-1-ene have been prepared by appropriate chemical transformation of isohydrazones of rotenone and amorphigenin. A study of their¹H- and¹³C-NMR spectra confirmed the presence of the twocis 3a, 9b, 2 and 3a, 9b, 2 diastereomers in the parent isohydrazones and revealed the strong predominance of the conformers withendo orientation of the 3-NAc group. The conformations due to rotation about the 1,5-bond between rings C and D in the 4-OH and 4-O-substituted compounds were also determined by taking into account the anisotropic effect of aromatic rings A and D, and the hydrogen bond between 4-OH and the 2-N atom, as well as by inspecting the Dreiding models.

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Darstellung und stereochemische Charakterisierung einiger N-Acyl-[1]benzopyrano[3,4-c]pyrazol-Derivate von Rotenoiden

Zusammenfassung Mittels geeigneter chemischer Transformationen von Isohydrazonen von Rotenon und Amorphigenin wurden einige neue N-Acyl-Derivate von 1-(4-Hydroxy-2,3-dihydrobenzofuran-5-yl)-7,8-dimethoxy-1,9 b,2,3,3 a,4-hexahydro-[1]benzopyrano[3,4-c]pyrazol-1-en hergestellt. Eine Untersuchung ihrer¹H und¹³C-NMR-Spektren zeigt die Gegenwart von zweicis 3a, 9b, 2- und 3a, 9b, 2-Diastereomeren in den Ausgangs-Isohydrazonen und eine starke Bevorzugung der Konformeren mitendo-Orientierung der 3-NAc-Gruppe. Die Konformationen bezüglich der Rotation um die 1,5-Bindung zwischen Ring C und D werden für die 4-OH und 4-O-substituierten Verbindungen unter Berücksichtigung von Anisotropie-Effekten der aromatischen A- und D-Ringe, der Wasserstoffbrücken zwischen 4-OH und dem 2-N Atom und auch der Betrachtung der entspechenden Dreiding-Modelle diskutiert.

     

Selective aziridination of olefinic esters

Summary Oxidation of 3-amino-2-isobutylquinazoline-4-one (2) with lead tetraacetate at –20°C gave N-acetoxyamino-2-isobutylquinazolin-4-one (3), which selectively aziridinated olefinic esters to yield substituted 1-(2-isobutylquinazolin-4-one-3-yl)-aziridine-2-carboxylates5a–q.

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Selektive Aziridinierung von olefinischen Estern

Zusammenfassung Oxidation von 3-Amino-2-isobutylchinazolin-4-on (2) mit Bleitetraacetat bei –20°C ergab N-Acetoxyamino-2-isobutylchinazolin-4-on (3), welches mit verschiedenen olefinischen Estern selektiv substituierte 1-(2-Isobutylchinazolin-4-on-3-yl)-aziridin-2-carbonsäureester5a–q lieferte.

     

1,4-bis(4′-hydroxy-1′,2′,5′-trimethyl-4-piperidyl)-1,3-butadiyne and its derivatives

1.4-Bis(4-hydroxy-1,2,5-trimethyl-4-piperidyl)-1.3-butadiyne has been synthesized from the individual isomers of 4-ethynyl-1,2,5-trimethyl-4-piperidol. Hydrogenation, bromination, and cleavage have given, respectively, 1,4-bis(4-hydroxy-1,2,5-trimethyl-4-piperidyl)butane, 1,4-bis(4-nydroxy-1,2,5-trimethyl-4-piperidyl)-1,2,3,4-tetrabromo-1, 3-butadiene, and 4-(1,3-butadiynyl)-1,2,5-trimethyl-4-piperidol.     

Über Dihydro-bzw. Tetrahydrospiro([1]benzopyran-2,4′(1′H)-pyrimidin)-2′(3′H)-one

On reaction of dihydro-4,4,6-trimethyl-2(1H)-pyrimidinone1 with o-hydroxybenzaldehydes, dihydro- and tetrahydrospiro([1]-benzopyran-2,4(1H)-pyrimidin)-2(3H)-ones resp.5, 6, 7 are formed.     

Investigations of 2,3′-biquinolyl. 8. Reduction of 1-alkyl-3-(2-quinolyl)-quinolinium halides with sodium borohydride

Reduction of 1-alkyl-3-(2-quinolyl)quinolinium halides with sodium borohydride leads to 1-alkyl-1,2-dihydro-2,3-biquinolyls which, except for the ethoxycarbonyl derivative, undergo rearrangement to 1-alkyl-1,4-dihydro-2,3-biquinolyls. The last can be synthesized by the alkylation of the corresponding 1,4-dihydro-2,3-biquinolyls under conditions of interphase catalysis and in the system KOH-DMSO.For Communication 7, see [1].Stavropol' State University, Stavropol' 355009, Russia; nauka@stavsu.ru. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1084–1087, August, 2000.     

1,1′-Disubstituted 2,2′-di(n-perfluoropropyl)-5,5′-bibenzimidazolyls

The synthesis of 4,4-di(methylamino)- and 4,4-dianilino-3,3-diaminobiphenyls is described. The condensation of the tetraaminobiphenyls mentioned with phenyl perfluorobutyrate has given, respectively, 1,1-dlmethyl- and 1,1-diphenyl-2,2-(n-perfluoropropyl)-5, 5-bibenzimidazolyls. A study of the thermal stability of the 2-perfluoroalkylbenzimidazoles has shown that the replacement of the hydrogen of the imino group in these compounds by a methyl or a phenyl radical considerably increases their heat stability.