Synthesis of 2′,3′-dideoxynucleosides from 5-alkoxymethyluracils

Summary A modified synthesis of protected 2,3-dideoxyribose5 starting fromL-glutamic acid (1) is described. Reaction of5 with silylated 5-hydroxymethyluracil7 a and 5-alkoxymethyluracils7 b–e in the presence of trimethylsilyl triflate afforded an anomeric mixture of 2,3-dideoxyuridine derivatives8 a–e and9 a–e. Deprotection with methanolic ammonia and separation by chromatography gave the corresponding nucleosides10 a–e and11 a–e. Treatment of9 b–e with tri(1H-1,2,4-triazol-1-yl)phosphine oxide and subsequent reaction of12 b–e with ammonia in dioxane afforded the cytosine derivatives13 b–e which on treatment with methanolic ammonia gave the corresponding 2,3-dideoxycytidine derivatives14 b–e and15 b–e. In contrast with the parent compounds, these alkoxymethyl derivatives had no appreciable activity against human immunodeficiency virus (HIV-1).

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Synthese von 2,3-Dideoxynucleosiden aus 5-Alkoxymethyluracilen

Zusammenfassung Ausgehend vonL-Glutaminsäure (1) wird eine modifizierte Synthese von geschützter 2,3-Dideoxyribose (5) beschrieben. Reaktion von5 mit silyliertem 5-Alkoxymethyluracilen7 b–e in Gegenwart von Trimethylsilyltriflat ergab anomere Mischungen der 2,3-Dideoxyuridinderivate8 a–e und9 a–e. Abspaltung der Schutzgruppe mit methanolischen Ammoniak und chromatographische Trennung ergab die entsprechenden Nucleoside10 a–e und11 a–e. Behandlung von9 b–e mit Tri(1H-1,2,4-triazol-1-yl)phosphinoxid und nachfolgende Reaktion von12 b–e mit Ammoniak in Dioxan ergab die Cytosinderivate13 b–e, welche nach Behandlung mit methanolischem Ammoniak die entsprechenden 2,3-Dideoxycytidinderivate14 b–e und15 b–e ergaben. Im Gegensatz zur Stammverbindung hatten diese Alkoxymethylderivate keine nennenswerte Wirksamkeit gegen den menschlichen Immunschwächevirus (HIV-1).

     

Investigation of the process of polyimide formation from complexes of the diester of benzophenonetetracarboxylic acid with diamines

The kinetics of thermal imidization of the H-complexes derived from the diethyl ester of 3,3,4,4-benzophenonetetracarboxylic acid (EBZP) and various diamines have been studied. A comparison of kinetic parameters obtained for the imidization of H-complexes based on ethyl or methyl esters of this acid has disclosed the differences in the behavior of each of the two H-bonds and the contribution of each bond to the mechanism of polyimide formation from the respective H-complexes.For part 5, see ref.¹ Translated fromIzyestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 300–303, February, 1993.     

Convergent synthesis of 2′,3′-dideoxy-3′-mercapto nucleosides — Potential anti-HIV agents

Summary Methyl 3-benzoylthio-5-O-tert-butyldiphenylsilyl-2,3-dideoxy--D-erythro-pentofuranoside (4) and its corresponding anomer5 were synthesized in four steps from 2-deoxy-D-ribose and used as substrates for the synthesis of nucleosides by condensation with silylated thymidine and N⁶-isobutyryladenine. The nucleosides were deprotected by treatment with Bu₄NF inTHF followed by reaction with MeONa in MeOH to give 3-deoxy-3-mercaptothymidine (8), 2,3-dideoxy-3-mercaptoadenosine (15) and its corresponding anomer16. In the latter reactions it was important to use degassed solvents to minimize formation of the corresponding disulfides of purine nucleosides. Using Bu₄NF, without subsequent reaction with MeONa in the deprotection reaction, resulted in intermolecular transesterification reactions.On leave from Chemistry Department, Faculties of Science and Education, Tanta University, Tanta, Egypt     

Polyimides from complexes of benzophenonetetracarboxylic acid diesters with diamines. 5. Mechanism of thermal cyclization of H-complexes

The results of a study, by thermal mass spectrometric analysis and NMR spectroscopy, of the polycondensation of H-complexes are presented from which it is possible to propose a mechanism for the reaction. It is shown that conversion of the H-complexes into polyimides takes place through the formation of intermediate zwitterions with an amino acid bond after initial separation of methanol, following which elimination of water commences in one stage to form an imide ring. The role of theortho position of the functional groups in the acid ester during the formation of the hydrogen bond is discussed.Institute of Macromolecular Compounds, Russian Academy of Sciences, 199004 St. Petersburg. Translated fromIzvestiya Akademii Nauk, Seriya Khimicheskaya, No. 11, pp. 2517–2524, November, 1992.     

Room temperature phosphorescence optosensing for gadolinium

An optosensing method for gadolinium based on the room-temperature phosphorescence behavior in aqueous solution induced by the transient adsorption of the complex formed by 1,4-bis (1-phenyl-3-methyl-5-pyrazolone-4-)butanedione (1,4) with Gd (III) on the chelating resin Chelex 100 (packed in a flow cell) is proposed. The proposed optosensing is satisfactory for the determination of the gadolinium ion in the range 8 × 10^–7–5 × 10^–5 M with a correlation coefficient of 0.995. The relative standard deviation was 2.0% for determination of 5× 10^–6 M gadolinium ion (n = 10). The response mechanism of the optosensing and the interferences of other lanthanide ions were also investigated. The method has been used to determine gadolinium ion in synthetic sample.     

Synthesis of a Calix[4]arene Containing 'Hard' and 'Soft' Metal Ion Binding Sites

Co-receptor 1,3-calix[4]-di(aza-benzo)crown-crown-6 (1-H) designed with one calix[4]arene in a 1,3-alternate conformation and hard and soft metal ion binding sites has been prepared according to three pathways (A-C). Pathway B, consisting of two different 1 + 1 condensations with ditosylate derivatives, was shown to be the most efficient.     

Synthesis of 1-(3-(1,2,4-triazol-1-yl)-2,3,6-trideoxy-L-arabino-hexofuranosyl)uracils via an α,β-unsaturated aldehydrohexose

Summary Mercuric catalyzed hydrolysis of acetylatedL-rhamnal1 gave the ,-unsaturated aldehyde2. 1,2,4-Triazole was coupled, in a Michael type addition reaction, to2 at C-3 in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) to give, after acetylation at the anomeric center, an anomeric mixture of 1,5-di-O-acetyl-3-(1,2,4-triazol-1-yl)-2,3,6-trideoxy-L-arabino-hexofuranose (3). Reaction of3 with silylated 2,4-dihydroxypyrimidines4 in the presence of trimethylsilyl triflate as catalyst followed by deprotection with 33% methylamine in absolute ethanol afforded the corresponding nucleosides7 and8.

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Synthese von 1-(3-(1,2,4-Triazol-1-yl)-2,3,6-trideoxy-L-arabino-hexofuranosyl)uracilen über eine ,-ungesättigte Aldohexose

Zusammenfassung Die quecksilberkatalysierte Hydrolyse von acetyliertemL-Rhamnal1 ergab die ,-ungesättigten Aldehyde2. 1,2,3-Triazol wurde in Gegenwart von 1,8-Diazabicyclo[5.4.0]-7-undecen mittels einer Addition vom Michael-Typ an C-3 von2 gekoppelt und ergab dann nach Acetylierung am anomeren Zentrum eine anomere Mischung von 1,5-Di-O-acetyl-3-(1,2,4-triazol-1-yl)-2,3,6-trideoxy-L-arabino-hexofuranose (3). Die Reaktion von3 mit silyliertem 2,4-Di-hydroxypyrimidinen4 in Gegenwart von Trimethylsilyltriflat in absolutem Ethanol ergab die entsprechenden Nucleoside7 und8.

     

Synthesis of formyl derivatives of benzocrown ethers containing N,S, and O heteroatoms in the macrocycle

A method for the synthesis of 4-bromobenzodithia-15(18)-crown-5(6) and 4-bromobenzodiaza-15 (18)-crown-5(6) by condensation of 3,4-di(2-haloethoxy)bromobenzene with polyoxaalkanes containing terminal SH or NHMe groups was suggested. The method for the synthesis of formyl derivatives of benzocrowns containing N, S, and O heteroatoms in the macrocycle based on the metallation of appropriate bromo derivatives with BuⁿLi followed by treatment of the resulting organolithium intermediates with DMF was developed. Oximes and semicarbazones of benzaldehydes containing a crown ether fragment were obtained, and their transformation into the original aldehydes by treatment with KNO₂ in an acid medium was studied.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 121–128, January, 1995.This study was financially supported by the Russian Foundation for Basic Research (Grant No. 94-03-08-531) and the International Science Foundation (Grant M8Q000).     

Synthese von 1,1′-Biphenyl-3-carbonsäure-und 3,5-dicarbonsäurederivaten unter Verwendung von Ethoxymethylenmalononitril

Reaction of ethoxymethylenemalononitrile with ethyl 4-phenylacetoacetate leads to ethyl 1,1-biphenyl-6-amino-5-cyano-2-hydroxy-3-carboxylate (3). Acid or basic hydrolysis of the ester and cyano group of3 affords the new derivatives4,5 and6.7 a, b are obtained bySandmeyer-reaction of3. Basic hydrolysis of7 a gives the 3,5-dicarboxylic acid derivative8.

     

Simple synthesis of benzo[f] pyrrolizidine and benzo[g]indolizidine with the use of products of the reductive allylation of indole and quinoline

Benzo[f]pyrrolizidine and benzo[g]indolizidine were synthesized by hydroboration-oxidation-intramolecular cyclization of the corresponding products of the reductive -allylation of indole (2) and quinoline (6) with allylboranes.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No, 11, pp. 2807–2809, November, 1996,     

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.

     

Notiz zur [1,2]-Heterorest-Verschiebung in einem Sulfinamidin

Reaction of methyl 1-pyrroline-2-carboxylate (3 a) with N,N-Ditosylsulphur-diimide affords the pyrrol-2-carboxylic acid derivative7. The sulfenamide function in7 is cleaved by trimethyl phosphite leading to8. Presumably the reaction sequence (3 a 7) takes its course via the sulfinamidine4 a and the rearrangement product5 a followed by elimination of tosylamide. An analogous reaction starting with the dimethyl-1-pyrrolin-2-carboxylate3 b yields the stable sulfinamidine4 b, which undergoes a rearrangement reaction with base producing6 b with the thioaminal5 b as the intermediate.

Herrn Prof. Dr. Dr. h. c.K. Kratzl zum 70. Geburtstag herzlich gewidmet.     

The structures of 1-(2′-hydroxybenzoyl)piperidine and 4-(2′-hydroxybenzoyl)morpholine

1-(2-hydroxybenzoyl)piperidine, C₁₂H₁₅NO₂, orthorhombic, Pbc2₁-C _2v ⁵ ;a=9.529 (1),b=10.001 (1),c=11.652 (1) Å;Z=4. The structure was determined from 1 510 single crystal X-ray data by direct methods and the refinement of the structure parameters yieldedR=0.040. There is one molecule in the asymmetric unit.4-(2-hydroxybenzoyl)morpholine, C₁₁H₁₃NO₃, orthorhombic, P2₁2₁2₁-D ₂ ⁴ ;a=13.006 (1),b=17.258 (2),c=9.125 (1) Å;Z=8. The structure parameters of the isotypic compound 4-(2-hydroxythiobenzoyl)morpholine were used in a starting set of refinement; finallyR=0.054 was obtained for 1 900 single crystal X-ray data. There are two molecules in the asymmetric unit.In both compounds the hydrogen atoms could be located by means of differenceFourier summations. The intermolecular hydrogen bonds with O ... O distances of 2.649 (2) Å for the piperidine derivate and 2.688 (3) resp. 2.754 (3) Å for the morpholine derivate are typical for intermediate bond strengths.

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Die Strukturen von 1-(2-hydroxybenzoyl)piperidin und 4-(2-hydroxybenzoyl)morpholin

Zusammenfassung 1-(2-hydroxybenzoyl)piperidin, C₁₂H₁₅NO₂, orthorhombisch, Pbc2₁-C _2v ⁵ ;a=9.529 (1),b=10.001 (1),c=11.652 (1) Å;Z=4. Die Struktur wurde aus 1 510 Einkristallröntgendaten mittels direkter Methoden bestimmt; die Strukturverfeinerung ergabR=0.040. Es ist ein Molekül in der asymmetrischen Einheit.4-(2-hydroxybenzoyl)morpholin, C₁₁H₁₃NO₃, orthorhombisch, P2₁2₁2₁-D ₂ ⁴ ;a=13.006 (1),b=17.258 (2),c=9.125 (1) Å;Z=8. Die Strukturparameter der isotypen Verbindung 4-(2-hydroxythiobenzoyl)morpholin wurden als Startsatz für die Strukturverfeinerung benutzt. Es wurdeR=0.054 aus 1 900 Einkristallröntgendaten erreicht. Es befinden sich zwei Moleküle in der asymmetrischen Einheit.In beiden Verbindungen konnten mittels Differenz-Fourier-Summierungen die Wasserstoffatome lokalisiert werden. Die intermolekularen Wasserstoffbrükken mit O ... O-Distanzen von 2.649 (2) Å für das Piperidinderivat und 2.688 (3) bzw. 2.754 (3) Å für das Morpholinderivat sind typisch für mittlere Bindungsstärken.

     

Diastereomeric Oxathia[n](1,1′)ferrocenophanes

Zusammenfassung Neue Oxathiaferrocenophane wurden durch Umsetzung von 1,1-Bis(hydroxymethyl)ferrocen mit Dithiolen dargestellt, welche Sauerstoff in den Alkylketten enthalten. Die Reaktion von 1,1-Bis(-hydroxyethyl)ferrocenen mit Dithiolen führte zu Mischungen von Diastereomeren, aus welchen reine Stereoisomere isoliert und charakterisiert wurden. Einige Aspekte des stereochemischen Verlaufes dieser Reaktionen werden diskutiert.

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Diastereomere oxathia[n](1,1)ferrocenophane

Novel oxathiaferrocenophanes have been synthesized by the reaction of 1,1-bis(hydroxymethyl)ferrocene with dithiols bearing oxygen in chains. The reactions of 1,1-bis(-hydroxyethyl)ferrocenes with dithiols afforded mixtures of diastereomeric products from which pure stereoisomers were isolated and characterized. Some aspects concerning a stereochemical course of the reactions described are discussed.

     

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.

     

Molecular structure of 1′,3′,3′-trimethyl-6-trifluoromethylsulfonyl-spiro-(indoline-2,2′-benzo[b]pyran)

Photochromic 1, 3, 3 -trimethyl-6-trifluoromethylsulfonyl-spiro(indoline-2,2-ben-zo[b]pyran) (1) was studied by X-ray diffraction analysis. In compound1, the C_spiro-O bond (1.49(1) Å (average)), broken on photoexcitation, is the longest of all the indoline spiropyrans studied.Translated fromIzyestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 1969–1971, November, 1994.     

Antioxidant Study and Assignments of NMR Spectral Data for 3′,4′,7-Trihydroxyflavanone 3′,7-Di-O-β-D-glucopyranoside (Butrin) and Its Hydrolyzed Product

The NMR spectral data including high resolution ¹H, ¹³C and 2D NMR for butrin, 3,4,7-trihydroxyflavanone 3,7-di-O--D-glucopyranoside, isolated from flowers of Butea monosperma, are reported here for the first time. Butrin was hydrolyzed using b-glucosidase to butin in high yield. They were subjected to free radical scavenging test using 2,2-diphenyl-1-picrylhydrazyl (DPPH) spectrophotometric assay. At a dose of 4 × 10^-8 mol of tested compounds, the percentage of reduced DPPH for butin was 14.5% while no reduction was observed for butrin (0%).     

Photochemical properties of 2,2′-biquinoxalyl and thieno[2,3-b:4,5-b′]biquinoxalyl

2,2-biquinoxyalyl and thieno[2,3-b:4,5-b]biquinoxyalyl can be photoreduced in acidified alcoholic solutions and in aqueous solutions of acids. Quantum yields of the photochemical reaction have been determined. The fluorescence and phosphorescence spectra of these compounds have been recorded and the fluorescence quantum yields have been determined. A mechanism of the photoreduction has been proposed.

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Photochemische Eigenschaften von 2,2-Bichinoxalyl und Thieno[2,3-b:4,5-b]bichinoxalyl

Zusammenfassung 2,2-Bichinoxalyl und Thieno[2,3-b:4,5-b]bichinoxalyl unterliegen photochemischer Reaktion in angesäuerten Alkohollösungen und in wäßrigen Säurelösungen. Es wurde die photochemische Quantenausbeute bestimmt. Außerdem wurden die Fluoreszenz- und Phosphoreszenz-Spektren aufgezeichnet und die Fluoreszenz-Quantenausbeuten bestimmt. Zugleich wurde ein Mechanismus zur Photoreduktion vorgeschlagen.

     

Zur Chemie des „Dinaphthyldichinhydron”

Dinaphthyldiquinhydrone (4) first obtained byStenhouse andGroves ² reacts as well as 4,4-bi-(1,2-naphthoquinone)¹ with aniline and substituted anilines to give anilinoquinones2 a-h. However, yields of2 are considerable higher if4 is used. The IR-Spectrum of4 is very similar to that of 2,11-dihydroxy-3,10-perylenquinone, therefore we suggest for4 a the structure of a 3,3-dihydroxy-4,4-dioxo-1,1, 4,4-tetrahydro-1,1-binaphthylidene, at least in the solid state.

Herrn Prof. Dr.G. Zigeuner in traditionsverbundener Freundschaft zum 60. Geburtstag gewidmet.