Synthesis of new pyridazino[4′,3′:4,5]-thieno[3,2-d]-1,2,3-triazine and pyrimido[4′,5′:4,5]thieno[2,3-c]pyridazine derivatives

Summary 8,9-Diphenylpyridazino[4,3:4,5]thieno[3,2-d]-1,2,3-triazin-4(3H)-one (2), 3-substituted 8,9-diphenylpyridazino[4,3:4,5]thieno[3,2-d]-1,2,3-triazin-4(3H)-ones (3a–c), 3,4-diphenylpyrimido[4,5:4,5]thieno[2,3-c]pyridazin-8(7H)-one (4), 8-chloro-3,4-diphenylpyrimido[4,5:4,5]thieno[2,3-c]pyridazine (5), 8-substituted 3,4-diphenylpyrimido[4,5:4,5]thieno[2,3-c]pyridazines (6a–h) and 7-substituted 3,4-diphenylpyrimido[4,5:4,5]thieno[2,3-c]pyridazin-8(7H)-ones(7a–c) were synthesized from 5-amino-3,4-diphenylthieno[2,3-c]pyridazine-6-carboxamide (1).

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Synthese neuer Pyridazino[4,3:4,5]thieno[3,2-d]-1,2,3-triazin-und Pyrimido[4,5:4,5]thieno[2,3-c]pyridazin-Derivate

Zusammenfassung Folgende Verbindungen wurden ausgehend von 5-Amino-3,4-diphenylthieno[2,3-c]pyridazin-6-carboxamid (1) synthetisiert: 8,9-Diphenylpyridazino[4,3:4,5]thieno[3,2-d]-1,2,3-triazin-4(3H)-on (2), 3-substituierte 8,9-Diphenylpyridazino[4,3:4,5]thieno[3,2-d]-1,2,3-triazin-4(3H)-one (3a–c), 3,4-Diphenylpyrimido[4,5:4,5]thieno[2,3-c]pyridazin-8[7H]-on (4), 8-Chlor-3,4-diphenylpyrimido[4,5:4,5]thieno[2,3-c]pyridazin (5), 8-substituierte 3,4-Diphenylpyrimido[4,5:4,5]thieno[2,3-c]pyridazine (6a–h) und 7-substituierte 3,4-Diphenylpyrimido[4,5:4,5]thieno[2,3-c]pyridazin-8(7H)-one (7a–c).

     

A general route for the synthesis of pyrimido[4′,5′:4,5]thieno[2,3-c]pyridazine derivatives

Summary A facile synthesis of 8-substituted pyrimido[4,5:4,5]thieno[2,3-c]pyridazines (6a–i) has been accomplished. The sequence involves the ring closure of a heterocyclic aminonitrile precursor (3) after reaction with (dichloromethylene)-dimethylammonium chloride.

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Eine allgemeine Synthese von Pyrimido[4,5:4,5]thieno[2,3-c]pyridazin-Derivaten

Zusammenfassung Es wurde ein einfacher Syntheseweg für 8-substituierte Pyrimido[4,5:4,5]thieno-[2,3-c]pyridazine entwickelt. Die Reaktion verläuft über den Ringschluß eines heterocyclischen Aminonitrilvorläufers (3) nach Umsetzung mit Dichlormethylen-dimethylammoniumchlorid.

     

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     

Synthesis of 5′-amino- and 5′-azido-2′,5′-dideoxy nucleosides from thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione

Summary Thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione (4) was silylated and condensed with methyl 5-azido-2,5-dideoxy-3-O-(4-methylbenzoyl)-D-erythro-pentofuranoside (2) in the presence ofTMS triflate to afford the corresponding protected nucleoside6 and acyclic nucleoside7. Deprotection of6 with MeONa/MeOH at room temperature gave 1-(5-azido-2,5-dideoxy--D-erythro-pentofuranosyl)-thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione (8) and the corresponding anomer9, whereas compound7 yielded 5-azido-2,5-dideoxy-1-(2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-1-yl)-1-O-methyl-D-erythro-pentitol (10) under the same reaction conditions. 1-(5-Amino-2,5-dideoxy--D-erythro-pentofuranosyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione (11) was obtained on treating9 with Ph₃P in pyridine followed by hyrolysis with NH₄OH. The anomeric nucleosides14 and15 and the corresponding acyclic nucleoside16 were obtained when4 was trimethylsilylated and condensed with methyl 2-deoxy-3,5-di-O-(4-methylbenzoyl)-D-erythro-pentofuranoside (3) followed by deprotection with MeONa in MeOH. Compounds8 and9 were also obtained when the anomeric mixture14/15 was treated with a mixture of NaN₃, Ph₃P, and CBr₄ in dryDMF at room temperature.On leave from Chemistry Department, Faculty of Science, Tanta University, Tanta, Egypt     

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).

     

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.     

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.

     

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.

     

Photochemical addition of diethyl ether to β,β,β',β'-tetrakis(trifluoromethyl)divinyl ether

The 1:1 adducts of diethyl and ,,','-tetrakis(trifluoromethyl)divinyl ether (1),i.e., 3,5-(ee)-bis[2,2,2-trifluoro-1-(trifluoromethyl)ethyl]-2,6-dimethyl-1,4-dioxane (2) (3 isomers) and 4-ethoxy-1,1,1-trifluoro-2-trifluoromethyl-3-[3,3,3-trifluoro-2(trifluoromethyl)propenyloxy]pentane (3), have been obtained by UV-irradiation of a solution of divinyl ether1 in diethyl ether. The X-ray structural investigation of the all-(e)-isomer of dioxane (2) has been carried out.Deceased.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 85–88, January, 1994.     

Crystal Structure of Two Dimethyl 1,3-Thiazolidinedicarboxylates Obtained in Thermal [2 + 3]Cycloaddition of an Azomethine Ylide with 2,2,4,4-Tetramethyl-3-Thioxocyclobutanone

The crystal structures of dimethyl 2,2,4,4-tetramethyl-3-oxocyclobutane-1-spiro-5-3,4-diphenyl-(1,3)-thiazolidine-2,2-dicarboxylate, C₂₆H₂₉NO₅S for V, and dimethyl 3,4-diphenyl-5-isopropylidene-(1,3)-thiazolidine-2,2-dicarboxylate, C₂₂H₂₃NO₄S for VI, have been solved. The 1,3-thiazolidine ring of compound V has got twisted conformation, while in compound VI this ring adopts envelope. In both structures short inter- and intramolecular contacts were found, which can be recognized as hydrogen bonds.     

2,2′-Diphenyl-Δ3,3′-bi-3H-indole-1,1′-dioxide: Molecular interactions and crystal structure

The Dinitrone 2,2-diphenyl-^3,3-bi-3H-indole-1,1-dioxide acts as a demethylating and dehydrogenating agent. The mechanism of interaction of the dinitrone with donors and acceptors does not involve intermediate charge-transfer complexes probably due to a self association between dinitrone molecules (as supported by X-ray determinations). The crystal structure of the dinitrone was obtained by direct methods;a=9.967 (2),b=19.817 (3),c=10.875 (2) Å, =111.2 (2)°, space group P2₁/n. The finalR andR _w were 0.089 and 0.063 for all measured reflexes.

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2,2-Diphenyl-^3,3-bi-3H-indol-1,1-dioxid: Molekulare Wechselwirkungen und Kristallstruktur

Zusammenfassung Das Dinitron 2,2-Diphenyl-^3,3-bi-3H-indol-1,1-dioxid wirkt als Demethylierungs- und Oxydationsmittel. Die Wechselwirkung des Dinitrons mit Elektronen-Acceptoren und Elektronen-Donatoren geht wegen der Selbstassoziation zwischen den Dinitron-Molekülen ohne die dazwischenliegende Bildung eines Charge-Transfer-Komplexes vor sich; das wird auch von Röntgenstrukturuntersuchungen gestützt. Die Kristallstruktur wurde mit direkten Methoden ermittelt:a=9.967 (2),b=19.817 (3),c=10.875 (2) Å; =111.2 (2)°. P2₁/n. Die endgültigen WerteR undR _w waren 0.089 und 0.063 für alle gemessenen Reflexe.

     

Synthesis,crystal structure and conformation of N-acetyl-Cα,α-diethylglycine-N′-methylamide

Summary Synthesis and X-ray structure analysis of N-acetyl-^,-diethylglycine-N-methylamide [CH₃-Co-NH-C(C₂H₅)₂-CO-NHCH₃] are described. The compound was obtained from the corresponding N-acetyl derivative [CH₃-CO-NH-C(C₂H₅)₂-COOH] through the mixed anhydride procedure. It crystallizes as monohydrate (C₉H₁₈N₂O₂·H₂O) in space group P2₁/c,a=7.139(1),b=11.823(2),c=15.778(3) Å, =122.23(1)°,V=1126.53 ų,D _m=1.20 Mgm^–3 (room temperature),R=0.046 for 1523 reflections. The crystal packing is dominated by two strong hydrogen bonds between the water molecule and two carbonyl oxygen atoms and two weak H-bonds to two amide-N-atoms of symmetry-equivalent molecules. The molecular conformation is closer to a 3₁₀-helix then ana-helix.

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Synthese, Kristallstruktur und Konformation von N-Acetyl-^,-diethylglycin-N-methylamid

Zusammenfassung Es wird über Synthese und die röntgenographische Strukturbestimmung von N-Acetyl-^,-diethylglycin-N-methyl-amid [CH₃-CO-NH-C(C₂H₅)₂-CO-NH-CH₃] berichtet. Die Verbindung wurde unter Anwendung der Methode der gemischten Anhydride aus dem entsprechenden N-Acetylderivat [CH₃-CO-NH-C(C₂H₅)₂-COOH] erhalten. Sie kristallisiert als Monohydrat (C₉H₁₈N₂O₂·H₂O) in der Raumgruppe P2₁/c mita=7.139(1),b=11.823(2),c=15.778(3) Å, =122.23(1)°,V=1126.53 ų,D _m=1.20 Mgm^–3,D _x=1.204 Mgm^–3 (Raumtemperatur).R=0.046 für 1523 Reflexe. Die Kristallpackung ist dominiert durch zwei starke H-Brücken vom Wassermolekül zu zwei Carbonylsauerstoffatomen sowie zwei schwachen H-Brücken zu zwei Amid-N-atomen symmetrieequivalenter Moleküle. Die Konformation des Peptidgerüstes ist näher einer 3₁₀ als einera-Helix.

     

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.     

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%).     

Condensed O-, N-heterocycles by the transformation of azidoacrylates

Summary A number of furo[3,2-c]pyridines (4a–4d) and benzo[b]derivative (4e), as well as pyrrolo[2,3-4,5]furo[3,2-c]pyridine (8) were prepared by reaction of the corresponding iminophosphoranes, available from ethyl azidoheteroacrylates and triphenylphosphine, with phenyl isocyanate. The appropriate azidoheteroacrylates were used for the preparation of some substituted furo[3,2-b:4,5-b]dipyrroles (6). The reactions of the prepared compounds are described.

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Kondensierte O-, N-Heterocyclen durch Umwandlung von Azidoacrylaten

Zusammenfassung Eine Anzahl von Furo[3,2-c]pyridinen (4a –4d), ein Benzo[b]derivat (4e) und Pyrrolo[2,3:4,5]furo[3,2-c]pyridin (8) wurden durch die Reaktion von Phenylisocyanaten mit den entsprechenden Iminophosphoranen dargestellt, die aus Ethyl-azidoheteroacrylaten und Triphenylphosphin leicht zugänglich sind. Die entsprechenden Azidoacrylate wurden zur Synthese einiger Furo[3,2-b:4,5-b]dipyrrole (6) verwendet. Die Reaktionen einiger dieser Verbindungen werden beschrieben.

     

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.

     

Stereochemistry of planarchiral compounds,part XIII: Crystal structure of Meso-10,10′-dibromo-2,2′-bi-(1,6-methano-[10]-annulenyl)

Summary Crystallization of the mesoform of the title compound1 from benzene-pentane in the presence of 5% of (+)(R) _p (S) _a (R) _p -1 afforded crystals, the structure of which was determined in the achiral spacegroup P2₁/a-C _2h ⁵ . The configuration (R) _p (S) _p was confirmed, the torsional angle around the 2,2-bond is 68.6° and 72.1° (C3-C2-C2-C3 and C1-C2-C2-C1, resp.). The twist of the best planes through the perimeter carbonatoms 3, 4, 5 and 7, 8, 9 (3, 4, etc., resp.) is 26.0° and 19.8°. The colours of the crystals of the stereoisomers of1 depend on the torsional angles and thereby on the conjugation of the -systems. Meso, monoclinic (70.3°): light yellow; racemate, opt. inactive (56.2°): yellow; enantiomer of the racemate (34.4°): orange (average -values).

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Stereochemie planarchiraler Verbindungen, 13. Mitt.: Die Kristallstruktur von Meso-10,10-dibrom-2,2-bi-(1,6-methano-[10]-annulenyl)

Zusammenfassung Kristallisation der Meso-Form der Titelverbindung1 aus Benzol-Pentan in Gegenwart von 5% (+)(R) _p (S) _a (R) _p -1 lieferte Kristalle, deren Struktur in der achiralen Raumgruppe P2₁/a-C _2h ⁵ bestimmt werden konnte: Die Konfiguration (R) _p (S) _p wurde bestätigt, der Torsionswinkel um die 2,2-Bindung beträgt 68.6 bzw. 72.1° (C3-C2-C2-C3 bzw. C1-C2-C2-C1). Die Verkippung der besten Ebenen, definiert durch die Perimeter-C-Atome 3, 4, 5 und 7, 8, 9 (bzw. 3, 4, etc.) beträgt 26.0 bzw. 19.8°. Die Farben der Kristalle der Stereoisomere von1 hängen von den Torsionswinkeln und damit von der Konjugation der -Systeme ab: Meso, monoklin (70.3°): hellgelb; Racemat, opt. inaktiv (56.2°): gelb: Enantiomer des Racemates (34.4°): orange (gemittelte Werte).

     

Stereochemistry of planarchiral compounds,part XII: Absolute chiralities and X-ray crystal structures of 2,2′-Bi(1,6-methano[10]annulenyl)s

Summary The absolute chirality of the dextrorotatory main rotamer of 10,10-dibromo-2,2-bi(1,6-methano[10]annulenyl) (1 b), obtained by low temperature chromatography or by crystallisation of the (+)-enantiomer of1 b, was established by observation of anomalous X-ray diffraction as (+)-(R) _p (R) _a (R) _p -1b. This result was confirmed by reduction of (+)-1 b to a dextrorotatory 2,2-bi(1,6-methano[10]annulenyl) (1 a), which in turn was accessible by coupling of (–)-2-Bromo-1,6-methano[10]annulene (3) of known chirality (S) _p and, moreover, by enantioselective chromatography of1 a on triacetyl cellulose in ethanol. This correlation determines also the chirality of (+)-1 a as (S) _p (S) _p .According to the X-ray analyses the main rotamer of (+)-1 b and the meso-form (2 b) adopt crystal structures in which the bromine atoms come close to the CH₂-bridges. The torsional angles around the 2,2-bonds vary between 33°, 53° and 65° for (+)-1 b, racem.1 b and the mesoform2 b, respectively.Dedicated to Prof. Dr. G. Snatzke (Bochum) with cordial wishes on the occasion of the 60th anniversary of his birthday     

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.

     

Vibrational spectra and structure of “staircase” carbonyl π-complexes of transition metals

FTIR spectra have been studied for staircase cyclopentadienyl complexes containing two or three metal carbonyl fragments bound by the metal-carbon bond Cp(CO)₂Fe-CpmMn(CO)₃ (1), Cp(CO)₂Fe-CpmFe(CO)₂CH₂Ph (2), Cp(CO)₂Fe-Cpm(CO)₂Fe-CpmMn(CO)₃ (3), Cp(CO)₂Mo-Cpm(CO)₂Fe-CpmMn(CO)₃ (4), Cp(CO)₃W-Cpm(CO)₂Fe-CpmMn(CO)₃ (5), Cp(CO)₂Fe-Cpm(CO)₂Fe-BmCr(CO)₃ (6), Cr(CO)₃Bm-CpmFe(CO)₂CH₂Ph (7), where Cp = ₅-C₅H₅, Cpm = ¹⁵-C₅H₄, Bm = ¹⁶-C₆H₅. Temperature-dependent FTIR spectra were measured inn-pentane solutions over a wide temperature range and in the low-temperature solid matrices of argon and nitrogen. Rotamers, formed due to rotation about the metal-carbon -bond, were found in solutions and matrices. A molecular mechanics calculation of1 proved the possibility of such rotation.Translated fromIzyestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 1952–1956, November, 1994.The authors are grateful to the Russian Foundation for Basic Research (project code No 93-03-18592) and to the International Science Foundation (project code No MEQ000).