C45- und C50-Carotinoide. 5. Mitteilung

C₄₅- and C₅₀-Carotenoids. Synthesis of an Optically Active Cyclic C₂₀-Building Block and of (2R,2′S)-3′,4′-Didehydro-1′,2′-dihydro-2-(4-hydroxy-3-methylbut-2-enyl)-2′-(3-methylbut-2-enyl)-β,ψ-caroten-1′-ol (= C. p. 473) The synthesis of the optically active C₂₀-building block (R)- 16 and of the optically active C₅₀-carotenoid C.p. 473 ( 1 ) starting from (?)-β-pinene is reported.     

Nucleoside und Nucleotide. Teil 20. Synthese von Desoxyribooligonucleotiden nach der Diester- und Triestermethode mit 2(1H)-Pyrimidinon als Base

Nucleosides and Nucleotides. Part 20, Synthesis of Desoxyribooligonucleotides According to the Diester and Triester Method with 2(1H)-Pyrimidinone as Base The syntheses of the dinucleosidemonophosphate 1-(2′-deoxy-b?-D -ribofuranosyl)-2(1H)-pyrimidinon-(3′-5′)-2′-deoxycytidine (M_dpC_d; 4 ) and the trinucleoside-diphosphate thymidyl-(3′-5′)-thymidylyl-(3′-5′)-1-(2′-deoxy-b?-D -ribofuranosyl)-2(1H)pyrimidinon (T_dpT_dpM_d; 1 ) are described, Compound 1 was synthesized by different variants of the triester method, and 4 by the diester method as well as the triester method.     

Synthese de polysiloxanes fluores. Partie IV. Obtention de disiloxanes fluores

New disiloxanes containing aromatic or aliphatic fluorinated groups are prepared and identified. The general formula of these compounds is: R_F-Q-CH₂-CH₂-Si(CH₃)₂-O-Si(CH₃)₂-CH₂-CH₂-Q′-R′_F · R_F and R′_F are halogenated groups such as C₆F₅-, C_nF_2n+1-, Cl(CFCl-CF₂)_n, CF₃-CFH-CF₂-, CF₃-, or CCl₃-. In most cases, Q or Q′ is an oxygen atom. Symmetrical disiloxanes are obtained by hydrolysis of corresponding fluorinated monochlorodimethylsilanes, and the asymmetrical ones are prepared in two steps by reacting the fluorinated olefins H₂C = CH-Q-R_F and H₂C = CH-Q′-R′_F with dihydrotetramethylsiloxane. The structures of these various compounds are elucidated by ¹H-, ¹³C- NMR and IR spectroscopy     

Nucleotides. Part. XXXII. Synthesis of 2′–5′ Connected oligonucleotides. Prodrugs for antiviral and antitumoral nucleosides

The cytotoxically and antivirally active compounds bvU_d ( 1 ), flU_d ( 4 ), acyclovir ( 7 ), and A_a ( 12 ) have chemically been combined with the appropriately protected (2′–5′)diadenylate 20 by the phosphotriester approach to give the 2′–5′ oligonucleotide trimers 21 – 24 . The deprotection of the various blocking groups by chemical means afforded the 2′–5′ trimers 25 – 28 , which can be regarded as new type of a potential prodrug form delivering nucleotides to the targets inside cells. In an analogous series of reactions, 9-(3′-azido-3′-deoxy-β-D-xylofuranosyl)adenine was coupled with 7 to the 2′–5′ trimer 31 . The antiviral screening of the oligonucleotides 25–27 and 31 showed biological activities closely related to the parent nucleosides, possibly indicating their release by enzymatic cleavage of the oligomers.     

Nucleoside und Nucleotide. Teil 10. Synthese von Thymidylyl-(3′-5′) -thymidylyl-(3′-5′)-1-(2′-desoxy-β-D-ribofuranosyl)-2(1 H)-pyridon

Nucleosides and Nucleotides. Part 10. Synthesis of Thymidylyl-(3′-5′)-thymidylyl-(3′-5′)-1-(2′-deoxy-β-D - ribofuranosyl)-2(1 H)-pyridone The synthesis of 5′-O-monomethoxytritylthymidylyl-(3′-5′)-thymidylyl-(3′-5′)-1-(2′-deoxy-β-D -ribofuranosyl)-2(1H)-pyridone ((MeOTr)T_dpT_dp∏_d, 5 ) and of thymidylyl-(3′-5′)-thymidylyl-(3′-5′)-1-(2′-deoxy-β-D -ribofuranosyl)-2(1 H)-pyridone (T_dpT_dp∏_d, 11 ) by condensing (MeOTr) T_dpT_d ( 3 ) and p∏_d(Ac) ( 4 ) in the presence of DCC in abs. pyridine is described. Condensation of (MeOTr) T_dpT_dp ( 6 ) with Π_d(Ac) ( 7 ) did not yield the desired product 5 because compound 6 formed the 3′-pyrophosphate. The removal of the acetyl- and p-methoxytrityl protecting group was effected by treatment with conc. ammonia solution at room temperature, and acetic acid/pyridine 7 : 3 at 100°, respectively. Enzymatic degradation of the trinucleoside diphosphate 11 with phosphodiesterase I and II yielded T_d, pT_d and p∏_d, T_dp and Π_d, respectively, in correct ratios.     

Total synthesis of nucleoside antibiotic. Ascamycin

Synthesis of ascamycin was achieved by the condensation of N⁶-t-butyloxy-carbonyl-2-chloro-9-(2′,3′-0-isopropylidene-5′-0-sulfamoyl-β-D-ribofuranosyl)adenine(4) with t-butyloxycarbonyl-L-alanylimidazole in the presence of Cs₂CO₃ in DMF as a key step.     

A study of the coumarins ofHaplophyllum obtusifolium. The structure of obtusidin and of obtusiprenin

The epigeal part ofHaplophyllum obtusifolium Ledeb has yielded scopoletin and the following new coumarins: obtusidin, C₁₅H₁₆O₅, mp 165–167°C, and obtusiprenin, C₁₅H₁₆O₅, mp 139–140°C. It has been established on the basis of chemical and spectral characteristics that obtusidin has the structure of 3-(1′-1′-dimethylallyl)-7,8-dihydroxy-6-methoxycoumarin, and obtusipernin that of 5-(3′,3′-dimethylallyl)-7,8-dihydroxy-6-methoxycoumarin.     

N.M.R. study of collective molecular motions in smectogen liquid crystals

Abstract

The proton spin relaxation dispersion, T ₁(v), was studied by field-cycling techniques over a broad Larmor frequency range in the nematic and smectic phases of several liquid crystals (4,4′-bis-heptyloxyazoxybenzene, 4-cyano-4′-8-alkylbiphenyl, 4-cyano-4′-9-alkylbiphenyl, 4-cyano-4′-11-alkylbiphenyl and 4-cyano-4′-9-alkoxybiphenyl) with different sites of the nitrogen atom. The results can be explained quantitatively in terms of nematic and smectic order fluctuations (T ₁ ∝ v ^1/2, T ₁ ∝ v ¹), molecular self-diffusion, molecular rotations and up to six cross-relaxation resonances due to a nitrogen-proton coupling The order fluctuations contribution and the transition from the v ^1/2 to the v ¹ dispersion profile occurs always at Larmor frequencies in the kilohertz range. Some additional measurements of the frequency dependence of the dipolar relaxation time T _1D(v), are not in accord with existing theories.     

Total synthesis of indole and dihydroindole alkaloids. IX. Studies on the synthesis of bisindole alkaloids in the vinblastine-vincristine series. The biogenetic approach.

A detailed study of the reaction of catharanthine N-oxide and vindoline has been carried out employing various conditions. Under optimum conditions, which involve low temperatures and trifluoroacetic anhydride as reagent, 3′, 4′-dehydrovinblastine (XIII, R = COOCH₃), in reasonable yields is essentially the exclusive product. However two additional products, 18′ (epi)- 3′, 4′-dehydrovinblastine (XIV, R = COOCH₃) and 1′-hydroxy- 3′, 4′-dehydrovinblastine (XVI, R = COOCH₃) are also often isolated. The reaction, which follows the course of a Polonovski-type fragmentation process, has been extended to the N-oxide derivatives of dihydrocatharanthine and decarbomethoxycatharanthine to provide again a series of bisindole alkaloid derivatives, also vinblastines. A mechanistic rationale is provided to explain the various results obtained.     

Purine nucleosides XXVIII. The synthesis of 7-(2′-deoxy-α- and β-d-ribofuranosyl)purines from 2′-deoxyribofuranosylimidazoles. Preparation of the 2′-deoxy derivative of the nucleoside from pseudovitamin B12 factor G

The synthesis of 1-(2′-deoxyribofuranosyl)imidazoles have been achieved for the first time via the fusion method of glycosidation. 4-Amino-5-carboxamido-1-(2′-deoxy-α-D-ribofuranosyl)-imidazole ( 8 ) and 4-amino-5-carboxamido-1-(2′-deoxy-β-D-ribofuranosyl)imidazole ( 10 ) have been obtained and their structures established by spectroscopic methods. The first examples of 7-(2′-deoxyglycosyl)purines [7-(2′-deoxy-α-D-ribofuranosyl)hypoxanthine ( 6 ) and 7-(2′-deoxy-β-D-ribofuranosyl)hypoxanthine ( 11 )] have been obtained from the requisite 2′-deoxyribofuranosylimidazoles. The preparation of 6 has furnished the 2′-deoxy derivative (α-configuration) of the nucleoside from pseudovitamin B₁₂ Factor G, which constitutes the first 2′-deoxy derivative of any nucleoside isolated from the various naturally occurring pseudovitamin B₁₂ factors.     

Nucleoside und Nucleotide. Teil 16. Verhalten von 1-(2′-Desoxy-β-D-ribofuranosyl)-2(1 H)-pyrimidinon-5′-triphosphat, 1-(2′-Desoxy-β-D-ribofuranosyl)-2(1 H)pyridinon-5′-triphosphat und 4-Amino-1-(2′-Desoxy-β-D-ribofuranosyl)-2(1 H)-pyridinon-5′-triphosphat gegenüber DNA-Polymerase

Nucleosides and Nucleotides. Part 16. The Behaviour of 1-(2′-Deoxy-β-D -ribofuranosyl)-2(1H)-pyrimidinone-5′-triphosphate, 1-(2′-Deoxy-β-D -ribofuranosyl-2(1H))-pyridinone-5′-triphosphate and 4-Amino-1-(2′-desoxy-β-D -ribofuranosyl)-2(1H)-pyridinone-5′-triphosphate towards DNA Polymerase The behaviour of nucleotide base analogs in the DNA synthesis in vitro was studied. The investigated nucleoside-5′-triphosphates 1-(2′-deoxy-β-D -ribofuranosyl)-2(1 H)-pyrimidinone-5′-triphosphate (pppM_d), 1-(2′-deoxy-β-D -ribofuranosyl)-2(1 H)-pyridinone-5′-triphosphate (pppII_d) and 4-amino-1-(2′-deoxy-β-D -ribofuranosyl)-2(1 H)-pyridinone-5′-triphosphate (pppZ_d) can be considered to be analogs of 2′-deoxy-cytidine-5′-triphosphate. However, their ability to undergo base pairing to the complementary guanine is decreased. When pppM_d, pppII_d or pppZ_d are substituted for pppC_d in the enzymatic synthesis of DNA by DNA polymerase no incorporation of these analogs is observed. They exhibit only a weak inhibition of the DNA synthesis. The mode of the inhibition is uncompetitive which shows that these nucleotide analogs cannot serve as substrates for the DNA polymerase.     

Nucleoside und Nucleotide. Teil 15. Synthese von Desoxyribonucleosid-monophosphaten und -triphosphaten mit 2(1H)-Pyrimidinon, 2(1H)-Pyridinon und 4-Amino-2(1H)-pyridinon als Basen

Nucleosides and Nucleotide. Part 15. Synthesis of Deoxyribonucleoside Monophosphates and Triphosphates with 2(1H)-Pyrimidinone, 2(1H)-Pyridinone and 4-Amino-2(1H)-pyridinone as the Bases The phosphorylation of the modified nucleosides 1-(2′-deoxy-β-D -ribofuranosyl)-2(1 H)-pyrimidinone (M_d, 4 ), 4-amino-1-(2′-deoxy-β-D -ribofuranosyl)-2(1 H)-pyridinone (Z_d, 6 ) and the synthesis of 1–2′-deoxy-β-D -ribofuranosyl-2(1 H)-pyrimidinone-5′-O-triphosphate (pppM_d, 1 ), 1-(2′-deoxy-β-D ribofuranosyl)-2(1 H)-pyridinone-5′-O-triphosphate (pppII_d, 2 ), and 4-amino-1-(2′-deoxy-βD -ribofuranosyl)-2(1 H)-pyridinone-5′-O-triphosphate (pppZ_d, 3 ) are described. The nucleoside-5′-monophosphates pM_d (5) and pZ_d (7) were obtained by selective phosphorylation of M_d (4) and Z_d (6) , respectively, using phosphorylchloride in triethyl phosphate or in acetonitril. The reaction of pM_d (5) pII _d (8) or pZ_d (7) with morpholine in the presence of DCC led to the phosphoric amides 9, 10 and 11 , respectively, which were converted with tributylammonium pyrophosphate in dried dimethylsulfoxide to the nucleoside-5′triphosphates 1, 2 and 3 , respectively.     

C45 und C50-Carotinoide. 6. Mitteilung. Synthese eines optisch aktiven cyclischen C20-Bausteins und von Decaprenoxanthin (= (2R, 6R, 2′R, 6′R)-2,2′-Bis(4-hydroxy-3-methylbut-2-enyl)-ϵ, ϵ-carotin)

C₄₅- and C₅₀-Carotenoids: Synthesis of an Optically Active Cyclic C₂₀-Building Block and of Decaprenoxanthin ( = (2R, 6R, 2′R, 6′R)-2,2′-Bis(4-hydroxy-3-methylbut-2-enyl)-?, ?-carotene) The synthesis of the optically active cyclic C₂₀-building block (R, R) -15 and of the optically active C₅₀-carotenoid (2R, 6R, 2′R, 6′R)-decaprenoxanthin ( 1 ) starting from (-)-β-pinene ((S)- 2 ) is reported.     

The mechanism of thermal elimination of urea and thiourea derivatives. Part 2. Rate data for pyrolysis of N-acetyl-N′-phenylthiourea and N-benzoyl-N′-arylthioureas

The first-order rate constants of N-acetyl-N′-phenylthiourea (1), N-benzoyl-N′-phenyl-(2a), N-benzoyl-N′-(4-nitrophenyl)-(2b), N-benzoyl-N′-(3-chlorophenyl) (2c), N-benzoyl-N′-(4-chlorophenyl) (2d), and N-benzoyl-N′-(4-methylphenyl)thiourea (2e) were measured between 423 and 500 K. The reactions were homogeneous and unimolecular with log A (s⁻¹) = 12.0, 13.2, 13.8, 10.9, 11.8, and 12.7 and E_a kJ mol⁻¹ = 130.3, 141.4, 134.6, 114.9, 124.1, and 141.1, respectively. The rate data gave good Hammett correlation with σ^o values, and ρ is 1.99 at 450 K. © 1997 John Wiley & Sons, Inc.     

Alkaloids of the flora of Siberia and Altai: XX. Synthesis of 5-aryl(hetaryl)-substituted anthranilic acid esters

Cross-coupling of methyl 2-acetylamino-5-bromobenzoate and 5′-bromolappaconitine with aryl-, furyl-, pyridyl-, and 5-acetylthiophen-2-ylboronic acids or 1-(2-fluoroquinolin-3-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane gave the corresponding 5-aryl(hetaryl)-substituted anthranilic acid derivatives. The use of the two-phase toluene-water system as reaction medium and addition of tetrabutylammonium bromide allows the cross-coupling to be accomplished under mild conditions. The catalytic system Pd(dba)₂-AsPh₃ was found to be efficient in the cross-coupling of methyl 2-acetylamino-5-bromobenzoate with furyl- and pyridylboronic acids, whereas the system Pd(OAc)₂-(o-Tol)₃P ensured good results in the reactions of 5′-bromolappaconitine with hetarylboronic acids. Facile esterification at the C⁸-OH and C⁹-OH groups of the aconitane skeleton was observed in the reactions of 5′-bromolappaconitine and 5′-phenyllappaconitine with phenylboronic acid. 5′-Bromo-8,9-O-(phenylboranediyl)lappaconitine under the Suzuki reaction conditions underwent hydrolysis of the boronic ester moiety with formation of the cross-coupling product of 5′-bromolappaconitine with phenylboronic acid.     

Nucleotides. Part XLV. Synthesis of new (2′–5′)adenylate trimers,containing 5′-amino-5′-deoxyadenosine residues at the 5′-end of the oligoadenylate chain,and of its analogues,carrying a 9-[(2-hydroxyethoxy)methyl]adenine residue at the 2′-terminus

The 5′-amino-5′-deoxy-2′,3′-O-isopropylideneadenosine ( 4 ) was obtained in pure form from 2′,3′-O-isopropylideneadenosine ( 1 ), without isolation of intermediates 2 and 3 . The 2-(4-nitrophenyl)ethoxycarbonyl group was used for protection of the NH₂ functions of 4 (→7) . The selective introduction of the palmitoyl (= hexadecanoyl) group into the 5′-N-position of 4 was achieved by its treatment with palmitoyl chloride in MeCN in the presence of Et₃N (→ 5 ). The 3′-O-silyl derivatives 11 and 14 were isolated by column chromatography after treatment of the 2′,3′-O-deprotected compounds 8 and 9 , respectively, with (tert-butyl)dimethylsilyl chloride and 1H-imidazole in pyridine. The corresponding phosphoramidites 16 and 17 were synthesized from nucleosides 11 and 14 , respectively, and (cyanoethoxy)bis(diisopropylamino)phosphane in CH₂Cl₂. The trimeric (2′–5′)-linked adenylates 25 and 26 having the 5′-amino-5′-deoxyadenosine and 5′-deoxy-5′-(palmitoylamino)adenosine residue, respectively, at the 5′-end were prepared by the phosphoramidite method. Similarly, the corresponding 5′-amino derivatives 27 and 28 carrying the 9-[(2-hydroxyethoxy)methyl]adenine residue at the 2′-terminus, were obtained. The newly synthesized compounds were characterized by physical means. The synthesized trimers 25–28 were 3-, 15-, 25-, and 34-fold, respectively, more stable towards phosphodiesterase from Crotalus durissus than the trimer (2′–5′)ApApA.     

Reaktionen von N-alkoxycyclimoniumsalzen—II. Heterocyclen aus ringöffnungsreaktionen von N-methoxypyridiniumsalzen

Rearrangement of 3-substituted N-methoxypyridinium-salts (R= COOH, COOCH₃, CONH₂) in aqueous solution by alkali resp. ammonia yields 3 - methoxyiminomethylpyridone - (2). Under the same conditions, 5 - hydroxy - 3′- (2′- methoxyiminoethylidene) - pyrrolidone - (2) is formed from N - Methoxypyridinium - 4 - carbonitrile.     

Decolorization Reactions Between Chromium (VI) and Three Colour Reagents. Determination of Chromium (VI) by Flow Injection Analysis

Abstract

Chromium (VI) can oxidize and decolor three colour reagents, i.e. 1,8-dihydroxy-2-(4′-chloro-2′-phosphonophenylazo)-7-(6″.8″-disulfonaphthylazo)-3,6-disulfonaphthalene (RI): 1,8-dihydroxy-2-(4′-chloro-2′-phosphonophenylazo)-7-(4″-sulfonamidephenylazo)-3,6-disulfonaphthalene (RII): and 1,8-dihydroxy-2-(4′-chloro-2′-phosphonophenylazo)-7-(p-hippuric acid azo)-3,6-disulfonaphthalene (RIII). Loss of absorbance of three colour reagents at maximum absorption wavelengths is proportional to the concentration of chromium (VI) in solution. We have made use of the decolorization reactions between chromium (VI) and three colour reagents to determine chromium in steel by flow injection analysis, and relative error in sample determination is less than 5.0%. Response is linear from 0.84 to 6.72 μg/mL and optimum measuring acidity is 1.3–1.7 mol/L H₂SO₄ in three systems. The effect of interference ions on determination has been studied.     

Über Chalkogenolate. 168. Reaktion von N,N′-Diphenylformamidin mit Kohlenstoffdisulfid 1. Darstellung und Eigenschaften von N,N′-Diphenyl-N-form-imidoyldithiocarbamaten

On Chalcogenolates. 168. Reaction of N,N′-Diphenyl Formamidine with Carbon Disulfide. 1. Synthesis and Properties of N,N′-Diphenyl N-Formimidoyl Dithiocarbamates N,N′-Diphenyl formamidine H? N(C₆H₅)? CH?NC₆H₅ reacts in different solvents with CS₂ in the presence of an alkali metal hydroxide to produce N,N′-diphenyl N-formimidoyl dithiocarbamate solvates. The properties of the prepared compounds (L = H₂O, acetonitrile, dioxane, dimethoxyethane, acetone, and mixed solvates) and of the Tl, Ba, and Pb salts are described.     

Nucleosides and Nucleotides. Part 13. Synthesis and spectral properties of 1- (3′-O-Phosphoryl-2′-deoxy-β -D-ribofuranosyl)-2(1H)-pyridone-(3′-5′)-1-(2′-deoxy-β-D-ribofuranosyl)-2 (1H)-pyridone

The dinucleoside phosphate Π_dpΠ_d ( 4 ) was synthesized from the monomers 1-(5′-O-monomethoxytrityl - 2′ - deoxy - β - D - ribofuranosyl) - 2 (1 H) - pyridone ((MeOTr) Π_d, 2 ) and 1-(5′-O-phosphoryl-3′-O-acetyl-2′-deoxy-β-D -ribofuranosyl)-(1H)-pyridone (pΠ_d(Ac), 3 ). Its 6.4% hyperchromicity and an analysis of the ¹H-NMR. spectra indicate that the conformation and the base-base interactions in 4 are similar to those in natural pyrimidine dinucleoside phosphates.