The synthesis of naphthothiopyranopyranones and naphthothiopyranopyranthiones

The synthesis of fused tetracyclic naphthothiopyranopyranones from dihydronaphthothiopyranones I or II has been studied. Compounds I or II have been cyclised in good yield to the corresponding dioxaborin difluoride complexes III, IV, XIII and XIV by treatment with acetic or propionic anhydride and boron trifluoride etherate. These complexes and the Vilsmeier reagent reacted to produce fused tetracyclic 3-substituted naphthothiopyranopyranones V, VI, XV or XVI . The reaction of dioxaborin difluoride complexes III or IV with dimethylthioformamide (DMTF) afforded dimethylaminovinyldioxaborin difluoride complexes IX or X . Treatment of IX or X with hydrochloric acid solution gave naphthothiopyranopyranones VII or VIII . The reaction of VII, VIII, XV or XVI with DMTF/acetic anhydride yielded new products, which was identified as naphthothiopyranopyranthions XI, XII, XVII or XVIII .     

Synthesis of pyrido[1,2-a]pyrimido[4,5-d]pyrimidin-5-ones. Cyclization reaction of 4-[(3-hydroxy-2-pyridyl)amino]-2-phenyl-5-pyrimidinecarboxylic acid with acetic anhydride

Treatment of 4-[(3-hydroxy-2-pyridyl)amino]-2-phenyl-5-pyrimidinecarboxylic acid (X) with acetic anhydride under refluxing conditions afforded 10-hydroxy-2-phenyl-5H-pyrido[1,2-a]-pyrimido[4,5-d]pyrimidin-5-one acetate (IX). The intermediate X was prepared from 4-chloro-2-phenyl-5-pyrimidinecarboxylic acid ethyl ester (V). The reaction of V with the sodium salt of 2-amino-3-hydroxypyridine at room temperature gave 4-(2-amino-3-pyridyloxy)-2-phenyl-5-pyrimidinecarboxylic acid ethyl ester (VI). Treatment of VI with a hot aqueous sodium hydroxide solution and subsequent acidification gave X. Involvement of 4-[(3-hydroxy-2-pyridyl)amino]-2-phenyl-5-pyrimidinecaroboxylic acid ethyl ester (VIII) (Smiles rearrangement product) as an intermediate in the above alkaline hydrolysis reaction of VI to X was demonstrated by the isolation of VIII and its subsequent conversion into X under alkaline hydrolysis conditions. Acetylation of VIII with acetic anhydride in pyridine solution gave 4-[(3-hydroxy-2-pyridyl)amino]-2-phenyl-5-pyrimidinecarboxylic acid ethyl ester acetate (XI), which afforded IX on fusion at 220°. This alternative synthesis of IX from XI supported the structural assignment of IX. Fusion of VI gave 10-hydroxy-2-phenyl-5H-pyrido[1,2-a]pyrimido]4,5-d]pyrimidin-5-one (VII). The latter was also obtained when VIII was fused at 210°. Acetylation of VII with acetic anhydride afforded IX.     

Three new pyrrolizidine alkaloids derivatives from Liparis nervosa

Three new pyrrolizidine alkaloids, nervosine VⅡ (1), nervosine VⅢ(2) and nervosine Ⅸ(3) were isolated from the whole plant extract of Liparis nervosa. Their structures were elucidated by extensive spectroscopic analyses(including 1D, 2D NMR, and HR-ESI-MS) and chemical methods. Compounds 1–3were evaluated for their cytotoxic activity against A549, MCF-7and H460 human cancer cell lines.     

Synthesis and some reactions of sulfides of the thiophene series

By the action of four equivalents of sodium in liquid ammonia on the bis(alkylmercapto)thiophenes I, II, and IX we have obtained the corresponding dimercaptothiophenes VII, IX, and VIII, which were characterizied in the form of their dibenzoyl derivatives XI–XIII. The dimercaptothiophenes VII and VIII and the o-alkylthiothiophenethiols III and IV form the internally complex compounds XIV–XVII with metal acetates.     

Über in 6-Stellung basisch substituierte Morphanthridine. 8. Mitteilung über siebengliedrige Heterocyclen

Morphanthridines III with a basic substituent in position 6, which show neuroleptic activity, have been synthesised as follows: Chlorination of the lactams I with POCl₃ gave the iminochlorides II, which were converted by bases to the amidines III. The 11-oxo-morphanthridines VI and VII were synthesised using the same procedure, 2-(1-methylpiperazine-4-carbonyl)-2′-amino-benzophenone (XI) was obtained directly from the 6-chloro-11-oxo-morphanthridine (V) or by extended heating of VI with N-methylpiperazine. Reduction of the 11-oxo-compounds VI and VII with NaBH₄ gave the 11-hydroxy-compounds IX and X. 3-(2-aminophenyl)-phtalide (VIII) resulted from the acid hydrolysis of IX.     

Synthese und Umlagerungsreaktionen von 2-(2-Amino-anilino)-2-imidazolin-Derivaten

The nitro-imidazolines V and VI are formed by addition reaction of ethylenediamine to the isothiocyanates III and IV. The nitro group is then converted by hydrogenation to the amino group, giving XI and XII, which can be acylated selectively to IX and X. By rearrangement in boiling xylene, the compounds XI and XII give the corresponding 2-(2-aminoethylamino)-benzimidazoles XIII and XIV. The benzoylated derivative IX gives the benzimidazole derivative XVIII by rearrangement and subsequent migration of the benzoyl group, while the benzylated derivative XVI gives the rearranged benzimidazole XXII. The benzimidazole structure of the rearranged products is proven by unambiguous synthesis of XIII, starting with 2-chlorobenzimidazole (VII) and mono-N-acetyl-ethylene-diamine to give compound VIII, from which XIII is obtained by hydrolysis.     

Metabolism of terniary compounds. V. Decomposition of diincarbonic acids and hydrocarbons in vivo

10,12-Heneicosadiynoic acid (I), 5,7-hexadecadiynoic acid (IV), and 10,12-docosadiynedioic acid (VI) were fed to rats. As metabolites 4,6-undecadiynedioic acid (II), 5,7-dodecadiynedioic acid (V), and 4,6-decadiynedioic acid (VII) respectively were isolated from the urine. 10,12-Heptadecadiynoic acid (III) also yielded metabolite II. Furthermore 9,11-eicosadiyne (X) and for comparison purposes eicosane (XI), hexadecanedioic acid (VIII), and docosanedioic acid (IX) were fed. X and XI were incorporated into depot fat and liver lipids to a cetain degree. The diynes I, II, IV, and X are new compounds.     

Alkaloids from Bulbocodium vernum L. Content material of Liliaceae-Wurmbaeoidaea

From whole plants of Bulbocodium vernum L. the flavone luteoline (I) and the alkaloids colchicine (II), N-formyl-N-deacetylcolchicine (III), 3-demethylcolchicine (V), (+)-bulbocodine (IX) and (?)-kreysigine (XI) were isolated in crystals. The presence of 2-demethylcolchicine (IV), ß- (VII) and γ-lumicolchicine (VIII), demecolcine (VI) and five not identified alkaloids was demonstrated by thin-layer chromatography. On the basis of ultraviolet, infrared and mass spectra, PMR.-analysis (Overhauser effect), and circular dichroism, the (6a-R, 8a-S)homo-proaporphine structure IX, with one methoxy group at C-2, has been assigned to (+)-bulbocodine. The (6a-R)-structure (XI) was deduced for (?)-kreysigine by comparing its optical rotation and circular dichroism which the values of (?)-multifloramine (X), the structure of which is known.     

Pheromones of insects and their analogs

Dodec-8Z-en-1-ol (VIII) and tetradec-8Z-en-1-ol (IX) and the corresponding acetates (X and IX) — components of the sex pheromones of many species of Lepidoptera — have been synthesized from cyclooctene (I) in three stages. The ozonolysis of (I) (–70°C, CH₂Cl₂-MeOH, NaHCO₃; –20°C, Ac₂O/Et₃N) led to methyl 8-oxooctanoate (II). The DNPH of (II), (III), mp 59–61°C. The coupling of (II) with n-C₃H₁₇ CH=PPh₃ (IV) or with n-C₅H₁₁ CH=PPh₃ (V) (–70°C, 2 h; 25°C, 15 h, Ar) gave the methyl esters of dodec-8Z-enoic (VI) and tetradec-8Z-enoic (VII) acids, respectively. The reduction of (VI) and (VII) [(i-Bu)₂AlH, 0°C, 2 h; 25°C, 15 h] gave the corresponding alcohols (VIII) and (IX) by the acetylation (Ac₂O-Py, 25°C, 24 h) of which, (X) and (XI), were obtained. The yields (%): (II) 80, (VI) 45, (VII) 60, (VIII) 95, (IX) 90, (X) 75, (XI) 74. The IR and PMR spectra of compounds (II) and (VI–XI) are given.Institute of Chemistry, Bashkir Scientific Center, Urals Branch, Academy of Sciences of the USSR, Ufa. Translated from Khimiya Prirodnykh Soedinenii, No. 2, pp. 276–279, March–April, 1989.     

Reactions with α-substituted cinnamonitriles. A novel synthesis of hexa-substituted pyridines

Whereas acetoacetanilide (II) reacted with α-cyano- and α-benzoylcinnamonitrile derivatives Ia-e to give hexa-substituted pyridines III and V, it reacted with α-carboxamido- and α-thiocarboxamidocinnammonitrile derivatives If-h to afford penta-substituted pyridines VI. One mole of acetonedicarboxylic acid dianilide (VII) reacted with two moles of each of α-cyano- and α-thiocarboxamidocinnamonitriles Ia,b,f,g to yield the dipyridyl ketones VIII and IX, respectively. On the other hand, α-benzoyl- and α-ethoxycarbonylcinnamonitriles Ic,d,i,j reacted with VII in equimolecular ratio to give the pyran derivaties X and XI, respectively. Several schemes were proposed to illustrate reactions steps. The structures of the synthesized compounds were proved by chemical and spectral methods.     

Relative evaluation of neutron activation,X-ray fluorescence and spark source mass spectrometry for multielement analysis of geothermal waters

To sulfide geothermal waters from the French Pyrenees region and bicarbonate and chloride waters from the French Vosges area, all of the following analysis techniques were applied in order to compose a broad inventory of trace elements: (1) for the dissolved material: neutron activation analysis after a freeze-drying step using a very short cycle (I), short cycle (II) or long cycle (III), neutron activation after co-crystallization on 1-(2-pyridylazo)-2-naphthol (PAN) using a short cycle (IV) or long cycle (V), X-ray fluorescence after co-crystallization on PAN (VI) and spark source mass spectrometry after evaporation on graphite (VII) or preconcentration on PAN, and, (2) for the filtered or suspended material: neutron activation using a very short (VIII), short (IX) or long cycle (X) and X-ray fluorescence (XI). Altogether, on the average some 30 elements could be determined above the detection limit in solution and 15 in suspension. It appeared, however, that for procedures (I), (II), (IV), (VI), (VIII) and (XI) the investment of time and cost had not been efficient enough. Invoking only procedures (III), (V), (IX), (X) and for low salinity geothermal waters only: (VII), the number of elements detected was almost as large.     

Mass spectrometry of hop compounds—III. Mass spectra of substituted 1,3-cyclopentanediones derived from hop constituents

The mass spectra of isohumulones (IV, V), tetrahydroisocohumulones (VI, VII), tetrahydroisohumulones (VIII) neohydroisocohumulones (XI, XII) cohumulinic acid (III), lupuloxinic acid (XV), humulinone (XIV) and related compounds are described. Ions which appear to be diagnostic for particular structures are discussed.     

High-Performance Liquid Chromatography of New Semisynthetic Daunomycinone Derivatives

Abstract

Reversed-phase HPLC utilizing LiChrosorb RP-8 was used to separate reaction mixtures of new semisynthetic daunomycinone derivatives and determine their relative occurrence.

Chromatographic behaviour of the following compounds was studied: daunomycinone (I), 7(S) and 7(R)-0-(2-hydroxyethyl)-13-ethyleneacetal daunomycinone (II and III), 13-ethyleneacetal daunomycinone (IV), 13-ethyleneacetal bisanhydrodaunomycinone (V), 7(S) and 7(R)-0-(3-hydroxypropyl)-13-propyleneacetal daunomycinone (VI and VII), 13-propyleneacetal daunomycinone (VIII), 13-propyleneacetal bisanhydrodaunomycinone (IX), 7(S) and 7(R)-0-(4-hydroxybutyl) daunomycinone (X and XI), 4-toluenesulfonylhydrazone daunomycinone (XII).     

Synthesis of certain 2-substituted-1H-benzimidazole derivatives as antimicrobial and cytotoxic agents

A series of 2-substituted-1H-benzimidazole derivatives were synthesized and evaluated for antimicrobial, antifungal and cytotoxic activities. The results showed that all tested compounds showed potent antimicrobial activity against some species of Gram-negative bacteria (Pseudomonas aeruginosa, Escherichia coli, Salmonella typhi) and fungi (Candida albicans) with minimum inhibitory concentrations (MICs) lower than 0.016 μg/mL. In contrast, all tested compounds were inactive against Staphylococcus aureus (Gram-positive bacterium). The final targets were also tested for their antitumor activity in vitro on cervical carcinoma (HeLa) cell line. Eight of the test compounds displayed more potent cytotoxic effect than doxorubicin at nanomolar concentrations. Compounds 2c and 3c exerted the strongest cytoyoxic effect with IC(50) 15 and 13 nM, respectively.     

Molecular dynamics study of crystalline water ices

The behavior of structures of H₂O crystalline ices Ih, Ic, XI, VII, VIII, VI is studied in molecular dynamics experiment using the potential offered by Poltev and Malenkov. The behavior of the system consisting of one of the two identical interpenetrating, but without any common hydrogen bonds, water frameworks comprising the ice VI structure is also simulated. As a result of simulations, the ice VII structure has collapsed, whereas other systems proved to be stable. The reasons of instability of the ice VII and previously studied ice IV structures in molecular dynamics experiments are discussed. Based on the simulation results of the above-mentioned ices and previous simulation of ices II, III, IX, IV, and XII, the general regularities of dynamic properties of water molecules in crystalline water ices are formulated. Unreliability of results obtained by molecular dynamics in the investigation of self-organizing processes in aqueous systems is shown.     

Electron-transfer polymers. XXIX. Copolymerizability of vinylhydroquinone derivatives

Ten vinylhydroquinone and one vinyl resorcinol derivatives are compared, particularly with respect to NMR spectra and copolymerizability with styrene. They are vinylhydroquinone dimethyl ether (I), vinyl-O,O′-bis(1-ethoxyethyl)hydroquinone (II), vinylhydroquinone di(2-pentyl)ether (III), 4-vinyl resorcinol bismethoxymethyl ether (IV), 2-vinyl-5-methylhydroquinone dimethyl ether (V), 2-vinyl-5-methyl-O,O′-bis(1-ethoxyethyl)hydroquinone (VI), 2-vinyl-6-methylhydroquinone dimethyl ether (VII), 2-vinyl-5-tert-butylhydroquinone dimethyl ether (VIII), 2-vinyl-5-chlorohydroquinone dimethyl ether (IX), 2-vinyl-3,6-dimethylhydroquinone dimethyl ether (X), and 2-vinyl-3,5,6-trimethylhydroquinone dimethyl ether (XI). All the vinyl protons have almost the same coupling constants. Though subtle distinctions are found among all the spectra, they can in general be put into two groups on the basis of the chemical shifts. Let the hydrogen on carbon-1 of the vinyl group be A, the hydrogen cis to A be B the hydrogen trans to A be C, then in the first group, (I) through (IX), the chemical shifts (τ) are (A) 3.02 ± 0.08, (C) 4.41 ± 0.05, and (B) 4.87 ± 0.07, and in the second group, (X) and (XI), they are (A) 3.30 ± 0.03, (C) 4.49 ± 0.01, and (B) 4.59 ± 0.03. It is supposed that in (X) and (XI) the vinyl group is out of the plane of the ring, because of the two ortho substituents, and this conformation is reflected in the NMR data. Ultraviolet spectra are consonant with this interpretation, since the λ_max of (X) and (XI) correspond closely with those of nonvinyl reference compounds, while those of (II), (V), and (VIII) are shifted to longer wavelengths. When these compounds are copolymerized separately with styrene, the behaviors are classifiable into the following three groups, where r₁ and r₂ are monomer reactivity ratios with styrene as the first monomer: (i) r₁ < 1 and r₂ < 1 for compounds (II) and (III) and the reference compound O,O′-dibenzoylvinylhydroquinone, (ii) r₁ < 1 and r₂ > 1 for compounds (I), (V), (VII), (VIII), (IX), and (iii) r₁ > 1 and r₂ = 0 for compounds (X) and (XI). These behaviors are correlated with the effect of electronegativity of groups on the stability of the radical at the growing end of the chain and with the simultaneous effects of steric hindrance.     

Fluorocyclohexanes. Part XVII. Dehydrofluorinations of the cis and the trans isomers of 2H-1-(difluoromethyl)decafluorocyclohexane

2H-1-(Difluoromethyl)octafluorocyclohex-1-ene (I) and cobalt trifluoride at 165 °C afforded 2H-1-(trifluoromethyl)octafluorocyclohex-1-ene (IV) and four decafluorocyclohexane derivatives: the cis (III), and trans (V), -2H-1-(trifluoromethyl)-; the cis (VII), and trans (VI), 2H-1-(difluoromethyl) compounds. Dehydrofluorination of VII, using aqueous potassium hydroxide, gave only one alkene, 1-(difluoromethyl)nonafluorocyclohex-1-ene (VIII). In a slower reaction VI afforded two alkenes, mainly VIII, But also an isomer, 1-(difluoromethyl)nonafluorocyclohex-2-ene (IX) (ratio 2:1).     

13C-NMR Spectra of 2- and 3-Phthalimido-3(2)-Benzimidazolylpropanoic Acid and 2- and 3-Phthalimidobenzimidazopyrrolone,Reaction Products of Phthaloylaspartic Anhydride with Ortho-Phenylenediamine

Two pairs of isomers of 3- and 2-phthalimido-3(2)benzimidazolylpropanoic acid (V and VI) and 2- and 3-phthalimidobenzimidazopyrrolone (VII and VIII) were produced from the reaction of phthaloylaspartic anhydride (I) with o-phenylenediamine (II). The ¹³C-NMR spectra of V and VI both showed 11 carbon signals indicating that the structures of their benzimidazole groups were symmetric. Isomers V and VI were easily distinguished from each other by the chemical-shift-differences (Δδ) of the methylene carbon and the methine carbon. Compounds VII and VIII displayed 14 carbon signals and no longer showed the symmetric structure of the benzimidazole moity, The chemical-shift-differences (Δδ) between methylene carbon and methine carbon in pyrrolones of VII and VIII can also be used to distinguish VII from VIII. The Δδ of compound VII is less than that of compound VIII.     

Synthese und reaktionen von zinn-substituierten pentadienderivaten

(1E, 4E)-1,5-Bis(trimethylstannyl)pentadiene-1,4 (III), 1E-1-trimethylstannyl-pent-1-ene-4-yne (IV) and the 1,1-dialkyl-1-stannacyclohexadienes-2,5 VII and VIII have been synthesized by hydrostannation of pentadiyne-1,4. (1E, 4E)1,5-Dibromapentadiene-1,3 (IX) is formed from III and 1,1,2,4,5,5-hexabromopentane (X) from IX by reaction with bromine. Butyllithium reacts with III to give (1E, 4E)-1,5-dilithium pentadiene-1,4 (XI). The reactions of butyl- and methyllithium with VII and VIII give only the monolithium compounds XIII, XV and XVII. All lithium compounds are characterised in the form of their trimethylsilyl derivatives XII, XIV, XVI and XVIII. ¹H NMR, IR, UV and mass spectral data are described.     

New routes to aroylthiadiazolines and arylazothiazoles from phenylglyoxalyl bromide arylhydrazones and phenacyl thiocyanate

Reaction of phenylglyoxalyl bromide arylhydrazones (III) with thiourea in ethanol produces 2-amino-4-phenyl-5-arylazothiazoles (XI) instead of the expected 2-benzoyl-4-aryl-5-imino-Δ^2?1,3,4-thiadiazolines (V) obtained from III and potassium thiocyanate. Phenacyl thiocyanate (IV) couples with diazotized anilines to give V. The mechanisms of formation of V and XI from VI and III, respectively, are postulated. Nitrosation of V gives the corresponding N-nitroso derivatives (VII), which decompose upon refluxing in xylene to give 2,4-disubstituted Δ² ?1,3,4-thiadiazolin-5-ones (VIII). The thiadiazolines V give the respective N-aeyl derivatives IX and X with acetic anhydride and benzoyl chloride in pyridine.