Tetrahydro Derivatives Research Articles

Annulation reactions with iron(III) chloride: oxidation of imines

Aromatic imines react with phenylacetylene or styrene in an acetonitrile solution of iron(III) chloride to give quinolines 3 or their tetrahydro derivatives 11 together with variable amounts of products 4 arising from the reduction of the imines. The initial atep appears to be a one-electron oxidation to generate iron(II) and an imine radical cation. When the reactions are carried out in the presence of stoichiometric amounts of tetrachloro-p-benzoquinone (chloranil), only quinolines 3 are obtained

Synthesis of 11H-Furo[3',2':7,8]benzopyrano[3,4-c]pyridin-11-one and 6,8-Dimethyl-10H-pyrano[2',3':4,5]benzofuro[3,2-c]pyridin-10-one (Pyridoangelicins)

11H-Furo[3',2': 7,8]benzopyrano[3,4-c]pyridin-11-one (3) was synthesized from 1-benzyl-3-ethoxycarbonylpiperidin-4-one and 2,3-dihydro-4-hydroxybenzofuran (5) by a von Pechmann reaction and subsequent aromatization of the hexahydro derivative (6). 6,8-Dimethyl-10H-pyrano[2',3': 4,5] benzofuro-[3,2-c]pyridin-10-one (4a) was obtained by dehydrogenation of the tetrahydro derivative (10b). This compound was prepared from piperidinone-O-(4,6-dimethylcoumarin-7-yl) oxime (9b) using acid catalyzed Fischer indole-like reaction

Olefin copolymerization with metallocene catalysts. I. Comparison of catalysts

AbstractA number of metallocene/methylaluminoxane (MAO) catalysts have been compared for ethylene/propylene copolymerizations to find relationship between the polymerization activities, copolymer structures, and copolymerization reactivity ratio with the catalyst structures. Stereorigid racemic ethylene bis (indenyl) zirconium dichloride and the tetrahydro derivative exhibit very high activity of 10 7 g (mol Zr h bar)−1, giving copolymers having comonomer compositions about the same as the feed compositions, molecular weights increasing with the increase of ethylene in the feed, random incorporation of comonomers, and narrow molecular weight distribution indicative of a single catalytic species. Nonbridged bis (indenyl) zirconium behaved differently, favoring the incorporation of ethylene over propylene, producing copolymers whose molecular weight decreases with the increase of ethylene in the feed, broad molecular weight distribution, and a methanol soluble fraction. This catalyst system contains two or more active species. Simple methallocene catalysts have much lower polymerization activities. CpTiCl2/MAO produced copolymers with tendency toward alternation, whereas Cp2HfCl2/MAO gave copolymer containing short blocks of monomers.

Synthesis and biological evaluation of a fluorescent analog of folic acid

A fluorescein derivative of the lysine analogue of folic acid, N alpha-pteroyl-N epilson-(4'-fluoresceinthiocarbamoyl)-L-lysine (PLF), was synthesized as a probe for dihydrofolate reductase (DHFR) and a membrane folate binding protein (m-FBP). Excitation of PLF at 282 nm and at 497 nm gave a fluorescence emission maximum at 518 nm. Binding of PLF to human DHFR or human placental m-FBP results in approximately a 20-fold enhancement in the magnitude of the fluorescence emission, suggesting that the ligand interacts with a hydrophobic region on these proteins. Additional evidence suggests that an energy transfer may occur between the pteridine and the fluorescein moieties. PLF binds to the active site of human DHFR since methotrexate (MTX) competes stoichiometrically and the denatured enzyme in the presence of PLF did not exhibit fluorescent enhancement. The dissociation constant for the fluorescein derivative with respect to human DHFR is 115 nM as compared to 111 nM for folic acid. The Ki value for the competitive inhibition of human DHFR by the fluorescent analogue of folic acid is 2.0 microM compared to 0.48 microM for folic acid. PLF was reduced to N alpha-(7,8-dihydropteroyl)-N epilson-(4'-fluoresceinthiocarbamoyl)-L-lysine (H2PLF) and assayed by the enzymatic conversion to the tetrahydro derivative. The Km value for human DHFR for the dihydrofolate analogue is 2.0 microM. The KD value for H2PLF to human DHFR is 47 nM as compared to 44 nM for dihydrofolate. The KD values for both H2PLF and PLF indicate that the fluorescein moiety does not significantly affect folate binding in enzyme binary complexes.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypertensiv wirksame 5‐(β‐Aminoethyl)aminoisoxazole: Synthese und Prüfung von Isoxazolopyrazinen und Isoxazolodiazepinen

The 5-aminoisoxazole 1 is converted via the 4-nitro derivative to the 4,5-diamino compound 4, which cyclises with glyoxal to yield the isoxazolo[4,5-b)pyrazine 5. Decomposition of the isoxazole moiety is always observed in experiments to hydrogenate partially the pyrazine ring and to phenylate the N-atom, respectively. Therefore, the corresponding tetrahydro derivative 6 is prepared from 4 and 1,2-ethandiol ditosylate. Starting with benzohydroxamic acid chloride and a cyanoacetic acid amide the tetrahydro isoxazolo[5,4-e]1,4-diazepinone-4 18 is synthesized. All new compounds are characterized by their spectroscopic data, the reaction mechanisms are discussed. Using the model of the pithed and the anaesthetized rat, resp., the pyrazino- and diazepino-isoxazoles (compounds 5, 6, 13, 18) have less or no hypertensive activity as compared to the corresponding derivatives with fully flexible side chains.

Induction of male sexual behavior by norethisterone: Role of its A-ring reduced metabolites

The estrogenic and androgenic potencies of norethisterone (NET), a synthetic nonaromatizable progestin, and three of its reduced metabolites (5α-NET; 3α, 5α-NET; 3β, 5α-NET) were assessed by their ability to restore male sexual behavior in castrated male rats following their chronic administration in combination with either 5α-dihydrotestosterone (DHT) or estradiol (E 2), or when given alone. Full restoration of mating was achieved when 3β, 5α-NET was administered with DHT, indicating an estrogenic effect of this compound. Lower estrogenic effects were noticed with 3α,5α-NET and 5α-NET had a very little estrogenic potency. The only effective compound to restore ejaculation, when administered with E 2, was NET, indicating its androgen-like intrinsic potency. When administered alone, NET exerted the most potent effect on male behavior, followed by 5α-NET, while the tetrahydro derivatives were ineffective. The observation that NET alone restored male sexual activity at a level identical to that induced by testosterone demonstrated an andronergic-estrogenic activity of this progestin exerted through its intrinsic androgenic effect, and the estrogenic effect of its tetrahydro derivatives. Overall results indicated that the metabolism of NET modulates its mode of action at the brain, and support the concept that both estrogenic and androgenic effects are required for mating activation.

Some observations on the electrochemical reduction of pyridazin-3-ones

Controlled potential electroreduction of three pyridazin-3-ones has been investigated in protic medium. Whatever the acidity, the first reduction always takes place at the 4,5-double bond. In an ammoniacal buffer, further reduction leads to the tetrahydro derivative. In acidic medium, reduction of N-2 unsubstituted 4,5-dihydropyridazine-3-ones gives N-amonipyrrolidin-2-ones, whereas 2-methyl 4,5-dihydropyridazin-3-one leads to a pyrrolin-2-one.

Novel Marine Sponge Amino Acids, 10. Xestoaminoh from Xestaspongia sp.

The study of the anthelminthic components from a Fiji sponge Xestospongia sp. has yielded new amino alcohols, xestoaminols A-C. Xestoaminol B, (2S*)-aminotetradeca-11, 13-dien-(3R*)-ol [2], is isomeric to known Xestospongia products, (2S)-aminotetradeca-5,7-dien-(3R)-ol [6] and (2S)-aminotetradeca-5,7-dien-(3S)-ol [7], recently reported by Gulavita and Scheuer. Xestoaminols A [1] and C [3] are, respectively, the dihydro and tetrahydro derivatives of xestoaminol B. A combined nmr and molecular mechanics study on the oxazolidinone of xestoaminol A provided the basis for the relative stereochemistry assigned at C-2 and C-3 in xestoaminol A. This compound was extremely active in assays testing for action against parasites, microbes, and reverse transcriptase.

Synthesis and spectra of 12‐(o‐ and p‐R‐phenyl)‐9,9‐dimethyl‐7,8,9,10,11,12‐hexahydro and 8,9,10,11‐tetrahydrobenz[a]acridin‐11‐ones. Structure correction of 1,2,3,4,5,6‐hexahydro and 1,2,3,4‐tetrahydro‐2,2‐dimethyl‐5‐aryl‐6‐aza‐9,10‐benzophenanthren‐4‐ones. II

AbstractIt has been reported that the reaction of β‐naphthylamine, dimedone and the appropriate aromatic aldehyde in ethanol gave 1,2,3,4,5,6‐hexahydro‐2,2‐dimethyl‐5‐aryl‐6‐aza‐9,10‐benzophenanthren‐4‐ones, III, which upon treatment with chromic anhydride, yielded the corresponding tetrahydro derivatives, IV. However, the attempted preparation of these compounds resulted instead of the formation of isomeric acridin‐11‐ones, V and VI. Structures were confirmed by ir, 1H nmr, ms and X‐ray spectroscopy.

Antimykobakteriell wirksame 2‐Hydroxychinolizin‐4‐one

Reaction of ethyl 2-pyridyl acetates and activated malonates (magic malonates) leads to 1-ethoxycarbonyl-2-hydroxy-quinolizin-4-ones, which yield the corresponding C-1 unsubstituted derivatives by hydrolysis and decarboxylation. These compounds are catalytically hydrogenated to afford the corresponding tetrahydro derivatives. Significant inhibitory effects on mycobacterium tuberculosis H 37 Ra are shown, a structure-activity relationship is discussed.

AM1 study of a β-carboline set: structural properties and potential reactivity

A set of β-carbolines derived from norharman and its corresponding dehydro and tetrahydro derivatives has been studied by means of the semiempirical AM1 method. Geometrical parameters, protonation affinities and static reactivity indices have been examined. Structural properties and protonation sites are well described by calculations. Orientation of electrophilic attack on different centres is only partially predicted by the frontier indices. The role of the protonated molecules as reactive species is also discussed.

Protoberberine alkaloids from the bark of Enantia chlorantha

Four protoberberine alkaloids, palmatine (Ia), jatrorrhizine (Ib), columbamine (Ic) and pseudocolumbamine (Id), were isolated from the bark of Enantia chlorantha and characterized. The corresponding acetylated tetrahydro derivatives (IIa-IId) were also identified.

Synthesis of Isoquino[1,2-b]quinazolines by Cycloaddition Reaction

The cycloaddition reaction of 3,4-dihydroiso- quinolinium salts (2c,d) with 2-aminobenzaldehydes (1a,b) was a convenient way to obtain 5,6,13,13a-tetrahydro-8H-isoquinol[1,2-b]quinazolinium salts (3a-d). The reduction, transposition and oxidation of these compounds gave 8H-isoquinol[1,2-b]quinazoline derivatives in good yields. The mechanism of the cycloaddition reaction is discussed. The cis and trans isomers of the tetrahydro derivative (5d) have been isolated and identified by an infrared spectroscopic study

ChemInform Abstract: Azacycloalkanes. Part 31. Aralkyl‐Substituted Pyrrolo(1,2‐a)pyrazines and Their Effects on the Ischemic Myocardium.

AbstractThe furyl β‐arylethyl ketones (I) undergo cyclocondensation with ethylenediamine (II) to give the pyrrolopyrazines (III) which are hydrogenated, producing the tetrahydro derivatives (IV).

Mononitration of derivatives of benzisatins

The mononitration of benz[e]-, benz[f]-, and benz[g]isatins and their tetrahydro derivatives was realized. It was established on the basis of an analysis of the 1H NMR and mass spectra that substitution takes place at position 5 in the derivatives of the [g] series and at the position adjacent to the NH group in derivatives of the [f] series and in the case of 6,7,8,9-tetrahydrobenz [e]isatin. This reaction path corresponds to the maximum electron density in the HOMO, calculated by the CNDO method. In benz[e]isatin, contrary to the general relationship and to the quantum-chemical prediction, the nitro group initially enters the ring annellated with the indole ring.

Determination of 21-hydroxycorticosteroids in human urine by high-performance liquid chromatography with fluorescence detection.

A simple and sensitive high-performance liquid chromatographic method with fluorescence detection for the determination of nineteen 21-hydroxycorticosteroids is described. The corticosteroids are oxidized by cupric acetate to form the corresponding glyoxal derivatives. The derivatives are converted into fluorescent quinoxalines by reaction with 1,2-diamino-4,5-methylenedioxybenzene, a fluorogenic reagent for alpha-dicarbonyl compounds. The quinoxalines are separated within 70 min on a reversed-phase column (TSK gel ODS-120T) by stepwise elution with mixtures of methanol, acetonitrile, and 1.0 M ammonium acetate. The detection limits are 0.14-29.4 pmol at a signal-to-noise ratio of 3 in a 50-microliter injection volume. This sensitivity permits precise determination of hydrocortisone, cortisone, corticosterone, and their tetrahydro derivatives in 500 microliters of normal human urine.

Unambiguous Carbon-13 NMR Assignments of Some Biologically Active Protoberberine Alkaloids

Unambiguous proton and carbon-13 nmr chemical shifts of the protoberberine quaternary alkaloids palmatine and jatrorrhizine, their tetrahydro derivatives and tetrahydroberberine have been determined-through the use of 2D, CSCM 1D and selective INEPT nmr techniques

ChemInform Abstract: Aromatic Carboxylic Acids as Latent Aromatic Ketones. New Regioselective Synthesis of Aromatic Ketones.

AbstractLithium/ammonia reduction of 1,8‐phenanthrenedicarboxylic acid (I) yields the tetrahydro derivative (II) which is hydrogenated with H2/ Pd‐C to give the octahydro derivative (III).

2-Phenylpyridine and 3-phenylpyridine, constituents of tea, are unlikely to cause idiopathic Parkinson's disease

Idiopathic Parkinson's disease (PD) is likely to be caused by one or more unidentified neurotoxins, present in the environment or formed endogenously, which progressively damage dopaminergic nigrostriatal neurons. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is an experimental neurotoxin which produces biochemical and neuropathological changes in lower primates and mice and in humans inadvertently exposed to it that closely resemble those found in PD. 2-Phenylpyridine (2-PP) and 3-phenylpyridine (3-PP), both of them present in tea, are the only MPTP analogues that are known to be present in the human diet. We exposed C57 black mice, animals very sensitive to the dopaminergic neurotoxicity of MPTP, to prolonged parenteral and oral administration of large doses of 2-PP, and to prolonged parenteral administration of the N-methylated tetrahydro derivatives of 2-PP and 3-PP. The latter are closer chemical analogues of MPTP than are 2-PP and 3-PP themselves. None of these MPTP analogues lowered the contents of dopamine and its metabolites in the striatum of mice. We speculate that the neurotoxins which cause PD are unlikely to resemble MPTP structurally, and we suggest that the search for chemical causes of PD should be directed to a wider variety of compounds encountered by humans.

ChemInform Abstract: Dissolving Metal Reduction of Aceanthrylene and NMR Analysis of a Rigid, Boat‐Shaped 9,10‐Dihydroanthracene.

AbstractReduction of aceanthrylene (I) with sodium/ammonia yields the 2,6‐dihydro derivative (II) as the primary product which is further reduced to give the tetrahydro derivative (III).