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A series of (aMnOx–CoOy)r/γ-Al2O3 catalysts with different molar ratio of metal and supports (r denotes as the molar ratio of metal and supports, r = 0.02,0.03,0.04,0.05,0.06,0.08) and varied metal molar ratio(a stands for the molar ratio of Mn:Co, r = 1/3,1/1,3/1,6/1,1/0) were fabricated through impregnation route and characterized using X-ray diffraction (XRD), Inductively coupled plasma-atomic emission spectrometry (ICP-AES), N2 adsorption–desorption, X-ray photoelectron spectroscopy (XPS), H2 temperature programmed reduction (H2-TPR) and Scanning emission microscope (SEM). Among the catalysts investigated, (3MnOx–CoOy)0.04/γ-Al2O3 exhibited the highest activity and stable recyclability in the selective oxidation of tetralin using oxygen as the oxidant with a tetralin conversion of 68% and α-tetralone selectivity of 75% under the optimized conditions, affording a TOF value of 6.53 h−1, where the optimal reaction temperature is 120 °C and the reaction time is 8 h.

Here, we report a formal synthesis of the marine cytotoxic meroterpenoid actinoranone. Key steps include a semipinacol rearrangement/Wittig reaction sequence and a chiral pool approach for the syntheses of the tetralone and the ocatalin fragments, respectively. The presented route provides access to the natural product in 14 steps in the longest linear sequence.

We have elaborated a two-step catalytic approach to nafoxidine, a key precursor to lasofoxifene. Firstly, an efficient α-arylation of 6-methoxy-3,4-dihydronaphthalen-1(2H)-one with chlorobenzene was developed, which operates at low 0.1 mol% Pd-132 catalyst loading in the presence of 1.9 equivalents of sodium tert-butoxide at 60 °C in 1,4-dioxane and provides 6-methoxy-2-phenyl-3,4-dihydronaphthalen-1(2H)-one in 90% yield. Secondly, we have demonstrated that 6-methoxy-2-phenyl-3,4-dihydronaphthalen-1(2H)-one can be converted to nafoxidine in 61% yield via CeCl3 promoted reaction with (4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)lithium, which is formed in-situ from the corresponding arylbromide precursor and n-butyllithium. Altogether, the shortest two-step approach to nafoxidine from simple tetralone commodity starting material has been developed with overall 55% yield. The developed synthetic approach to nafoxidine has several beneficial aspects over the one used in the synthetic route primarily developed for the preparation of lasofoxifene.

Ginger root, strawberry tree and mandarin growing in Algeria were evaluated for their ability to stereoselective reduction of prochiral ketones. The reactivity and the enantioselectivity are strongly dependent on the biocatalyst used, and the structure of ketone. High enantioselectivities were observed for some substrates (70–99% ee) especially for the bioreduction of acetophenone 1, p-chloroacetophenone 2, tetralone 5, thiochromanone 6 and chromanone 7. Using two different batchs of Citrus reticulata from two regions of our country Annaba and Skikda, the corresponding optically active alcohols were obtained with high enantioselectivity and Skikda's variety was the best biocatalyst. The results reveal that these plants species can be a promising biocatalysts for the production of key intermediates.

Made available in DSpace on 2022-04-29T08:36:57Z (GMT). No. of bitstreams: 0 Previous issue date: 2022-01-15 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) The halido-α-bridge cleavage reactions between [Pd(C2,N-tetrox)(μ-Cl)]2 precursor (tetrox = E-α-tetralone oxime) with phosphines, in 1:2 molar ratio, have afforded mononuclear cyclopalladated compounds of the type [PdCl(C2,N-tetrox)(L)] {L = triphenylphosphine (1); tris(4-methylphenyl)phosphine (2); tris(4-fluorophenyl)phosphine (3) and tris(4-methoxyphenyl)phosphine (4)}. The compounds have been characterized by elemental analyses, infrared (FT-IR) and 1H, 13C{1H} and 31P{1H}-NMR spectroscopies. The molecular structure of 3 has been determined by single crystal X-ray diffraction (SC-XRD) and the Hirshfeld Surface calculation (HS) has been performed. The antiproliferative activity of compounds 1–4 has been evaluated against breast (MCF-7) and lung (A549) human cancer cells, and human lung fibroblast (MRC-5). All cyclopalladated compounds have been more active than cisplatin against MCF-7 cells, with IC50 values ranging from 19 to 26 µM. Binding experiments involving compound 3 with ct-DNA and human serum albumin (HSA) have been carried out using spectroscopic techniques. The interaction between compound 3 and HSA has been studied by means of molecular docking. UNESP – Univ Estadual Paulista Institute of Chemistry Department of Analytical Physical Chemistry and Inorganic Chemistry UEL – Univ Estadual de Londrina Departamento de Química USP – Univ de São Paulo Instituto de Física de São Carlos UFS – Univ Federal de Sergipe Departamento de Química UNESP – Univ Estadual Paulista Institute of Chemistry Department of Analytical Physical Chemistry and Inorganic Chemistry FAPESP: 2012/15486–3 FAPESP: 2016/17711­5 FAPESP: 422105/2016–3 FAPESP: 475322/2009–6

International audience; As an extension of our previous work on donepezil-based “bio-oxidizable” prodrug approach, two new classes of N-benzylpyridinium donepezil analogues in tetralone B2 and acetophenone B3 series and a new set of indanone derivatives B1 were investigated along with the corresponding dihydropyridine prodrugs A1-3. A total of fifty one N-benzylpyridinium quaternary donepezil analogues B1-3 and twenty two prodrugs A1-3 were synthesized and evaluated for their inhibitory activities against hAChE and eqBuChE. While most prodrugs A1-3 were demonstrated to be inactive against AChE (IC50 > 10 μM), a large number of the corresponding N-benzylpyridinium salt B1-3 exhibited appealing three-to-one-digit nanomolar hAChE inhibitory activities and even reaching subnanomolar activity (IC50 = 0.36 nM). In addition, in silico docking studies were conducted for several compounds to explain the more relevant in vitro results. Lastly, the influence of the two stereogenic centers in prodrugs A was also evaluated, highlighting not only marked differences in residual AChE inhibitory activity of the four separated isomers of prodrug 23h (IC50 ranging from 173 nM to 10 μM) but also significant variations of the oxidation rate between two separated diastereoisomers of prodrug 24a. This work provides useful information in the search of a preclinical candidate to conduct further development of this attractive “bio-oxidizable” prodrug strategy.

The chemosynthesis and potential as green herbicides of 4,8-dihydroxy-1-tetralone (4, 8-DHT) and its derivates were emphatically addressed in this study. Firstly, the synthesis of 4, 8-DHT from commercially available material 1, 5-dihydroxynaphthalene was carried out through a novel route of five reaction steps. Then, its five derivates including 4-benzoyl-8-hydroxy-1-tetralone, 4-(3-hydroxypropoxy)- 8-hydroxy-1- tetralone, 4-(2,3-dihydroxypropoxy)-8-hydroxy-1-tetralone, 4-hydroxy-8-(3-hydroxy propoxy) −1-tetralone and 4-hydroxy-8-(2,3-dihydroxypropoxy)-1- tetralone were prepared by modifying alcoholic and phenolic hydroxyl in C-4 and C-8 position of 4,8-DHT molecular structure. After that, these synthesized compounds were examined for their toxicity against six kinds of weeds (Lolium perenne, Phalaris arundinacea, Elymus dahuricus, Cichorium intybus, Sorghum sudanense, and Trifolium repens) in vitro. In general, high concentration could generally inhibit while low concentration might promote the growth of weeds. Among these compounds, 4-(3-hydroxypropoxy)-8 −hydroxy-1-tetralone and 4-hydroxy-8- (3-hydroxypropoxy) −1-tetralone showed significant phytotoxic activities against the six tested weeds, while 4-hydroxy-8-(2,3-dihydroxypropoxy) −1-tetralone was less toxic. For all the six tested weeds, E. dahuricus appeared the most sensitive to the treatments of 4, 8-DHT compounds. Hence, it has been suggested that variables including compound type and concentration as well as weed species should be seriously considered in order to develop and utilize the group of 4, 8-DHT compounds as herbicide in future.

The intramolecular Friedel-Crafts acylation of 4,5-diarylpentanoic acids has the possibility to cyclise to either a 6-membered ring to give 4-benzyltetral-1-one or a 7-membered ring to give 4-arylbenzosuber-1-one. Of these, only the former compound class has previously been reported. The impact of the substituents positioning on the outcome of the cyclisation has been investigated. The complete formation of either the tetralone or the benzosuberone regioisomer was possible under the same reaction conditions, dependent upon the ring activation and/or deactivation of the chosen substituents. Selected bromo or methoxy substituents could be used as auxiliaries, included in precursors to afford the desired regioisomer and then subsequently removed.

Rotigotine is a launched drug for the treatment of Parkinson’s disease and restless legs syndrome. The key steps of an alternative route for the synthesis of rotigotine have been demonstrated. Formation of a prochiral enamide, asymmetric hydrogenation of the enamide with high enantioselectivity, and reduction of the resulting amide to an amine have been proved to work successfully. The best conditions screened to date for the asymmetric hydrogenation of enamide 9 to amide 10 were with [(RuCl(( R )-T-BINAP)) 2 (μ-Cl) 3 ][NH 2 Me 2 ] at 25 bar H 2 and 30 °C (500:1 S/C ratio, 99% conversion, 91% ee S ). Reduction of amide 10 to amine 5 was best achieved with Red-Al giving 95% conversion.

An efficient and concise asymmetric synthesis of ( R )-(+)-ar-curcumene, ( R )-4,7-dimethyl-l-tetralone, and their enantiomers was accomplished. The key step to construct the stereogenic benzylmethyl centers of these natural products is the cobalt-catalyzed asymmetric Kumada cross-coupling reaction of a racemic α-bromo ester.

The synthesis of a novel series of 1-carba-isoflavanones through the α-arylation of α-tetralones is described. Several of these compounds demonstrated potent activity and selectivity in-vitro against HCV replicon reporter cells. Compound 10 (LQB-314) exhibited the best profile being active and selective in both replicon reporter cells (IC50 1.8 μM, SI > 111 and IC50 4.3 μM, SI > 46 in Huh7/Rep-Feo1b and Huh7.5-FGR-JC1-Rluc2A, respectively). Compound 3 (LQB-307) was the more potent and selective for Huh7.5-FGR-JC1-Rluc2A replicon reporter cells (IC50 1.5 μM, SI > 101.4).

In the present study, a series of fifteen a-tetralone (3,4-dihydro-2H-naphthalen-1-one) derivatives were synthesised and evaluated as inhibitors of recombinant human monoamine oxidase (MAO) A and B. The a-tetralone derivatives examined are structurally related to a series of chromone (1-benzopyran-4-one) derivatives which has previously been shown to act as MAO-B inhibitors. The results document that the a-tetralones are highly potent MAO-B inhibitors with all compounds exhibiting IC50 values in the nanomolar range (

Chemical investigation of the pericarps of Juglans regia led to the isolation of sixteen compounds, including five α-tetralone (1-5), five phenolic acids (6-10), two phenylpropanoids (11, 12), one diarylheptanoid (13), one sesquiterpene (14), and two α- tetralone dimers (15, 16). Among them, compounds 2, 4, 5, 11, 12 and 13 were isolated from J. regia for the first time, and compounds 10 and 14 were reported for the first time from Juglandaceae. The chemotaxonomic significance of these compounds was summarized.

A series of push–pull molecular systems 5–14 were designed, and synthesized by the Sonogashira cross-coupling, Knoevenagel condensation, and cycloaddition reactions. The donor ‘ferrocenyl substituted triphenylamine’ was kept constant, whereas the acceptors were varied (malononitrile, indanone, and tetralone). The electronic absorption spectra of the ferrocenyl substituted triphenylamine based donor–acceptor (D–A) compounds 5–9 exhibit intense intramolecular charge transfer (ICT) band in the visible region (415–502 nm). The incorporation of the tetracyanoethylene (TCNE) group in compounds 5–9 results in new D–A system 10–14, which exhibits the ICT band in the region 630–700 nm. The electrochemical studies suggest considerable donor–acceptor interaction. The computational studies reveal strong D–A interaction, and show good agreement with the experimental results.

(2E,4E,6Z,8Z)-8-(3′,4′-Dihydro-1′(2H)-naphthalen-1′-ylidene)-3,7-dimethyl-2,3,6-octatrienoinic acid, 9cUAB30, is a selective rexinoid for the retinoid X nuclear receptors (RXR). 9cUAB30 displays substantial chemopreventive capacity with little toxicity and is being translated to the clinic as a novel cancer prevention agent. To improve on the potency of 9cUAB30, we synthesized 4-methyl analogs of 9cUAB30, which introduced chirality at the 4-position of the tetralone ring. The syntheses and biological evaluations of the racemic homolog and enantiomers are reported. We demonstrate that the S-enantiomer is the most potent and least toxic even though these enantiomers bind in a similar conformation in the ligand binding domain of RXR.

Synthesis of naphthyl pyrrolidine/pyrrolizidine-spirooxindoles has been achieved by a one pot three component 1,3-dipolar cycloaddition (1,3-DC) reaction. The azomethine ylides generated in situ from isatin/N-substituted isatin and secondary amino acids (sarcosine/ l -proline) reacted with naphthylidene tetralone as a dipolarophile to give naphthyl dispiro heterocycles, in good yields. However anthrylidene tetralone, failed to react under the same conditions as a dipolarophile to give the products as expected in 1,3-DC reaction possibly due to steric and electronic properties. The structures and stereochemistry of cycloadducts were confirmed by 1H and 13C NMR spectroscopy, mass spectrometry, and single crystal X-ray diffraction studies.

A highly diastereoselective synthesis of heritol and heritonin by intramolecular cyclization on a preformed sensitive butenolide functionality is described.

Chemoselective Suzuki–Miyaura reactions of 2-bromo-1-(trifluoromethanesulfonyloxy)naphthalene, 1-bromo-2-(trifluoromethanesulfonyloxy) naphthalene and 2-acetyl-4-bromo-1-(trifluoromethanesulfonyloxy)naphthalene, which are all readily available from the corresponding tetralone derivatives, afforded a variety of mono- and diarylnaphthalenes. The reactions generally proceed with excellent chemoselectivity in favour of the bromide position, no matter whether the bromide is located at position 1 or 2 of the naphthalene or whether the carbon attached to the triflate group is electronically more deficient by the presence of a neighbouring acetyl group.

The full-structure of a norlabdane terpenoid, kujigamberol (1) was determined by total synthesis. Key features of the total synthesis are (1) installation of isopentyl group through an o-lithiation of benzamide, (2) construction of tetralone by the RCM reaction, and (3) optical resolution of (±)-1 using chromatographical separation of the corresponding camphanates. X-ray crystallographical analysis of p-bromobenzoate obtained from the more polar camphanate that was identical with a natural derivative, revealed natural kujigamberol to have an S-configuration. Both the natural enantiomer and its (R)-antipode showed the same inhibitory activity toward the mutant yeast and HL-60 cells, while simple analogs without alkyl groups at the C-8 and 9 positions of (±)-1 had no such activity.

α-Methylene-α-tetralone dimers ( 8 – 10 ) are shown to undergo a diastereoselective Prins reaction with paraformaldehyde in the presence of N -methylanilinium trifluoroacetate resulting in 2 , 4, and 5 . The structure of the new scaffold 2 was confirmed by X-ray crystallographic analysis.

The conversion of pure 1-tetralone and its mixtures with n-decane, decalin, tetralin, or 1,5-dimethyl tetralin (DMT) has been investigated over HY zeolite. The dominant reactions undergone by 1-tetralone are the dehydrogenation to 1-naphthol and the subsequent isomerization to 2-naphthol. In the presence of hydrocarbons, the hydrogen transfer/dehydration of naphthols is accelerated, and naphthalene is formed in different amounts, depending on the nature of the co-fed hydrocarbon. In this contribution, it is demonstrated how the product distribution from the tetralone conversion can be used as an indicator of the hydrogen transfer ability of a particular hydrocarbon, or mixture of hydrocarbons. The relative order of hydrogen transfer ability of the various hydrogen donating compounds, as inferred from the naphthalene-to-naphthol product ratio, is DMT > tetralin ≈ decalin > n-decane. This trend agrees well with the hydride dissociation energy of individual donors calculated by DFT.

A general and efficient synthetic approach to tricyclic spiroketones of interest as useful scaffolds in drug discovery was developed. Starting from commercially available benzyl 4-oxo-1-piperidinecarboxylate (5), spirocyclic tetralone 4, spirocyclic indanone 14, and spirocyclic benzocycloheptanone 15 were synthesized via six reaction steps in excellent overall yield.

Two new tetralone derivatives named xylariol A (1) and B (2) were isolated from the EtOAc extract of the culture broth of Xylaria hypoxylon AT-028 (Xylariaceae), and their structures were elucidated by MS, IR, 1D- and 2D-NMR spectra, and by X-ray diffraction analysis. 1 and 2 showed moderate cytotoxic activities against Hep G2 cells in the in vitro cytotoxic assay with IC50 values of 22.3 and 21.2 μg/mL, respectively.

Novel multifunctional chemotypes based on α-tetralone, α-indanone, and chromanone have been synthesized by a chemo-enzymatic approach by applying an enzymatic irreversible transesterification strategy. The scaffolds synthesized can be further elaborated with subsequent enzymatic as well as chemical transformations for the generation of new sets of structurally related organic molecules.

A fast capillary zone electrophoresis (CZE) method for the simultaneous determination of four cyclic diarylheptanoids (rhoiptelol, RH; juglanin A, JA; juglanin B, JB; juglanin C, JC) and an alpha-tetralone derivative (sclerone, SC) in the extract of the green walnut husks (Juglans regia L.) was developed. The optimized buffer was composed of 25 mM sodium tetraborate at pH 10.3. The applied voltage was 20 kV and the capillary temperature was kept constant at 20 degrees C. The detection wavelength was set at 220 nm using a photodiode array detection. The effects of several CE parameters, including pH value, buffer concentration, applied voltage and separation temperature on the separation were investigated systematically. Regression equations showed good linear relationships (correlation coefficients: 0.9996-0.9999) between the peak area of each compound (RH, JA, JB, JC and SC) and its concentration accordingly. The relative standard deviations (R.S.D.) of the migration time and peak area were less than 0.57 and 3.44% (intra-day), and 0.97 and 3.71% (inter-day), respectively. The contents of the five active compounds in the green walnut husks (J. regia L.) from different origins were determined with satisfactory repeatability and recovery.

Microwave heating as an alternative to conventional heating for K-OMS catalyzed oxidation of tetralin under atmospheric pressure conditions has been described. The conversions and selectivities obtained by microwave and conventional heating are compared for K-OMS-2 catalysts. Significant differences were found in conversion and product distribution when comparing the conventional and microwave heated experimental results performed under the same reaction conditions. Conversions up to 88% and turnover frequencies up to 20 were achieved under microwave irradiation. The major products of oxidation of tetralin were tetralone and tetralol (>75%). In addition, the effects of using different solvent systems in the reactions were studied. The characterization of catalysts before and after the reactions using XRD, SEM, and Raman are reported.

Treatment of chromanone, thiochromanone, tetralone and benzo[b]thiepinone derived allylic alcohols with phosphorous tribromide furnished unexpected products instead of desired bromo derivatives. Reaction of 7-methoxy-2,2-dimethylchromenyl-aryl-methanols and 7-methoxy-2,2-dimethylthiochromenyl-aryl-methanols with PBr3 gave saturated carbonyls and exocyclic olefins depending on the substituents at R4, whereas allylic alcohols without 7-methoxy substituent furnished rearranged products. Several related analogs varying in ring size, heteroatom in the ring and substituents at various positions were synthesized and studied. Reactions of other phosphorous-based reagents like PPh3, PPh3/I2 and PPh3Br2 on allylic alcohols were also attempted. A case study is presented here.

By optimizing extraction, separation and analytical conditions, a reliable and accurate high-performance liquid chromatographic (HPLC) method coupled with photodiode array detector (DAD) at room temperature is developed for simultaneous determination of three diarylheptanoids (juglanin A, juglanin B, rhoiptelol) and an α-tetralone derivative (regiolone) in methanol extracts from the green walnut husks ( Juglans regia L.) The sample pretreatment process involved the reflux extraction using methanol as the extract with a ratio of liquor to sample of 15 mL/g. The separation was achieved on a SinoChrom ODS-AP C 18 column with gradient elution using acetonitrile and 2% (v/v) acetic acid in water. The intra-day and inter-day precision (RSD%) for the analytes ranged from 1.08 to 1.51 and 0.60 to 1.13, respectively. The average recoveries obtained were from 88.4% to 96.2% for the analytes with RSDs below 3.13%. The correlation coefficients of the calibration curve exceeded 0.999. The detection limits were 0.51, 0.25, 0.32 and 0.35 ng at a signal-to-noise ratio of 3, respectively. Quantitative analyses of the samples from different grown sites and in obtained different months showed that the contents of the analytes varied significantly. The method was then successfully applied for the detection and isolation of a new diarylheptanoid derivative in the green walnut husks ( J. regia L.). The structure of the new compound was elucidated by various spectroscopic methods including 2D NMR techniques (COSY, HMQC, HMBC), HR-ESI-MS and X-ray single-crystal diffraction analysis.

Two metal–organic frameworks, [Cu(2-pymo) 2 ] and [Co(PhIM) 2 ] (2-pymo = 2-hydroxypyrimidinolate; PhIM = phenylimidazolate), containing respectively Cu 2+ and Co 2+ ions and anionic diazaheterocyclic ligands (pyrimidinolate and phenylimidazolate) as organic linkers, have been successfully used for the aerobic oxidation of tetralin, yielding α -tetralone (T O) as the main product. Both materials are stable and recyclable under the reaction conditions. Kinetic studies revealed significant differences between the two MOFs, as a consequence of the different catalytic behavior of their central metal ions. [Cu(2-pymo) 2 ] is highly active for the activation of tetralin to produce tetralinhydroperoxide (T OOH), and less efficient in reacting the peroxide. Meanwhile, the use of the cobalt catalyst involves a long induction period for the reaction. However, once T OOH is formed, Co 2+ rapidly and efficiently transforms this into T O, with high tetralone-to-tetralol ratio (T O/T OH of ca . 7). The combination of both materials has revealed as a convenient strategy for preparing a highly efficient, selective and reusable catalyst for the liquid phase aerobic oxidation of tetralin.

Cu/P(4-PVP) catalyst was used as catalyst for oxidation of tetralin in liquid phase. The catalyst was prepared by reaction of a Cu(II) salt with a 4-vinylpyridine-co-divinylbenzene polymer receptor and characterized by solid 1 H and 13 C NMR, XPS, FTIR, ESR spectroscopies, and by chemical reaction with pure tetralin. That information was used to gain insight into the stereochemistry of the active site needed to orient the reaction toward tetralone production. It was found that the Cu coordination with the pyridine was critical in influencing the peroxy-radical catalytic reaction, and that polyvinylpyridine was able to limit the autothermal oxidation. The active center is postulated to be based on a (Cu 2+ –Cu + )-pyridine distorted tetrahedric structure that is modified by the oxireduction reactions with tetralin.

3′,4′-Di-O-(−)-camphanoyl-(+)-cis-khellactone (DCK, 1) demonstrated extremely potent inhibitory activity against HIV-1 replication in H9 lymphocytic cells with an EC50 value of 2.56 × 10−4 μM and a therapeutic index (TI) of 1.37 × 105 in our prior research.1 In subsequent structural modification studies, numerous DCK derivatives were synthesized and at least 20 DCK analogs have shown promising inhibitory activity against HIV-1 replication in H9 lymphocytes.2 Among them, 3-methyl, 4-methyl, and 5-methyl substituted DCKs were much more potent than DCK and AZT in the same assay with EC50 and TI values ranging from 5.25 × 10−5 to 2.39 × 10−7 μM and 2.15 × 106 to 3.97 × 108, respectively.3 In addition, a preliminary mechanistic study showed that 3-hydroxymethyl-4-methyl DCK inhibits HIV reverse transcriptase (RT) via a different mechanism of action from those of current clinical anti-HIV/AIDS drugs.4 It was also found that DCK analogs are strongly synergistic with approved drugs such as AZT and act at a point in the virus life cycle immediately following the target for AZT and nevirapine.4 In our recent research on structural modification of 4-methyl DCK (2), the ring oxygen atom in the A or C ring of DCK was replaced by a sulfur atom, and these sulfur-containing analogs also exhibited potent inhibitory effects on HIV-1 replication in H9 lymphocytes.5,6 Moreover, gem-dimethyl substitution at the 8-position was found to be preferable to larger alkyl substituents or hydrogen atoms.7 In a continuing effort to identify the pharmacophores in this class of potent anti-HIV agents, we designed a new series of DCK analogs, namely 7-carbon-DCK derivatives (3a–c). In these compounds, a methylene group replaces the oxygen in the C ring of DCK. Thus, these analogs are bioisosteres of DCK, and the effect of the 7-oxygen atom on the anti-HIV activity of DCK-type compounds can be further explored. In addition, to help determine the possible impact of the 8,8-dimethyl groups, both unsubstituted (3a–b) and dimethylated (3c) analogs were prepared. Herein, we report the synthesis of compounds 3a–c and their preliminary anti-HIV bioassay results (Fig. 1). Figure 1 Structures of DCK (1), 4-methyl DCK (2) and 7-carbon-DCK analogs (3a–c). The synthesis of 3a–b was accomplished by a 7-step sequence, as illustrated in Scheme 1. The key intermediates 7,8-dihydro-benzo[h]chromen-2-one (10a) and its 4-methyl analog (10b) were prepared according to the procedure reported in our prior work.8 Sharpless asymmetric dihydroxylation (AD) of 10a and 10b afforded dihydroxy derivatives 11a and 11b in moderate yield (45–49%).9 Finally, 7-carbon-DCK analogs 3a and 3b were obtained in 62% and 82% yields, respectively, by acylation of 11a and 11b with (S)-(−)-camphanic chloride in CH2Cl2 at room temperature with pyridine as acid scavenger. Scheme 1 Synthesis of 3c: (i) t-BuOK/THF, reflux, 5 h, CH3I, 0.5 h; (ii) H2, Pd-C, CH3SO3H, HOAc, CH3COOC2H5, C2H5OH, rt, 36 h; (iii) BBr3/CH2Cl2, −78°C; (iv) CH3COCH2COOC2H5, POCl3, Benzene, reflux, 24 h, 66.0%; (v) CrO3, HOAc, rt, 30 h, (yield: ... As shown in Scheme 2, the preparation of 3c followed a slightly different synthetic route with 5-methoxy-1-tetralone (12) as starting material. Dimethylation of 12 with CH3I in the presence of t-BuOK afforded 2,2-dimethyl-5-methoxy-1-tetralone (13) in 91% yield.10 Reduction of dimethylated tetralone 13 with H2 catalyzed with 10% Pd-C gave 1,2,3,4-tetrahydro-5-methoxy-2,2-dimethylnaphthalene (14) quantitatively.11 Demethylation of 14 with BBr3 resulted in the formation of phenol derivative 15 in 98% yield.11 The remaining synthetic steps followed those detailed above for 3a–b from phenol 5. The target compound 3c was thus obtained in an overall yield of 5% via a six-step reaction sequence starting from 15. Scheme 2 Synthesis of 3a–b: (i) Raney Ni-Al alloy, 1% aq. KOH/water, 90°C, 2 h; (ii) L-Malic acid, H2SO4, HOAc, 140°C, 6 h (R=H); CH3COCH2COOC2H5, POCl3, 100°C, 18 h (R=CH3); (iii) CrO3, HOAc, rt, 3 days; (iv) NaBH4, CH3OH, 1 h; ... The anti-HIV activities of compounds 3a–c were evaluated in H9 lymphocytes, with AZT as the reference compound. The bioassay data are shown in Table 1 and indicated that all three compounds inhibited HIV replication and had reasonable therapeutic index (TI) values. Compounds 3a and 3b had significant EC50 values of 0.068 and 0.083 μM, respectively. Thus, the presence of the C-4 methyl in these 7-carbon DCK analogs did not lead to increased potency, in contrast to results with DCK and 4-methyl DCK. Although an absence of gem-dimethylation was detrimental in the 7-oxy DCK series,7 it was hard to make a definitive conclusion in the 7-carbon DCK series (comparison of 3c with 3b) due to solubility problems with 3c. However, the 7-carbon analog 3b was more potent and had a higher TI than the corresponding demethylated 7-oxy DCK derivative, 2′,2′-dihydro-4-methyl DCK (EC50 = 6.9 μM, TI > 6).7 Compound 3b was also more potent against HIV replication but was more cytotoxic than the analogous 7-thio analog (EC50 = 0.141 μM, TI = 1,110).6 Table 1 Anti-HIV data of compounds 3a–c in acutely infected H9 lymphocytes Further structural modification and biological screening are in progress as these promising bioassay results demonstrate that 7-carbon-DCK analogs merit attention as potential HIV-1 inhibitors.

Stereoselective reduction of prochiral ketones to the corresponding alcohols using biocatalysts has attracted much attention, from the viewpoint of green chemistry. Asymmetric reduction of indanone, tetralone and hydroxyl trimonoterpene ketones to the corresponding enantiomerically pure (S)-alcohols, using Daucus carota plant homogenate and fermented baker's yeast cells, is described. The present study illustrates the broad substrate selectivity of the dehydrogenase enzymes present in the D. carota in the synthesis of a wide range of chiral secondary alcohols of biological importance.

An innovative and efficient route to the synthesis of 9,10-dihydro-3-formylphenanthrenes 7 has been delineated through the ring transformation of 2-oxo-4-sec-amino-5,6-dihydro-2H-benzo[h]chromene-3-carbonitriles 4 with methyl glyoxaldimethylacetal 5 to masked 3-dimethoxymethyl-1-sec-amino-9,10-dihydrophenanthrene-3-carbonitriles 6 followed by deacetalation with Amberlyst 15 in excellent yields.

A new approach to the rational design of Lewis acids based on face-face π-π interactions is described. The synthesis of two novel diols (-)(1R,3R)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalene-1,3-diol (I) and (-)(1S,3R)-trans-2,2-dimethyl-1,2,3,4-tetrahydronaphthalene-1-3-diol (II) is reported in six and five steps resp. starting from α-tetralone. Complexation of (-)(1R,3R)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalene-1,3-diol to phenylboronic acid shows the interplanar distance between the boron atom and the arom. ring to be 3.05 A, which is ideal for the proposed interactions. [on SciFinder(R)]

A new, efficient and convenient method for the synthesis of resin-bound α,β-unsaturated ketones is described. Reaction of polystyrene-linked benzaldehydes with methyl ketones or tetralone in the presence of zinc acetate, 2,2′-bipyridine and an amidine base at elevated temperature gave resin-bound (E)-enones in high purity. These were transformed into thioethers by reaction with thiophenol.

A series of novel dispiroheterocyclic systems have been synthesized by the cycloaddition of a new azomethine ylide generated by the decarboxylative route from tetrahydroisoquinoline-3-carboxylic acid and isatin with various dipolarophiles containing exocyclic double bond such as 3-arylidene-4-chromanone, 3-arylidene-4-flavanone and 2-arylidenetetrahydro-1-naphthalenone in moderate to good yield. The regio and stereochemistry of the title compounds was established by single crystal X-ray structure and spectroscopic techniques.

A stereocontrolled approach to the construction of the angularly ester substituted trans-octahydrophenanthrene ring system related to diterpenes involving an aryl participated diazoketone cyclisation strategy is delineated. The tetrahydrophenanthrenone 7 was prepared from the tetralone 6 through the intermediates 13 , 14 , 16 and 17 . The formyl derivative of 7 was treated with alkaline H2O2 to give the diacid 18 which was converted into the diazomethyl ketone 9 . Aryl participated cyclisation of 9 afforded the enedione 10 which was stereoselectively converted into the keto-ester 11 . The transformation of 11 into the diterpenes 1 and 4 has been efficiently accomplished.

Enantioselective protonation of 2-methyl tetralone enolate using a stoichiometric amount of 2-sulfinyl alcohol ( S , R s )- 1 as a chiral proton donor yields the corresponding chiral ketone with a high level of enantioselectivity, provided that the chiral proton donor (CPD) is regenerated with an achiral proton source (APS). In contrast, stereoselectivity was only moderate if catalytic CPD (0.2 equiv.) and an APS are used.

Dearomatising anionic cyclisation of N -cumyl- N - p -methoxybenzyl-4-methoxy-1-naphthamide 8 diastereoselectively generates a pyrrolidinone-fused tetralone 12 which may be transformed in seven steps to the racemic form of a known non-natural member of the aryl kainoid family 4 having potent biological activity. Key steps of the synthesis are ruthenium-catalysed oxidation of the C2- p -methoxybenzyl ring of 12 to a carboxylic acid and Baeyer–Villiger cleavage of the tetralone to a lactone whose hydrolysis reveals the two-carbon substituent at C3 and the 2-hydroxyphenyl substituent at C4. Selective reduction of the lactam yields the kainoid 4 . Control of epimerisation at the C-4 centre during the lactone hydrolysis leads to either the (active) 3,4- cis or the (inactive) 3,4- trans epimers of the target.

The absolute configuration of (+)-isoshinanolone, a wide-spread acetogenic metabolite from higher plants, has been determined by X-ray structure analysis of its new dibromide; accordingly, this natural tetralone is 3R,4R-configured, in agreement with previous degradative results. In addition, a first chiroptical on-line stereoanalysis for isoshinanolones is presented, i.a. by HPLC on a chiral phase coupled to CD spectroscopy, giving pure CD spectra of all of the four stereoisomers of isoshinanolone directly from stereoisomeric mixtures.

We have developed an efficient synthesis of novel racemic spiropyrrolidine–tetralones via an unexpected ring-contraction reaction of a 4-disubstituted piperidine to 3-disubstituted pyrrolidine. We suggest that intramolecular quaternization of the piperidine nitrogen of compound 7 occurs to form a bridged bicyclic quaternary ammonium salt intermediate 10. The ring opening of 10 with cyanide resulted in pyrrolidine 9. The synthesis of racemic spiropyrrolidine–tetralone 15 is described as well as the related spiropiperidine–indanone, 1b.

Dimethyljadomycin A was synthesized as the first example for the construction of 8 H -benzo[ b ]oxazolo[3,2- f ]phenanthridine skeleton.

A suitable method for the preparation of the chiral mixed O/S ligands 1,2-sulfinyl thiols is described. These compounds have then been used as a chiral proton source in the enantioselective protonation of 2-methyl tetralone enolate and the results are compared with those obtained from the analogous alcohols. A theoretical model is proposed to explain the different behaviors exhibited in the protonation reaction for each of these proton sources. Configurational assignments for the new chiral thiols have been carried out by means of X-ray analysis.

The heterocyclic mesomeric betaines 6a–c reacted with dimethyl acetylenedicarboxylate and ethyl propiolate giving the 1,3-dipolar cycloaddition products 7a–c and 8a–c, respectively. With esters of maleic, fumaric, acrylic and methacrylic acids, mesomeric betaines 6a and 6b gave substituted tetralone derivatives.

Ortho -(2-triethoxysilylethyl) derivatives of aryl ketones undergo oxidative desilylation with H 2 O 2 . Tetralone derivatives have served as model substrates for 14-2-(triethoxysilylethyl)-7-oxopodocarpanes, which have been converted into 2-arylethanols in a four-step sequence (BH 3 ·BMS, H 2 O 2 , Et 3 SiH/CF 3 COOH, TBAF) without isolation of intermediate products (oxasilepin, diol, trifluoroacetate). Use of the 14-(2-diethoxysilylmethyl) analogue improved the overall yield significantly (75 versus 40%). Re-oxidation of ring B with CAN gave the Δ 5 -7-oxo derivative, which was converted into an enone–aldehyde by treatment with Collins' reagent. The conjugated alkene was reduced stereoselectively with SmI 2 , which, however, did not promote pinacol coupling of the resulting 1,5-keto aldehyde.

4-Methoxystyrene 1 underwent dimerization to 1,4-diphenylbutane derivatives 5 and 6 in presence of CAN in methanol. But in ethanol the same reaction afforded a tetralone derivative along with 5 and 6. 3,4-Dimethoxystyrene 10 underwent dimerization in presence of CAN in methanol to afford acyclic as well as cyclic products. 3,4,5-Trimethoxystyrene 12 in presence of CAN in methanol afforded only the cyclized dimers, the tetralone 21 and the tetralin derivative 22.

Hydrogenation of ruthenium chloride in acetonitrile yields complexes of the type Ru(CH3CN)nCl6−n of which three are isolated (n=2, 3, 4). Their formation is traced by voltammetry. Ru(CH3CN)2Cl4 and Ru(CH3CN)3Cl3 have been characterized by single-crystal X-ray diffraction. Voltammetry shows that Ru(CH3CN)3Cl3 acts as a mediator for oxidation of cyclohexene, methylcyclohexene, 1-tetralol and tetralin. Its role in tetralin oxidation is illustrated by preparative scale electrolysis. The compounds Ru(CH3CN)2Cl4 and Ru(CH3CN)4Cl2 did not react with any of the mentioned hydrocarbons.

The favourable effect of lithium bromide enhancing the facial enantioselectivity in the protonation of methyl tetralone enolate with α-sulfinyl alcohols is described. Theoretical calculations allow to propose a model to explain the stereochemical course of the protonation reaction.

Aromatase is a cytochrome P450 isozyme, whose inhibition is known to be therapeutically relevant in the treatment of the breast cancer. A comparative molecular field analysis (CoMFA) has been carried out on a series of non-steroidal aromatase inhibitors belonging to two different structural classes. One subset of compounds consists of fadrozole analogues and was studied in a previous work, from which a ‘local’ 3-D quantitative structure--activity relationship (QSAR) model for the inhibition of aromatase was obtained. In the present paper, that model is extended to include a second subset of compounds bearing a tetralone nucleus and acting at the same enzyme site with the same mechanism as the azoles. The critical alignment step has been solved by using two different steroidal inhibitors of aromatase as rigid templates, on which the non-steroidal compounds have been superimposed. The final 3-D QSAR models are discussed in terms of predictivity and some implications regarding the steric and electronic requirements of steroidal and non-steroidal inhibitors are pointed out.

The indium and tin-mediated carbonyl allylations of 1,3-dicarbonyl compounds have been studied in aqueous medium. The study led to the development of a novel two-atom carbocycle-enlargement in water. Five-, six-, seven-, eight-, and twelve-membered rings are enlarged by two carbon atoms into seven-, eight-, nine-, ten-, and fourteen-membered ring derivatives respectively. Tetralone derivatives are similarly expanded to 6–8 fused ring systems; and indanone derivatives are expanded to 5–7 fused ring systems. The use of both indium and zinc as the metal mediators provided the ring expansion products successfully. The use of water as a solvent was found to be essential for the ring expansion reaction.