Enantioselective Lewis‐Base‐Catalyzed Asymmetric Hydrosilylation of Substituted Benzophenone N‐Aryl Imines: Efficient Synthesis of Chiral (Diarylmethyl)amines

Lewis‐base‐catalyzed asymmetric hydrosilylation of substituted benzophenone N‐aryl imines was investigated. Among various chiral Lewis‐base catalysts, a catalyst derived from L ‐Serine was found to be the most favorable one which promote the reaction to afford a series of (diarylmethyl)amines with high yields (up to 97 %) in moderate to good enantioselectivities (up to 97 % ee). The absolute configuration of the product was determined by the X‐ray crystallographic analysis.

     

Synthesis of N-acetylmuramic acid derivatives as potential inhibitors of the D-glutamic acid-adding enzyme

Compounds containing N-acetyl-D-muramic acid and (L-1-aminoethyl)phosphonic acid were designed as potential inhibitors of the D-glutamic acid-adding enzyme of the biosynthesis of bacterial peptidoglycan. 2-Acetamido-2-deoxy-3-O-[(R)-2-propionyl-(L-1-aminoethyl)phosphonic acid]-D-glucopyranose ( 3 ) was synthesized. 2-Acetamido-1,4,6-tri-O-acetyl-2-deoxy-3-O[(R)-2-propionyl-(L-1-aminoethyl)phosphonic acid dimethyl ester]-α,β-D-glucopyranose ( 9 ) was also prepared and was submitted to the MacDonald reaction in order to introduce a phosphate group on the anomeric position. A complex mixture of phosphorylated or/and methylated derivatives of 3 was obtained. They were purified by h.p.l.c. and characterized by analyses of hexosamine, amino acid and labile phosphate, and by plasma desorption mass spectrometry. Neither 3 nor its derivatives inhibited the D-glutamic acid-adding enzyme from Escherichia coli.     

The Use of an Unusual Rearrangement Sequence for the Syntheses of 3‐(1‐Aminoalkylidene)‐3H‐thiophen‐2‐ones and two Examples of their Surprising Electrophilic‐Induced Dimerization Reactions

The reaction of 2‐amino‐3‐carbomethoxythiophene ( 1a ) and 2‐amino‐3‐carboethoxy‐4,5‐dimethylthiophene ( 1b ) with methyl‐ or ethylmagnesium chloride leads to new 3‐(1‐aminoalkylidene)‐3H‐thiophen‐2‐ones 4a—d in good yields (60—87%). Treatment of the compounds 4a and 4c with catalytic amounts of p‐TsOH in boiling CHCl₃ afforded the (±)‐4,4′‐bis‐(1‐aminoalkylidene)‐3′,4′‐4H,2′H‐[2,3′]bithiophenyl‐5,5′‐diones 9a and 9b as new interesting heterocycles in preparatively useful yields (60/mdash;65%).     

Novel Pyridine-Based Hydroxamates and 2′-Aminoanilides as Histone Deacetylase Inhibitors: Biochemical Profile and Anticancer Activity

Starting from the N-hydroxy-3-(4-(2-phenylbutanoyl)amino)phenyl)acrylamide ( 5 b ) previously described by us as a HDAC inhibitor, we prepared four aza-analogues, 6 – 8 , 9 b , as regioisomers containing the pyridine nucleus. Preliminary screening against mHDAC1 highlighted the N-hydroxy-5-(2-(2-phenylbutanoyl)amino)pyridyl)acrylamide ( 9 b ) as the most potent inhibitor. Thus, we further developed both pyridylacrylic- and nicotinic-based hydroxamates ( 9 a , 9 c – f , and 11 a – f ) and 2′-aminoanilides ( 10 a – f and 12 a – f ), related to 9 b , to be tested against HDACs. Among them, the nicotinic hydroxamate 11 d displayed sub-nanomolar potency (IC₅₀: 0.5 nM) and selectivity up to 34 000 times that of HDAC4 and from 100 to 1300 times that of all the other tested HDAC isoforms. The 2′-aminoanilides were class I-selective HDAC inhibitors, generally more potent against HDAC3, with the nicotinic anilide 12 d being the most effective (IC₅₀^HDAC3=0.113 μM). When tested in U937 leukemia cells, the hydroxamates 9 e , 11 c , and 11 d blocked over 80 % of cells in G2/M phase, whereas the anilides did not alter cell-cycle progress. In the same cell line, the hydroxamate 11 c and the anilide 10 b induced about 30 % apoptosis, and the anilide 12 c displayed about 40 % cytodifferentiation. Finally, the most potent compounds in leukemia cells 9 b , 11 c , 10 b , 10 e , and 12 c were also tested in K562, HCT116, and A549 cancer cells, displaying antiproliferative IC₅₀ values at single-digit to sub-micromolar level.     

Dibenzofuran, 4-Chromanone,Acetophenone, and Dithiecine Derivatives: Cytotoxic Constituents from Eupatorium fortunei

Five new compounds, eupatodibenzofuran A (1), eupatodibenzofuran B (2), 6-acetyl-8-methoxy-2,2-dimethylchroman-4-one (3), eupatofortunone (4), and eupatodithiecine (5), have been isolated from the aerial part of Eupatorium fortunei, together with 11 known compounds (6‒16). Compounds 1 and 2 featured a new carbon skeleton with an unprecedented 1-(9-(4-methylphenyl)-6-methyldibe nzo[b,d]furan-2-yl)ethenone. Among the isolates, compound 1 exhibited potent inhibitory activity with IC₅₀ values of 5.95 ± 0.89 and 5.55 ± 0.23 μM, respectively, against A549 and MCF-7 cells. The colony-formation assay demonstrated that compound 1 (5 μM) obviously decreased A549 and MCF-7 cell proliferation, and Western blot test confirmed that compound 1 markedly induced apoptosis of A549 and MCF-7 cells through mitochondrial- and caspase-3-dependent pathways.     

Synthesis of well-defined poly[(2-β-D-glucopyranosyloxy)ethyl acrylate] by atom transfer radical polymerization

The ‘living’ radical polymerization of 2-(2′,3′,4′,6′-tetra-O-acetyl-β-D -glucopyranosyloxy)ethyl acrylate (AcGEA) by atom transfer radical polymerization (ATRP) is reported. It has been found that the polymerization kinetics are first-order, the molecular weights increase linearly with conversion, and the molecular weight distribution remains narrow when the polymerization conversion is below 70%. Well-defined P(AcGEA) was obtained, and the O-protecting acetyl groups of P(AcGEA) were quantitatively removed by reacting with dilute CH₃ONa solution in CHCl₃/CH₃OH to afford well-defined poly[(2-β-D -glucopyranosyloxy)ethyl acrylate] (PGEA). © 1999 Society of Chemical Industry     

Reactivity of 4-acetyl-3-chloro-5,6-diphenylpyridazine towards some nucleophilic reagents,Synthesis of Some Fused Pyridazine Derivatives

4-Acetyl-3-chloro-5,6-diphenylpyridazine ( 1 ), prepared by the action of phosphorus oxychloride on 4-acetyl-5,6-diphenylpyridazin-3(2H)-one ( 2 ), reacts with hydrazine hydrate and phenylhydrazine to give the pyrazolinopyridazine derivatives ( 3a , b ) respectively. Reaction of 1 with hydroxylamine hydrochloride gave the isoxazolopyridazine derivative ( 5 ), while its reaction with sodium azide in dimethyl formamide gave the tetrazolopyridazine derivative ( 8 ). Primary amines react with 1 to give either 9 or 10 depending upon the reaction conditions. Treatment of 1 with piperidine or morpholine gave the products 11a , b , respectivly. 4-Acetyl-5,6-diphenylpyridazin-3(2H)-thione ( 13 ) was readily obtained by the action of thiourea on ethanolic solution of 1 . The reactions of 1 with phenols were also investigated.     

4-(1-Methyl-2-sulfamoylvinyl)pyrazoles by Ring Transformation of 1,1-dioxo-2H-1,2-thiazine-4-carbaldehydes with hydrazines

As masked 1,3-dicarbonyl compounds, 1,1-dioxo-2H-1,2-thiazine-4-carbaldehydes ( 2a–e, 7 ) undergo ring transformations with nucleophilic hydrazines to produce 4-[1-methyl-2-(arylsulfamoyl)vinyl]pyrazoles ( 9a–i ). For 9h , an X-ray structural analysis is reported. With less nucleophilic semicarbazide and p-nitrophenylhydrazine the hydrazones ( 11a, b ) were isolated. The carbaldehydes 2a–e , 7 and 8a, b were synthesized by formylation of the 1,1-dioxo-2H-1,2-thiazines 1a–e, 5 and 6a, b with dichloromethyl methyl ether/TiCl₄. In the case of 1a–e mixtures of 4- and 6-carbaldehydes ( 2a–e/3a–e ) were obtained, which, however, could be used for the synthesis of pyrazoles.     

Bioactive Chemical Constituents from the Brown Alga Homoeostrichus formosana

A new chromene derivative, 2-(4'',8''-dimethylnona-3''E,7''-dienyl)-8-hydroxy-2,6-dimethyl-2H-chromene (1) together with four known natural products, methylfarnesylquinone (2), isololiolide (3), pheophytin a (4), and β-carotene (5) were isolated from the brown alga Homoeostrichus formosana. The structure of 1 was determined by extensive 1D and 2D spectroscopic analyses. Acetylation of 1 yielded the monoacetylated derivative 2-(4'',8''-dimethylnona-3''E,7''-dienyl)-8-acetyl-2,6-dimethyl-2H-chromene (6). Compounds 1–6 exhibited various levels of cytotoxic, antibacterial, and anti-inflammatory activities. Compound 2 was found to display potent in vitro anti-inflammatory activity by inhibiting the generation of superoxide anion (IC₅₀ 0.22 ± 0.03 μg/mL) and elastase release (IC₅₀ 0.48 ± 0.11 μg/mL) in FMLP/CB-induced human neutrophils.     

Convenient synthesis of perhydroindene derivatives from 2,7-dimethyl-1,3,7-octatriene

Several perhydroindene derivatives were prepared from 2,7-dimethyl-1,3,7-octatriene ( I ) via Diels Alder reaction followed by cyclisation. For example, the Diels Alder reaction between I and methyl vinyl ketone ( II ) in the presence of Lewis acid afforded 4-acetyl-3-(3-methylbut-3-enyl)-1-methylcyclohexene ( IIIa ), which, upon treatment with phosphoric acid, was converted to a mixture of 2-acetyl-5,7,7-trimethyl-bicyclo [4,3,0]-non-1-(6)-ene ( IV ), 2-acetyl-5,7,7-trimethylbicyclo[4,3,0]-non-1-ene ( VI ) and 2-isopropyl-3,6-dimethylindene ( V ).     

Expeditious Synthesis of Functionalized 1‐Arylcyclooctadienes via Palladium‐Catalyzed Lithium Cross‐Coupling

The palladium‐catalyzed direct cross‐coupling of aryl bromides and (1Z,5Z)‐cycloocta‐1,5‐dien‐1‐yllithium is described as an important method to synthesize 1‐arylcyclooctadienes. The use of a well‐established Pd₂dba₃/XPhos catalytic system affords the desired new compounds in good to excellent yields; the reaction proceeds at room temperature with both high efficiency and selectivity. Finally we found the best conditions to combine a suitable lithium‐halogen exchange with a cross‐coupling reaction.

     

The Behaviour of Some 4-Hydroxy-1-thiocoumarins toward amines and phenylhydrazine

Acetylation of 4-hydroxy-1-thiocoumarin 1 b in the presence of phosphorus oxychloride yields the 3-acetyl derivative 2 , which condenses with aromatic aldehydes to give the corresponding 3-cinnamoyl derivatives 3 a – e , and yields 3-arylazo-4-hydroxy-1-thiocoumarins 4 a – d upon treatment with aromatic diazonium salts. Whereas treatment of 1 b with primary amines results in the formation of 4-substituted amino derivatives 5 a – c , 3-acetyl-4-hydroxy-1-thiocoumarin 2 reacts with the same reagents to yield the 3-α-alkyliminoethyl derivatives 7 a – c . Treatment of 1 b with phenylhydrazine affords the 4-phenylhydrazine derivative 5 d . On the other hand, 2 reacts with the same reagent to yield a mixture of the phenylhydrazone 9 and the pyrazolo-1-thiocoumarin 10 .     

Oxokohlenstoffe und verwandte Verbindungen. 27. Synthese von Dihydrocyclobuta[a]naphthalen-1,2-dionen und Cyclobuta[a]naphthalen-1,2-dionen durch Anellierung von Alkoxy-(1-alkenyl)benzolen mit 3-Chlor-3-cyclobuten-1,2-dion. Anwendungsbereich und Grenzen

Oxocarbons and Related Compounds. 27. Synthesis of Dihydrocyclobuta[a]naphthalene-1,2-diones and Cyclobuta[a]naphthalene-1,2-diones via Annulation of Alkoxy-(1-alkenyl)benzenes with 3-Chloro-3-cyclobutene-1,2-dione. Scope and Limitations The reaction of alkoxy-(1-alkenyl)benzenes with semisquaric chloride ( 3 ) has been investigated systematically. 1,2-Dialkoxy- and 1-alkoxy'-2-alkoxy″-4-(1-alkenyl)benzenes ( 6a–j ) and ( 11a–i ) react with 3 to give the 3,4-dihydrocyclobuta[a]naphthalene-1,2-diones ( 8a–j ) and ( 12a–i ). Treatment of the dihydrocyclobuta[a]naphthalene-1,2-diones with 1.2 equiv. bromine effects dehydrogenation and affords cyclobuta[a]naphthalene-1,2-diones ( 9a–e ) and ( 13b–f ). Any efforts to extend this annulation reaction to dimethoxy-(1-alkenyl)benzenes with the methoxy groups in other than the 1,2-positions, e. g. 14a, b, 16a, b have been unsuccessful. The reaction of 1,2,3-trimethoxy-4-(1-propenyl) [and 4-(1-butenyl)]-benzenes ( 18a ) and ( 18b ) with semisquaric chloride ( 3 ) leads to the elimination of HCl and CH₃OH and gives 5,6-dimethoxy-3-methyl [and 3-ethyl]-cyclobuta[a]naphthalene-1,2-diones ( 20a ) and ( 20b ). The reaction pathway of this novel annulation reaction is discussed.     

Gold(I)‐Catalyzed Tandem Reaction of γ‐Amino‐Substituted Propargylic Esters to Pyrrolines and its Application in the Formal Synthesis of (±)‐Aphanorphine

An effective synthesis of structurally diverse pyrroline derivatives has been accomplished by a gold(I)‐catalyzed tandem 1,3‐acyloxy rearrangement/intramolecular azacylization reaction of γ‐amino‐substituted propargylic esters in good to excellent chemical yields (52–98%). The reaction proceeds under extremely mild conditions and has also demonstrated its potential in a concise formal synthesis of (±)‐aphanorphine with a catalyst loading as low as 0.5 mol% to provide the key intermediate 5‐(4‐methoxybenzyl)‐1‐tosyl‐2,5‐dihydro‐1H‐pyrrol‐3‐yl pivalate on a gram scale.

     

An Enantioselective Three‐Component Sulfa‐Michael/Aldol Cascade Reaction and its Application to the Synthesis of Thioaryl Substituted (−)‐Bestatin Derivatives

An efficient catalytic asymmetric three‐component sulfa‐Michael/aldol cascade reaction has been developed using a chiral multi‐functional catalyst. This reaction provided facile access to γ‐sulfur‐β‐nitro‐α‐hydroxy esters bearing three consecutive linear stereocenters in high yields (up to 97%) with excellent diastereo‐ (up to >97:3 dr) and enantioselectivities (>99% ee). These compounds were readily converted into 2‐nitroallylic alcohols and potentially bioactive γ‐sulfur‐β‐amino‐α‐hydroxy esters, which could be further used for the synthesis of Bestatin derivatives.

     

Reaction of nitrilimines with alkoxycarbonyl-hydrazines: Synthesis of 6-Acetyl-4-aryl-2-ethoxycarbonyl-1,2,3,4-tetrahydro-s-tetrazines

Nitrilimines 2 are found to react with alkoxycarbonylhydrazines 3 – 5 to afford the acyclic adducts 6 – 8. 6c is oxidized upon heating with charcoal in refluxing toluene to the corresponding formazan 9c . Compounds 8 cyclize upon heating with charcoal in refluxing toluene to the corresponding 6-acetyl-4-aryl-2-ethoxycarbonyl-1,2,3,4-tetrahydro-s-tetrazines ( 10 ) rather than to the expected corresponding tetrazinones 11 . NMR study of compounds 10 showed that these compounds exist in a tautomeric equilibrium.     

Dynamic mechanical properties of conductive carbon black‐reinforced closed cell microcellular oil‐extended EPDM rubber vulcanizates: Effect of blowing agent,temperature, frequency,and strain

Dynamic viscoelastic properties of Vulcan XC 72 (excess conductive carbon black)‐reinforced solid‐ and closed‐cell microcellular controlled long chain branching grade oil‐extended EPDM (Keltan 7341A) rubber vulcanizates were studied at four frequencies of 3.5, 11, 35, and 110 Hz, and at a temperature range of ?100 to 160°C.The effect of blowing agent (ADC 21) loading on storage modulus (E′) and loss tangent (tan δ) was studied. The log of storage modulus bears a linear relationship with the log of density for both solid and microcellular rubber. Relative storage modulus (E/E) decreases with decrease in relative density (ρ_f/ρ_s). Both E′ and tan δ were found to be dependent on frequency and temperature. The master curves of the storage modulus versus log temperature‐reduced frequency were formed by superimposing E′ results and by using shift factors calculated by Arrhenius equation. Strain‐dependent isothermal dynamic viscoelastic properties were carried out for dynamic strain amplitude of 0.08–7%. Cole–Cole plots of microcellular vulcanizates show a circular arc with blowing agent (density). Empirical relationship between tan δ versus E′ is found to be linear, whose slope is independent of blowing agent loading or density. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102: 1600–1608, 2006     

Reaction of α-tocopherol with alkyl and alkylperoxyl radicals of methyl linoleate

α-Tocopherol was reacted with alkyl and alkylperoxyl radicals at 37°C in bulk phase. The lipid-free radicals were generated by the reaction of methyl linoleate with the free radical initiator, 2,2′-azobis(2,4-dimethylvaleronitrile) (AMVN) under air-insufficient conditions. The products were isolated by high-performance liquid chromatography. Their structures were identified as 2-(α-tocopheroxy)-2,4-dimethylvaleronitrile (1), a mixture of methyl 9-(8a-peroxy-α-tocopherone)-10(E),12(Z)-octadecadienoate and methyl 13-(8a-peroxy-α-tocopherone)-9(Z),11(E)-octadecadienoate (2), methyl 9-(α-tocopheroxy)-10(E),12(Z)-octadecadienoate (3a), methyl 13-(α-tocopheroxy)-9(Z),11(E)-octadecadienoate (3b), α-tocopherol spirodiene dimer (4) and α-tocopherol trimer (5). When methyl linoleate containing α-tocopherol was oxidized with AMVN under airsufficient conditions, the main products were 8a-alkyl-peroxy-α-tocopherones (2). In addition to these compounds, 6-O-alkyl-α-tocopherols (1, 3a and 3b) were formed when the reaction was carried out under air-insufficient conditions. The results indicate that α-tocopherol can react with both alkyl and alkylperoxyl radicals during the autoxidation of polyunsaturated lipids.     

Addition von α-Ketoenaminen an 2-Acetyl-p-benzochinon

Addition of α-Ketoenamines to 2-Acetyl-p-benzoquinone Addition of 2-morpholino-2-cyclohex-1-en-one 2 to 2-acetyl-quinone 1 yields benzo[c][4 H]chromen-4,7,10-trion 4 which is unstable and rearranges to 5. 4 is converted to 3-(2,5-dihydroxy-phenyl)-2-morpholino-2-cyclohex-1-en-on 3 thermically and to dibenzo[b,d]furan-4-on 7 acid catalyzed. The structure of 7 is secured by independent synthesis. Dibenzo[b,d]furan-4-on 14 is the product of reaction from 2-(p-toluidino)-2-cyclohex-1-en-on 9 and 1 with benzo[c][4 H]chromen-4,7,10-trion 10 as intermediate. By proton catalysis 5-acetyl-6-hydroxy-carbazol-1-on 13 and 4-oxo-cyclohexa[c]isochinolinium hydrochlorid 15 is obtained from 10 . 1 H-cyclopenta[d]furan-3-on 17 is formed by addition of 2-(p-toluidino)-2-cyclopent-1-en-on 16 to 1 . It is rearranged by proton catalysis to 3-oxo-1 H-cyclopenta[c]isochinolinium salt 18 . Reaction of cyclopentan-1,2-dione and 1 yields 3 aH-cyclopenta[c]isochromen-3,6,9-trion 20 , rearranging to 1 H-cyclopenta[b]benzo[d]furan-3-on 21 . The stereochemistry of adducts is discussed in connection with the course of the reaction, spectroscopical evidence, molecular modelling and calculation of HOMO/LUMO and AO-coefficients.     

Oxidative coupling of methane over a La2O3/CaO catalyst. Optimization of reaction conditions in a bubbling fluidized-bed reactor

Oxidative coupling of methane over a La₂O₃/CaO catalyst was investigated in laboratory-scale fluidized-bed reactors (ID = 5 and 7 cm) in the following range of reaction conditions: T = 700 – 880°C, P = 41 – 72 kPa and P = 6 – 29 kPa. The maximum C₂₊ selectivity and yield amounted to 73.8% (T = 800°C, X = 13.1%, Y = 9.7%) and 16.0% (T = 840°C, X = 34.0%, S = 47.2%), respectively. Axial gas concentration profiles revealed that C₂₊ selectivity was not only influenced by oxidative consecutive reactions, but also by steam reforming of ethylene. When diluting the catalytic bed (m_cat = 145 g) with quartz (m = 200 and 400 g), a slight decrease of the selectivity (1–2%) was observed. The dilution of the feed gas with nitrogen only led to only a small increase (< 2%) of the C₂₊ selectivity.