New 2-methyl-6-alkylamino-5,8-quinolinequinones and 1,2,3,4-tetrahydro derivatives

The syntheses of six new 2-methyl-6-alkylamino-5,8-quinolinequinones, three 1,2,3,4-tetrahydro-5,8-quinolinequinones, and 7-(2′,6′,10′-trimethylundecyl)-6-hydroxy-5,8-quinolinequinone are described as potential antimetabolites of coenzyme Q and as potential antimalarial agents. The six 2-methyl-6-alkylamino-5,8-quinolinequinones were prepared by a six-step synthesis. 2-Methyl-6-methoxy-8-nitroquinoline was prepared from 2-nitro-4-methoxyaniline and crotonaldehyde by a Skraup reaction. Raney nickel reduction gave 2-methyl-6-metboxy-8-aminoquinoline, which upon diazotization followed by dithionite reduction yielded 2-methyl-6-methoxy-5,8-diaminoquinoline. Subsequent dichromate oxidation gave 2-methyl-6-methoxy-5,8-quinolinequinone, which yielded the corresponding 2-methyl-6-alkylamino-5,8-quinolinequinone in good yield when treated with the appropriate alkylamine. The telrahydro-5,8-quinolinequinones were prepared by catalytic hydrogenation of the appropriate 5,8-quinolinequinones at elevated H₂ pressure followed by air oxidation of the reduction product. 7-(2′,6′,10′-Trimethylundecyl)-6-hydroxy-5,8-quinolinequinone was synthesized by radical alkylation of 6-hydroxy-5,8-quinolinequinone by thermal decomposition of di-3,7,11-trimethyldodecanoyl peroxide, which was prepared by a multistep procedure from farnesol. Of the five new 2-methyl-6-alkylamino-5,8-quinoline-quinones tested against P. berghei in mice (blood schizonticidal test), only 2-methyl-6-cycloheptylamino-5,8-quinolinequinone was active (T-C = 6.1 at 320 mg./kg.). Both 7-(2′,6′,10′-trimelhytundecyl)-6-hydroxy-5,8-quinolinequinone and the tetrahydro derivatives were inactive in this same test system.     

2－氯／2－甲磺酰基－5－（2－苯基－4－喹啉基）－1，3，4－噁二唑化合物的合成及其亲核取代的研究

借处理２－羟基－５－（２－苯基－４－喹啉基）－１，３，二唑同ＰＣｌ＿５／ＰＯＣｌ＿３之间的反应合成了２－氯－５－（２－苯基－４－喹啉基）－１，３，４－二唑（３）和通过２－基－５－（２－苯基－４－喹啉基）－１，３，４－二唑的甲基化，然后氧化制得２－甲磺酰基－５－（２－苯基－４－喹啉基）－１，３，４－二唑（６）．并分别研究了３和６同胺、叠氮及肼的反应，得到２，５－二取代的二唑新衍生物．初步观察了部分化合物的抗菌活性．     

New Monoterpene-Substituted Dihydrochalcones from Piper aduncum

Five New unusual monoterpene-substituted dihydrochalcones, the adunctins A–E (1″S)-1-{2′-hydroxy-4′-methoxy-6′-[4″-methyl-1″-(1?-methylethyl)cyclohex-3″ -en-1″ -yloxy]phenyl}-3-phenylpropan-1-one ( 1 ), (5aR*,8R*,9aR*)-3-phenyl-1-[5′,8′,9′,9′a-tetrahydro-3′-hydroxy-1′-methoxy-8′-(1″-methylethyl)-5′-a-methyldibenzo-[b,d]furan-4′-yl]propan-1-one ( 2 ), (2′R*,4″S*)-1-{6′-hydroxy-4′-methoxy-4″-(1?-methylethyl)spiro[benzo[b]-furan-2′(3′H),1″ -cyclohex-2″ -en]-7′-yl}-3-phenylpropan-1-one ( 3 ), (2′R*,4″R*)-1-{6′-hydroxy-4′-methylethyl-4″-(1?-methylethyl)spiro[benzo[b]furan-2′(3′H),1″-cyclohex-2″-en]-7′-yl}-3-phenypropan-1-one ( 4 ), and (5′aR*,6′S*, 9′R*,9′aS*)-1-[5′a,6′,7′,8′,9′a-hexahydro-3′,6′-methoxy-6′-methyl-9′-(1″-methylethyl)dibenzo[b,d]-furan-4′-yl]-3-phenylpropan-1-one ( 5 ) were isolated from the leaves of Piper aduncum (Piperaceae) by preparative liquid chromatography. In addition, (?)-methyllindaretin ( 6 ), trans-phytol, and α-tocopherol ( = vitamin E) were also isolated and identified. The structures were elucidated by spectroscopic methods, including 1D- and 2D-NMR spectroscopy as well as single-crystal X-ray diffraction analysis. The antibacterial and cytotoxic potentials of the isolates were also investigated.     

Six new 2-(2-phenylethyl)chromones from Agarwood

Six new chromones, 6-methoxy-2-[2-(3-methoxy-4-hydroxyphenyl)ethyllchromone (2), 6,8-dihydroxy-2-(2-phenylethyl)chromone (3), 6-hydroxy-2-[2-(4-hydroxyphenyl)ethyl]chromone (4), 6-hydroxy-2-[2-(2-hydroxyphenyl)ethyl]chromone (5), 7-hydroxy-2-(2-phenylethyl)chromone (6), and 6-hydroxy-7-methoxy-2-(2-phenylethyl)chromone (7) were isolated from the ether extract of agarwood in addition to a known compound, 2-(2-phenylethyl)chromone or flidersiachromone (1). Their structures were determined by spectroscopic methods including UV, IR, and NMR spectral data and comparisons with the calculated values using the hydroxyl and methoxyl substituent increments of the chromone ring.     

2-R-7-Hydroxy-8-methyl-3-(2-quinolyl)chromones

By condensation of 2-methyl resorcinol with 2-quinolyl acetonitrile, we have synthesized α-(2-quinolyl)-2,4-dihydroxy-3-methylacetophenone, which when reacted with carboxylic acid anhydrides followed by hydrolysis yields 2-R-7-hydroxy-8-methyl-3-(2-quinolyl)chromones.__________Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 407–415, March, 2005.     

Reaction of ethyl γ-bromo-β-methoxycrotonate with carbonyl compounds. Synthesis of 4-methoxy-6-substituted-5,6-dihydro-2H-pyran-2-ones and 3-substituted 3-pyrazolin-5-ones

Ethyl β-methoxycrotonate I reacts with substituted carbonyl compounds II in benzene to give 4-methoxy-6-substituted-5,6-dihydro-2H-pyran-2-ones III. The reaction of IIIa and j with hydrazine hydrate in ethanol leads to 3-[(1′-thienyl-1-hydroxy)methyl]-5-hydroxy-1H-pyrazole (IVa) and 3-[1′-styryl-1′-hydroxy)methyl]-5-hydroxy-1H-pyrazole (IVj) in good yields. The structure of the products were assigned and confirmed on the basis of their elemental analysis and the electronic absorption, infrared and nmr spectra.     

Synthesis and properties of 5-(1,2-dihaloethyl)-2′-deoxyuridines and related analogues

The regiospecific reaction of 5-vinyl-3′,5′-di-O-acetyl-2′-deoxyuridine ( 2 ) with HOX (X = Cl, Br, I) yielded the corresponding 5-(1-hydroxy-2-haloethyl)-3′,5′-di-O-acetyl-2′-deoxyuridines 3a-c . Alternatively, reaction of 2 with iodine monochloride in aqueous acetonitrile also afforded 5-(1-hydroxy-2-iodoethyl)-3′,5′-di-O-acetyl-2′-deoxyuridine ( 3c ). Treatment of 5-(1-hydroxy-2-chloroethyl)- ( 3a ) and 5-(1-hydroxy-2-bromoethyl)-3′,5′-di-O-acetyl-2′-deoxyuridine ( 3b ) with DAST (Et₂NSF₃) in methylene chloride at -40° gave the respective 5-(1-fluoro-2-chloroethyl)- ( 6a , 74%) and 5-(1-fluoro-2-bromoethyl)-3′,5′-di-O-acetyl-2′-deoxyuridine ( 6b , 65%). In contrast, 5-(1-fluoro-2-iodoethyl)-3′,5′-di-O-acetyl-2′-deoxyuridine ( 6e ) could not be isolated due to its facile reaction with methanol, ethanol or water to yield the corresponding 5-(1-methoxy-2-iodoethyl)- ( 6c ), 5-(1-ethoxy-2-iodoethyl)- ( 6d ) and 5-(1-hydroxy-2-iodoethyl)-3′,5′-di-O-acetyl-2′-deoxyuridine ( 3c ). Treatment of 5-(1-hydroxy-2-chloroethyl)- ( 3a ) and 5-(1-hydroxy-2-bromoethyl)-3′,5′-di-O-acetyl-2′-deoxyuridine ( 3b ) with thionyl chloride yielded the respective 5-(1,2-dichloroethyl)- ( 6f , 85%) and 5-(1-chloro-2-bromoethyl)-3′,5′-di-O-acetyl-2′-deoxyuridine ( 6g , 50%), whereas a similar reaction employing the 5-(1-hydroxy-2-iodoethyl)- compound 3c afforded 5-(1-methoxy-2-iodoethyl)-3′,5′-di-O-acetyl-2′-deoxyuridine ( 6c ), possibly via the unstable 5-(1-chloro-2-iodoethyl)-3′,5′-di-O-acetyl-2′-deoxyuridine intermediate 6h . The 5-(1-bromo-2-chloroethyl)- ( 6i ) and 5-(1,2-dibromoethyl)-3′,5′-di-O-acetyl-2′-deoxyuridine ( 6j ) could not be isolated due to their facile conversion to the corresponding 5-(1-ethoxy-2-chloroethyl)- ( 6k ) and 5-(1-ethoxy-2-bromoethyl)-3′,5′-di-O-acetyl-2′-deoxyuridine ( 61 ). Reaction of 5-(1-hydroxy-2-bromoethyl)-3′,5′-di-O-acetyl-2′-deoxyuridine ( 3b ) with methanolic ammonia, to remove the 3′,5′-di-O-acetyl groups, gave 2,3-dihydro-3-hydroxy-5-(2′-deoxy-β-D-ribofuranosyl)-furano[2,3-d]pyrimidine-6(5H)-one ( 8 ). In contrast, a similar reaction of 5-(1-fluoro-2-chloroethyl)-3′,5′-di-O-acetyl-2′-deoxyuridine ( 6a ) yielded (E)-5-(2-chlorovinyl)-2′-deoxyuridine ( 1b , 23%) and 5-(2′-deoxy-β-D-ribofuranosyl)furano[2,3-d]pyrimidin-6(5H)-one ( 9 , 13%). The mechanisms of the substitution and elimination reactions observed for these 5-(1,2-dihaloethyl)-3′,5′-di-O-acetyl-2′-deoxyuridines are described.     

A novel quinoline alkaloid possessing a 7-benzyl group from the centipede, Scolopendra subspinipes.

The novel quinoline alkaloid scolopendrine was isolated from the centipede, Scolopendra subspinipes mutilans L. Koch. The structure was determined to be 2-hydroxy-7-[(4-hydroxy-3-methoxyphenyl)methyl]-3-methoxy-8-quinolyl sulfate on the basis of high-resolution electron-spray ionization mass spectroscopy and two-dimensional NMR spectral data. Unlike quinoline alkaloids so far reported, scolopendrine is unique in having a 7-benzyl moiety in the quinoline ring.     

Electron impact mass spectrometry of 3-hydroxy-3,4,5,6-tetrahydro-2H-[1]benzoxocines. A comparison with the behaviour of isomeric 2-hydroxymethyl-2,3,4,5-tetrahydro-[1]-benzoxepines and 1,2-epoxy-5-(2-hydroxyphenyl)pentane

The mass spectrometric behavior of 3-methyl-3-hydroxybenzoxocines has been studied in detail by means of linked scans and mass analyzed ion kinetic energy spectrometry. The structure of the molecular ion and the fragmentation processes are strictly related to the structure of the neutral moieties. The possible isomerization of 3-hydroxy-10-methoxy-3-methyl-3,4,5,6-tetrahydro-2H-[1]benzoxocine to 2-methyl-2-[3-(3′-methoxy-2′-hydroxy)phenyl]pentyloxirane and to 2-hydroxymethyl-9-methoxy-2-methyl-2,3,4,5-tetrahydro[1]benzoxepine is investigated.     

Cyclization of 2-methoxy-6-(substituted benzyloxy)acetophenone hydrazones in the presence of polyphosphoric acid(PPA)

Cyclization of 2-methoxy-6-benzyloxy acetophenone hydrazone gave 3-methyl-4-meth-oxy indazole and 3-methyl-4-methoxy-7-benzyl indazole in the presence of polyphosphoric acid(PPA).The hydrazone was probably converted to 2-hydroxy-6-methoxy acetophenone hydra-zone and 2-hydroxy-3-benzyl-6-methoxy acetophenone hydrazone followed by cyclization to thecorresponding indazoles in acidic conditions.Cyelization of 2-methoxy-6-(halo or alkyl or arylbenzyloxy)acetophenone hydrazones gave similar products.Cyclization of 2-methoxy-6-(p-nitrobenzyloxy)acetophenone hydrazone gave 2-(p-nitrophenyl)-3-methyl-4-methoxy benzo-furan and 3-methyl-4-methoxy indazole while 2-methoxy-6-(m-nitrobenzyloxy)acetophenonehydrazone gave 3-methyl-4-methoxy indazole,3-methyl-4-methoxy-7-(m-nitrophenyl)indazole and3-methyl-4-(m-nitrobenzyloxy)indazole.     

Synthesis of 2-amino-4-hydroxy-1,3,5-triazanaphthalenes

The synthesis of 2-amino-4-hydroxy-6-amyl-1,3,5-triazanaphthalene (8) is described as a model sequence pertinent to preparation of 8-deazafolic acid and its analogs. Condensation of 2-acet-amido-4-hydroxy-6-pyrimidinealdehyde (3) with dimethyl 2-oxoheptylphosphonate afforded 1-(2′-acetamido-4′-hydroxy-6′-pyrimidinyl)-1-octene-3-one (4) as a key intermediate. Conversion of 4 to 1-(2′-amino-4′-hydroxy-5′ -phenylazo-6′ pyrimidinyl)-3-octanone (7) followed by reductive cyclization yielded 8 or its tetrahydro derivative (9) .     

Streptonigrin and related compounds III. Synthesis and microbiological activity of destrioxyphenylstreptonigrin and analogues

Synthesis of three tricyclic analogues of streptonigrin, based on the 2-(2′-pyridyl)quinoline-5,8-dione system and with the characteristic substitution pattern of rings A and C of streptonigrin is described. The C-ring precursor, in the form of a substituted 2-acetylpyridine was condensed with either 3-hydroxy-5-methoxy-2-nitrobenzaldehyde or 3-hydroxy-4-methoxy-2-nitrobenzaldehyde, followed by reductive cyclization and oxidation to the corresponding quinones 12 and 29 . The 7-amino substitution was introduced in 12 via bromination and azidation. The 6-amino substitution was introduced through direct reaction of 29 with sodium azide. Destrioxyphenylstreptonigrin 2 was twice as active and the 6-amino-7-inethoxy analogue 4 was as active as streptonigrin in a microbiological assay. A 4′-bromo analogue of 2 was 60% as active as streptonigrin.     

Two new natural substituted hexenophenones from the fungus Scytalidium

Two metabolites of the fungus Scytalidium Sp. FY strain, have been shown to be 5′-formyl-2′-hydroxy-4′-methoxy-(E)-4-hexenophenone 3 and 5′-formyl-2′-hydroxyl-4′-methoxy-(E,E)-sorbophenone 4.     

Four new 2-(2-phenylethyl)chromone derivatives from withered wood of Aquilaria sinensis

Four new chromone derivatives, 5-hydroxy-6-methoxy-2-(2-phenylethyl)chromone (1), 6-hydroxy-2-(2-hydroxy-2-phenylethyl)chromone (2), 8-chloro-2-(2-phenylethyl)-5,6,7-trihydroxy-5,6,7,8-tetrahydrochromone (3), 6,7-dihydroxy-2-(2-phenylethyl)-5,6,7,8-tetrahydrochromone (4) were isolated from the MeOH extract of withered wood of Aquilaria sinensis, together with seven known constituents of agarwood.     

Phenolic compounds from Anaphalis aureo-punctata

From the ethanolic extract of the whole plant of Anaphalis aureo-punctata, a new acylated flavonoid glycoside 3-O-kaempferol-3-O-acetyl-6-O-(p-coumaroyl)-β-D-glucopyranoside (1), and five known phenolic compounds 3-O-kaempferol-6- O- ( p-coumaroyl )-β-D-glucopyranoside ( 2 ), kaempferol-3- O-β-D-glucopyranoside 3,6-(4′-hydroxystyryl)-4-methoxy-2-pyrone (4), 2H-pyran-2-one, 6-[ 2-( 4-(β-D-glucopyranosyloxy ) phenyl ) ethenyl ]-4-methoxy-( E ) (5) and 4-hydroxy-3-methoxycinnamic hexacosyl ester (6) were isolated. Their structures were established by spectral methods (UV, IR, MS, 1D, 2D-NMR). The flavonoid glycosides, 1, 2 and 3 showed markedly inhibited oxidative DNA strand breaks induced by Fenton reaction and NADH/PMS in a concentration-dependent manner.     

Synthesis of Tri- and Disalicylaldehydes and Their Chiral Schiff Base Compounds

A suitable procedure for convenient preparation of 1,3,5-tris(4-hydroxy-5-formylphenyl)benzene (6) was exploited via 5-bromosalicylaldehyde as starting reactant. Among the obtained products, compound 6, 4-methoxy-3-formylphenylboronic acid (9), 1,3,5-tris(4-methoxy-5-formylphenyl)benzene (10), and 4-methoxy-4′-hydroxyl-3,3′-diformyl-1,1′-diphenyl (11) had not been reported previously. Two new chiral Schiff base ligands, L1 and L2, were obtained from the tri- or disalicylaldehydes.     

3-(2喹啉基) 酚酮的卤代和硝化反应

本文首次报道了3-(2喹啉基) 酚酮的卤代和硝化反应在冰乙酸介质中,3-(2喹啉基) 酚酮与溴反应,在不同条件下分别得到单溴代产物和双溴代产物; 与硝酸反应得到单硝酸化产物,与过量硝酸反应,得到的硝化产物。     

Synthesis of Derivatives of 4-Hydroxy-2-methyl-3-[2-(5-mercapto-1H-1,2,4-triazol-3-yl)ethyl]quinoline and 2-[2-(4-Hydroxy-2-methyl-3-quinolyl)ethyl]-4H-3,1-benzoxazin-4-one

From 4-hydroxy-2-methylquinoline-3-propionyl chlorides hydrochlorides the corresponding thiosemicarbazides were synthesized. The cyclization of the latter both in alkaline and acidic media furnished 4-hydroxy-2-methyl-3-[2-(5-mercapto-1H-1,2,4-triazol-3-yl)ethyl]quinolines. The reaction of the above propionyl chlorides with anthranilic acid afforded the corresponding 2-[2-(4-hydroxy-2-methyl-3-quinolyl)ethyl]-4H-3,1-benzoxazin-4-ones.     

Pseurotin, a new metabolite of Pseudeurotium ovalis Stolk having an unusual hetero-spirocyclic system.

The structure and absolute configuration of pseurotin ( 1 ), a new metabolite, isolated from culture filtrates of Pseudeurotium ovalis STOLK (Ascomycetes), has been shown to be 2-[1′(S), 2′ (S)-dihydroxhex-3′-ene-yl]-3-methyl-8(S)-methoxy-8-benzoyl-9(R)-hydroxy-(5S)-1-oxa-7-aza-spiro[4.4]non-2-ene-4, 6-dione ( 1 ), by spectral data and chemical transformations, and by X-ray analysis of its dibromo derivative 2 [1].     

2-Polyfluoroalkylchromones. 6. Synthesis of substituted 2-morpholino-2-trifluoromethylchroman-4-ones

Morpholine adds smoothly at the double bond of substituted 5- and 8-nitro-2-trifluoromethylchromones to form the corresponding 2-morpholino-2-trifluoromethylchroman-4-ones. 6-Methoxy-5-nitro-2-trifluoromethylchromone adds also benzylamine, whereas 7-methoxy-8-nitro-2-trifluoromethylchromone undergoes ring opening under the action of benzylamine to give 3-benzylamino-4,4,4-trifluoro-1-(2-hydroxy-4-methoxy-3-nitrophenyl)but-2-en-1-one.