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.     

Sesquiterpenoid derivatives from Ferula ferulaeoides [correction of ferulioides]. V

Nine novel prenyl-dihydrofurocoumarin-type sesquiterpenoid derivatives, 2,3-dihydro-7-hydroxy-2R*,3R*-dimethyl-2-[4,8-dimethyl-3(E),7-nonadienyl]-furo[3,2-c]coumarin, 2,3-dihydro-7-hydroxy-2S*,3R*-dimethyl-2-[4,8-dimethyl-3(E),7-nonadien-6-onyl]-furo[3,2-c]coumarin, 2,3-dihydro-7-hydroxy-2S*,3R*-dimethyl-2-[4-methyl-5-(4-methyl-2-furyl)-3(E)-pentenyl]-furo[3,2-c]coumarin, 2,3-dihydro-7-hydroxy-2R*,3R*-dimethyl-2-[4-methyl-5- (4-methyl-2-furyl)-3(E)-pentenyl]-furo[3,2-c]coumarin, 2,3-dihydro-7-methoxy-2S*,3R*-dimethyl-2-[4,8-dimethyl-3(E),7-nonadienyl]-furo[3,2-c]coumarin, 2,3-dihydro-7-methoxy-2R*,3R*-dimethyl-2-[4,8-dimethyl-3(E),7-nonadienyl]-furo[3,2-c]coumarin, 2,3-dihydro-7-methoxy-2S*,3R*-dimethyl-2-[4,8-dimethyl-3(E),7-nonadien-6-onyl]-furo-[3,2-c]coumarin, and 2,3-dihydro-7-methoxy-2S*,3R*-dimethyl-2-[4-methyl-5-(4-methyl-2-furyl)-3(E)-pentenyl]-furo[3,2-c]coumarin, were isolated from the roots of Ferula ferulaeoides [corrected]. The structures were established by comprehensive spectral analysis. The biosynthetic pathway leading to these prenyl-furocoumarin-type sesquiterpenoids is proposed based on their structures.     

Preparation of 1-dialkylamino-1,2,3-trienes,a novel type of cumulenes

Solutions of α-lithiated cumulenic amines are produced upon treatment of l-dialkylamino-4-methoxy-4-methyl-2-pentynes with two equivalents of butyllithium. Subsequent protonation with t-butyl alcohol gives the corresponding cumulenic amines, while treatment with trimethylchlorosilane gives the α-trimethylsilylated derivatives.     

A Facile One-Step Synthesis of New Types of 8-Thiazolyl and 8-Thiadiazinyl Coumarins

N-[4-(7-Methoxy-4-methyl-2-oxo-2H-chromen-8-yl)-thiazol-2-yl]-guanidine ( 2 ) has been prepared by the condensation of 4-methyl-7-methoxy-8-(2-bromoacetyl)coumarin ( 1 ) with guanylthiourea. 4-Methyl-7-methoxy-8-[2-(N′-(1-phenyl-ethylideneisopropylidene)-hydrazino]-thiazol-4-yl]chromen-2-ones ( 3 , 4 , and 5 ) have been prepared by reaction of 4-methyl-7-methoxy-8-(2-bromoacetyl) coumarin ( 1 ) and thiosemicarbazide in presence of acetophenone or acetone without any solvent. The formation of these compounds was further confirmed by the condensation of acetophenone/acetone thiosemicarbazones with 4-methyl-7-methoxy-8-(2-bromoacetyl)coumarin ( 1 ) in anhydrous ethanol in a two-step process. Similarly 8-[2-[N′-(benzylidene)hydrazine]-thiazol-4-yl]-7-methoxy-4-methyl-chromen-2-ones ( 6 , 7 , and 8 ) have been prepared by the condensation of 4-methyl-7-methoxy-8-(2-bromoacetyl)chromen-2-one with thiosemicarbazide and various aromatic aldehydes in a single step without any solvent. The formation of these compounds was further confirmed by the condensation of appropriately substituted benzaldehyde thiosemicarbazones with 4-methyl-7-methoxy-8-(2-bromoacetyl)coumarin in anhydrous ethanol. 4-Methyl-7-methoxy-8-(2-bromoacetyl) chromen-2-one (1) upon condensation with 3,5-dimercapto-4-amino-s-triazole in anhydrous ethanol resulted in the formation of 8-(3-mercapto-3H-[1,2,4]triazolo[3,4-b]thiadiazin-6-yl)-7-methoxy-4-methyl chromen-2-one (9). This compound ( 9 ) on reaction with various alkyl and phenacyl halides in anhydrous ethanol gave corresponding 4-methyl-7-methoxy-8-[3-(2-oxo-substituted sulphanyl)-7H-[1,2,4]triazolo[3,4-b]thiadiazin-6-yl]chromen-2-ones ( 10 to 18 ). The structures of newly prepared compounds have been confirmed from analytical and spectral data.     

Synthesis and cytotoxicity of complex compounds of tin, vanadium, and molybdenum with quinolinethiol and its methyl and methoxy derivatives

A series of 8-quinolinethiolates, and 3-methyl-, 4-methyl-, 5-methyl-, 6-methyl-, 7-methyl-, and 6-methoxy-8-quinolinethiolates of tin(II), vanadium(IV), and molybdenum(VI) has been synthesized. Their cytotoxicity on HT-1080 tumor cells (human fibrosarcoma) and MG-22A (mouse hepatoma) cells has been studied. It was established that all of the investigated complexes of 8-quinolinethiol and majority of the complexes of 8-quinolinethiol derivatives possessed very high cytotoxicity towards both cell lines. Their toxicity in relation to mouse embryo fibroblasts NIH 3T3 depended on the position of the substituent in the quinoline ring. Complexes of tin and vanadium with 4-methyl-, 5-methyl-, and 6-methoxy-8-quinolinethiol derivatives were less toxic. 4-Methyl-, 5-methyl-, and 6-methoxy-8-quinolinethiolates of vanadium demonstrated the highest selectivity of cytotoxic action.     

Total synthesis of (±)-fangchinoline

(±)-Fangchinoline was synthesized by condensation of (±)-1-(3-bromo-4-methoxy-benzyl)-2-methyl-6-methoxy-7-hydroxy-8-bromo-1,2,3,4-tetrahydroisoquinoline ( 2 ) and (±)-1-(4-hydroxy-benzyl)-2-methyl-6-methoxy-7-hydroxy-1,2,3,4-tetrahydroisoquinoline ( 3 ) in the presence of copper, pyridine and potassium carbonate.     

Solvent polarity indicators: Extraction of some coumarin indicator dyes

Study of the extraction of ten different coumarins (unsubstituted, 6-methyl-, 7-methyl-, 4-hydroxy-, 7-hydroxy-, 7-hydroxy-4-methyl-, 7-methoxy-, 7-amino-4-methyl-, 7-diethyl-amino-4-methyl-, and 3-carboxy-) with nine organic solvents shows that the percentage extraction is generally high. Cyclohexanone and heptane were found to be, respectively, the most and least effective extracting solvents for the compounds under study. The results are discussed in terms of the effect of different solvent polarity parameters on the extraction process.     

Synthesis of key intermediates for a concise and convergent approach to the marine natural product eleutherobin

Synthesis of 1,6-syn-5,6-anti-2-methyl-5-isopropyl-bicyclo[4.3.0]-non-2-en-8-one in three steps from (rac)-phellandrene; and 1,6-syn-1-methyl-6-methoxy-3-aza-9-oxabicyclo[4.2.1]-non-7-en-4-one in five steps from 2-methoxy-5-methylfuran and tetrabromoacetone, provided these key intermediates for the construction of the skeleton of eleutherobin.     

A novel antioxidant isobenzofuranone derivative from fungus Cephalosporium sp.AL031

Bioassay-guided fractionation of metabolites from the fungus Cephalosporium sp.AL031 isolated from Sinarundinaria nitida led to the discovery of a new isobenzofuranone derivative, 4,6-dihydroxy-5-methoxy-7-methylphthalide (1), together with three known compounds: 4,5,6-trihydroxy-7-methyl-1,3-dihydroisobenzofuran (2), 4,6-dihydroxy-5-methoxy-7-methyl-1,3-dihydroisobenzofuran (3) and 4,5,6-trihydroxy-7-methylphthalide (4). The structure of the new compound 1 was determined based on MS, 1D and 2D NMR spectral data. Compounds 1-4 showed potent antioxidant activity with EC?? values of 10, 7, 22 and 5 μM by 1,1-diphenyl-2-picryhydrazyl (DPPH) radical-scavenging assay.     

Synthetic studies of the antitumor antibiotic streptonigrin. I. Synthesis of the A-B ring portion of streptonigrin

Bromination of 6-methoxy-5,8-quinolinedione gave the 7-bromo derivative in quantitative yield. Treatment of the bromo compound with sodium azide followed by hydrogenation yielded 7-amino-6-methoxy-5,8-quinolinedione, the A-B ring portion of the antitumor antibiotic strep tonigrin. The corresponding 2-methyl homolog was prepared in a similar manner from 6-methoxy-2-methyl-8-nitroquinoline, which in turn, was obtained by a Skraup synthesis from 2-nitro-anisidine and crotonaldehyde.     

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.     

Cyclopalladate complex of 3-benzyl-7-methyl-3,7-diazabicyclo[3.3.1]nonane

Russian Chemical Bulletin - A new (C,N,N)-pincer cyclopalladate unsymmetrical complex of 3-benzyl-7-methyl-3,7-diazabicyclo[3.3.1]nonane (3-benzyl-7-methylbispidine) was synthesized and...     

New Fluoroaryl-containing β,β'-Dioxoesters in the Synthesis of Fluorobenzopyran-2(4)-ones

For the first time were obtained ethyl 2-(2-methoxy-3,4,5,6-tetrafluorobenzoyl)-3-oxobutanoate and ethyl 2-pentafluorobenzoyl-3-oxobutanoate and their copper chelates. The compounds were prepared by acylation of ethyl acetoacetate with 2-methoxy-3,4,5,6-tetrafluoro- and pentafluorobenzoyl chlorides. Cyclization of these ,'-dioxoesters afforded substituted chromones. 2-Methyl-5-methoxy-6,7,8-trifluoro-3-ethoxycarbonylchromone hydrolyzes depending on reaction conditions either to 5-hydroxy-2-methyl-6,7,8-trifluorochromone or to 5-hydroxy-2-methyl-6,7,8-trifluorochromone-3-carboxylic acid. Reaction with morpholine provided 7-substituted product, and with aqueous ammonia as a result of rearrangement forms 3-acetimidoyl-4-hydroxy-5-methoxy-6,7,8-trifluorocoumarin. Hydrolysis of the latter yields 3-acetyl-4-hydroxy-5-methoxy-6,7,8-trifluorocoumarin.     

Investigations toward the total syntheses of proapoiphine and homoproaporphine alkaloids

The reaction of 1,2,3,5-telrahydro-6-methoxy-1 -[2-(4-methoxy-1,4-eyelohexadien-1 -yl)eth-yl]-l-methyl-7-isoquinolinol ( 12 ) with hot phosphoric acid afforded (±)-tetrahydro-homoglazio-vine ( 14 ) in good yield. Similar treatment of 1,2,3,4-tetrahydro-6-methoxy-l -[2-(4-methoxy-1,4-cyelohexadien-l-yl)methyl]-2-methyl-7-isoquinolinol ( 13 ) did not produce the desired (±)-tetra-hydroglaziovine ( 18 ) but rather a mixture of diastereomeric 4,5,6,6a?,7,7a?,8,9,11, 11a?-deca-hydro-l-hydroxy-2-metlu>xy-6-methyl-10H-dibenzo[(de,g]quinolin-l-ones (16 and 17) was obtained.     

Synthesis and molecular structure study of 3-methoxy-7α-methyl-6-oxa-9β,14β-estra-1,3,5(10)-trien-17-one in solution

It was established by NMR spectroscopy that the catalytic hydrogenation of 3-methoxy-7α-methyl-6-oxa-14β-estra-1,3,5(10),8-tetraen-17-one leads to the formation of 3-methoxy-7α-methyl-6-oxa-9β,14β-estra-1,3,5(10)-trien-17-one, the structure of which was investigated in solution. The corresponding analog with a free hydroxyl group at the position 3 possesses an antiradical activity at the absence of uterotropic effect.     

若干D环带硝基的小檗因衍生物的光环化合成

通过酰烯胺的光环化反应, 合成了六个D环带硝基的小檗因类化合物。在酰烯胺的制备中, 还得到了几个非预期的副产物, 阐明了它们的结构。     

Addition-Rearrangement of Aryl- and Alkoxysulfonyl Isocyanates with 5-Methyl-Substituted 3,4-Dihydro-2-methoxy-2H-pyrans. Selective Synthesis of Functionalized 2-Piperidones(1)

3,4-Dihydro-2-methoxy-5-methyl-2H-pyran and 3,4-dihydro-2-methoxy-5,6-dimethyl-2H-pyran undergo addition-rearrangement reactions with arylsulfonyl isocyanates to generate the corresponding 3-formyl- and 3-acetyl-6-methoxy-3-methyl-1-(arylsulfonyl)-2-piperidones. For example, 3,4-dihydro-2-methoxy-5-methyl-2H-pyran and phenylsulfonyl isocyanate afforded 3-formyl-6-methoxy-3-methyl-1-(phenylsulfonyl)-2-piperidone as a separable trans/cis mixture in high yield. The more reactive phenoxysulfonyl and alkoxysulfonyl isocyanates provided analogous results.     

Unequivocal syntheses of 6-methyl- and 6-phenylisoxanthopterin

Although 6-methyl- ( 1 ) and 6-phenylisoxanthopterin ( 2 ) have previously been synthesized, the requirement of high purity necessary for immunological testing has necessitated our development of the first reported synthesis of these compounds by unequivocal methods. In the process of so doing four new pyrazines, ethyl 3-amino-5-chloro-6-methyl-2-pyrazinecarboxylate ( 11 ), N,N-dimethyl-N'-(6-chloro-3-cyano-5-phenylpyrazin-2-yl)methanimidamide ( 16 ), 2-amino-3-ethoxycarbonyl-5-phenylpyrazine 1-oxide ( 19 ), and ethyl 3-amino-5-chloro-6-phenyl-2-pyrazinecarboxylate ( 20 ) were synthesized. Four new pteridines, 7-methoxy-6-methyl-2,4-pteridinediamine ( 7 ), 7-methoxy-6-phenyl-2,4-pteridinediamine ( 17 ), 2-amino-7-ethoxy-6-methyl-4(3H)-pteridinone ( 12 ), and 2-amino-7-ethoxy-6-phenyl-4(3H)-pteridinone ( 21 ) have also been synthesized enroute to these isoxanthopterins.     

Synthesis of 7-methoxy-2-methyl-3,5,8-isoquinolinetrione

Synthesis of 7-methoxy-2-methyl-3,5,8-isoquinolinetrione from either 7- or 8-isoquinolinol is described. 3,5,8-Isoquinolinetrione is a novel heteroeyelic quinune which constitutes the aromatic carbon skeleton of mimosamycin.     

Condensation of 1,4-diacetylpiperazine-2,5-dione with aldehydes

Condensation of 1,4-diacetylpiperazine-2,5-dione with aldehydes has been applied to the synthesis of albonoursin and unsymmetrical 3,6-diarylidenepiperazine-2,5-diones. The reaction has been extended to 1,4-diacetyl-3,6-dimethylpiperazine-2,5-dione, which gives derivatives of 2-methyl-3- phenylserine. The mechanism and stereochemistry are discussed; cis 1-acetyl-3-isobutylidene- piperazine-2,5-dione has been isolated.