Benzo[b] thiophene derivatives. XVIII. The sulfur isosteres of harmaline,harmine and related isomers

The sulfur analogs of harmaline, 7-methoxy-3,4-dihydro-1-methyl[1]benzothieno[2,3-c]-pyridine (Ib), harmine, 7-methoxy-1-methyl[1]benzothieno[2,3- c ]pyridine (IIb), and corresponding 6-methoxy isomers (Ic and IIc) have been synthesized for pharmacological evaluation as monoamine oxidase inhibitors.     

Synthetic analogues of Peganum alkaloids. III. Pentamethylenequinazolones

Monosubstituted 5-, 6-, and 8-methoxy-3,4-dihydro-2,3-pentamethylenequinazolones (1–3) have been syntehsized by the condensation of monosubstituted methoxyanthranilic acids with caprolactam. Demethylation with hydrobromic acid gave the corresponding hydroxy compounds [4–6]. When the 6- and 8-methoxy- and 6- and 8-hydroxy-3,4-dihydro-2,3-pentamethylenequinazolones (2, 3, 5, and 6) were reduced with zinc in hydrochloric acid, the corresponding quinazoline derivatives (7–10) were obtained. The melting points of the basis and their hydrochlorides are given. Some features of their UV, mass, and PMR spectra are reported.     

Analytical chemistry of synthetic routes to psychoactive tryptamines. Part I. Characterisation of the Speeter and Anthony synthetic route to 5-methoxy-N,N-diisopropyltryptamine using ESI-MS-MS and ESI-TOF-MS

5-Methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT), a new psychoactive tryptamine derivative, has been synthesised by the Speeter and Anthony procedure. This synthetic route was characterised by ESI-MS-MS, ESI-TOF-MS and NMR. Side products have been identified as 3-(2-N,N-diisopropylamino-ethyl)-1H-indol-5-ol (5), 2-N,N-diisopropylamino-1-(5-methoxy-1H-indol-3-yl)-ethanol (6), 2-(5-methoxy-1H-indol-3-yl)-ethanol (7) and 2-N,N-diisopropylamino-1-(5-methoxy-1H-indol-3-yl)-ethanone (8).     

The crystal and molecular structures of an unusual estra-steroid and of its dihydroproduct

The crystal and molecular structures of 17 -ethylenedioxy-3-methoxy-6,7,8-methylidyne-1,3,5(10)-estratriene ( 1 ) and of 17β-bromo-acetoxy-3-methoxy-8α-methyl-1,3,5(10),6-estratetraene ( 3 ) have been determined by X-ray analysis. A short discussion of the structures is given, and a new picture of the structure-activity relation of estrogenics is proposed.     

Synthetic analogues of Peganum alkaloids. III. Pentamethylenequinazolones

Monosubstituted 5-, 6-, and 8-methoxy-3,4-dihydro-2,3-pentamethylenequinazolones (1–3) have been syntehsized by the condensation of monosubstituted methoxyanthranilic acids with caprolactam. Demethylation with hydrobromic acid gave the corresponding hydroxy compounds [4–6]. When the 6- and 8-methoxy- and 6- and 8-hydroxy-3,4-dihydro-2,3-pentamethylenequinazolones (2, 3, 5, and 6) were reduced with zinc in hydrochloric acid, the corresponding quinazoline derivatives (7–10) were obtained. The melting points of the basis and their hydrochlorides are given. Some features of their UV, mass, and PMR spectra are reported.Institute of the Chemistry of Plant Substances, Academy of Sciences of the Uzbek SSR, Tashkent. Translated from Khimiya Prirodnykh Soedinenii, No. 4, pp. 465–469, July–August, 1986.     

Mass spectrometry in structural and stereochemical problems. CCLVI—electron impact induced fragmentation of juvenile hormone analogs

Complete high resolution mass spectra of several analogs of the juvenile hormones have been analyzed with the aid of our recently developed INTSUM program and mass spectra of deuterated analogs. Representative compounds chosen for study included the biologically interesting (2E, 4E)-3,7,11-trimethyl-2,4-dodecadienoates (1,2), (2E,4E)-11-methoxy-3,7,-11-trimethyl-2,4-do-decadienoates (3,4) and three analogs (5-7) of the trans-trans-farnesoate skeleton. These compounds display characteristic fragmentations which can be used to detect the presence of the compounds in complex mixtures using mass fragmentography or aid in the structure elucidation of related compounds.     

Synthesis of methoxy and hydroxy containing tetralones: versatile intermediates for the preparation of biologically relevant molecules

The synthesis of 5-hydroxy-6-methoxy-1-tetralone and the 7-hydroxy regioisomer along with the corresponding 5,7-dihydroxy analog has been achieved using an efficient directed metallation procedure followed by a regioselective methylene oxidation. This methodology represents a general synthetic route for the preparation of highly oxygenated tetralone analogs which are versatile building blocks for the construction of molecules of biological interest.     

Antimalarials. 15. Side-chain analogues of 8-(4-amino-1-methylbutylamino)-6-methoxy-4-methyl-5-(3-trifluoromethylphenoxy)quinoline

Six side chain analogs of the highly active antimalarial agent 8-(4-amino-1-methylbutylamino)-6-methoxy-4-methyl-5-(3-trifluoromethylphenoxy)quinoline (I) were prepared and evaluated for blood and tissue schizonticidal activity. Although most examples were markedly superior to primaquine none was superior to the parent compound I.     

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.     

Synthesis and antimycobacterial activity of agelasine E and analogs

Agelasine E, previously isolated from the marine sponge Agelas nakamurai, has been synthesized for the first time, together with analogs with various terpenoid side chains. Treatment of N6-methoxy-9-methyl-9H-purin-6-amine with allylic bromides gave the desired 7,9-dialkylpurinium salts together with minor amounts of the N6-alkylated isomer. The N6-methoxy group was finally removed reductively. 1H-15N HMBC and 1H-15N HSQC NMR spectroscopy gave additional information on tautomerism and charge delocalization in the purine derivatives studied. The heterocyclic products were screened for activity against Mycobacterium tuberculosis and agelasine analogs carrying a relatively long terpenoid substituent in the purine 7-position and a methoxy group at N-6 were potent inhibitors of bacterial growth. Since agelasine analogs with the geranylgeranyl chain at N-7 exhibited antimicrobial activity, several strategies for synthesis of geometrically pure (2E,6E,10E)-geranylgeranyl bromide from geranyllinalool were evaluated.     

Alkaloids of Aconitum kirinense. Structure of akirine

The known alkaloid lepenine and the new diterpene alkaloid akirine have been isolated from the epigeal part ofAconitum kirinense Nakai. To establish the structure of akirine, its spectral characteristics have been studied and an x-ray structural analysis has been made. It is 1α,8β-dihydroxy-16β-methoxy-9β,14β-methylenedioxy-3β,4β-epoxy-N-ethylaconitane — the first diterpene alkaloid with a lycoctonine skeleton containing a 9,14-methylenedioxy group and a β-oriented substituent at C14.     

Synthesis of some 5-aryl-2,2′-dipyrromethenes as analogs of prodigiosin

Three new dipyrromethenes have been synthesized as analogs of prodigiosin: 3-methoxy-5-phenyl-2,2′-dipyrromethene (10a) , 3-methoxy-4 -pentyl-5-phenyl-5′-methyl-2,2′-dipyrromethene (10b) , and 3-methoxy-4′-pentyl-5′-methyl-5-(2″-thienyl)-2,2′-dipyrromethene (10c). The Michael addition of ethyl glycinate to an appropriate arylidenemalonate, quenched with ethyl chloroformate and followed by a Dieckmann cyclization gave diethyl 1-ethoxycarbonyl-3-oxo-5-phenyl and thienylpyrrolidine-2,4-dicarboxylate, 2a and 2b. Methylation of the highly enolic keto-esters, followed by oxidation to N-ethoxycarbonylpyrroles led, after appropriate elaboration of the pyrrole nucleus, to 2-phenyl- and 2-thienyl-4-methoxypyrroles. The acid catalyzed condensation of these arylmethoxypyrroles with either pyrrole-2-carboxaldehyde or 5-methyl-4-pentylpyrrole-2-carboxaldehyde led to 10a, 10b and 10c.     

Synthetic analogs of natural flavolignans. IV. Synthesis of benzodioxocane analogs of silandrin and hydnocarpin

1,6-Benzodioxocane analogs of chalcones have been synthesized. From them have been obtained benzodioxocane analogs of silandrin and hydnocarpin. The PMR spectra of the substances synthesized are given and are discussed.Taras Shevchenko Kiev University, Ukraine. KIEN, Karakalpak Division, Academy of Sciences of the Republic of Uzbekistan, Nukus. Translated from Khimiya Prirodnykh Soedinenii, No. 4, pp. 490–493, July–August, 1994.     

Synthesis of thiazole derivatives

By condensing aldehydes of the benzothiazole series with dimethylaniline, leuco-bases of dyes of the type of Malachite Green have been synthesized. The oxidation of these bases has given new analogs of Malachite Green containing benzothiazole nuclei; the main absorption maxima of the dyes have been determined.For Communication XXIV, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1037–1039, August, 1973.     

Synthetic analogs of natural flavolignans. IV. Synthesis of benzodioxocane analogs of silandrin and hydnocarpin

1,6-Benzodioxocane analogs of chalcones have been synthesized. From them have been obtained benzodioxocane analogs of silandrin and hydnocarpin. The PMR spectra of the substances synthesized are given and are discussed. Taras Shevchenko Kiev University, Ukraine. KIEN, Karakalpak Division, Academy of Sciences of the Republic of Uzbekistan, Nukus. Translated from Khimiya Prirodnykh Soedinenii, No. 4, pp. 490–493, July–August, 1994.     

Indolic urinary melanogens: separation and identification by gas chromatography with selected-ion monitoring mass spectrometry of 5-hydroxy-6-methoxyindole-2-carboxylic and 5-methoxy-6-hydroxyindole-2- carboxylic acids.

Two isomeric urinary melanogens, 5-hydroxy-6-methoxyindole-2-carboxylic acid and 5-methoxy-6-hydroxyindole-2-carboxylic acid, have been separated by gas chromatography with selected-ion monitoring mass spectrometry. After chemical synthesis of one of these two isomers, 5-methoxy-6-hydroxyindole-2-carboxylic acid, and the establishment of the mass spectrum of its trimethylsilylated derivative, a 30-ml sample of a melanotic 24-h urine was adjusted to pH 1 and extracted twice with 10 ml of ethyl acetate. The extract was evaporated to dryness and the residue derivatized with methyl-8, followed by Tri-Sil/TBT. Silylated derivatives were analysed by gas chromatography with selected-ion monitoring mass spectrometry. The mass spectrum of the 5-methoxy-6-hydroxyindole-2-carboxylic acid allowed the determination of the retention times of both isomers.     

Synthesis of 2,5-diisoxazolyltetrahydrofurans

The synthesis of 2,5-bis(3-bromo-5-isoxazolyl)tetrahydrofuran ( 2 ) and 2,5-bis(3-methoxy-5-isoxazolyl)tetrahydrofuran ( 3 ) have been accomplished in three and four steps respectively. Cis- and trans-isomers have been separated and fully characterized. Differently from synthetic schemes so far utilized for the preparation of the 2,5-diheteroaryltetrahydrofuran analogs, our approach involves the direct synthesis of a key intermediate containing both isoxazole rings and diol function for the final cyclization. Starting from succinic aldehyde, the new 1,7-octadiyne-3,6-diol ( 4 ) was prepared and was submitted to a double cycloaddition with bromonitrile oxide to yield the key intermediate 1,4-bis(3-bromo-5-isoxazolyl)-1,4-butanediol. The methoxy analogs 3 were obtained by methanolysis of the bromo derivatives 2 .     

Synthesis of nectriapyrone

A totally synthetic route to the antibacterial fungal metabolite nectriapyrone ( 1 ) has been achieved by condensation of methylmalonyl dichloride with ethyl trans-4-methyl-3-oxo-4-hexenoate followed by hydrolysis, decarboxylation, and methylation of the resulting 3-methyl-4-hydroxy-5-carbethoxy-6-(trans-1-methyl-1-propenyl)-2-pyrone. Exploration of an alternate scheme involving the dehydrogenation of 6-substituted-4-methoxy-5,6-dihydro-2-pyrones, prepared by Reformatsky reaction of ethyl γ-bromo-β-methoxycrotonate with various aldehydes, was abandoned since it did not appear to have general applicability to the preparation of nectriapyrone and its analogs.     

Reaction of levoglucosenone with Dane’s diene

Cycloaddition of levoglucosenone to 7-methoxy-4-vinyl-1,2-dihydronaphthalene has been studied under different conditions, including heating under atmospheric pressure, in a sealed ampule, and under high pressure, as well as under microwave irradiation and in the presence of various catalysts. The chiral Diels–Alder adduct thus obtained can be used in the synthesis of estrone and its analogs.