Condensed thiazoles,I: Synthesis of 5,7-disubstituted thiazolo[4,5-d]pyrimidines as possible anti-HIV,anticancer, and antimicrobial agents

Summary A convenient and simple synthesis of 5-mercapto-3-phenyl-2-thioxo-2,3-dihydrothiazolo-[4,5-d]pyrimidin-7(6H-one(2) and its 5,7-dichloro (3), 5,7-diazido (4), 5,7-diamino (5), 5,7-dimerapto (6), 5,7-dimethylthio (7), and 6-methyl-5-methylthio (8) derivatives is described. The prepared compounds were screened for theirin vitro anti-HIV, anticancer, antibacterial and antifungal activities.

---

Kondensierte Thiazole, 1. Mitt.: Synthese von 5,7-disubstituierten Thiazolo[4,5-d]pyrimidinen als potentielle anti-HIV, anticancerogene und antimikrobielle Verbindungen

Zusammenfassung Die Synthese von 5-Mercapto-3-phenyl-2-thioxo-2,3-dihydrothiazolo[4,5-d-pyrimidin-7(6H)-on (2) und seiner 5,7-dichloro-(3), 5,7-diazido-(4), 5,7-dimanio-(5), 5,7-dimercapto-(6), 5,7-dimethylthio- (7) und 6-methyl-5-methylthio-Derivaten (8) wird beschrieben. Die hergestellten Verbindungen wurden auf ihrein vitro anti-HIV, anticancerogenen, antibakteriellen und antimykotischen Aktivitäten geprüft.

     

Bisabocurcumin, a new skeleton curcuminoid from the rhizomes of Curcuma longa L.

A new skeleton bisabolane-type sesquiterpene curcuminoid,bisabocurcumin(1),along with 5 known compounds,curcumin(2), demethoxycurcumin(3),bidemethoxycurcumin(4),(1E,4E)-1,5-bis(4-hydroxy-3-methoxyphenyl)-penta-1,4-dien-3-one(5),and (1E,4E)-1-(4-hydroxy-3-methoxyphenyl)-5-(4-hydroxy phenyl-)-penta-1,4-dien-3-one(6)were isolated from the rhizomes of Curcuma longa L.Their structures were determined on the basis of spectroscopic analysis.Bisabocurcumin(1) is firstly obtained from nature with a new skeleton combined by a bisabolane-type sesquiterpene and a 1,7-diphenylheptanoid through a C-C bond.     

A new furanosteroid from Talaromyces sp. lgt-4, a fungal endophyte isolated from Tripterygium wilfordii

Wortmannolol (1), a new furanosteroid, along with five known compounds, wortmannolone (2), ergosterol (3), p-hydroxyphenyl ethanol (4), trans-6-dodecene (5), (2Z, 4E) -5-(8-hydroxy-1,5-dimethyl-3-oxo-6-oxabicyclo [3.2.1] octan-8-yl) -3-methylpenta-2,4-dienoic acid (6) were isolated from a fungal endophyte Talaromyces sp. lgt-4. Their structures were elucidated by IR, MS, 1D and 2D NMR spectra. Compound 1 show weak monoamine oxidase inhibitory activity.     

Balanochalcone,a new chalcone from Balanophora laxiflora Hemsl.

A new chalcone named as balanochalcone (1) together with eight known compounds, methyl caffeate (2), β-hydroxydihydrochalcone (3), methyl gallate (4), dimethyl-6,9,10-trihydroxybenzo[kl]xanthene-1,2-dicarboxylate (5), p-coumaric acid (6), quercetin (7), scopoletin (8) and pinoresinol (9) have been isolated from the ethyl acetate extract of Vietnamese Balanophora laxiflora Hemsl. Their structures were characterised by IR, UV, HR-ESI-MS, 1D and 2D NMR and CD spectroscopies. Compounds 2 and 5 showed moderate cytotoxicity against four cancer cell lines, KB (a human epidermal carcinoma), MCF7 (human breast carcinoma), SK-LU-1 (human lung carcinoma) and HepG2 (hepatocellular carcinoma). In addition, compounds 1 and 5 showed moderate antioxidant activity.     

Rubescins I and J,further limonoid derivatives from the stem bark of Trichilia rubescens (Meliaceae)

Two new tetranorterpenoid derivatives named rubescins I (1) and J (2), were isolated along with six known compounds including rubescin D (3), lichexanthone (4), scopoletin (5), scopoletin O-glycoside (6), β-sitosterol (7) and stigmasterol (8) from the stem bark of Trichilia rubescens (Meliaceae). The structures of the compounds were determined by means of MS, different NMR and by comparison with related data reported in the literature.     

Microporotriol,a new cadinane-type sesquiterpenoid from the cultures of the wood-decay fungus Microporus affinis HFG829

Abstract

A new cadinane-type sesquiterpenoid, microporotriol (1), together with four known compound, 5-methylresorcinol (2), (22E,24R)-ergosta-4,6,8(14),22-tetraen-3-one (3), (22E,24R)-ergosta-5,7,22-trien-3β-ol (4), (22E,24R)-5α,8α-epidioxy-ergosta-6,22-dien-3β-ol (5), were isolated from the fermentation broth of the wood decaying fungus Microporus affinis HFG829. The structures of the compounds were established by extensive spectroscopic methods, including 1D & 2D NMR, along with HRMS spectroscopic analysis. The relative configuration of 1 was confirmed by NMR calculation. Compound 1 was evaluated for the cytotoxicity against five human cancer cell lines.     

SYNTHESES AND SOME PROPERTIES OF SULFOXIDES,SULFILIMINES, AMINOSULFONIUM SALTS AND SULFOXIMINES CONTAINING PYRIDINE NUCLEI

Abstract

Several 2-pyridyl sulfides (1) (e.g., methyl (1a), ethyl (1b), isopropyl (1c), benzyl (1d), 1-phenylethyl (1e), l-menthyl (If) 2-pyridyl sulfides; and bis(2-pyridylthio)methane (1g), and methyl 2-(N-oxy-pyridyl) sulfide (1h) were prepared by the usual method. Sulfoxides (2) were prepared by oxidation of the corresponding sulfides with m-chloroperbenzoic acid in good yields. A few sulfoxides were found to work as phase-transfer catalysts for some typical nucleophilic reactions in nonpolar solvents such as benzene, and in two-phase systems such as benzene-water. S-2-Pyridyl-N-(p-toluenesulfonyl) sulfilimines (3) were prepared upon treatment of sulfides with Chloramine-T. Hydrolysis of N-(p-toluenesulfonyl)-2-pyridyl-o-tolylsulfilimine (3i) with conc. sulfuric acid gave the corresponding free sulfilimine in a moderate yield. S-2-Pyridyl sulfoximines (4) were not obtained by the general method from the sulfoxides and hydrazoic acid. Alkyl-2-pyridyl sulfoximines, however, were obtained by oxidation of the free sulfilimines derived from the corresponding aminosulfonium salts (5) prepared by reaction of the sulfides with mesitylene-sulfonylhydroxylamine (MSH). These free sulfilimines and sulfoximines thus prepared were found to give adducts with a few copper salts.     

Ascomycotin A,a new citromycetin analogue produced by Ascomycota sp. Ind19F07 isolated from deep sea sediment

A new citromycetin analogue, ascomycotin A (1), together with eight known compounds, wortmannilactone E (2), orcinol (3), orsellinic acid (4), isosclerone (5), (3R,4S)-( ? )-4-hydroxymellein (6), diorcinol (7), chaetocyclinone B (8) and 2,5-dimethoxy-3,6-di(p-methoxypheny1)-1,4-benzoquinone (9), was isolated from the fungal strain Ascomycota sp. Ind19F07, which was isolated from the deep sea sediment of the Indian Ocean. The structures of the compounds were established by spectroscopic data including 1D and 2D NMR and HR-ESI-MS. Compounds (1–9) were evaluated for antibacterial activity.     

Antibacterial constituents from Antarctic fungus,Aspergillus sydowii SP-1

One new alkaloid, named as acremolin C (1), was isolated from static culture of Antarctic fungus, Aspergillus sydowii SP-1, in an investigation of the antimicrobial constituents of this Antarctic microorganism, and its structure was determined by spectroscopic methods. Additionally, four known compounds, cyclo-(L-Trp-L-Phe) (2), 4-hydroxyphenylacetic acid (3), (7S)-(+)-hydroxysydonic acid (4) and (7S, 11S)-(+)-12-hydroxysydonic acid (5), were isolated and identified. Biological studies disclosed that compounds 2, 4 and 5 showed moderate inhibitions against methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant Staphylococcus epidermidis (MRSE) as comparing to tigecycline, while compound 1 displayed weak inhibition activities against MRSA and MRSE.     

Über Reaktionen von Nitrosophenolen, 2. Mitt.: Reaktion von 1-Nitroso-2-naphthol mit Orein

Zusammenfassung In der vorliegenden Arbeit wurde die Reaktion von 1-Nitroso-2-naphthol mit Orcin in Äther bei Anwesenheit von HNO₃ studiert. Als Reaktionshauptprodukte wurden 11-Methylbenzo[a]-phenoxazon-(9) (1) sowie dessen 12-Oxid (2) isoliert. Der Reaktionsmechanismus und die Konstitution der erhaltenen Substanzen werden diskutiert. Ferner wurden auch 11-Methyl-5-hydroxy-benzo[a]phenoxazon-(9) (6), 11-Methyl-5-äthoxybenzo[a]phenoxazon-(9), 11-Methyl-5-methoxybenzo[a]phenoxazon-(9) (4), 11-Methyl-5-aminobenzo[a]phenoxazon-(9) (7) und 11-Methyl-5-anilinobenzo[a]phenoxazon-(9) (8) dargestellt.

---

In this paper the reaction of 1-nitroso-2-naphthol with orcin in an ether medium in presence of HNO₃ is described. As main products 11-methylbenzo[a]phenoxazone-(9) (1) as well as its 12-oxide (2) were isolated. The reaction mechanism is presented. Identity of the reaction products is verified. 11-methyl-5-hydroxybenzo[a]phenoxazone-(9) (5), 11-methyl-5-methoxybenzo[a]phenoxazone-(9) (4), 11-methyl-5-aminobenzo[a]phenoxazone-(9) (7) and 11-methyl-5-anilinobenzo[a]phenoxazone-(9) (8) are prepared.

---

---

Mit 2 Abbildungen     

Tagetnoic acid,a new lipoxygenase inhibitor peroxy fatty acid from Tagetes minuta growing in Saudi Arabia

Abstract

A new peroxy fatty acid, tagetnoic acid (5) [4-((3S,6S)-6-((3E,8E)-octadeca-3,8-dien-1-yl)-3,6-dihydro-1,2-dioxin-3-yl)butanoic acid] and four known metabolites: ecliptal (5-formyl-α-terthiophene) (1), 5-(4-hydroxybut-1-ynyl)-2,2′-bithiophene (2), 22,23-dihydrospinasterone (3), and stigmasterol (4) were separated from the n-hexane fraction of the aerial parts of Tagetes minuta L. (Asteraceae). Their chemical structures were verified using IR, UV, 2D and 1D NMR, and HRMS. Compounds 3–5 displayed potent lipoxygenase inhibitory potential with IC₅₀s 2.26, 1.83, and 1.17?μM, respectively compared to indomethacin (IC₅₀ 0.89?μM). Moreover, molecular docking study revealed that the potent activity of 5 is due to H-bonding and hydrophobic interaction. The results of this study suggested that Tagetes minuta dietary consumption would be useful for the individuals at risk of acute and chronic inflammatory disorders.     

Trichocitrin,a new fusicoccane diterpene from the marine brown alga-endophytic fungus Trichoderma citrinoviride cf-27

One new diterpene, trichocitrin (1), and four known secondary metabolites, nafuredin (2), 5-hydroxy-2,3-dimethyl-7-methoxychromone (3), 24-methylenecycloartanol (4) and citrostadienol (5), were isolated from the culture of marine brown alga-endophytic Trichoderma citrinoviride cf-27. Trichocitrin (1) represents the first Trichoderma-derived and furan-bearing fusicoccane diterpene, and its structure and relative configuration were identified by analysis of 1D/2D NMR and mass spectroscopic data. Compounds 1 and 2 exhibited 8.0- and 9.5-mm inhibition zones, respectively, against Escherichia coli at 20 μg/disc and 54.1 and 36.7% growth inhibition, respectively, of Prorocentrum donghaiense at 80 μg/mL.     

Pholiotone A,a new polyketide derivative from Pholiota sp

Abstract

Pholiotone A (1), a new polyketide derivative, with tetrahydrobenzofuran-4(2H)-one skeleton, together with four known compounds, trichodermatides A (2) and B (3) and koninginins B (4) and E (5), were isolated from the crude extract of Pholiota sp. The structures of all the isolated compounds were determined mainly by NMR experiments, the modified Mosher method and electronic circular dichroism (ECD) calculations. The antifungal and cytotoxicity of all isolates were evaluated.     

Pseudolycorine N-oxide,a new N-oxide from Narcissus tazetta

Abstract

A new N-oxide, Pseudolycorine N-oxide (1) was characterised along with eleven known alkaloids homolycorine (2), O-methylmaritidine (3), 8-O-demethylhomolycorine (4), homolycorine N-oxide (5), lycorine (6), narciclasine (7), pseudolycorine (8), ungeremine (9), 8-O-demethylmaritidine (10), zefbetaine (11) and lycorine N-oxide (12), from Narcissus tazetta. Their structures were established on the basis of spectroscopic data analysis. The extract, fractions and isolated compounds were screened for in vitro cytotoxicity against two human cancer cell lines, human cervical cancer (SiHa) and human epidermoid carcinoma (KB) cells. The study demonstrated the cytotoxic potential of extract and its chloroform and n-butanol fractions. Further, the results revealed the bioactive potential of narciclasine, pseudolycorine and homolycorine alkaloids. However, new N-oxide (1) was not active against these cell lines.     

Secoiridoids and other chemotaxonomically relevant compounds in Pedicularis: phytochemical analysis and comparison of Pedicularis rostratocapitata Crantz and Pedicularis verticillata L. from Dolomites

We compared the respective metabolite patterns of two Pedicularis species from Dolomites. Seven phenylethanoid glycosides, i.e., verbascoside (1), echinacoside (2), angoroside A (3), cistantubuloside B1 (4), wiedemannioside C (5), campneoside II (11) and cistantubuloside C1 (12), together with several iridoid glucosides as aucubin (6), euphroside (7), monomelittoside (8), mussaenosidic acid (9) and 8-epiloganic acid (13) were identified. Pedicularis verticillata showed also the presence of greatly unexpected secoiridoids, ligustroside (14) and excelside B (15), very rare compounds in Lamiales. Both PhGs and iridoids are considered of taxonomical relevance in the Asteridae and their occurrence in Pedicularis was discussed. In particular, the exclusive presence of several compounds such as 8-epiloganic acid (13), campneoside II (11), cistantubuloside C1 (12), ligustroside (14) and excelside B (15) in Pedicularis rostratocapitata, and angoroside A (3), cistantubuloside B1 (4) and wiedemannioside C (5) in P. verticillata could be considered specific markers for the two botanical entities.     

Antimicrobial and antioxidant activities of a new benzamide from endophytic Streptomyces sp. YIM 67086

A new benzamide (1) and four known compounds (2–5) were isolated from endophytic Streptomyces YIM67086, and their structures were determined as 2-amino-3,4-dihydroxy-5-methoxybenzamide (1), 4-hydroxy-3-methoxybenzoic acid (2), phenylacetic acid (3), N-acetyltyramine (4) and p-hydroxytruxinic acid (5). Compound 5 was first found in the microorganism. The antimicrobial activities of compounds 1–5 and antioxidant activity of compound 1 were investigated.     

UV-stability and UV-protective activity of alkaloids from the marine sponge Zyzzya fuliginosa

Alkaloids from the marine sponge Zyzzya fuliginosa damirones A (1) and B (2); makaluvamines H (3), C (4), G (5), and L (6); and zyzzyanones A (8) and B (9) were investigated for the ability to protect egg-cell membranes of the sea urchin Strongylocentrotus nudus from UV-radiation. Damirones, zyzzyanones, and tricyclic makaluvamines C (4) and H (3) exhibited the greatest membrane-protective activity. It was shown that makaluvamines G (5) and L (6) were converted by UV-irradiation into damirones A (1), B (2), tricyclic makaluvamines H (3), C (4), and zyzzyanones A (8) and B (9), respectively. __________ Translated from Khimiya Prirodnykh Soedinenii, No. 1, pp. 62–64, January–February, 2006.     

Pestalotiopisorin B,a new isocoumarin derivative from the mangrove endophytic fungus Pestalotiopsis sp. HHL101

Abstract

A new isocoumarin derivative pestalotiopisorin B (1), along with six known compounds, (R)-(-)- mellein methyl ether (2), pestalotiopyrone G (3), (R)-mevalonolactone (4), pestalotiollides A–B (5–6) and pestalotiopsol A(7) were isolated from Pestalotiopsis sp., an endophytic fungus obtained from Chinese mangrove plant Rhizophora stylosa. Their structures were elucidated unambiguously by the comprehensive analysis of extensive spectroscopic data. Compound 1 exhibited modest antibacterial activity against Escherichia coli and Pseudomonas aeruginosa with 12.5?μg/ml, 50?μg/ml, respectively. Compound 4 showed moderate calcineurin inhibitory activity towards p-nitrophenyl phosphate (IC₅₀ =134.29?±?5.377?μM).     

Benzimidazole condensed ring systems,VI: Organic azides in heterocyclic synthesis,X: Synthesis of some substituted pyrimido[1,6-a]-benzimidazoles as potential antimicrobial agents

Summary The syntheses of 3-chloro derivatives of 2-alkyl-pyrimido[1,6-a]benzimidazol-1(2H)-ones2a, b as well as of 4,4-dichloro and 4,4-dibromo derivatives of 2-alkylpyrimido[1,6-a]benzimidazole-1,3(2H,4H)-diones3 a, b and4 are reported. Methods for converting some of the chloro compounds to azido (5, 6), amino (8), morpholino (9 a,10,11), piperidino (9 b), cyano (12), and methoxy (13) derivatives of the adopted tricyclic system are also described.

---

Kondensierte Ringsysteme des Benzimidazols, 6. Mitt.: Organische Azide in der Heterocyclen-Synthese, 10. Mitt.: Synthese von substituierten Pyrimido[1,6-a]benzimidazolen als mögliche antimikrobielle Wirkstoffe

Zusammenfassung Die Synthese von 3-Chlor-2-alkyl-pyrimido[1,6-a]benzimidazol-1(2H)-onen (2 a, b) und von 4,4-Dichlor- und 4,4-dibrom-pyrimido[1,6-a]benzimidazol-1,3(2H,4H)-dionen (3 a, b, 4) wird beschrieben. Diese Verbindungen lassen sich zu den entsprechenden Azido- (5, 6), Amino- (8), Morpholino- (9 a, 10, 11), Piperidino- (9 b), Cyano- (12) und Methoxy- (13) Derivaten umwandeln.

     

New 1, 2-naphthoquinone-derived pigments from the mycobiont of lichen Trypethelium eluteriae Sprengel

A new yellow pigment trypethelonamide A (1), and a new dark violet-red pigment 5′-hydroxytrypethelone (2), as well as three known dark violet-red pigments (+)-8-hydroxy-7-methoxytrypethelone (3), (+)-trypethelone (4) and (-)-trypethelone (5) were isolated from the cultured lichenized fungus Trypethelium eluteriae. The structures of 1 and 2 were determined to be 1, 2-naphthoquinone derivatives by extensive spectroscopic analysis. The absolute configurations of 1 and 2 were assigned by quantum electronic circular dichroism (ECD) calculation. All isolated compounds were evaluated for cytotoxicities against A549, HepG2 and RKO cell lines, and antioxidant effects on DPPH. Compounds 1–5 showed moderate and weak cytotoxicities against RKO cell line with IC₅₀ from 22.6 to 113.5 μM.