Syntheses,characterizations and crystal structures of monomeric or macrocyclic compounds of di- or triorganotin (IV) moieties with 4,4′-thiodibenzenethiol

Six organotin compounds with 4,4′-thiodibenzenethiol (LH₂) of the type R_nSnL_4−nSnR_n (n = 3: R = Me 1, Ph 2, PhCH₂3, n = 2: R = Me 4, Ph 5, PhCH₂6) have been synthesized. All compounds were characterized by elemental analysis, IR and NMR (¹H, ¹³C, and ¹¹⁹Sn) spectra. The structures of compounds 1, 2, 4, 5 and 6 were also determined by X-ray diffraction analysis, which revealed that compounds 1 and 2 were monomeric structures, compounds 4, 5 and 6 were centrosymmetric dinuclear macrocyclic structures, and all the tin(IV) atoms are four-coordinated. Furthermore, supramolecular structures were also found in compounds 1, 2, 4, 5 and 6, which exhibit one-dimensional chains, two-dimensional networks or three-dimensional structures through intermolecular C–H?S weak hydrogen bonds (WHBs), non-bonded Sn?S interactions or C–H?π interactions.     

Mg-promoted reductive coupling of aromatic carbonyl compounds with trimethylsilyl chloride and bis(chlorodimethylsilyl) compounds

Mg-promoted reductive coupling of aromatic carbonyl compounds (1) with chlorosilanes, such as trimethylsilyl chloride (TMSCl:2), 1,2-bis(chlorodimethylsilyl)ethane (3) and 1,5-dichlorohexamethyltrisiloxane (4), in N,N-dimethylformamide (DMF) at room temperature brought about selective and facile reductive formation of both of carbon-silicon and oxygen-silicon bonds to give the corresponding α-trimethylsilylalkyl trimethylsilyl ethers (5) and cyclic siloxanes (6), (7) in moderate to good yields, respectively. The present facile and selective coupling may be initiated through electron transfer from Mg metal to aromatic carbonyl compounds (1).     

Synthesis, characterization, and derivatization of some novel types of fluorinated mono- and bis-imidazolidineiminothiones with antitumor, antiviral, antibacterial, and antifungal activities

A series of thirty eight novel imidazolidineiminothiones (6a-g, 10a-h, 13a,b, 15a-d, and 16a), 5-thioxoimidazolidine-2,4-diones (7a-d, 11a-e, 14a,b, and 16b), and bis-imidazolidineiminothiones (17-20) with various fluorinated aromatic substituents at N-(1) and N-(3) were prepared in 75-85% yields. The imidazolidineiminothiones were synthesized from fluorinated N-arylcyanothioformanilides and substituted aromatic isocyanates, and by the reactions of fluorinated aromatic isocyanates with fluorinated and non-fluorinated aromatic N-arylcyanothioformanilides. Subsequent hydrolysis of selected products produced the corresponding 5-thioxoimidazolidine-2,4-diones. Preliminary screening of several compounds against Ehrlich ascites carcinoma (EAC) cells indicated that 6f and 16a were the most active (90% and 80% inhibition, respectively). Further evaluation for cytotoxicity against other tumor cell lines gave IC₅₀ values ranging from 0.67 to 3.83 μg/mL, where compounds 15a and 16a were markedly active against all cell lines. This highlights the synergistic effect of the suitably positioned fluorinated substituents on N-(1) and N-(3) of the imidazolidineiminothiones. Compounds 6a,e-g, 10a-c, 13b, 15a-d, and 17-20 were tested against microbial organisms (Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Salmonella typhi, and Sarcina lutea), and fungal strains (Candida albicans, Aspergillus niger, and Aspergillus flavus). Whereas compound 6a exhibited the highest antibacterial activity against Gram positive and Gram negative bacteria, 13b displayed the strongest antifungal activity against all fungal strains, reaching as high as 30 mm. Finally, 15a,b,d were subjected to in vitro testing of antiviral activity against hepatitis A virus (HAV), human herpes simplex virus 1 (HSV1), and Coxsackie B4 (COxB4) viral strain, where 15b was the most effective, reducing virus plaque count of HSV1 and COxB4 by 50% and 60%, respectively.     

Absolute stereochemistry of antifouling cembranoid epimers at C-8 from the Caribbean octocoral Pseudoplexaura flagellosa. Revised structures of plexaurolones

Eight cembranoid epimers at C-8 (1-8) were isolated from the organic extract of the Colombian Caribbean octocoral Pseudoplexaura flagellosa. Compounds 2, 4, and 6 are reported for the first time. Although compounds 1, 3, 5, 7, and 8 have been reported previously, their structures and NMR assignments are revised, completed or corrected. The structures of these compounds were established on the basis of detailed analysis of their spectroscopic data. Furthermore, the relative configurations of compounds 1-3 and 7 were confirmed by single-crystal X-ray diffraction. The absolute configurations of compounds 1-8 were determined using a combination of the modified Mosher method and unambiguous chemical interconversions. Evaluation of their antifouling properties using quorum sensing inhibition (QSI) and biofilm inhibition bioassays showed that compounds 3, 6, and 7 have excellent QSI activity against Chromobacterium violaceum, as measured by inhibition of the production of violacein pigment, without interfering with its growth. Furthermore, compounds 3, 5, 6, and 8 exhibited inhibition of biofilm maturation without interfering in the growth of Pseudomonas aeruginosa, Vibrio harveyi, and Staphylococcus aureus. This is the first report of cembranoids as inhibitors of bacterial biofilm and as compounds that interfere with QS in C. violaceum.     

A facile synthesis and herbicidal activities of novel fluorine-containing thiazolo[4,5-d]pyrimidin-7(6H)-ones

Eighteen novel 5-alkylamino-6-aryl-3-phenyl-2-thioxo-2,3-dihydrothiazolo[4,5-d]pyrimidin-7(6H)-ones 5a-r were designed and easily synthesized via a tandem aza-Wittig reaction. Treatment of iminophosphorane 2 with aromatic isocyanate gave carbodiimide 3, which reacted with fluoro-substituted alkylamines to provide the title compounds in 65-87% isolated yields using sodium ethoxide as catalyst. All compounds 5 were confirmed by IR, ¹H NMR, MS and elemental analysis, and compound 5p was further analyzed by single-crystal X-ray diffraction. The preliminary bioassay indicated that some compounds showed significant inhibition activities against the root growth of rape and barnyard grass at a dosage of 100 mg/L.     

Synthesis and photochromic behaviour of new methyl induced linear and angular thieno-2H-chromenes

New methyl induced linear and angular thieno-2H-chromenes 4, 5 and 6 were prepared by reaction of new methylated 6-hydroxybenzo[b]thiophenes 2 (a, b and c) and propargylic alcohols 3a and 3b, using acidic Alumina Brockmann I as catalyst and drying agent. Compounds 2 were prepared in good to excellent yields in a ‘one pot’ three step reaction from the corresponding bromo compounds 1. The photochromic behaviour of compounds 4, 5 and 6b was evaluated with the aid of a classical set of spectrokinetic parameters, and compared to reference compounds that are benzoannellated in the 5,6 and 6,7 positions of the chromene (naphthopyrans) and also to thieno-2H-chromenes 7 and 8, previously prepared, which are analogues of 5a. The resistance to fatigue (photodegradation) under continuous irradiation was also evaluated.     

Polyhedral monocarbaborane chemistry : Reactions of the [6-Ph-nido-6-CB9H11] anion with two-electron donors to yield a series of neutral arachno and closo ten-vertex monocarbaborane derivatives

Reaction of the ten-vertex [6-Ph-nido-6-CB₉H₁₁]⁻ anion (1) with two-electron donor ligands L, where L is SMe₂, NH₂Ph, NC₅H₅, NC₅H₄-para-CH₂Ph, NC₅H₄-para-Ph or NC₉H₇ (where NC₉H₇ is quinoline) in the presence of {FeCl₃(OH₂)₆} gives the six neutral arachno ten-vertex monocarbaboranes [6-Ph-9-L-arachno-6-CB₉H₁₂], compounds 2, 3, 4, 7, 9 and 11, respectively, isolatable in yields of up to 63%. On prolonged treatment with {FeCl₃(OH₂)₆} oxidative cluster closure of the four compounds 4, 7, 9 and 11 that have pyridine-type ligands gives the neutral closo ten-vertex monocarbaboranes [1-Ph-6-L-closo-1-CB₉H₈], compounds 6, 8, 10 and 12, respectively, in yields of 49-92%. All new species 2, 3, 4, 6, 7, 8, 9, 10, 11 and 12 are characterised by single-crystal X-ray diffraction analysis and NMR spectroscopy. [This paper is an annotated exposition of parts of an oral presentation at the Third Pan-European Meeting of Boron Chemists, EUROBORON-3, Pruhonice, The Czech Republic, September 2004, of which the proceedings constitute this volume of Journal of Organometallic Chemistry.]     

Synthesis of a series of novel 2′,3′-dideoxy-6′,6′-difluoro-3′-thionucleosides

A series of novel 2′,3′-dideoxy-6′,6′-difluoro-3′-thionucleosides 1a-d, analogues of 3TC that has high biological activities against HIV and HBV, have been synthesized from the gem-difluorohomoallyl amine 7 in a straightforward fashion. Our synthesis featured the construction of thiofuranose skeleton through ring closure of key intermediates and installation of pyrimidine ring with amino group in compounds 13a,b.     

Dioxadispiroketal Compounds and a Potential Acyclic Precursor from Amomum aculeatum

Four new compounds having an unusual 1,7-dioxadispiro[5.1.5.2]-12-ene-11-one tricyclic ring system (1-4), their potential precursor, 5R-hydroxy-1-(4-hydroxyphenyl)-eicosan-3-one (5), and two known compounds, aculeatins A (6) and B (7), have been isolated from Amomum aculeatum. All compounds were characterized by spectroscopic methods and the configurations were established by 2D NOE correlations. Compounds 1-4, 6, and 7 showed cytotoxic activity against several human cancer cell lines.     

Induced production of novel prenyldepside and coumarins in endophytic fungi Pestalotiopsis acaciae

Concomitant supplementation of a histone deacetylase inhibitor, suberoylanilide hydroxamic acid, and a DNA methyltransferase inhibitor, 5-azacytidine, to the culture medium of a plant endophytic fungus, Pestalotiopsis acaciae, dramatically altered its metabolic profiles. As a result, three novel aromatic compounds, 2′-hydroxy-6′-hydroxymethyl-4′-methylphenyl-2,6-dihydroxy-3-(2-isopentenyl)benzoate (1), 4,6-dihydroxy-7-hydroxymethyl-3-methylcoumarin (2) and 4,6-dihydroxy-3,7-dimethylcoumarin (3), were isolated, along with five known polyketides, endocrocin (4), pestalotiollide B (5), pestalotiopyrone G (6), scirpyrone A (7) and 7-hydroxy-2-(2-hydroxypropyl)-5-methylchromone (8).     

Stabilization of (N-methyleneamino)imidoylketenes: synthesis of dipyrazolo[1,2-a;1′,2′-d][1,2,4,5]tetrazines

Thermolysis of substituted methyl 1-methyleneamino-4,5-dioxo-4,5-dihydro-1H-pyrrole-2-carboxylates 2a,b led to substituted dimethyl 3,9-dioxo-1,5,7,11-tetrahydro-1H,7H-dipyrazolo[1,2-a;1′,2′-d][1,2,4,5]tetrazine-1,7-dicarboxylates 4a,b and methyl 2,5-dihydro-5-oxo-1H-pyrazole-3-carboxylates 5a,b as minor products. The structure of compound 4a was determined by X-ray crystallography. The proposed mechanism of this conversion includes generation of (N-methyleneamino)imidoylketenes 6a,b and its intramolecular transformation to azomethine imines—5-oxo-2,5-dihydropyrazole-1-methylium-2-ides 7a,b, which undergo dimerization in head-to-tail manner yielding products 4a,b and partially hydrolyse to compounds 5a,b.     

Synthesis and properties of 3-arylcyclohepta[4,5]imidazo[1,2-a]-1,3,5-triazine-2,4(3H)-diones and related compounds: photo-induced autorecycling oxidation of some amines

Novel 3-phenyl- and 3-(4-nitrophenyl)cyclohepta[4,5]imidazo[1,2-a]-1,3,5-triazine-2,4(3H)-diones and the corresponding imino derivatives 5a,b and 6a,b were synthesized in modest to moderate yields by the abnormal and normal aza-Wittig reaction of 2-(1,3-diazaazulen-2-ylimino)triphenylphosphorane with aryl isocyanates and subsequent heterocyclization reaction with a second isocyanate. The related cationic compound, 1-methyl-3-phenylcyclohepta[4,5]imidazo[1,2-a]-1,3,5-triazine-2,4(3H)-dionylium tetrafluoroborate 7a, was also prepared. The electrochemical reduction of these compounds exhibited more positive reduction potentials as compared with those of the related compounds of 3,10-disubstituted cyclohepta[4,5]pyrrolo[2,3-d]pyrimidine-2,4(1H,3H)-dione systems. In a search of the oxidizing ability, compounds 5a, 6a, and 7a were demonstrated to oxidize some amines to give the corresponding imines in more than 100% yield under aerobic and photo-irradiation conditions, while even benzylamine was not oxidized under aerobic and thermal conditions at 100 °C. The oxidation reactions by cation 7a are more efficient than that by 5a and 6a. Quenching of the fluorescence of 5a was observed, and thus, the oxidation reaction by 5a probably proceeds via electron-transfer from amine to the excited singlet state of 5a. In the case of cation 7a, the oxidation reaction is proposed to proceed via formation of an amine-adduct of 7a and subsequent photo-induced radical cleavage reaction.     

Bis-spiro-azaphilones and azaphilones from the fungi Chaetomium cochliodes VTh01 and C. cochliodes CTh05

Four new dimeric spiro-azaplilones, cochliodones A-D (1-4), two new azaphliones, chaetoviridines E and F (5 and 6), a new epi-chaetoviridin A (7), together with five known compounds, chaetoviridin A (8), ergosterol (9), chaetochalasin A (10), 24(R)-5α,8α-epidioxyergosta-6-22-diene-3β-ol (11), and ergosterol-β-d-glucoside (12) were isolated from the fungi Chaetomium cochliodes VTh01 and C. cochliodes CTh05. Structures and stereochemistry of the atropisomers 1-3 were determined by single-crystal X-ray diffraction analysis. Compounds 5, 10, and 11 exhibited antimalarial activity against Plasmodium falciparum, while 3, 5, 6, 10, and 11 showed antimycobacterial activity against Mycobacterium tuberculosis. In addition, 5 and 6 also showed cytotoxicity against the KB, BC1, and NCI-H187 cell lines.     

Biotransformation of triptolide by Cunninghamella blakesleana

Biotransformation of triptolide 1 by Cunninghamella blakesleana (AS 3.970) was carried out. Seven biotransformation products were obtained and four of them were characterized as new compounds. On the basis of their NMR and mass spectral data, their structures were characterized as 5α-hydroxytriptolide 2, 1β-hydroxytriptolide 3, triptodiolide 4, 16-hydroxytriptolide 5, triptolidenol 6, 19α-hydroxytriptolide 7 and 19β-hydroxytriptolide 8. All the new transformed products (2, 3, 7 and 8) were found to exhibit potent in vitro cytotoxicity against some human tumor cell lines.     

Bioactive meroterpenoids and alkaloids from the fungus Eurotium chevalieri

Five new meroterpenoids, chevalones A-D (1-4), aszonapyrone B (8), and a new sequiterpene alkaloid, eurochevalierine (5), together with four known compounds, sequiterpene (6), terpenoid pyrrolobenzoxazine named CJ-12662 (7), meroterpenoid, aszonapyrone A (9), and ergosterol were isolated from the fungus Eurotium chevalieri. The structures were established on the basis of spectroscopic evidence. The configurations of 1 and 5 were determined by X-ray analysis. The biosynthetic pathway of 1-3, 8, and 9 were proposed. Chemical transformation of aszonapyrone A (9) was also studied. Compounds 4, 5, and 7 exhibited antimalarial activity against Plasmodium falciparum, while 3, 5, and 7 showed antimycobacterial activity against Mycobacterium tuberculosis. In addition, compounds 2-7 showed cytotoxicity against cancer cell lines.     

Silylative N-hydroxyalkylation of amide compounds: application to the synthesis of acyclic alditol-based nucleoside analogues

A rare silylative hydroxyalkylation of amide compounds with chiral aldehydes has been developed utilizing a Lewis acid-Lewis base promoter system consisting of an equimolecular mixture of tert-butyldimethylsilyl trifluoromethanesulfonate and N-diisopropylethylamine. This approach culminated in the synthesis of several enantiopure acyclic nucleoside representatives comprising thymidine analogues 6, 7, 9, 10, 12 and 13, uridine analogues 15 and 16, and 6-chloropurine derivatives 18 and 19.     

Bioactive polyketides from the fungus Astrocystis sp. BCC 22166

Five new compounds, phthalide 1, dihydroisocoumarin 2, and 3, pyrone 4, and benzophenone 5, together with nine known compounds, 3,4-dihydro-4,5,8-trihydroxy-3-methylisocoumarin, sclerotinin A, methyl-8-hydroxy-6-methylxanthone-1-carboxylate, sydowinin A, conioxanthone A, 1,3,8-trihydroxy-6-methylxanthone, 1,8-dihydroxy-3-methoxy-6-methylxanthone, coniochaetone B, and xylaranol B, were isolated from the fungus Astrocystis sp. BCC 22166. Structures of these compounds were elucidated using NMR spectroscopic and MS spectrometric analyses. Compound 1 exhibited antibacterial activity against Bacillus cereus (IC₅₀=12.5 μg/mL) while compound 2 showed cytotoxicity to KB and Vero cells (IC₅₀=22.6 and 48.2 μg/mL).     

Rubischumanins A–C,new cytotoxic cyclopeptides from Rubia schumanniana

Three new cyclic hexapeptides, designated as rubischumanins A–C (1–3), together with three known ones (4–6) were isolated from the roots and rhizomes of Rubia schumanniana. The structures were elucidated on the basis of extensive spectroscopic analysis. Cytotoxicity of these compounds was evaluated and compounds 1, 2, 4, and 5 showed cytotoxicity against A549, BGC-823, and Hela cell lines.     

Dihydronaphthalenones from endophytic fungus Fusarium sp. BCC14842

Eleven new dihydronaphthalenones 1-11, together with five known compounds; 5-hydroxydihydrofusarubin C (12), javanicin, bostrycoidin, anhydrofusarubin, and 3-O-methylfusarubin, were isolated from the endophytic fungus Fusarium sp. BCC14842. Structures were elucidated by analyses of the NMR spectroscopic and mass spectrometry data. Javanicin, 3-O-methylfusarubin, compounds 3 and 7 exhibited antimycobacterial and cytotoxic activities. Javanicin also displayed antifungal activity with IC₅₀ of 6.16 μg/mL, while compounds 2, 4, 5, 8, and 12 showed only cytotoxic activity.     

6,7-Seco-ent-kaurane-type diterpenoids from Isodon eriocalyx var. laxiflora

Twenty nine 6,7-seco-ent-kaurane-type diterpenoids including 18 new ones, laxiflorolides C–T (1–18), along with 21 known ones were obtained from Isodon eriocalyx var. laxiflora. Laxiflorolides E–G (3–5) are the first identified naturally occurring 6,7-seco-ent-kauranoids that feature a 3,6-epoxy unit, and laxiflorolide M (11) is the first identified naturally occurring 6-nor-6,7-seco-ent-kauranoid. The absolute configurations of compounds 1, 3, 6, and 11 were determined by single-crystal X-ray diffraction analyses. The cytotoxic activity of the isolates was evaluated by an MTT assay.