Design and synthesis of (E)-4-((3-ethyl-2,4,4-trimethylcyclohex-2-enylidene)methyl)benzoic acid

(E)-4-((3-Ethyl-2,4,4-trimethylcyclohex-2-enylidene)methyl)benzoic acid, 6, was synthesized in 87% starting from β-cyclocitral. The target compound 6 was synthesized starting from 1 via a Grignard reaction to form alcohol 2. Compound 2 was converted to Wittig salt 3 by treatment with aldehyde 4 in butyllithium and hexane at −78 °C to form ester 5. Ester 5 was saponified and, following acidification, acid 6 was isolated as white solid yield 87%.     

Mercury assisted fluorescent supramolecular assembly of hexaphenylbenzene derivative for femtogram detection of picric acid

Aggregates of hexaphenylbenzene derivatives 3, having pyrene groups form network of fluorescent nanofibres in presence of mercury ions. Further, fluorescent nanofibres of 3-Hg²⁺ supramolecular ensemble exhibit sensitive and pronounced response towards the picric acid. In addition, the solution coated paper strips of 3-Hg²⁺ supramolecular ensemble can detect picric acid in the range of 2.29 fg/cm², thus, providing a simple, portable and low cost method for detection of picric acid in solution and in contact mode.     

Formation and skeletal transformations of perfluoroindan-1-one and perfluoroindan-1,3-dione in the reaction of perfluoroindan with SiO2/SbF5

Perfluoroindan-1-one (2) is obtained in the reaction of perfluoroindan (1) with SiO₂/SbF₅ at 70 °C. Compound 1 heated with SiO₂/SbF₅ at 130 °C and then treated with water, gives 3-hydroxy-perfluoro-3-methylphthalide (4). Ketone 2 is converted, under the action of SbF₅ at 130 °C, to perfluoro-2-ethylbenzoic acid (9) and disproportionates to compound 1 and perfluoroindan-1,3-dione (3); the latter is transformed to phthalide 4 under the reaction conditions.     

Synthesis, antitumor and DNA photocleaving activities of novel naphthalene carboxamides: effects of different thio-heterocyclic rings and aminoalkyl side chains

Two kinds of thio-heterocyclic fused naphthalene carboxamides, 3a-b, 4a-b, were designed, synthesized and quantitatively evaluated as efficient antitumor and DNA photocleaving agents. Compound 3a or 3b, having the thiophene ring, intercalated into DNA more strongly than compound 4a or 4b, having the thioxanthene ring. Compound 4a or 4b, photocleaved DNA more efficiently than 3a or 3b via superoxide anion. Compound 4a was the strongest inhibitor for P388 (murine leukemia cell), while 3a was the most cytotoxic one against A549 (human lung cancer cell). Each new compound showed stronger DNA photocleaving activity than corresponding naphthalimide.     

Synthesis and chemistry of tricyclic cyclopropene-tricyclo[3.2.2.0]nona-2(4),6-diene

The 1,2-bridged tricyclic cyclopropene, tricyclo[3.2.2.0^2,4]nona-2(4),6-diene (1), has been synthesized by the elimination of 2-bromo-4-chlorotricyclo[3.2.2.0^2,4]-non-6-ene (5). Cyclopropene 1 will undergo different isomerizations in ether solution and in neat conditions. Compound 1 rearranged to an anti-Bredt compound 4 via diradical mechanism in ether and tricyclic compound 6 via vinyl carbene mechanism in neat conditions. Compound 1 can be trapped with DPIBF at different temperatures yielding different results: the exo-endo adduct 2 (exo-addition from the view of the cyclopropene and endo-addition from the view of bicyclo[2.2.2]octene) is a sole product at 0°C by slowly addition of methyllithium, and the exo-endo adduct 2, endo-endo adduct 9, anti-Bredt adduct 3, and styrene 8 are isolated at ether refluxing temperature. Styrene 8 is proposed to be formed from endo-endo adduct 9 by diradical mechanism. The chemistry of exo-endo adduct 2 and endo-endo adduct 9 is as well studied. The exo-endo adduct 2 undergoes hydration in trifluoroacetic acid to generate 1,3-cis-diol 11 followed by eliminations of water and formaldehyde to give naphthalene 12. The endo-endo adduct 9 reacts with water in tetrahydrofuran-containing silica gel to yield 1,4-cis-diol 10. Both 9 and 10 react with trifluoroacetic acid to form trans-3-hydroxy trifluoroacetate 13. Compound 13 will undergo hydrolysis and isomerization to generate 1,3-cis-diol 11 in trifluoroacetic acid.     

On the relative stereochemistry of atomaric acid and related compounds

The stereochemistry at C-3 of the known compounds atomaric acid 2a, 5′a-desmethyl-5′-acetylatomaric acid 4a, and stypoquinonic acid 5a is revised to 2, 4, and 5 on the basis of a careful study of 2D NOESY experiments and also from comparison of their ¹H and ¹³C chemical shifts with those of the related metabolites 6 and 7 isolated from Stypopodium zonale. Compound 7 is a novel unusually functionalized 1-keto-5′a-desmethyl atomaric acid derivative whose structure and stereochemistry were determined by spectroscopic means.     

Synthesis and characterization of a rare arsenic trithiolate with an organic disulfide linkage and 2-chloro-benzo-1,3,2-dithiastibole

The synthesis and structural characterization of bis(2-(1,3,2-benzodithiarsol-2ylsulfanyl)-benzenesulfide) (1) and 2-chloro-benzo-1,3,2-dithiastibole (2) are reported. Both compounds contain a five-membered ring with sulfur bound to the central group 15 atom. In compound 1, the centroidal distance between each opposing arene is 3.819 Å. An alternating arene sandwich structure is created in the solid state with an intramolecular centroid distance between each set of stacked rings of 5.467 Å. Compound 2 is an example of a three coordinate antimony dithiolate. It does not possess any of the secondary interactions seen in 1. Compound 2 demonstrates trigonal bypyramidal geometry around the antimony if secondary interactions are considered.     

Four new dimeric triterpene glucosides from Sanguisorba officinalis

In search for bioactive compounds from the roots of Sanguisorba officinalis L. (Rosaceae), four new dimeric triterpene glucosides, namely sanguidioside A, B, C, and D (1-4) were isolated. Alkaline hydrolysis of 1-2 afforded the corresponding dimeric aglycones (1a and 2a). Meanwhile, a ready intra-molecular transesterification was observed, providing dimeric triterpenes 1b and 2b. Alkaline hydrolysis of the crude dimmeric saponin also provided a new dimeric triterpene, sanguidiogenin (9). The structures of all these compounds are elucidated via spectroscopic and chemical methods, and are further confirmed by the X-ray diffraction analysis of the dimeric aglycone 2a. Compound 3 represents the first dimeric saponin of an oleanolic acid and an ursonic acid derivative, while compound 4 is the first dimeric saponin of oleanolic acid derivatives.     

Tosylation/mesylation of 4-hydroxy-3-nitro-2-pyridinones as an activation step in the construction of dihydropyrido[3,4-b] benzo[f][1,4]thiazepin-1-one based anti-HIV agents

Reaction of 4-hydroxy-3-nitropyridinone 8 with TsCl and MsCl, respectively, resulted in rapid and quantitative formation of ditosylate 13 and dimesylate 16. Through chemoselective reaction of 16 with thiophenol 17 the key 4-thioaryl substituted intermediate 18 was obtained in 78% yield. This compound was efficiently converted to the target tricyclic products 4a and b. Compound 4a, in particular, is a potent inhibitor in vitro (IC₅₀ = 2 nM) of wild type HIV-1 replication.     

1,N-Etheno-2′-deoxytubercidin and pyrrolo-C: synthesis, base pairing, and fluorescence properties of 7-deazapurine nucleosides and oligonucleotides

The synthesis of 1,N⁶-etheno-7-deaza-2′-deoxyadenosine (12b) which was prepared from 7-deaza-2′-deoxyadenosine (5a) with chloroacetaldehyde is described. Also the regioselective glycosylation of the 7-deazapurine-2-one at nitrogen-1 (19) furnishing the pyrrolo-C nucleoside 7a is reported and a side chain derivative with a terminal triple bond (7d) is prepared. The fluorescence properties of these nucleosides and related compounds were determined. The etheno nucleoside 12b is strongly fluorescent showing a Stokes shift of 134 nm and a quantum yield of Φ=0.53. It proved to be stable, both in acidic and in alkaline medium while the parent purine compound 10b is labile under both conditions. Compound 12b was converted into its phosphoramidite 14 and was incorporated into oligonucleotides. Compound 12b destabilizes oligonucleotide duplexes when it is located in the center of the molecule; it stabilizes when it is incorporated in the terminal base pair or acts as an overhanging nucleoside. Temperature-dependent fluorescent measurements yielded sigmoidal melting profiles when compound 12b is stacked to the terminal base pair while a linear decrease of the fluorescence is observed when the molecule is located opposite to the four canonical nucleosides in the center of the duplex.     

Cytotoxic and anti-HIV-1 constituents from leaves and twigs of Gardenia tubifera

Two new natural cycloartanes, tubiferolide methyl ester (1) and tubiferaoctanolide (2), together with the known coronalolide (3) and coronalolide methyl ester (4) have been isolated from leaves and twigs of Gardenia tubifera. In addition, a new flavone 5,3′,5′-trihydroxy-7,4′-dimethoxyflavone (5), five known flavones 6-10 and hexacosyl 4′-hydroxy-trans-cinnamate (11) were also obtained from the same source. The structures were assigned on the basis of spectroscopic methods. Compounds 3, 7, 9, and 10 showed significant cytotoxic activities only in P-388 cell line. Compound 1 was cytotoxic against P-388, KB, Col-2 and Lu-1, while 4 was active in P-388 and BCA-1. Compounds 3 and 4 displayed significant anti-HIV activities in the HIV-1RT assay; compound 7 showed moderate activity in this assay. Compounds 5-10 were also found to be active in the ^ΔTat/RevMC 99 syncytium assay.     

Polyhydroxylated steroids from the octocoral Isis hippuris

The specimens for previous studies on the secondary metabolites of the Formosan octocoral Isis hippuris were all collected at Green Island. In the course of our studies on bioactive compounds from marine organisms, the acetone-solubles of the Formosan octocoral I. hippuris collected at Orchid Island has led to the isolation of six new polyoxygenated steroids (1-6), along with a known compound 7. Compound 6 possesses a new type of steroid side chain moiety. The structures of these compounds were determined on the basis of their spectroscopic and physical data. The anti-HCMV (human cytomegalovirus) activity and cytotoxicity against selected cell lines of 1-7 were evaluated. Compound 3 exhibited inhibitory activity against HCMV, with an EC₅₀ values of 2.0 μg/mL, respectively. Compound 7 displayed cytotoxicity against P-388 and A-549 cell lines with ED₅₀ values of 3.2 and 3.86 μg/mL, respectively.     

Isolation of key intermediates during formation of oolongtheanins

Oolongtheanin-3′-O-gallate (2b) was obtained by treatment of (−)-EGCg (1d) with CuCl₂. This transformation was achieved over three steps, with the isolation of two intermediates; their chemical structures were determined through derivatization reactions, MS, and 1D/2D NMR techniques. One intermediate was identified as dehydrotheasinensin A (3); the other was identified as the novel dimer pro-oolongtheanin-3′-O-gallate (6). Compound 3 was converted to 6 by heating in aprotic solvent, and compound 6 was converted to 2b by addition of water.     

A novel synthesis of 2-arylhydrazono-6-amino-4-arylbenzene-1,3-dicarbonitriles and their conversion into phthalazines

Compounds 1a-d react with benzylidenemalononitrile 2 to yield dihydroaminopyridazines 3a-d and, in contrast, compounds 1e,f react with 2 under the same conditions to yield aminobenzenedicarbonitriles 8e,f compound 8e underwent intramolecular cyclization to phthalazine 9e. Compound 10e reacted with 2a to yield 11e.     

Njaoamines G and H, two new cytotoxic polycyclic alkaloids and a tetrahydroquinolone from the marine sponge Neopetrosia sp.

Two new polycyclic alkaloids, njaoamines G (1) and H (2) and 1,2,3,4-tetrahydroquinolin-4-one (3) have been isolated from the sponge Neopetrosia sp. collected at Pemba Island, Tanzania. Compounds 1 and 2 are close in structure to njaoamines A-F. Compound 3, known synthetically, is a new natural compound. The structures and relative stereochemistries of compounds 1 and 2 were elucidated on the basis of spectroscopic data. Njaoamines G and H are potent brine shrimp toxins with LD₅₀ values of 0.17 μg/mL and 0.08 μg/mL for 1 and 2, respectively.     

Preparation and characterization of two three-dimensional metal–organic photoluminescent supramolecular networks

Two novel photoluminescent coordination compounds of the formula [Cd(atpt)phen(H₂O)] · H₂O (1) and [Zn₂(atpt)₂(bipy)₂(H₂O)₂] (2) (H₂atpt = 2-aminoterephthalic acid, bipy = 2,2′-bipyridine and phen = 1,10-phenanthroline) were synthesized through the self-assembly of H₂atpt and N-containing ligands (bipy for 1 and phen for 2) with metal(II) ions in the presence of NaOH, and were characterized by FT-IR spectroscopy, thermogravimetric analysis (TG), X-ray analysis and photoluminescence spectra in the solid state. Compound 1 is the first structurally characterized Cd(II) complex with the atpt ligand. The coordination mode of the atpt ligand in 2 is novel and is first reported in this presentation. X-ray crystallographic studies reveal that compound 1 shows a 1D architecture. Compound 1 further assembles into a 3D supramolecular network via interchain hydrogen bonds and π–π stacking interactions. Compound 2 exhibits a binuclear structure with intramolecular π–π stacking interactions, which is further extended into a 3D supramolecular framework via intermolecular hydrogen bonds and C–H?π interactions. Compounds 1 and 2 exhibit green photoluminescence in the solid state at room temperature.     

Solid-state syntheses, crystal structures and properties of two novel metal sulfur chlorides—Zn6S5Cl2 and Hg3ZnS2Cl4

Two novel metal sulfur chlorides - Zn₆S₅Cl₂ (1) and Hg₃ZnS₂Cl₄ (2) - were obtained by solid-state reactions and structurally characterized by single-crystal X-ray diffraction. Compound 1 is characteristic of a 1-D tunnel-like structure, which connects to each other to construct a 3-D framework with the chlorine atoms locating at the voids. Compound 2 crystallizes in the acentric space group P6₃mc of the hexagonal system. Compound 2 features a 2-D layered motif, which is composed by the interconnected 12-membered Hg₆S₃Cl₃ rings with chair-like conformation. There are ZnSCl₃ tetrahedra located between the layers, yielding a sandwich-like structure. TG-DTA measurement shows that compound 1 is thermally stable up to 220 °C. Optical absorption spectra reveal the presence of sharp optical gap of 2.71 and 2.65 eV for 1 and 2, respectively.     

Fries rearrangement: scalable synthesis of key fluoro building blocks 3-fluoro-4-methoxybenzoyl chloride and 1,2-diethoxy-3-fluorobenzene

Lewis acid catalyzed Fries rearrangement of 2-fluorophenyl acetate (3) was performed on kg scale. The ortho5 and para4 isomers obtained were separated in an industrially feasible way. Compound 4 was then converted into fluorinated building block 3-fluoro-4-methoxybenzoyl chloride (1) while compound 5 was converted into 1,2-diethoxy-3-fluorobenzene (2) in high yields.     

Four- and five-coordinate magnesium compounds containing ketiminate ligands. Synthesis and characterization of L2Mg, L2Mg(LH), and L2Mg(Py), where L = MeC(O)CHC(NAr)Me

Magnesium complexes containing ketiminate ligands were synthesized and characterized. MgBu₂ reacted readily in toluene with two equiv. of [MeC(O)CHC(NHAr)Me], where Ar = 2,6-diisopropylphenyl, to generate [MeC(O)CHC(NAr)Me]₂Mg (1) in 43% yield. The four-coordinate magnesium compound 1 is very moisture sensitive and acts as a Lewis acid, accepting one equiv. of Lewis base to form five-coordinate magnesium compounds. Compound [MeC(O)CHC(NAr)Me]₂Mg[MeC(O)CHC(NHAr)Me] (2) was obtained in 57% yield from the reaction in toluene of MgBu₂ with three equiv. of [MeC(O)CHC(NHAr)Me]. Treatment of 1 with one equiv. of free ketimine ligands [MeC(O)CHC(NHAr)Me] also led to the formation of 2. The bulky η¹-ketimine of 2 can be replaced with a less bulky Lewis base such as pyridine. Treatment of 1 with excess pyridine in toluene at ambient temperature led to the formation of compound [MeC(O)CHC(NAr)Me]₂Mg[NC₅H₅] (3) as colorless crystalline solids in 51% yield. Compounds 1, 2, and 3 were characterized by NMR and X-ray crystallography. Compounds 2 and 3 showed no activity toward the polymerization of ε-caprolactone at 25 °C after 3 h. However, when the temperature was increased to 70 °C, compounds 2 and 3 efficiently catalyzed polymerization of ε-caprolactone to generate high molecular weight poly-ε-caprolactones. The polydispersity index (PDI) of these poly-ε-caprolactones is in the range 1.57-3.18.     

Malonganenones A-C, novel tetraprenylated alkaloids from the Mozambique gorgonian Leptogorgia gilchristi

Three novel tetraprenylated alkaloids, malonganenones A-C (1-3), were isolated from the gorgonian Leptogorgia gilchristi collected near Ponto Malongane, Mozambique. Compound 1 is the first 3,7-disubstituted hypoxanthine to be discovered from a marine source, while 2 and 3 represent the first formamides to be isolated from gorgonians. The unexpected facile exchange of the formamide proton of 2 with a deuteron originating from the NMR solvent used for spectroscopic analysis hampered initial attempts at the structural elucidation of this compound. The anti-oesophageal cancer activities of 1-3 are compared with that of rietone (4), a related triprenylated compound previously isolated from a South African soft coral.