Synthesis,characterization and biological evaluation of purine nucleoside analogues

We present a convenient route for the synthesis of C6-amino-C5′-N-cyclopropyl carboxamido-C2-alkynylated purine nucleoside analogues 11a–g via Sonogashira coupling reaction. The nine step synthesis is easy to perform, employing commercially available reagents. Compound 9 is used as key intermediate for the synthesis of analogues 11a–g. Synthetic intermediates and final products are appropriately characterized by IR, ¹H NMR, ¹³C NMR and Mass. The modified nucleoside analogues 11a–g is evaluated for in vitro anticancer activity against MDA-MB-231 and Caco-2 cell lines. Screening data reveals that compounds 11b and 11e displayed potent IC₅₀ value of 7.9, 6.8 µg/mL respectively against MDA-MB-231 and of 7.5, 8.3 µg/mL respectively against Caco-2 than the standard drug doxorubicin, thus establishing the potential anti-cancer properties of these newer derivatives.     

Synthesis and antiviral bioactivity of novel chalcone derivatives containing purine moiety

A series of novel chalcone derivatives containing purine group was synthesized and evaluated for their antiviral activities against cucumber mosaic virus and tobacco mosaic virus. Compound 3o exhibited remarkable antiviral activities and strong combining capacity to tobacco mosaic virus coat protein.     

Design,synthesis, and fungicidal activity of novel 1,3,4-oxadiazole derivatives

Employing the intermediate derivatization method (IDM), a series of 1,3,4-oxadiazole derivatives containing arylpyrazoloxyl moiety were designed and synthesized. In vitro bioassays showed that these compounds have moderate to significant fungicidal activity against rice sheath blight and sorghum anthracnose. Furthermore, compound 20 is a promising fungicide for further development.     

Trichothiazole A,a dichlorinated polyketide containing an embedded thiazole isolated from Trichodesmium blooms

Mass spectrometry-guided isolation of the lipophilic extract of Trichodesmium bloom material led to the isolation and structure characterization of a new thiazole-containing di-chlorinated polyketide (1). The structure of 1 was deduced using 1D and 2D NMR analysis, high-resolution mass spectrometry analysis and complementary spectroscopic procedures. Trichothiazole A possesses interesting structural features, such as a terminal alkyne, two vinyl chlorides and a 2,4-disubstituted thiazole. Trichothiazole A showed moderate cytotoxicity to Neuro-2 A cells (EC₅₀: 13.3 ± 1.1 μM).     

A new luminescent sulfate bridged dimeric copper(II) complex with DNA binding and SO2 fixation ability: Synthesis and structure

New luminescent mononuclear and dinuclear copper(II) (S = 1/2) complexes [Cu(HL)(H₂O)₂](ClO₄)₂ (1a) and [Cu₂(HL)₂(μ-SO₄)₂]·2H₂O (1b) were synthesized with the acyclic tridentate pyridine-2-carboxaldehyde-2-pyridylhydrazone ligand, HL (1). Interestingly, the mononuclear complex 1a can be converted into the disulfate bridged dimeric copper(II) complex 1b by passing freshly prepared SO₂ through the basic medium. On excitation at 290 nm, the ligand fluoresces at 364 nm due to an intraligand ¹(π–π1) transition. Upon complexation with copper(II), the emission peak is slightly blue shifted (356 nm, F/F₀ 0.76 for 1a and 354 nm, F/F₀ 0.89 for 1b) with a little quenching in the emission intensity. The association constants (K_ass (5.06 ± 0.004) × 10⁴ for 1a and K_ass (5.46 ± 0.006) × 10⁴ for 1b at 298 K) and the thermodynamic parameters have been determined by UV–Vis spectroscopy. The molecular structure of the complex 1b (Cu?Cu 4.456 Å) has been determined by single crystal X-ray diffraction studies. The complex 1b exhibits a strong interaction towards DNA as revealed from the K_b (intrinsic binding constant) 6.3 × 10⁴ M^?1 and K_sv (Stern–Volmer quenching constant) 2.93 values.     

Synthesis and characterization of novel five-membered palladacycles

3-(2-Chloroquinolin-3-yl)-1,5-bis(3,4,5-trimethoxy-phenyl)-pentane-2,4-dione derivatives 3a–b were conveniently synthesized in excellent yields (82% each) by tandem Knoevenagel condensation reactions of 2-chloro-3-carbaldehyde-quinoline 1a–b with 3,4,5-trimethoxy acetophenone, followed by a base catalyzed Michael addition, such as DBU (1,8-diazabicyclo[5,4,0]undec-7-ene) with or without solvent. The reactions of 3a–b with Pd(dba)₂ in the presence of PPh₃ (1:2) in degassed acetone provided the dinuclear palladium complexes {Pd(C,N-2-C₉H₄N–CH–[–CH₂CO(3,4,5-(OMe-)₃–C₆H₂-]₂–3-R-6)Cl(PPh₃)}₂ [(R = H (4a), R = OMe (4b)] in moderate yields (38% and 43%), which in turn reacted with an excess of isonitrile XyNC (Xy = 2,6-Me₂C₆H₃) to give the corresponding palladacycles 5a–b in moderate yields (45% and 43%). The palladacycles 5a–b were also obtained in similar yields (32% and 33%) via a one-pot oxidative addition reaction of 3a-b with isonitrile XyNC:Pd(dba)₂ (4:1). The products were characterized by satisfactory elemental analysis and spectral studies (IR, ¹H, and ³¹P NMR). The crystal structure of 5a was determined by X-ray crystallography diffraction studies.     

Synthesis and biological evaluation of novel 1,2,4-triazole containing 1,2,3-thiadiazole derivatives

A series of novel 1,2,4-triazoles containing 1,2,3-thiadiazole derivatives were designed and synthesized. Their structures were confirmed by melting points, IR, 1H NMR, and elemental analysis and ESI-MS or HRMS. Preliminary bioassays indicated that these compounds exhibited very good insecticidal activity against Aphis laburni at 100 μg/mL, with mortality no less than 95%. Compounds 6a, 6c, 6f, 61 showed higher curative activity against TMV and compound 6h showed a higher induction effects against TMV in vivo at 100 μg/mL. Collectively, our data demonstrate a new strategy for control of insects and viruses.     

Dialkyl- and diaryl-platinum(II) complexes with secondary phosphines: Preparation,structure and thermal reaction giving the metallopolymer

Alkyl and arylplatinum complexes with 1,5-cyclooctadiene ligand, [PtR₂(cod)] (R = Me, Ph, C₆H₄-p-CF₃, C₆F₅), react with secondary phosphines, PHR′₂ (R′ = i-Bu, t-Bu, Ph), to afford the mononuclear platinum complexes, cis-[PtR₂(PHR′₂)₂] (1a: R = Me, R′ = i-Bu; 1b: R = Me, R′ = t-Bu; 1c: R = Me, R′ = Ph; 2a: R = Ph, R′ = i-Bu; 2b: R = Ph, R′ = t-Bu; 2c: R = R′ = Ph; 3a: R = C₆H₄-p-CF₃, R′ = i-Bu; 3b: R = C₆H₄-p-CF₃, R′ = t-Bu; 3c: R = C₆H₄-p-CF₃, R′ = Ph; 4a: R = C₆F₅, R′ = i-Bu; 4c: R = C₆F₅, R′ = Ph) in 81–98% yields. Molecular structures of the complexes except for 1a, 1c and 2a were determined by X-ray crystallography. Complex 1b has a square-planar structure with Pt–C(methyl) bonds of 2.083(8) and 2.109(8) Å, while the Pt–C(aryl) bonds of 2b–c, 3a–c, 4a and 4c (2.055(1)–2.073(8) Å) are shorter than them. Thermal decomposition of 1b, 2a–c, and 3a–c releases methane, biphenyl or 4,4′-bis(trifluoromethyl)biphenyl as the organic products, which are characterized by NMR spectroscopy. The solid product of the thermal reactions of 2b and 2c were characterized as the metallopolymers formulated as [Pt(PR′₂)₂]_n (5b: R′ = ^tBu; 5c: R′ = Ph), based on the solid-state NMR and elemental analyses.     

Diiron chelate complexes relevant to the active site of the iron-only hydrogenase

A novel unsymmetrically disubstituted propanedithiolate compound [Fe₂(CO)₄(κ²-dmpe)(μ-pdt)] (1) (pdt = SCH₂CH₂CH₂S, dmpe = Me₂PCH₂CH₂PMe₂) was synthesized by treatment of [Fe₂(CO)₆(μ-pdt)] with dmpe in refluxing THF. Compound 1 was characterized by single-crystal X-ray diffraction analysis. Protonation of 1 with HBF₄·Et₂O in CH₂Cl₂ gave at room temperature the μ-hydrido derivative [Fe₂(CO)₄(κ²-dmpe)(μ-pdt)(μ-H)](BF₄)] (2). At low temperature, ¹H and ³¹P–{¹H} NMR monitoring revealed the formation of a terminal hydride intermediate 3. Comparison of these results with those of a VT NMR study of the protonation of symmetrical compounds [Fe₂(CO)₄L₂(μ-pdt)] [L = PMe₃, P(OMe)₃] suggests that in disubstituted bimetallic complexes [Fe₂(CO)₄L₂(μ-pdt)], dissymmetry of the complex is required to observe terminal hydride species. Attempts to extend the series of chelate compounds [Fe₂(CO)₄(κ²-L₂)(μ-pdt)] by using arphos (arphos = Ph₂AsCH₂CH₂PPh₂) were unsuccessful. Only mono- and disubstituted derivatives [Fe₂(CO)_6−n(Ph₂AsCH₂CH₂PPh₂)_n(μ-pdt)] (n = 1, 4a; n = 2, 4b), featuring dangling arphos, were isolated under the same reaction conditions of formation of 1. Compound 4b was structurally characterized.     

Ruthenium(II) and iron(II) complexes of N-pyridyl substituted imidazolin-2-ylidenes

N-mesityl-N′-pyridyl-imidazolium chloride 1a and the corresponding bromide salt 1b have been deprotonated with NaH in THF giving the free N-heterocyclic carbene N-mesityl-N′-pyridyl-imidazolin-2-ylidene 2 in 80% yield (starting from 1a). Imidazolium salt 1a reacts with RuCl₃ · xH₂O to give a racemic mixture of dinuclear di-μ-chloro bridged ruthenium complexes [(κ²-2)₂Ru(μ-Cl)₂Ru(κ²-2)₂]²⁺ [3a]²⁺. The carbene carbon atoms as well as the halides are arranged in cis-positions to each other whereas the nitrogen atoms adopt a trans-configuration. The di-μ-bromo bridged derivative [(κ²-2)₂Ru(μ-Br)₂Ru(κ²-2)₂]²⁺ [3b]²⁺ was obtained from RuCl₃ · xH₂O and 1b. The bridging halide ligands can be removed by the reaction with silver or sodium salts of bidentate Lewis acids. Complex [3a]²⁺ reacts with silver pyridylcarboxylate to give a racemic mixture of the mononuclear complex [4]⁺. Reaction of [3a]²⁺ with the sodium salt of l-proline resulted in a diastereomeric mixture of complexes [5]⁺. The free N-heterocyclic carbene 2 reacts with [FeCl₂(PPh₃)₂] to give after anion exchange with NaBPh₄ cis/cis/trans coordinated [Fe(κ²-2)₂(MeCN)₂](BPh₄)₂ [6](BPh₄)₂. The molecular structures of [3b](PF₆)₂, [4]PF₆ and [6](BPh₄)₂ · H₂O are reported.     

Design and synthesis of novel water-soluble amino acid derivatives of chlorin p6 ethers as photosensitizer

Eight new water-soluble amino acid derivatives of chlorin p₆ ethers 6a-h were designed and synthesized using purpurin-18 (2) as key intermediate. All target compounds exhibited better phototoxicity than talaporfin and the most phototoxic compound 6d showed IC₅₀ values of 0.20 μmol/L against A549 cell and 0.41 μmol/L against B16-F10 cell, which represented 31- and 24-fold increase of PDT antitumor efficacy compared to talaporfin.     

Diterpenoids from the aerial parts of Leonurus macranthus

One cis clerodane-type (1) and three highly oxygenated labdane-type diterpenes (2-4) were isolated from the aerial parts of Leonurus macranthus. Compound 1 represents the first example of cis clerodane-type diterpene in the plants of Leonurus genus.     

Synthesis,structure, and property of a triruthenium cluster having a μ-alkyl ligand: Transformation of a μ3(⊥)-alkyne ligand into a μ-alkyl ligand via a μ3-vinylidene complex

A triruthenium μ-alkyl complex, (Cp¹Ru)₃(μ-η²-HCHCH₂R)(μ-CO)₂(μ₃- CO) (2a, R = Ph; 2b, R = ^tBu, Cp¹ = η⁵-C₅Me₅), which contains a two-electron and three-center interaction among Ru, C, and H atoms, has been synthesized by the reaction of a perpendicularly coordinated 1-alkyne complex, {Cp¹Ru(μ-H)}₃(μ₃-η²:η²(⊥)-RCCH) (1a; R = Ph, 1b; R = ^tBu), with carbon monoxide. A diffraction study for 2b clearly represented the bridging neohexyl group on one Ru–Ru edge. This μ-alkyl group exhibited dynamic behavior resulting in site-exchange of the α-hydrogen atoms between the terminal and bridging positions, which was synchronized with the migration of the μ-alkyl groups between the two ruthenium atoms. The agostic C–H bond was readily cleaved upon pyrolysis. Whereas the μ-phenethylidene intermediate resulting from the σ-C–H bond cleavage has never been observed, a μ₃-phenethylidyne complex, {Cp¹Ru(μ-CO)}₃(μ₃-CCH₂Ph) (7a), and a μ₃-methylidyne complex, {Cp¹Ru(μ-CO)}₃(μ₃-CH) (8), were obtained by the successive C–H/C–H and C–H/C–C bond cleavages at the μ-alkyl moiety, respectively.     

Asymmetric hydrogenation reactions with Rh and Ru complexes bearing phosphine–phosphites with an oxymethylene backbone

Phosphine–phosphites 3a and 3b, derived from diphenylhydroxymethyl phosphine have been prepared. From these ligands [Rh(COD)(3a)]BF₄ 5a and RuCl₂(3b)[(S,S)-DPEN] 6b (DPEN = 1,2-diphenylethylenediamine) were synthesized and their structure determined by X-ray diffraction. Ligands 3 are characterized by a small bite angle of 83°. In addition, 5a led to an active catalyst for the hydrogenation of olefins, giving enantioselectivities of up to 96% ee. Likewise, compound 6b showed good activity and enantioselectivity in the hydrogenation of N-1-phenyl ethylidene aniline and a completed reaction at S/C = 500 in 24 h with 83% ee.     

Synthesis and characterization of thiosemicarbazone derivatives of 2-chloro-4-hydroxy-benzaldehyde and their rhenium(I) complexes

N-Thioamide thiosemicarbazone derived of 2-chloro-4-hydroxy-benzaldehyde (R = H, HL¹; R = Me, HL² and R = Ph, HL³) have been prepared and their reaction with fac-[ReX(CO)₃(CH₃CN)₂] (X = Br, Cl) in chloroform gave the adducts [ReX(CO)₃(HL)] (1a X = Cl, R = H; 1a′ X = Br, R = H; 1b X = Cl, R = CH₃; 1b′ X = Br, R = CH₃; 1c X = Cl, R = Ph; 1c′ X = Br, R = Ph) in good yield. Complexes 1a′ and 1b’ were also obtained by the reaction of HL¹ and HL³ with [ReBr(CO)₅] in toluene.All the compounds have been characterized by elemental analysis, mass spectrometry (FAB), IR and ¹H NMR spectroscopic methods. Moreover, the structures of HL², HL³ and 1a·H₂O were also established by X-ray diffraction. In 1a, the rhenium atom is coordinated by the sulphur and the azomethine nitrogen atoms, forming a five-membered chelate ring, as well as three carbonyl carbon and chloride atoms. The resulting coordination polyhedron can be described as a distorted octahedron.The study of the crystals obtained by slow evaporation of methanol and DMSO solutions of the adducts 1a′ and 1b, respectively, showed the formation of dimer structures based on rhenium(I) thiosemicarbazonates [Re₂(L¹)₂(CO)₆]·3H₂O (2a)·3H₂O and [Re₂(L²)₂(CO)₆]·(CH₃)₂SO (2b)·2(CH₃)₂SO. Amounts of these thiosemicarbazonate complexes [Re₂(L)₂(CO)₆] (2) were obtained by reaction of the corresponding free ligands with [ReCl(CO)₅] in dry toluene.In 2a·3H₂O and 2b·2(CH₃)₂SO the dimer structures are established by Re–S–Re bridges, where S is the thiolate sulphur from a N,S-bidentate thiosemicarbazonate ligand. In both structures the rhenium coordination sphere is similar; the dimers are in the same diamond Re₂S₂ face.     

Activation of C–H and H–H bonds by dinuclear iridium complexes. Oxidative addition to highly active unsaturated 32e− diiridium species

Reactions of [(Cp¹Ir)₂(μ-dmpm)(μ-H)₂][OTf]₂ (1) with NaO^tBu in aromatic solvent at room temperature give [(Cp¹Ir)(H)(μ-dmpm)(μ-H)(Cp¹Ir)(Ar)][OTf] [Ar = Ph (3), p-Tol (4a), m-Tol (4b), 2-furyl (5a), 3-furyl (5b)] via intermolecular aromatic C–H activation. Treatment of [(Cp¹Ir)₂(μ-dppm)(μ-H)₂][OTf]₂ (2) with weak base (Et₂NH) results in intramolecular C–H activation of a phenyl group in the dppm ligand to give [(Cp¹Ir)(H){μ-PPh(C₆H₄)CH₂PPh₂}(μ-H)(Cp¹Ir)][OTf] (6). Reaction of 1 with NaO^tBu in tetrahydrofuran under H₂ (1 atm) results in activation of the H–H bond to give [{(Cp¹Ir)(H)}₂(μ-dmpm)(μ-H)][OTf] (7). Reaction of 1 with NaO^tBu in dichloromethane under carbon monoxide (1 atm) gives a carbonyl-bridged Ir^II–Ir^II complex, [(Cp¹Ir)₂(μ-dmpm)(μ-H)(μ-CO)][OTf] (8-OTf). These results strongly suggest that the active species in C–H and H–H bond activation starting with 1 and 2 would be unsaturated 32e^? diiridium species. The structures of 3, 5a, 6, 7, and 8-BPh₄ have been determined by X-ray diffraction methods.     

Visconata: A rare flavonol having long chain fatty acid from Dodonaea viscosa which inhibits Human neutrophil elastase (HNE)

A series of flavonoids were isolated from Dodonaea Viscosa and tested for inhibition of human neutrophil elastase (HNE), enzyme involved in inflammatory disorders. Isolated compounds were identified as a novel flavonol (1) along with eight known flavonoids (2–9). Novel flavonol, visconata (1) has a very rare skeleton having odd numbered long chain (C19) fatty acid, which was completely identified by mass fragmentation and 2D NMR analysis. All compounds (1–9) inhibited HNE in dose dependent manner with IC₅₀s ranging between 2.4 and 150 μM. Visconata (1) emerged to be the most potent compound with 2.4 μM of IC₅₀. In kinetic studies, compound (1) was observed to be reversible, noncompetitive inhibitor having K_i = 1.8 μM, whereas other flavonoids (2–9) displayed mixed type inhibition.     

Synthesis and structural characterization of a photoresponsive organodirhodium complex with active S–S bonds: [(CpPhRh)2(μ-CH2)2(μ-O2SSO2)] (CpPh = η5-C5Me4Ph)

A photoresponsive rhodium dinuclear complex having phenyltetramethylcyclopentadienyl (Cp^Ph = η⁵-C₅Me₄Ph) and photosensitive dithionite (μ-O₂SSO₂) ligands, [(Cp^PhRh)₂(μ-CH₂)₂(μ-O₂SSO₂)] (1), has been synthesized. The crystal of complex 1 (monoclinic, C2/m (No. 12), a = 24.805(2) Å, b = 29.111(2) Å, c = 10.8475(11) Å, β = 105.9830(7)°, V = 7530.0(12) Å³, Z = 8) consists of two independent molecules, 1-cis and 1-trans, with different arrangement of the Cp^Ph ligands. The flexibility, volume, and shape of the reaction cavities around the dithionite unit of 1-cis and 1-trans in the crystal are discussed. The crystal structures of the precursors of 1, trans-[(Cp^PhRh)₂(μ-Cl)₂Cl₂] and trans-[(Cp^PhRh)₂(μ-CH₂)₂Me₂], are also reported.     

Syntheses and properties of NCN-bridged tri- and tetranuclear complexes of cobalt and rhodium

The reaction of [Cp¹CoI₂]₂ (1b) with 2 equiv of NaNCNH affords the 16-membered macrocyclic NCNH-bridged tetracobalt(III) complex [Cp¹CoI(μ₂-NCNH-N,N′)]₄ (2b), while that with 2 equiv of Na₂NCN yields the C₃-elongated cubane-like NCN-bridged tetracobalt(III) complex [Cp¹Co(μ₃-NCN-N,N,N′)₃(CoCp¹)₃(μ₃-NCN-N,N,N)] (4b). Treatment of [Cp¹RhCl₂]₂ (1c) with 2 equiv of NaNCNH gives the C₃-elongated cubane-like tetrarhodium(III) complex [Cp¹Rh(μ₃-NCN-N,N,N′)₃(RhCp¹)₃(μ₃-NCN-N,N,N)] (4c) via the macrocyclic complex [Cp¹RhCl(μ₂-NCNH-N,N′)]₄ (2c). On the other hand, the reaction of [Cp¹CoCl]₂ (7) with Na₂NCN affords the anionic bis(NCN)-capped tricobalt(II) complex Na[(Cp¹Co)₃(μ₃-NCN-N,N,N)₂] (6). The molecular structures of complexes 2b · CH₂Cl₂ and 4c · 2C₆H₆ have been confirmed by X-ray analyses. The electrochemical properties of these types of NCN-bridged group 9 metal complexes have also been examined.     

Catalytic dehydrocoupling of thienyl/furyl-substituted carbosilanes – Synthesis and characterization of functional poly(hydrosilane)s [RMe2Si(CH2)xSiH]n, (R = 2-Th, 4-Me-2-Th, 2-Fu, 5-Me-2-Fu; x = 2 and 3)

The carbosilanes RMe₂Si(CH₂)_xSiH₃, [R = 2-Th (1a, 2a), 4-Me-2-Th (3a, 4a), 2-Fu (5a, 6a), 5-Me-2-Fu (7a, 8a); x = 2 and 3], with primary SiH₃ end groups undergo a facile dehydropolymerization under ambient conditions (50 °C, 48 h) in presence of Cp₂TiCl₂/2.2 n-BuLi catalyst to afford the corresponding poly(hydrosilane)s 1–8 bearing carbosilyl side chains appended with thienyl/furyl groups. These have been characterized by GPC, IR, multinuclear (¹H, ¹³C{¹H}, ²⁹Si{¹H}) NMR, UV and PL spectral studies.