Synthesis,characterization and cytotoxic investigations of novel bis(indole) analogues besides antimicrobial study

Two series of novel bis(indole) analogues viz., N′-((5-substituted-1H-indol-3-yl)methylene)-n-(1H-indol-3-yl)alkanehydrazides (7a–f) and N′-((5-substituted-1-(3-methylbut-2-enyl)-1H-indol-3-yl)methylene)-n-(1H-indol-3-yl)acetohydrazide (8a–f) were synthesized and characterized by spectral analysis. The target molecules were screened for their antimicrobial, anticancer activities and structure and activity relationship (SAR) was investigated. Compounds 7a, 7c and 8a were found to be active in antimicrobial screening. Anticancer screening reveals that Compound 7c was active against HeLa cell line with an IC₅₀ of 43.1 μM and compound 7d was found to be interesting candidate with an IC₅₀ of 26.0 and 30.2 μM against Colo-205 and Hep G2 cell lines respectively.     

Synthesis and cytotoxicity studies of new dimethylamino-functionalised and heteroaryl-substituted titanocene anti-cancer drugs

From the carbolithiation of N,N-dimethylamino fulvene (3a) and different ortho-lithiated heterocycles (furan, thiophene and N-methylpyrrole), the corresponding lithium cyclopentadienide intermediate (4a-c) was formed. These three lithiated intermediates underwent a transmetallation reaction with TiCl₄ resulting in dimethylamino-functionalised titanocenes 5a-c. When these titanocenes were tested against LLC-PK cells, the IC₅₀ values obtained were of 240, and 28 μM for titanocenes 5a and 5b, respectively. The most cytotoxic titanocene 5c with an IC₅₀ value of 5.5 μM is found to be almost as cytotoxic as cis-platin, which showed an IC₅₀ value of 3.3 μM, when tested on the LLC-PK cell line, and titanocene 5c is approximately 400 times better than titanocene dichloride itself.     

Crystal structure,DNA interaction,and antiproliferative activity of the cobalt(II) complex of demethylcantharate and imidazole

A new cobalt(II) complex, [Co(C₃H₄N₂)(C₈H₈O₅)(H₂O)₂]·2H₂O, of demethylcantharate(7-oxabicyclo[2,2,1]heptane-2,3-dicarboxylate, C₈H₈O₅) with imidazole has been synthesized from cobalt chloride, demethylcantharidin (NCTD) and imidazole. The complex was characterized by elemental analysis, IR, and X-ray single crystal diffraction. The complex crystallized in the monoclinic crystal system and P2₁/m space group with a?=?0.634790(10)?nm, b?=?0.963030(10)?nm, c?=?1.221770(10)?nm, α?=?90°, β?=?95.9700(10)°, γ?=?90°, V?=?0.742844(15)?nm³, M_r ?=?383.22, D_c ?=?1.713?g?cm^?3, Z?=?2, F(0?0?0)?=?398, μ?=?1.206?mm^?1, the final R?=?0.0291, and wR?=?0.0837 [I?>?2σ(I?)]. The interaction of the complex with deoxyribonucleic acid (DNA) was studied by electronic absorption spectra, fluorescence spectra, and viscosity measurements, which indicate that the complex binds to calf thymus DNA through a partially intercalative mode. The binding constant K _b for the complex was 2.62?×?10⁴?L?mol^?1. The antiproliferation activity test showed that the complex has high antiproliferative ability against human hepatoma cells SMMC7721 (with IC₅₀ being 42.8?±?0.9?µmol?L^?1) and human lung cancer cells A549 (with IC₅₀ being 65.1?±?3.2?µmol?L^?1). The inhibition rates of the complex are much higher than those of NCTD.     

Design and synthesis of some novel pyridothienopyrimidine derivatives and their biological evaluation as antimicrobial and anticancer agents targeting EGFR enzyme

A new series of pyridothienopyrimidine derivatives was designed and evaluated as antimicrobial and anticancer agents. The target compounds were synthesized starting with 3-aminothieno[2,3-b]pyridine-2-carboxamide derivative 1 which underwent cyclocondensation reaction with aromatic aldehydes to give the key intermediates 2a,b. By further treatment of 2a,b with various reagents, the target 2,4-disubstituted-pyrido[3′,2′:4,5]thieno[2,3-d]pyrimidines 3a,b–11a,b were obtained. To evaluate the antimicrobial activity of the new compounds, they were tested against five bacterial and five fungal strains. Compounds 6c, 8b, 9a and 9b revealed the most significant antimicrobial activity against the tested microorganisms with MIC values range (4–16 μg/mL). Also, compounds 2a,b–11a,b were screened for their in vitro cytotoxic activity against HepG-2 and MCF-7 cancer cell lines compared with doxorubicin and cisplatin as references drugs. Moreover, compounds (2b, 4a, 6a, 7b, 7c and 9a) which exhibited the most potent anticancer activity, were further subjected to EGFR^WT enzyme inhibition assay utilizing erlotinib as a standard drug. The compounds 6a, 7b, 7c and 9a which showed the most promising suppression effects were also evaluated as inhibitors against the mutant forms EGFR^L858R and EGFR^T790M. The 4-aminopyrazolone analogue 9a showed superior anticancer activity against both HepG-2 and MCF-7 cell lines (IC50 = 1.27, 10.80 μM, respectively) and more potent enzymatic inhibition activity against EGFR^WT and its mutant forms EGFR^L858R and EGFR^T790M than that obtained by erlotinib (IC₅₀ = 0.021, 0.053, 0.081 µM, respectively, IC_50erlotinib; 0.027, 0.069, 0.550 µM, respectively). Finally, the molecular docking study showed good binding patterns of the most active compounds with the prospective target EGFR^WT.     

Highly active ferrocenylamine-derived palladacycles for carbon–carbon cross-coupling reactions

{[(N-Methyl-N-p-R-benzyl)amino]benzyl}ferrocenes 4a–c (R = H(a), OCH₃(b), CH₃(c)) were synthesized by N-methylation of the corresponding sec-amines 3a–cwith the reagent CH₃I-t-BuOK. Treatment of 4a–c with Na₂PdCl₄ in the presence of NaOAc produced a pair of palladacycles σ-Pd[(η⁵-C₅H₅)Fe(η⁵- C₅H₃CH(C₆H₅)N(CH₃)CH₂-C₆H₄-R)]Cl(PPh₃) 5a–c (R = same as before) consisting of R_NR_P and S_NS_P configurations. The structure of 5a was determined by single crystal X-ray analysis. High catalytic activities of 5a–c for the Suzuki coupling of aryl chlorides with phenylboronic acid and the Heck reaction of bromobenzene with styrene were observed.     

Preparation and characterization of cobalt-containing P,N-ligands and an unusual palladium complex ion pair: their applications in amination reactions

Several cobalt-containing P,N-ligands, alkyne-bridged dicobalt phosphines [(μ-PPh₂CH₂PPh₂)Co₂(CO)₄(μ,η-Me₂NCH₂CCPR₂)] (4a: R=^tBu; 4b: R=Ph; 4c: R=Cy), were prepared from the reactions of corresponding alkynylphosphines Me₂NCH₂CCPR₂ (2a: R=^tBu; 2b: R=Ph; 2c: R=Cy) with a dppm-bridged dicobalt complex [Co₂(CO)₆(μ-P,P-PPh₂CH₂PPh₂)] 3. A unique palladium complex ion pair [(μ-PPh₂CH₂PPh₂)Co₂(CO)₄(μ,η-Me₂NCH₂CCP (^tBu)₂)Pd(η³-C₃H₅)]⁺[(η³-C₃H₅)PdCl₂]⁻7a was obtained from the reaction of 4a with [(η³-C₃H₅)PdCl]₂. Compounds 4a, 4b, and 4c are authentic cobalt-containing P,N-bidentate ligands and can be used for ligation of palladium from various sources such as Pd(OAc)₂ or [(η³-C₃H₅)PdCl]₂. Satisfactory efficiencies were observed for the amination reactions of aryl bromides with morpholine employing either a 4a-chelated palladium complex formed in situ or pre-formed 7a as the catalytic precursor.     

Design,modification, and bio-evaluation of salazinic acid derivatives

Data on synthesized derivatives of salazinic acid are scarce, with existing reports addressing only derivative hexaacetyl salazinic acid. This study investigated a set of novel potential antidiabetic agents. Analogs of salazinic acid were designed and synthesized using bromination, nucleophilic addition, Friedel-Crafts alkylation, and esterification. Ten synthetic compounds were prepared and structurally elucidated, including eight new compounds (1a-1c, 2a, 3a, 3b, 4a, 4b) and two known analogs. Under bromination, salazinic acid (1) enabled the following reaction chain: oxidation, decarboxylation, and substitution. This yielded products 1a-1c, which were found to have unprecedented scaffolds. Parmosidone F (5) was prepared from 1 with orsellinic acid via Friedel-Crafts alkylation, confirming a previously reported biosynthesis route. These analogs were evaluated for enzyme inhibition of α-glucosidase, and all showed more potent activity than that of acarbose, a positive control (IC₅₀ 332 μM), with IC₅₀ values in the range 9.32–39.96 μM. An in silico molecular docking model confirmed that, in terms of enzyme inhibition, the compounds ranked as follows: 3b > 4b > 4a > 1c > 2a > 1b > 1a > 3a. The kinetics of enzyme inhibition showed 4a and 5 to be a non-competitive-type and mixed-type inhibitors, respectively.     

Synthesis and anti-α-glucosidase activity evaluation of betulinic acid derivatives

In this article, a series of betulinic acid derivatives (3a ～ 3u, 4a ～ 4e) were synthesized through a stepwise structure optimization and evaluated for their anti-α-glucosidase activities. All synthesized derivatives exhibited stronger anti-α-glucosidase activities (IC₅₀: 0.56 ± 0.05 ～ 3.99 ± 0.23 μM) than betulinic acid (IC₅₀: 7.21 ± 0.58 μM) and acarbose (IC₅₀: 611.45 ± 15.51 μM). Compound 3q presented the outstanding inhibitory activity (IC₅₀: 0.56 ± 0.05 μM), which was ～ 1100 time stronger than that of acarbose. Compound 3q was revealed as a reversible and noncompetitive α-glucosidase inhibitor by inhibitory mechanism assay. Fluorescence spectra, 3D fluorescence and CD spectra results showed that the interaction of compound 3q with α-glucosidase caused the conformational and secondary structure content change of α-glucosidase. Finally, the molecular docking simulated the interaction between compound 3q with α-glucosidase and the physicochemical parameter was assessed using SwissADME software.     

N-Hydroxypyridone alkaloids,chromone derivatives,and tetrahydroxanthones from the scale-insect pathogenic fungus Orbiocrella sp. BCC 33248

Six new compounds, an N-hydroxypyridone glucoside, orbiocrellin A (1), its aglycone orbiocrellin B (2), chromone glucosides 3 and 4, a dihydrochromone 5a/5b, and a chromone 6, were isolated from the scale-insect pathogenic fungus Orbiocrella sp. BCC 33248. Orbiocrellin A (1) exhibited antimalarial activity against Plasmodium falciparum K1 (IC₅₀ 3.1 μg/mL) while it was non-cytotoxic. In contrast, orbiocrellin B (2) showed both antimalarial (IC₅₀ 2.1 μg/mL) and cytotoxic (NCI-H187 cells, IC₅₀ 0.70 μg/mL) activities.     

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.     

Olefin-aminocarbyne coupling in diiron complexes: Synthesis of new bridging aminoallylidene complexes

The bridging aminocarbyne complexes [Fe₂{μ-CN(Me)(R)}(μ-CO)(CO)₂(Cp)₂][SO₃CF₃] (R = Me, 1a; Xyl, 1b; 4-C₆H₄OMe, 1c; Xyl = 2,6-Me₂C₆ H₃) react with acrylonitrile or methyl acrylate, in the presence of Me₃NO and NaH, to give the corresponding μ-allylidene complexes [Fe₂{μ-η¹:η³- C_α(N(Me)(R))C_β(H)C_γ(H)(R′)}(μ-CO)(CO)(Cp)₂] (R = Me, R′ = CN, 3a; R = Xyl, R′ = CN, 3b; R = 4-C₆H₄OMe, R′ = CN, 3c; R = Me, R′ = CO₂Me, 3d; R = 4-C₆H₄OMe, R′ = CO₂Me, 3e). Likewise, 1a reacts with styrene or diethyl maleate, under the same reaction conditions, affording the complexes [Fe₂{μ-η¹:η³-C_α(NMe₂)C_β(R′)C_γ(H)(R″)}(μ-CO)(CO)(Cp)₂] (R′ = H, R″ = C₆H₅, 3f; R′ = R″ = CO₂Et, 3g). The corresponding reactions of [Ru₂{μ-CN(Me)(CH₂Ph)}(μ-CO)(CO)₂(Cp)₂][SO₃CF₃] (1d) with acrylonitrile or methyl acrylate afford the complexes [Ru₂{μ-η¹:η³-C_α(N(Me)(CH₂Ph))C_β(H)C_γ(H)(R′)}(μ-CO)(CO)(Cp)₂] (R′ = CN, 3h; CO₂Me, 3i), respectively.The coupling reaction of olefin with the carbyne carbon is regio- and stereospecific, leading to the formation of only one isomer. C-C bond formation occurs selectively between the less substituted alkene carbon and the aminocarbyne, and the C_β-H, C_γ-H hydrogen atoms are mutually trans.The reactions with acrylonitrile, leading to 3a-c and 3h involve, as intermediate species, the nitrile complexes [M₂{μ-CN(Me)(R)}(μ-CO)(CO)(NC-CHCH₂)(Cp)₂][SO₃CF₃] (M = Fe, R = Me, 4a; M = Fe, R = Xyl, 4b; M = Fe, R = 4-C₆H₄OMe, 4c; M = Ru, R = CH₂C₆H₅, 4d).Compounds 3a, 3d and 3f undergo methylation (by CH₃SO₃CF₃) and protonation (by HSO₃CF₃) at the nitrogen atom, leading to the formation of the cationic complexes [Fe₂{μ-η¹:η³-C_α(N(Me)₃)C_β(H)C_γ(H)(R)}(μ-CO)(CO)(Cp)₂][SO₃CF₃] (R = CN, 5a; R = CO₂Me, 5b; R = C₆H₅, 5c) and [Fe₂{μ-η¹:η³-C_α(N(H)(Me)₂)C_β(H)C_γ(H)(R)}(μ-CO)(CO)(Cp)₂][SO₃CF₃] (R = CN, 6a; R = CO₂Me, 6b; R = C₆H₅, 6c), respectively.Complex 3a, adds the fragment [Fe(CO)₂(THF)(Cp)]⁺, through the nitrile functionality of the bridging ligand, leading to the formation of the complex [Fe₂{μ-η¹:η³-C_α(NMe₂)C_β(H)C_γ(H)(CNFe(CO)₂Cp)}(μ-CO)(CO)(Cp)₂][SO₃CF₃] (9).In an analogous reaction, 3a and [Fe₂{μ-CN(Me)(R)}(μ-CO)(CO)₂(Cp)₂][SO₃CF₃], in the presence of Me₃NO, are assembled to give the tetrameric species [Fe₂{μ-η¹:η³-C_α(NMe₂)C_β(H)C_γ(H)(CN[Fe₂{μ- CN(Me)(R)}(μ-CO)(CO)(Cp)₂])}(μ-CO)(CO)(Cp)₂][SO₃CF₃] (R = Me, 10a; R = Xyl, 10b; R = 4-C₆H₄OMe, 10c).The molecular structures of 3a and 3b have been determined by X-ray diffraction studies.     

Synthesis of thiazole clubbed pyrazole derivatives as apoptosis inducers and anti-infective agents

Fourteen N-[{(substituted-phenylthiazol-2-yl)-3-aryl-1H-pyrazol-4-yl}methylene]-5-substituted-thiazol-2-amine (5a-n) analogs were synthesized by the reaction of 3-aryl-1-(thiazol-2-yl)-1H-pyrazole-4-carbaldehyde and substituted thiazole amines. The structures of prepared compounds were delineated by elemental analysis, FT-IR and ¹H NMR spectra. These analogs were scrutinized for in vitro anti-infective and cytotoxic activities. Some thaizole clubbed pyrazole derivatives were assessed for their cytological changes in germ cells of Capra hircus by using histomorphological analysis, fluorescence assay and apoptosis quantification. Compound 5l having 4-NO₂ substituent induced the significant apoptosis in tested cells of Capra hircus. The results revealed that compounds 5c, 5e, 5k, and 5l have commendable antibacterial activity within MIC range of 62.5–250 μg/ml. Compound 5c emerged as a potent antimalarial compound by exhibiting IC₅₀ value of 0.23 μg/ml and compound 5j induced paralysis of Pherentima posthuma at 8.6 ± 1.94 min and death at 20 ± 5.04 min, respectively. Compound 5j revealed an excellent cytotoxicity at IC₅₀ value of 30.7 and < 10 μg/ml against MCF-7 and HeLa cells, respectively. Individually, compounds 5c, 5j and 5l could be considered as promising anti-infective and cytotoxic compounds.     

A novel and easy two-step,microwave-assisted method for the synthesis of halophenyl pyrrolo[2,3-b]quinoxalines via their pyrrolo precursors. Evaluation of their bioactivity

A novel, two-step, facile route for the synthesis of pyrrolo[2,3-b]quinoxalines via 2,3-dioxopyrroles, enhanced by microwave irradiation, is presented. The newly synthesized 2,3-dioxo-5-halophenyl pyrrolo precursors 4a–c as well as the non-aromatized ethyl 2-(4-halophenyl)-1-methyl-2,4-dihydro-1H-pyrrolo[2,3-b]quinoxaline-3-carboxylates 6a–c and the aromatized ethyl 2-(4-halophenyl)-1-methyl-1H-pyrrolo[2,3-b]quinoxaline-3-carboxylates 7a–c were evaluated for their antioxidant, cytostatic, and antiviral properties. Most of them proved to be potent hydroxyl radical scavengers and inhibited in vitro lipid peroxidation. The compounds showed moderate antiproliferative activity, while 6a inhibited vaccinia virus at an EC₅₀ value of 2 μM, and 4c and 6c inhibited Sindbis virus at EC₅₀ values of 4 μM.     

4-C-Me-DAB and 4-C-Me-LAB - enantiomeric alkyl-branched pyrrolidine iminosugars - are specific and potent α-glucosidase inhibitors; acetone as the sole protecting group

The syntheses of 4-C-Me-DAB [1,4-dideoxy-1,4-imino-4-C-methyl-d-arabinitol] from l-erythronolactone and of 4-C-Me-LAB [from d-erythronolactone] require only a single acetonide protecting group. The effect of pH on the NMR spectra of 4-C-Me-DAB [pK_a of the salt around 8.4] is discussed and illustrates the need for care in the analysis of both coupling constants and chemical shift. 4-C-Me-DAB (for rat intestinal sucrase K_i 0.89 μM, IC₅₀ 0.41 μM) is a competitive—whereas 4-C-Me-LAB (for rat intestinal sucrase K_i 0.95 μM, IC₅₀ 0.66 μM) is a non-competitive—specific and potent α-glucosidase inhibitor. A rationale for the α-glucosidase inhibition by DAB, LAB, 4-C-Me-DAB, 4-C-Me-LAB and isoDAB—but not isoLAB—is provided. Both are inhibitors of endoplasmic reticulum (ER) resident α-glucosidase I and II.     

C-methyl flavonoid from the leaves of Cleistocalyx conspersipunctatus: α-glucosidase inhibitory,molecular docking simulation and biosynthetic pathway

We extracted one new C-methyl flavonoid, farrerol 7-O-β-d-(6-O-galloyl)glucopyranoside (1), along with 11 known flavonoids, from the Cleistocalyx (C.) conspersipunctatus leaves. Elucidation of these flavonoid structures was accomplished through spectroscopic investigation and electronic circular dichroism (ECD) computation. Compared to corosolic acid (IC₅₀: 15.5 ± 0.9 μM), an established inhibitor, the compound 1 (IC₅₀: 6.9 ± 1.2 μM) was found more active in suppressing α-glucosidase. These findings imply the potential of compound 1 as a valid α-glucosidase inhibitor, which also offer evidence for future animal experiments and clinical trials. Besides, molecular docking was employed to explore the probable mechanism for α-glucosidase–compound 1 interaction. The biosynthetic pathway of these flavonoids in C. conspersipunctatus were proposed.     

Hydride addition at μ-vinyliminium ligand obtained from disubstituted alkynes

New μ-vinylalkylidene complexes cis-[Fe₂{μ-η¹:η³-C_γ(R′)C_β(R″)C_αHN(Me)(R)}(μ-CO)(CO)(Cp)₂] (R = Me, R′ = R″ = Me, 3a; R = Me, R′ = R″ = Et, 3b; R = Me, R′ = R″ = Ph, 3c; R = CH₂Ph, R′ = R″ = Me, 3d; R = CH₂Ph, R′ = R″ = COOMe, 3e; R = CH₂ Ph, R′ = SiMe₃, R″ = Me, 3f) have been obtained b yreacting the corresponding vinyliminium complexes [Fe₂{μ-η¹:η³-C_γ(R′)C_β(R″)C_αN(Me)(R)}(μ-CO)(CO)(Cp)₂][SO₃CF₃] (2a-f) with NaBH₄. The formation of 3a-f occurs via selective hydride addition at the iminium carbon (C_α) of the precursors 2a-f. By contrast, the vinyliminium cis-[Fe₂{μ-η¹:η³-C_γ (R′) = C_β(R″)C_α = N(Me)(Xyl)}(μ-CO)(CO)(Cp)₂][SO₃CF₃] (R′ = R″ = COOMe, 4a; R′ = R″ = Me, 4b; R′ = Prⁿ, R″ = Me, 4c; Prⁿ = CH₂CH₂CH₃, Xyl = 2,6-Me₂C₆H₃) undergo H⁻ addition at the adjacent C_β, affording the bis-alkylidene complexes cis-[Fe₂{μ-η¹:η²-C(R′)C(H)(R″)CN(Me)(Xyl)}(μ-CO)(CO)(Cp)₂], (5a-c). The cis and trans isomers of [Fe₂{μ-η¹:η³-C_γ(Et)C_β(Et)C_αN(Me)(Xyl)}(μ-CO)(CO)(Cp)₂][SO₃CF₃] (4d) react differently with NaBH₄: the former reacts at C_α yielding cis-[Fe₂{μ-η¹:η³-C_γ(Et)C_β(Et)C_αHN(Me)(Xyl)}(μ-CO)(CO)(Cp)₂], 6a, whereas the hydride attack occurs at C_β of the latter, leading to the formation of the bis alkylidene trans-[Fe₂{μ-η¹:η²-C(Et)C(H)(Et)CN(Me)(Xyl)}(μ-CO)(CO)(Cp)₂] (5d). The structure of 5d has been determined by an X-ray diffraction study. Other μ-vinylalkylidene complexes cis-[Fe₂{μ-η¹:η³-C_γ(R′)C_β(R″)C_αHN(Me)(Xyl)}(μ-CO)(CO)(Cp)₂], (R′ = R″ = Ph, 6b; R′ = R″ = Me, 6c) have been prepared, and the structure of 6c has been determined by X-ray diffraction. Compound 6b results from treatment of cis-[Fe₂{μ-η¹:η³-C_γ(Ph)C_β(Ph)C_αN(Me)(Xyl)}(μ-CO)(CO)(Cp)₂][SO₃CF₃] (4e) with NaBH₄, whereas 6c has been obtained by reacting 4b with LiHBEt₃. Both cis-4d and trans-4d react with LiHBEt₃ affording cis-6a.     

C-C bond formation through olefin-thiocarbyne coupling in diiron complexes

The bridging diiron thiocarbyne complex [Fe₂{μ-CS(Me)}(μ-CO)(CO)₂(Cp)₂][SO₃CF₃] (1) reacts with activated olefins (methyl acrylate, acrylonitrile, styrene, diethyl maleate), in the presence of Me₃NO and NaH, to give the corresponding μ-allylidene complexes [Fe₂{μ-η¹:η³-C_α(SMe)C_β(R′)C_γ(H)(R″)} (μ-CO)(CO)(Cp)₂] (R″ = CO₂Me, R′ = H, 3a; R″ = CN, R′ = H, 3b; R″ = C₆H₅, R′ = H, 3c; R″ = R′ = CO₂Et, 3d). The coupling reaction of olefin with thiocarbyne is regio- and stereospecific, leading to the formation of only one isomer. C-C bond formation occurs between the less substituted alkene carbon and the thiocarbyne. Moreover, olefinic hydrogens of the bridging ligands are mutually trans.The reactions of 3a-b with MeSO₃CF₃ result, selectively, in the formation of the cationic μ-sulphonium allylidene complexes [Fe₂{μ-η¹:η³-C_α(SMe₂)C_β (H)C_γ(H)(R)}(μ-CO)(CO)(Cp)₂][SO₃CF₃] (R = CO₂Me, 4a; R = CN, 4b). Compound 4a undergoes displacement of the SMe₂ group by nucleophiles such as NaBH₄, NBu₄CN and NaOMe, affording the complexes [Fe₂{μ-η¹:η³-C_α(R)C_β (H)C_γ(H)(CO₂Me)}(μ-CO)(CO)(Cp)₂] (R = H, 5a; R = CN, 5b; R = OMe, 5c), respectively. The molecular structures of 3a and 5a have been determined by X-ray diffraction studies.     

Hydrazinocarben-Metallkomplexe—synthese aus allenylidenkomplexen und hydrazinen, umlagerung und cyclisierung

The diarylallenylidene pentacarbonyl complexes (CO)₅M=C=C=C(C₆H₄NMe₂-p)₂ (M = W (1), Cr (2)) add 1,2,-disubstituted hydrazines RNH-HNR to form alkenyl hydrazino carbene complexes (CO)₅M=C(C(H)=C(C₆H₄NMe₂-p)₂) NR-N(H)R (M = W, R = Bn (3b), ⁱPr (3c), ^cHex (3d); M = Cr, R = Me (4a), ⁱPr (4b)) in good yield. 3c and 4b are formed selectively as E-conformers (E arrangement of N_βHR and (CO)₅M with respect to the C(carbene)-N_α bond). In contrast, all other derivatives of 3 and 4 are obtained as a mixture of E/Z-isomers. On heating, E-3a and E-3b rearrange to give the acrylamidine complexes (CO)₅W-NR=C(NHR)C(H)=C(C₆H₄NMe₂-p)₂ (R = Me (5a), Bn (5b). The structure of complex 5b was established by X-ray analysis. Acid-catalyzed, the alkenyl hydrazino carbene complexes E-3a, E-3b and 3c are transformed by intramolecular cyclization into the pyrazolidinylidene complexes

Full-size image

(R =Me (6a), Bn (6b), ⁱPr (6c)).

Zusammenfassung

Die Diarylallenyliden(pentacarbonyl)komplexe (CO)₅M=C=C=C(C₆H₄NMe₂-p)₂ (M = W (1), Cr (2)) addieren 1,2-disbustituierte Hydrazine RNH-HNR in guten Ausbeuten zu Alkenylhydrazinocarbenkomplexen (CO)₅M=C(C(H)=C(C₆H₄NMe₂p)₂) NR-N(H)R (M = W, R = Bn (3b), ⁱPr (3c), ^cHex (3d); M = Cr, R =Me(4a), ⁱPr (4b)). 3c und 4b entstehen hierbei selektiv in der E-Konformation (E-Anordnung von N_βHR und (CO)₅M bezülich der C(Carben)-N_α-Bindung). Alle anderen Derivate von 3 und 4 werden dagegen als E/Z-Isomerengemisch gebildet. E-3a und E-3b lagern sich beim Erwärmen in die Acrylamidinkomplexe (CO)₅W-NR=C(NHR)C(H)=C(C₆H₄NMe₂-p)₂ (R = Me (5a), Bn (5b)) um. Die Struktur von 5b wurde anhand einer Röntgenstrukturanalyse gesichert. Säurekatalysiert cyclisieren die Alkenylhydrazinocarbenkomplexe E-3a, E-3b und 3c zu den Pyrazolidinylidenkomplexen

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(R = Me (6b), ⁱPr (6c)).     

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.     

The formation and molecular structure of di-η5-cyclopentadienyl{2-1(dimethylamino)methyl]phenyl-C,N}yttrium

A reaction between 2-lithio-N,N-dimethylbenzylamine (1) and di-μ-chlorotetra-η⁵-cyclopentadienyldiyttrium (2) in ethyl ether solution has produced di-η⁵-cyclopentadienyl{2-[(dimethylamino)methyl]phenyl-C, N}yttrium (η⁵-C₅H₅)₂Y(C₆H₄-CH₂NMe₂) (3), in 71% yield. The product, which represents the second known aryl derivative of yttrium, has been characterized by elemental analysis and ¹H NMR data as well as by a single-crystal X-ray diffraction study.(η⁵-C₅H₅)₂Y(C₆H₄-2-CH₂NMe₂) crystallizes in the monoclinic space group P2₁/c with lattice parameters a 8.310(3), b 26.972(8), c 15.548(6) Å, β 95.88(3)°, and D_calc 1.35 g cm^?3 for Z = 4. Least-squares refinement gave a final R value of 0.102 using 1739 independent observed reflections. There are two molecules in the asymmetric unit. Each yttrium atom is η⁵-coordinated to two cyclopentadienyl ligands and sigma bonded to the ortho-carbon and -nitrogen atoms of the dimethylbenzylamine ligand. The YC(σ) bond distances are identical at 2.41(2) Å; the two YN bond lengths are 2.43(2) and 2.54(2) Å.