Synthesis of Novel Ethyl (substituted)phenyl‐4‐oxothiazolidin‐3‐yl)‐1‐ethyl‐4‐oxo‐1,4‐dihydroquinoline‐3‐Carboxylates as Potential Anticancer Agents

A series of ethyl (substituted)phenyl‐4‐oxothiazolidin‐3‐yl)‐1‐ethyl‐4‐oxo‐1,4‐dihydroquinoline‐3‐carboxylates ( 7a , 7b , 7c , 7d , 7e , 7f , 7g ) has been prepared from reactions between aminoquinolones 6 with arenealdehydes and mercaptoacetic acid. The critical intermediates, 6 a and 6b , were obtained from appropriate amines by a sequence of steps involving (i) reaction with diethylethoxymethylenemalonate, (ii) thermal cyclization in diphenyl ether, (iii) ethylation and (iv) Pd/C catalyzed reduction. New compounds 7a , 7b , 7c , 7d , 7e , 7f , 7g were fully identified and characterized by NMR (¹H and ¹³C) and specifically for 7d by X‐ray crystallography. Compounds 7b , 7c , 7d , 7e , 7f were found not to exhibit activity at 10 uM concentrations against gastric ascitis (AGP‐01), gastric adenocarcinoma kind intestinal (ACP‐02), colon (HCT‐116) and murine melanome (B16F10) cancer cells. However, none exhibited cytotoxicity against normal cells human fibroblast (MRC‐5), murine fibroblast (NIH3T3) and normal human melanocyte (Melan‐A).     

Synthesis of 11-hydroxydrim-8(9)-en-7-one and 11,12-dihydroxydrim-8(9)-en-7-one from drim-8(9)-en-7-one

A synthetic route to 11-hydroxydrim-8(9)-en-7-one and 11,12-hydroxydrim-8(9)-en-7-one, valuable key intermediates for the preparation of naturally occurring biologically active drimanic sesquiterpenoids, starting from easily available drim-8(9)-en-7-one was developed. 11-Hydroxydrim-8(9)-en-7-one was obtained by peracidic oxidation of the enol acetate of drim-8(9)-en-7-one. 11,12-Dihydroxydrim-8(9)-en-7-one was synthesized from drim-8(9)-en-7-one by two routes, namely, by a five-step procedurevia 11-hydroxydrim-8(9)-en-7-one and by bromination of drim-8(9)-en-7-one with NBS to give 11,12-dibromodrim-8(9)-en-7-one followed by its acetoxylation and deacetylation. Deceased Translated fromIzvestiya Akademii Nauk, Seriya Khimicheskaya, No. 1, pp. 95–98, January, 2000.     

Synthesis of 11-hydroxydrim-8(9)-en-7-one and 11,12-dihydroxydrim-8(9)-en-7-one from drim-8(9)-en-7-one

A synthetic route to 11-hydroxydrim-8(9)-en-7-one and 11,12-hydroxydrim-8(9)-en-7-one, valuable key intermediates for the preparation of naturally occurring biologically active drimanic sesquiterpenoids, starting from easily available drim-8(9)-en-7-one was developed. 11-Hydroxydrim-8(9)-en-7-one was obtained by peracidic oxidation of the enol acetate of drim-8(9)-en-7-one. 11,12-Dihydroxydrim-8(9)-en-7-one was synthesized from drim-8(9)-en-7-one by two routes, namely, by a five-step procedurevia 11-hydroxydrim-8(9)-en-7-one and by bromination of drim-8(9)-en-7-one with NBS to give 11,12-dibromodrim-8(9)-en-7-one followed by its acetoxylation and deacetylation. Deceased Translated fromIzvestiya Akademii Nauk, Seriya Khimicheskaya, No. 1, pp. 95–98, January, 2000.     

A slipped multi-decker zirconium complex with an η7:η2-bridging cycloheptatrienyl ligand

The complex [(η(7)-C(7)H(7))Zr{N(SiMe(3))(2)}(thf)] (2) loses THF upon sublimation to afford a chain polymer consisting of [(η(7)-C(7)H(7))Zr{N(SiMe(3))(2)}] (3) units; they are connected by cycloheptatrienyl ligands in an unprecedented antifacial η(7):η(2)-bridging mode. The basicity of the bis(trimethylsilyl)amido ligand can also be used to introduce other ligands by acid-base reactions.     

C---H bond activation by rhodium(I) and the mechanism of the olefin isomerization: new synthesis of β,γ-unsaturated ketones via η- or η-alkylallylrhodium(III) complexes by reductive elimination

Acylrhodium(III)-η³-1-ethylallyl complex (7) was prepared by the reaction of 8-quinolinecarboxaldehyde (3) and 1,4-pentadienerhodium(I) chloride (2) by C---H bond activation, followed by hydrometallation, and double bond migration. Higher concentrations of pyridine as coordinating ligand transforms η³-1-ethylallylrhodium(III) complexes (8a,8b) into η¹-pent-2-enylrhodium(III) complex (11a). Acylrhodium(III)-η³-syn,anti-1,3-dimethylallyl complex (14) was also prepared from 1,3-pentadienerhodium(I) chloride (16) and 3. The reductive elimination of acylrhodium(III)-η¹- and -η³-1-alkylallyl complexes by trimethylphosphite gives various β,γ-unsaturated ketones.     

Diisophorone and related compounds—II: 1-Alkoxy- and 1-carboxy-diisophorane derivatives

The acid catalysed interaction in dioxan of trialkyl orthoformates with diisophor-2(7)-en-ol-3-one, diisophor-2(7)-en-ol, and their bisnor-homologues, provides the corresponding 1-alkoxy-compounds. Their structure is established by the identity of -methoxydiisophor-2(7)-en-3-one obtained by this method, and by the action of sodium methoxide on 1-chlorodiisophor-2(17)-en-3-one. The latter is regenerated from 1-methoxy(or ethoxy) diisophor-2(7)-en-3-one by the action of stannic chloride-acetyl chloride. Catalytic hydrogenation reduces the 3-keto-function in 1-alkoxydiisophor-2(7)-en-3-ones to a methylene unit; simultaneous removal of the 1-alkoxy-group in the case of the 1-isopropoxy-homologue yields the penultimate parent hydrocarbon of this series, diisophor-2(7)-ene.The combined action of silver sulphate and formic acid in concentrated sulphuric acid on 1-chlorodiisophor-2(7)-en-3-one (and its bisnor-homologue) produces the corresponding 1-carboxylic acids. These are also obtainable by the hydrolysis of the 1-cyano-compound, and are esterifiable by the standard methods.     

Synthesis and Antimicrobial Activities of Novel Series of 3‐(4‐(2‐substituted thiazol‐4‐yl)phenyl)‐2‐(4‐methyl‐2‐substituted thiazol‐5‐yl)thiazolidin‐4‐one Derivatives

In the present investigation, a novel series of 3‐(4‐(2‐substituted thiazol‐4‐yl)phenyl)‐2‐(4‐methyl‐2‐substituted thiazol‐5‐yl)thiazolidin‐4‐one derivatives were synthesized by condensation of 2‐substituted‐4‐methylthiazole‐5‐carbaldehyde with 4‐(2‐substituted thiazol‐4‐yl)benzenamine followed by cyclo‐condensation with thioglycolic acid in toluene. All the newly synthesized compounds were characterized by spectral (IR, ¹H NMR, ¹³C NMR, and Mass) methods. The title compounds were screened for quantitative antibacterial activity (minimal inhibitory concentration). All compounds 7a , 7b , 7c , 7d , 7e , 7f , 7g , 7h and 8a , 8b , 8c , 8d , 8e , 8f , 8g , 8h show moderate to good antimicrobial activity, whereas compounds ( 7a , 7b , 7c , 7d , 7e , 7f , 7g , 7h ) also show moderate antifungal activity.     

Derivatives of 1,5-diamino-1H-tetrazole: a new family of energetic heterocyclic-based salts

1,5-Diamino-1H-tetrazole (2, DAT) can easily be protonated by reaction with strong mineral acids, yielding the poorly investigated 1,5-diaminotetrazolium nitrate (2a) and perchlorate (2b). A new synthesis for 2 is introduced that avoids lead azide as a hazardous byproduct. The reaction of 1,5-diamino-1H-tetrazole with iodomethane (7a) followed by the metathesis of the iodide (7a) with silver nitrate (7b), silver dinitramide (7c), or silver azide (7d) leads to a new family of heterocyclic-based salts. In all cases, stable salts were obtained and fully characterized by vibrational (IR, Raman) spectroscopy, multinuclear NMR spectroscopy, mass spectrometry, elemental analysis, X-ray structure determination, and initial safety testing (impact and friction sensitivity). Most of the salts exhibit good thermal stabilities, and both the perchlorate (2b) and the dinitramide (7c) have melting points well below 100 degrees C, yet high decomposition onsets, defining them as new (7c), highly energetic ionic liquids. Preliminary sensitivity testing of the crystalline compounds indicates rather low impact sensitivities for all compounds, the highest being that of the perchlorate (2b) and the dinitramide (7c) with a value of 7 J. In contrast, the friction sensitivities of the perchlorate (2b, 60 N) and the dinitramide (7c, 24 N) are relatively high. The enthalpies of combustion (Delta(c)H degrees ) of 7b-d were determined experimentally using oxygen bomb calorimetry: Delta(c)H degrees (7b) = -2456 cal g(-)(1), Delta(c)H degrees (7c) = -2135 cal g(-)(1), and Delta(c)H degrees (7d) = -3594 cal g(-)(1). The standard enthalpies of formation (Delta(f)H degrees ) of 7b-d were obtained on the basis of quantum chemical computations using the G2 (G3) method: Delta(f)H degrees (7b) = 41.7 (41.2) kcal mol(-)(1), Delta(f)H degrees (7c) = 92.1 (91.1) kcal mol(-)(1), and Delta(f)H degrees (7d) = 161.6 (161.5) kcal mol(-)(1). The detonation velocities (D) and detonation pressures (P) of 2b and 7b-d were calculated using the empirical equations of Kamlet and Jacobs: D(2b) = 8383 m s(-)(1), P(2b) = 32.2 GPa; D(7b) = 7682 m s(-)(1), P(7b) = 23.4 GPa; D(7c) = 8827 m s(-)(1), P(7c) = 33.6 GPa; and D(7d) = 7405 m s(-)(1), P(7d) = 20.8 GPa. For all compounds, a structure determination by single-crystal X-ray diffraction was performed. 2a and 2b crystallize in the monoclinic space groups C2/c and P2(1)/n, respectively. The salts of 7 crystallize in the orthorhombic space groups Pna2(1) (7a, 7d) and Fdd2 (7b). The hydrogen-bonded ring motifs are discussed in the formalism of graph-set analysis of hydrogen-bond patterns and compared in the case of 2a, 2b, and 7b.     

Equilibrium geometries and associated energetic properties of mixed metal-silicon clusters from global optimization

The structural properties of the cluster series Me(m)Si(7-m) (Me = Cu and Li, m < or = 6) are studied by density functional theory (DFT) employing a plane wave basis. The equilibrium geometries and energetic properties of these clusters are obtained by use of the simulated annealing procedure in conjunction with the Nosé thermostat algorithm. The lowest energy isomer thus obtained is analyzed by density functional theory at the B3LYP/6-311+G(d,p) level including all electrons. Pentagonal ground state structures derived from the D(5)(h) equilibrium geometries of both Si(7) and Cu(7) are obtained for Cu(m)Si(7-m) with m < 6. The Li(m)Si(7-m) clusters, in contrast, tend toward adsorption geometries where m Li atoms are attached to a Si(7-m)framework with pronounced negative charge. For both Li(m)Si(7-m) and Cu(m)Si(7-m), a marked decrease of the energy gap is found as the number of metal atom constituents increases.     

Investigation of hydrogen absorption in Li7VN4 and Li7MnN4

The hydrogen storage properties of Li(7)VN(4) and Li(7)MnN(4) were investigated both by experiment and by density functional theory calculations. Li(7)VN(4) did not sorb hydrogen under our experimental conditions. Li(7)MnN(4) was observed to sorb 7 hydrogen atoms through the formation of LiH, Mn(4)N, and ammonia gas. An applied pressurized mixture of H(2)/Ar and H(2)/N(2) gases was helpful to mitigate the release of NH(3) but could not prevent its formation. The introduction of N(2) also caused weight gain of the sample by re-nitriding the absorbed products LiH and Mn(4)N, which correlated with the presence of Li(2)NH, LiNH(2), and Mn(2)N detected by X-ray diffraction. While our observed results for Li(7)VN(4) and Li(7)MnN(4) differ in detail, they are in overall qualitative agreement with our theoretical work, which strongly suggests that both compounds are unlikely to form quaternary hydrides.     

Syntheses,structures and properties of five chiral quaternary sulfides,AlxLn_3(Si_yAl_(1-γ))S_7 (Ln=Y,Gd,Dy) and In_(0.33)Sm_3SiS_7

Five new quaternary isostructural rare-earth sulfides, Al0.57Gd3(Si0.27Al0.73)S7 (1), Al0.55Dy3(Si0.34Al0.66)S7 (2), Al0.50Y3(Si0.50Al0.50)S7 (3), Al0.44Gd3(Si0.70Al0.30)S7 (4) and In0.33Sm3SiS7 (5), have been synthesized by facile solid-state reactions. They crystallize in the 3-D ALn3EQ7 structure type in the hexagonal chiral space group P63. The structures feature a 3-D host framework constructed by Ln-S bicapped trigonal prisms, in which the octahedral and tetrahedral interspaces are occupied by A and E...     

Synthesis of derivatives of 7-iodo-4-aminoquinolines

7-Iodo- and 7,8-diiodo-4-(3-dimethylaminopropylamino)quinolines and 7-iodo-4-(3) dipropyl-aminopropylamlno)- and 7-iodo-4-(3-diallylaminopropylamino)quinoline were obtained by the reaction of 7-iodo- and 7,8-diodo-4-chloroquinolines with the corresponding diamines. The catalytic hydrogenation of 7-iodo-4-(3-diallylaminopropylamino)quinoline at normal pressure leads to 7-iodo-4-(3-dipropylaminopropylamino)quinoline.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 972–975, July, 1980.     

Comparative Structural Study of Three Tetrahalophthalic Anhydrides: Recognition of X···O(anhydride) Halogen Bond and πh···O(anhydride) Interaction

Structures of three tetrahalophthalic anhydrides (TXPA: halogen = Cl (TCPA), Br (TBPA), I (TIPA)) were studied by X-ray diffraction, and several types of halogen bonds (HaB) and lone pair···π-hole (lp···πh) contacts were revealed in their structures. HaBs involving the central oxygen atom of anhydride group (further X···O(anhydride) were recognized in the structures of TCPA and TBPA. In contrast, for the O(anhydride) atom of TIPA, only interactions with the π system (π-hole) of the anhydride ring (further lp(O)···πh) were observed. Computational studies by a number of theoretical methods (molecular electrostatic potentials, the quantum theory of atoms in molecules, the independent gradient model, natural bond orbital analyses, the electron density difference, and symmetry-adapted perturbation theory) demonstrated that the X···O(anhydride) contacts in TCPA and TBPA and lp(O)···πh in TIPA are caused by the packing effect. The supramolecular architecture of isostructural TCPA and TBPA was mainly affected by X···O(acyl) and X···X HaBs, and, for TIPA, the main contribution provided I···I HaBs.     

Synthesis and crystal structure of the complex [MoW(OEt)(μ-CH2){μ-C(C6H4Me-4)C(Me)O}(η-C7H7)(η-C2B9H10Me)]

The complex [MoW(μ-CC₆H₄Me-4)(CO)₂(η⁷-C₇H₇)(η⁵-C₂B₉H₁₀Me)] reacts with diazomethane in Et₂O containing EtOH to afford the dimetal compound [MoW(OEt)(μ-CH₂){μ-C(C₆H₄Me-4)C(Me)O}(η⁷-C₇H₇)(η⁵-C₂B₉H₁₀Me)]. The structure of this product was established by X-ray diffraction. The Mo---W bond [2.778(4) Å] is bridged by a CH₂ group [μ-C---Mo 2.14(3), μ-C---W 2.02(3) Å] and by a C(C₆H₄Me-4)C(Me)O fragment [Mo---O 2.11(3), W---O 2.18(2), Mo---C(C₆H₄Me-4) 2.41(3), W---C(C₆H₄Me-4) 2.09(3), Mo---C(Me) 2.26(3) Å]. The molybdenum atom is η⁷-coordinated by the C₇H₇ ring and the tungsten atom is η⁵-coordinated by the open pentagonal face of the nido-icosahedral C₂B₉H₁₀Me cage. The tungsten atom also carries a terminally bound OEt group [W---O 1.88(3) Å]. The ¹H and ¹³C-{¹H} NMR data for the dimetal compound are reported and discussed.     

Benzo‐Fused Double [7]Carbohelicene: Synthesis,Structures, and Physicochemical Properties

A benzo‐fused double [7]carbohelicene (D7H) was synthesized through a regioselective cyclodehydrogenation of a tetranaphthyl‐p ‐terphenyl‐based precursor. The twisted (D7H‐1) and anti ‐folded (D7H‐2) conformers of D7H were separated by recrystallization, and their double helicene structures with overlapping terminal benzene rings were unambiguously elucidated by X‐ray crystallography. A record‐high isomerization barrier (46.0 kcal mol⁻¹) in double helicenes was estimated based on density functional theory (DFT) calculation, which resulted in the excellent conformational stability of D7H. The physicochemical properties of D7H‐1 and D7H‐2 were investigated by UV/Vis absorption spectroscopy and cyclic voltammetry, displaying the variation of electronic structure upon conformational changes. The optical resolution of the racemic D7H‐1 was carried out by chiral HPLC, offering enantiopure D7H‐1‐(P ,P ) and D7H‐1‐(M ,M ), which were further characterized by circular dichroism spectroscopy.     

Preparation of 7-Halo-indoles by Thallation of N-formylindoline and their attempted use for synthesis of the right-hand segment of chloropeptin

7-Substituted (Cl, Br, I) indoles were synthesized by using thallation of N-formylindoline as a key reaction. Two precursor tripeptides for the right-hand segment of chloropeptin were synthesized by using (R)-7'-iodo and 7'-bromotryptophans derived from each 7-substituted indole (I, Br) obtained by the above procedure.     

A fragmentation study of a flavone triglycoside, kaempferol-3-O-robinoside-7-O-rhamnoside

A mass spectrometric method based on the combined use of electrospray ionization, collision-induced dissociation and tandem mass spectrometry has been applied to the structural characterization of the flavone triglycoside, robinin (3,5,7,4'-tetrahydroxyflavone-3-O-robinoside-7-O-rhamnoside). The deprotonated molecule fragments by loss of the rhamnose glycan residue to yield the Y(7) (-) ion (m/z 593) and by scission of the robinose glycan residue to yield the radical anion [Y(3,0)-H](-.) (m/z 430). The Y(7) (-) ion fragments by scission of the robinose glycan residue to yield the radical anion of Y(7)[Y(3,0)-H](-.) (m/z 284). The [Y(3,0)-H](-.) radical anion fragments by loss of the rhamnose glycan residue to yield the radical anion Y(7)[Y(3,0)-H](-.) (m/z 284) and by scission to yield [Y(7)-H][Y(3,0)--H](-) (m/z 283). A fragmentation mechanism has been proposed.     

Synthesis and characterization of the dimercury(I)-linked compound [PPn]4[(Re7C(CO)21Hg)2]. Oxidative cleavage of the mercury-mercury bond leading to carbidoheptarhenate complexes of mercury(II), including [PPN][Re7C(CO)21Hg(S=C(NME2)2)

The reaction of [PPN](3)[Re(7)C(CO)(21)] with Hg(2)(NO(3))(2).2H(2)O in dichloromethane formed the complex [PPN](4)[(Re(7)C(CO)(21)Hg)(2)] ([PPN](4)[1]), isolated in 60% yield. Analogous salts of [1](4-) with [PPh(4)](+) and [NEt(4)](+) were also prepared. The crystal structure of [PPN](4)[1] showed that two carbidoheptarhenate cores are linked by a dimercury(I) unit (d(Hg-Hg) = 2.610(4) A), with each individual mercury atom face-bridging. Oxidative cleavage of the Hg-Hg bond in [1](4-) was effected by 4-bromophenyl disulfide to form [Re(7)C(CO)(21)HgSC(6)H(4)Br](2-) ([4](2-)), by I(2) to form [Re(7)C(CO)(21)HgI](2-) ([5](2-)), and by Br(2) to form [Re(7)C(CO)(21)HgBr](2-) ([6](2-)). Oxidation of [1](4-) by ferrocenium ion (2 equiv) in the presence of tetramethylthiourea resulted in the derivative [Re(7)C(CO)(21)HgSC(NMe(2))(2)](-) ([7](-)). The molecular structure of [PPN][7] was determined by X-ray crystallography. This is the first example of a carbidoheptarhenate-mercury complex with a neutral ligand on mercury, and ligand exchange was demonstrated by displacement with triethylphosphine. Complex [7](-) can also be prepared by protonating [Re(7)C(CO)(21)HgO(2)CCH(3)](2-) in the presence of tetramethylthiourea. Cyclic voltammetry data to calibrate and compare the redox properties of compounds [1](4-) and [7](-) have been measured.     

Photooxygenation of the helimers of (-)-isocolchicine: regio- and facial selectivity of the [4 + 2] cycloaddition with singlet oxygen and surprising endoperoxide transformations

Photooxygenation of the helimeric mixture of (-)-(M,7S)/(P,7S)-isocolchicine (6) with the superdienophile singlet oxygen has been studied. Cycloaddition occurred with high regioselectivity at the 7a,11-positions of the alkaloid and predominantly at the diene face anti to the amidic substituent at the stereogenic center C-7, leading to two endoperoxides 7 (syn) and 8 (anti) with an 1:7 ratio. The structure of the minor product 7 was established by X-ray analysis. Investigation of the triethylamine induced transformation of the predominant endoperoxide 8 furnished a mixture of two isomers (M,7S)-10a/(M,7S)-10b in a 2:1 ratio possibly with constitutional interconversion and with (M,7S)-9 as plausible intermediate. Treatment of this mixture with silica gel/ethyl acetate at ambient temperature surprisingly led to an atropenantiomerically pure colchicinoid (M,7S)-12 characterized by an eightmembered oxocine B-ring, the structure and absolute configuration of which could be determined by X-ray analysis. For the unprecedented formation of the novel colchicinoid (M,7S)-12 a plausible reaction pathway is suggested, involving a complete transfer of the (M) helical asymmetry of the intermediate (M)-11 into (S) asymmetry of the newly formed carbon center of (M,7S)-12. Prerequisite for such a scenario is the configurational stability of the intermediate pseudobiaryl (M)-11, under the conditions employed, allowing to transmit the axial chirality onto the chiral center of the product (M,7S)-12.     

Further Characterization of UVB Radiation Effects on Langerhans Cells: Altered Expression of the Costimulatory Molecules B7-1 and B7-2

We have reported previously that low-dose UVB radiation (UVBR, 50-200 J/m²) perturbs the antigen-presenting cell (APC) function of murine Langerhans cells (LC) by interfering with yet undefined costimulatory signals. In this study, we investigated (1) the effects of UVBR on the expression of the costimulatory molecules B7-1 and B7-2 on murine LC, (2) the functional consequences of defective B7-1 and B7-2 signalling on primary and secondary T-cell responses induced by LC and (3) the mechanism by which UVBR interferes with B7-1 and B7-2 expression. Ultraviolet-B radiation dose-dependently inhibited the culture-induced upregulation of B7-1 and B7-2 on LC from both UVB-susceptible (UVB_s, C57BL/6) and UVB-resistant (UVB_R, Balb/c) mice and abrogated their capacity to stimulate proliferation of naive alloreactive T cells and of the KLH (keyhole limpet hemocyanin)-specific T helper (Th)1 clone HDK-1. The UVBR-induced suppression of B7-1 and B7-2 on LC and their perturbed APC function were related, because exogenous triggering of the B7/CD28 pathway with a stimulatory monoclonal antibody (mAb) for CD28 to UVB-irradiated LC partially restored T-cell proliferation. Such reconstitution was not observed when the mAb was added to killed LC, indicating that the UVBR-induced suppression of APC function was not due to lethal effects on LC. Conditioned supernatants from UVB-irradiated epidermal cells did not inhibit the functional upregulation of B7-1 and B7-2, suggesting that UVBR inhibits B7-1 and B7-2 upregulation by acting directly on LC and not by altering LC costimulatory function via release of soluble immunosuppressive factors. In conclusion, UVBR distorts the functional expression of B7-1 and B7-2 on LC from both UVBs and UVBR mice, thereby contributing to the failure of UVB-irradiated LC to stimulate resting alloreactive T cells or KLH-specific Thl cells.