Synthesis and properties of novel 5-(cyclohepta-2′,4′,6′-trienylidene)pyrimidine-2(1H),4(3H),6(5H)-triones: methodology for synthesizing cyclohepta[b]pyrimido[5,4-d]furan-8(7H),10(9H)-dionylium tetrafluoroborates

Novel condensation reaction of tropone with N-substituted and N,N′-disubstitued barbituric acids in Ac₂O afforded 5-(cyclohepta-2′,4′,6′-trienylidene)pyrimidine-2(1H),4(3H),6(5H)-trione derivatives (8a-f) in moderate to good yields. The ¹³C NMR spectral study of 8a-f revealed that the contribution of zwitterionic resonance structures is less important as compared with that of 8,8-dicyanoheptafulvene. The rotational barriers (ΔG^‡) around the exocyclic double bond of mono-substituted derivatives 8a-c were obtained to be 14.51-15.03 kcal mol⁻¹ by the variable temperature ¹H NMR measurements. The electrochemical properties of 8a-f were also studied by CV measurement. Upon treatment with DDQ, 8a-c underwent oxidative cyclization to give two products, 7 and 9-substituted cyclohepta[b]pyrimido[5,4-d]furan-8(7H),10(9H)-dionylium tetrafluoroborates (11a-c·BF₄⁻ and 12a-c·BF₄⁻) in various ratios, while that of disubstituted derivatives 8d-f afforded 7,9-disubstituted cyclohepta[b]pyrimido[5,4-d]furan-8(7H),10(9H)-dionylium tetrafluoroborate (11d-f·BF₄⁻) in good yields. Similarly, preparation of known 5-(1′-oxocycloheptatrien-2′-yl)-pyrimidine-2(1H),4(3H),6(5H)-trione derivatives (14a-d) and novel derivatives 14e,f was carried out. Treatment of 14a-c with aq. HBF₄/Ac₂O afforded two kinds of novel products 11a-c·BF₄⁻ and 12a,c·BF₄⁻ in various ratios, respectively, while that of 14d-f afforded 11d-f. The product ratios of 11a-c·BF₄⁻ and 12a-c·BF₄⁻ observed in two kinds of cyclization reactions were rationalized on the basis of MO calculations of model compounds 20a and 21a. The spectroscopic and electrochemical properties of 11a-f·BF₄⁻ and 12a-c·BF₄⁻ were studied, and structural characterization of 11c·BF₄⁻ based on the X-ray crystal analysis and MO calculation was also performed.     

Structure of N,C,N-chelated organotin(IV) fluorides

The set of starting tri-, di- and monoorganotin(IV) halides containing N,C,N-chelating ligand (L^NCN = {1,3-[(CH₃)₂NCH₂]₂C₆H₃}⁻) has been prepared (1-5) and two compounds structurally characterized ([L^NCNPh₂Sn]⁺I₃⁻ (1c), L^NCNSnBr₃ (5)) in the solid state. These compounds were reacted with KF with 18-crown-6, NH₄F or L^CNnBu₂SnF to give derivatives containing fluorine atom(s). Triorganotin(IV) fluorides L^NCNMe₂SnF (2a) and L^NCNnBu₂SnF (3a) revealed monomeric structural arrangement with covalent Sn-F bond both in the coordinating and non-coordinating solvents, except the behaviour of 3a that was ionized in the methanol solution at low temperature. The products of fluorination of L^NCNSnPhCl₂ (4) and 5 were described by NMR in solution as the ionic hypervalent fluorostannates or the oligomeric species reacting with chloroform, methanol or moisture to zwitterionic monomeric stannate L^NCN(H)⁺SnF₄⁻ (5c), which was confirmed by XRD analysis in the solid state.     

Naupliolide, a sesquiterpene lactone with a novel tetracyclic skeleton from Nauplius graveolens subsp. odorus

The aerial parts of Nauplius graveolens subsp. odorus (Schousb) Wikl. afforded a novel sesquiterpene lactone (1) named naupliolide together with the known 6,7,9,10-tetradehydroasteriscanolide 2 and asteriscunolides A-D 3a-d. The structure of compound 1 corresponds to a novel skeleton of 14,15-dimethyl-7,13-dioxotricyclic[6.4.0.0^9,11]dodeca-12,13-olide, and was established on the basis of spectroscopic methods including 2D-NMR. The coexistence of naupliolide 1 together with the structurally related sesquiterpene lactones asterisculolides A-D (3a-d) and 6,7,9,10-tetradehydroasteriscanolide 2, seems to indicate their biosynthetic relationship.     

Synthesis and characterization of new Rh complexes bearing CO, PPh3 and chelating P,O- or Se,Se-ligands: Application to hydroformylation of styrene

The complexes [Rh(CO)(PPh₃){Ph₂PNP(O)Ph₂-P,O}] (3), [Rh(CO)₂{Ph₂P(Se)NP(Se)Ph₂-Se,Se′}] (5), and [Rh(CO)(PPh₃){Ph₂P(Se)NP(Se)Ph₂-Se,Se′}] (6), were synthesised by stepwise reactions of CO and PPh₃ with [Rh(cod){Ph₂PNP(O)Ph₂-P,O}] (2) and [Rh(cod){Ph₂P(Se)NP(Se)Ph₂-Se,Se′}] (4), respectively. The complexes 3, 5 and 6 have been studied by IR, as well as ¹H and ³¹P NMR spectroscopy. The ν(CO) bands of complexes 3 and 6 appear at approximately 1960 cm⁻¹, indicating high electron density at the Rh^I centre. The structure of complexes 3 and 6 has been determined by X-ray crystallography, and the ³¹P NMR chemical shifts have been resolved via low temperature NMR experiments. Both complexes exhibit square planar geometry around the metal centre, with the five-membered ring of complex 3 being almost planar, and the six-membered ring of complex 6 adopting a slightly distorted boat conformation. The C-O bond of the carbonyl ligand is relatively weak in both complexes, due to strong π-back donation from the electron rich Rh^I centre. The catalytic activity of the complexes 2, 3 and 6 in the hydroformylation of styrene has been investigated. Complexes 2 and 3 showed satisfactory catalytic properties, whereas complex 6 had effectively no catalytic activity.     

Synthesis, characterizations and crystal structures of di-n-butyltin(IV) complexes with heteroatomic (N, O or S) acid

Two types of di-n-butyltin(IV) complexes {[ⁿBu₂Sn(O₂CR)]₂O}₂ · L 1-4 and ⁿBu₂Sn(O₂CR)₂Y 5-8 (when L=H₂O, R=2-pyrazine 1; L=0, R=2-pyrimidylthiomethylene 2, 1-naphthoxymethylene 3; L=C₆H₆, R=2-naphthoxymethylene 4; when Y=H₂O, R=2-pyrazine 5; Y=0, R=2-pyrimidylthiomethylene 6, 1-naphthoxymethylene 7, 2-naphthoxymethylene 8) have been prepared in 1:1 or 1:2 molar ratios by reactions of di-n-butyltin oxide with the heteroatomic (N, O or S) carboxylic acids. The complexes 1-8 are characterized by elemental, IR, ¹H and ¹³C NMR spectra. And except for complexes 6 and 7, the complexes 1-5 and 8 are also characterized by X-ray crystallography diffraction analyses, which reveal that the tin atom of complex 5 is seven-coordinated, while the complexes 1-4 and 8 are all hexa-coordinated. The nitrogen atom of the aromatic ring in complexes 1 and 5 participates in the interactions with the Sn atom.     

Synthesis of N,N-di(arylmethylidene)arylmethanediamines by flash vacuum pyrolysis of arylmethylazides

Flash vacuum pyrolysis of arylmethylazides 7a-d gave 2,4-diazapentadienes 5a-d in high yield (76-92%). The thermal cyclization of 5a-d gave cis-imidazolines 1a-d, further heating or Swern oxidation of 1a-d gave dehydrogenated products, imidazoles 2a-d.     

Caldaphnidines A-F, six new Daphniphyllum alkaloids from Daphniphyllum calycinum

Six new Daphniphyllum alkaloids, namely caldaphnidines A-F (1-6), together with eight known ones, deoxycalyciphylline B, deoxyisocalyciphylline B, bukittiggine, calycicine A, methyl homosecodaphniphyllate, daphnilactone B, and daphnezomines L-M, were isolated from the leaves and the seeds of Daphniphyllum calycinum. The structure of 1 was determined by a single-crystal X-ray diffraction study, and the structures of 2-6 were established by spectral methods, especially two-dimensional NMR techniques (¹H-¹H COSY, HMQC, HMBC, and NOESY).     

Essential structure of co-pigment for blue sepal-color development of hydrangea

Blue sepal-color of Hydrangea macrophylla might be due to a supramolecular metal-complex pigment consisting of delphinidin 3-glucoside (1), co-pigments (5-O-caffeoylquinic acid (2), and/or 5-O-p-coumaroylquinic acid (3)) and Al³⁺ in an aqueous solution around pH 4.0. To clarify the mechanism of blue sepal-color development of hydrangea, we tried to reproduce the blue color in vitro by mixing 1 with designed synthetic co-pigments in the presence of Al³⁺ at pH 4.0. We at first succeeded in clarifying the essential functional structure in the co-pigment that could form the stable blue solution. Here, we present the structure of the blue pigment caused by an Al-complex coordinating of 1 at ortho-dihydroxyl groups of the B-ring, 1-hydroxy, 1-carboxylic acid, and the carbonyl residue in the ester at 5-position of 2 and/or 3. The hydrophobic interaction between the aromatic acyl residue at 5-position and the nucleus of 1 may also contribute to stabilize the complex.     

A clay-mediated, regioselective synthesis of 2-(aryl/alkyl)amino-thiazolo[4,5-c]carbazoles

The 3-aminocarbazoles 1a-e were condensed with phenyl and benzyl isothiocyanates on montmorillonite K10 clay or TLC-grade silica gel at room temperature to furnish efficiently the N-phenyl and N-benzylthioureidocarbazoles, 2a-e and 2f, respectively, within minutes. When adsorbed on montmorillonite K10 clay impregnated with para-toluene sulfonic acid (1:1, w/w) and heated at 60-70 °C, 2a-e and 2f furnished the 2-anilino and 2-benzylaminothiazolo[4,5-c]carbazoles, 3a-e and 3f, respectively, regioselectively in high yields. The cyclisation was also effective for the N-methylthioureidocarbazoles 2g-i.     

Electrostatic forces that determine O,O-trans versus O,S-cis conformers in the aminated porphyrin complexes of Cd(N-NHCO-2-C4H3O-tpp)(OAc) and Cd(N-NHCO-2-C4H3S-tpp)(OAc)

Two new diamagnetic, mononuclear and aminated porphyrin complexes of O,O-trans-Cd (3-trans) and O,S-cis-Cd (4-cis) have been synthesized and characterized by ¹H, ¹³C NMR spectroscopy. The crystal structures of (acetato)(N-2-furancarboxamido-meso-tetraphenylporphyrinato)cadmium(II) [Cd(N-NHCO-2-C₄H₃O-tpp)(OAc); 3-trans] and (acetato)(N-2-thiophenecarboxamido-meso-tetraphenylporphyrinato)cadmium(II) [Cd(N-NHCO-2-C₄H₃S-tpp)(OAc); 4-cis] were determined. The coordination sphere around Cd²⁺ is a distorted square-based pyramid in which the apical site is occupied by a bidentate chelating OAc⁻ group for 3-trans and 4-cis. The plane of three pyrrole nitrogen atoms [i.e., N(1), N(2), N(4) for 3-trans and N(1), N(2), N(3) for 4-cis] strongly bonded to Cd²⁺ is adopted as a reference plane 3N. The N(3) and N(4) pyrrole rings bearing the 2-furancarboxamido (Fr) and 2-thiophenecarboxamido groups in 3-trans and 4-cis, respectively, deviate mostly from the 3N plane, thus orienting separately with a dihedral angle of 33.4° and of 31.0°. In 3-trans, Cd²⁺ and N(5) are located on different sides at 1.06 and −1.49 Å from its 3N plane, while in 4-cis, Cd²⁺ and N(5) are also located on different sides at 1.04 and −1.53 Å from its 3N plane. An attractive electrostatic interaction between the Cd²⁺ and O(4)⁻ atoms in furan stabilizes the O,O-trans conformer of 3. A repulsive electrostatic interaction between Cd²⁺ and S(1)⁺ destabilizes the O,S-trans conformer of 4. Both of these repulsive and the mutually attractive interactions between S(1)⁺ and O(3)⁻ atoms favor the O,S-cis rotamer of 4 both in the vapor phase and in low polarity solvents. NOE difference spectroscopy, HMQC and HMBC were employed for the unambiguous assignment of the ¹H and ¹³C NMR resonances of 3-trans and 4-cis in CDCl₃ at 20 and −50 °C.     

Facile synthesis of 4-phenylquinolin-2(1H)-one derivatives from N-acyl-o-aminobenzophenones

An efficient synthesis of 4-phenylquinolin-2(1H)-one derivatives has been achieved in a one-pot reaction from N-acyl-o-aminobenzophenones 1a-c (a: acyl=acetyl; b: acyl=propanoyl; c: acyl=heptanoyl) using NaH as a base. Treatment of 1 with NaH provided the quinolones 2a-c with 62-83% yields, whereas the reaction in the presence of alkyl iodide (alkyl=methyl, ethyl, n-octyl) gave the corresponding N-alkylated quinolones 3a-g in 75-95% yields. The alkylation reaction of 4-phenylquinolin-2(1H)-one 2a with alkyl halide gave a mixture of N-alkylated and O-alkylated products. Comparison of IR and NMR data of the N-alkylated and O-alkylated compounds with those of 2a-c indicated that 2a-c exist as the lactam form.     

Two-stage formation of chloro (N-o-chlorobenzamido-meso-tetraphenylporphyrinato) zinc(II) methylene chloride solvate: Zn(N-NHCO(o-Cl)C6H4-tpp)Cl · CH2Cl2

The coordinating properties of N-o-chlorobenzamido-meso-tetraphenylporphyrin (N-NHCO(o-Cl)C₆H₄-Htpp; 11) have been investigated for the Zn²⁺ ion. Insertion of Zn results in the formation of the zinc complex Zn(N-NCO(o-Cl)C₆H₄-tpp)(MeOH) · MeOH (12 · MeOH). The diamagnetic 12 · MeOH can be transformed into the diamagnetic Zn(N-NHCO(o-Cl)C₆H₄-tpp)Cl · CH₂Cl₂ (13 · CH₂Cl₂) in a reaction with aqueous hydrogen chloride (2%). X-ray structures for 12 · MeOH and 13 · CH₂Cl₂ have been determined. The coordination sphere around the Zn²⁺ ion in 12 · MeOH is a distorted trigonal bipyramid with N(2), N(4) and O(2) lying in the equatorial plane, whereas for the Zn²⁺ ion in 13 · CH₂Cl₂, it is a square-based pyramid in which the apical site is occupied by the Cl(1) atom.     

Transannular Anti-Michael Addition: Formation of 4H-Pyrazolo[5,1-c]thiazines

The reaction of 2-(diphenylmethylene)thietan-3-one (2) with 1,2,4,5-tetrazines (3a-c) in KOH/MeOH/THF gives 4H-pyrazolo[5,1-c]thiazines (7a-c). This novel condensation reaction proceeds via the intermediacy of an 8-(diphenylmethylene)-2H-1,4,5-thiadiazocin-7(8H)-one (5), which undergoes a multi-step rearrangement including a rare anti-Michael addition.     

Sequential homo-coupling Diels-Alder/retro Diels-Alder reaction of 5,5′-bi-1,2,4-triazine-containing thiamacrocycles as a new route to thiacrown ethers incorporating a 2,2′-bipyridine subunit

A new route to thiacrown ethers 5a-d and 6a-d incorporating a 2,2′-bipyridine subunit is elaborated using, (1) homo-coupling of 1,2,4-triazine sulfides 3a-d tethered to poly(ethylene glycol) chains with potassium cyanide and (2) Diels-Alder/retro Diels-Alder reaction with norbornadiene or 1-pyrrolidino-1-cyclopentene as the key steps.     

Takaneones A-C, prenylated butylphloroglucinol derivatives from Hypericum sikokumontanum

Three new prenylated butylphloroglucinol derivatives, takaneones A-C (1-3), were isolated from the MeOH extracts of the aerial parts of Hypericum sikokumontanum together with two new prenylated phloroglucinol derivatives, takaneols A and B (4 and 5). The structures of the isolated compounds were elucidated by exhaustive spectroscopic analysis. The cytotoxicities of the isolated compounds against human cancer cell lines were evaluated. Compounds 2-4 showed cytotoxicities against K562/Adr multi-drug resistant (MDR) cancer cells with IC₅₀ values ranging from 4.7 to 10.0 μg/mL, which were slightly more potent than doxorubicin. Their potency of cytotoxicities against MDR cancer cell lines (KB-C2 and K562/Adr) were similar to those against sensitive cell lines (KB and K562).     

Agelasines O-U, new diterpene alkaloids with a 9-N-methyladenine unit from a marine sponge Agelas sp.

New diterpene alkaloids, agelasines O-U (1-7), have been isolated from an Okinawan marine sponge Agelas sp. The gloss structures and relative stereochemistries of 1-7 were elucidated from the spectroscopic data. Agelasines O-R (1-4) were the third examples of diterpene alkaloid with a 9-N-methyladenine and a pyrrole units. Agelasine O (1) has a halimane skeleton, while agelasines P-R (2-4) have a clerodane skeleton. Agelasines S-U (5-7) were new diterpene alkaloids with a 9-N-methyladenine unit consisting of a halimane skeleton, a labdane skeleton, and a clerodane skeleton, respectively. Agelasines O-R (1-4) and T (6) showed antimicrobial activities against several bacteria and fungi.     

Substituent-induced regioselective synthesis of 1,2-teraryls and pyrano[3,4-c]pyran-4,5-diones from 2H-pyran-2-ones

Substituent-controlled regioselective synthesis of highly functionalized 1,2-teraryls 3a-k has been achieved through ring transformation of 6-aryl-4-(pyrrolidin-1-yl/piperidin-1-yl)-2H-pyran-2-one-3-carbonitriles 1a-g by aryl acetones 2a-c in the presence of powdered KOH in DMF in very good yield. Under similar reaction conditions, 6-aryl-4-methylsulfanyl-2H-pyran-2-ones 5a-f afforded 1,7-diaryl-2-methyl-4H,5H-pyrano[3,4-c]pyran-4,5-diones 6a-j as major products and 3,4-diaryl-2-methyl-6-methylsulfanylbenzonitriles as minor constituents 7a-j.     

The effect that 6-tert-butoxyhexyl functionalization has on ethylene polymerization in ansa-zirconocene dichlorides

Ethylene polymerization studies have been carried out with novel precatalysts of the type: [(η⁵-C₁₃H₈)-X(t-BuOC₆H₁₂)Me-(η⁵-C₅H₄)]ZrCl₂ [X=C [1a], Si [2a]], [(η⁵-C₁₃H₈)-XMe₂-(η⁵-(t-BuOC₆H₁₂C₅H₃))] ZrCl₂ [X=C [3a], Si [4a]] in the presence of excess methylalumoxane (MAO) to compare their catalytic activity and to delineate the effect of the 6-t-butoxyhexyl functionality on ethylene polymerization. The precatalysts [1a] and [2a] with the bridge functionality showed higher activity in ethylene polymerization than the corresponding complexes [3a] and [4a] which have it on the Cp ring moiety. On the other hand the silyl bridged complexes [2a] and [4a] produced a higher molecular weight polyethylene than the carbon-bridged one, regardless of the location of functional group.     

New antimitotic bicyclic peptides, celogentins D-H, and J, from the seeds of Celosia argentea

Six new bicyclic peptides, celogentins D-H (1-5) and J (6) have been isolated from the seeds of Celosia argentea, and the structures including its absolute stereochemistry were determined by using extensive NMR methods and chemical means. Celogentins E-H (2-5) and J (6) showed potent inhibition of tubulin polymerization, while the inhibitory activity of celogentin D (1) was modest. Structure-activity relationship study indicates that ring size of the bicyclic ring system including unusual β^s-Leu, Trp, and His residues would be important for their biological activity.     

A novel transformation of 1-exo-substituted 2a-aroyl-1,2,2a,8b-tetrahydro-3H-benzo[b]cyclobuta[d]pyran-3-ones with sulfoxonium ylide to highly strained 2a-(1-arylethenyl)-1,2,2a,7b-tetrahydrocyclobuta[b]benzofurans

When 1-substituted 2a-aroyl-1,2,2a,8b-tetrahydro-3H-benzo[b]cyclobuta[d]pyran-3-ones (1) were treated with dimethylsulfoxonium methylide, 1-endo isomers (endo-1) gave 1-substituted 3-aroyl-1,2,4a,9b-tetrahydrodibenzofuran-4-ols (2) exclusively as expected. On the other hand, 1-exo isomers (exo-1) underwent a novel transformation to 1-substituted 2a-(1-arylethenyl)-1,2,2a,7b-tetrahydrocyclobuta[b]benzofurans (3), together with 2.