Furopyridines. X. Synthesis of tricyclic heterocycles,furo[2,3-b:4,5-c']-, furo[3,2-b:4,5-c']-, furo[2,3-c:4,5-c']- and furo[3,2-c:4,5-c']dipyridine

This paper describes the synthesis of four tricyclic heterocycles, furo[2,3–6:4,5-c']- ( 5a ), furo[3,2-b:4,5-c']- ( 5b ), furo[2,3-c:4,5-c']- ( 5c ) and furo[3,2-c:4,5-c']dipyridine ( 5d ). Starting with 2-formylfuropyridines ( 1a-d ), β-(2-furopyridyl)acrylic acids 2a-d were obtained by condensing with malonic acid. The acrylic acids were converted to the acid azides by reaction with ethyl chloroformate and the subsequent reaction with sodium azide. Heating of the acid azides at 230–240° with diphenylmethane and tributylamine gave tricyclic pyridinones 3a-d , which were converted to the respective chloro derivatives 4a-d by reaction with phosphorus oxychloride. Reduction of the chloro compounds over palladium-charcoal yielded compounds 5a-d respectively. All the compounds 2 to 5 were characterized by elemental analysis and spectral data. The H and ¹³C nmr and electronic spectral features of the furodipyridines were discussed comparing with those of the parent furopyridines.     

Furopyridines. V. A simple synthesis of furo[2,3-c]pyridine and its 2-and 3-methyl derivatives

A simple synthesis of furo[2,3-c]pyridine and its 2- and 3-methyl derivatives from ethyl 3-hydroxyisonicotinate ( 2 ) is described. The hydroxy ester 2 was O-alkylated with ethyl bromoacetate or ethyl 2-bromopropionate to give the diester 3a or 3b . Cyclization of compound 3a afforded ethyl 3-hydroxyfuro [2,3-c]pyridine-2-carboxylate ( 4 ) which was hydrolyzed and decarboxylated to give furo[2,3-c]pyridin-3(2H)-one ( 5a ). Cyclization of 3b gave the 2-methyl derivative 5b . Reduction of 5a and 5b with sodium borohydride yielded the corresponding hydroxy derivative 6a and 6b , respectively, which were dehydrated with phosphoric acid to give furo[2,3-c]pyridine ( 7a ) and its 2-methyl derivative 7b . 4-Acetylpyridin-3-ol ( 8 ) was O-alkylated with ethyl bromoacetate to give ethyl 2-(4-acetyl-3-pyridyloxy) acetate ( 9 ). Saponification of compound 9 , and the subsequent intramolecular Perkin reaction gave 3-methylfuro[2,3-c]pyridine ( 10 ). Cyclization of 9 with sodium ethoxide gave 3-methylfuro[2,3-c]pyridine-2-carboxylic acid, which in turn was decarboxylated to give compound 10 .     

ESTIMATION OF AN INDEX OF HYDROPHOBICITY OF DNA INTERIOR USING 5-METHOXYPSORALEN AS A FLUORESCENT PROBE

The index of hydrophobicity of DNA interior was estimated by measuring fluorescence spectra of psoralen derivatives associated with DNA. The environment around 5-MOP associated with DNA was as hydrophobic (D_k = 34) as methanol, suggesting that the molecules reside at the space between the base-pairs in B-form DNA. This is also true for 8-MOP. Thus, planar and aromatic molecules of 5- and 8-MOP are more stable in the interior of DNA than in aqueous medium due to hydrophobic affinity.     

Diarylurea-linked zinc porphyrin dimer as a dual-mode artificial receptor: supramolecular control of complexation-facilitated photoinduced electron transfer

A novel porphyrinic receptor 1 in which two zinc porphyrins are bridged by two diarylurea linkers was developed for recognition of a viologen derivative (hexyl viologen, HV). The electronic absorption spectra as well as the 1H NMR experiments revealed that the HV molecule was bound to the cleft in 1 mainly through carbonyl dipole-charge interactions to afford a 1:1 complex. From the steady-state fluorescence spectroscopic study, the photoinduced electron transfer (PET) from 1 to HV was extremely facilitated by the receptor-substrate complexation. The receptor 1 also formed a 1:1 complex with 1,4-diazabicyclo[2.2.2]octane (DABCO) through two Zn-N coordination interactions, and, using DABCO as an inhibitor, we suppressed the PET reaction via the substrate exchange.     

Thalidomide as a nitric oxide synthase inhibitor and its structural development

Thalidomide has been found to exhibit weak nitric oxide synthase (NOS)-inhibitory activity. Structural development studies of thalidomide showed that some N-2,6-dimethylphenylhomophthalimide analogs possess NOS-inhibiting activity.     

One-dimensional ion transport in self-organized columnar ionic liquids

New fan-shaped ionic liquids forming columnar liquid crystalline phases have been prepared to obtain one-dimensional ion-transporting materials. The ionic liquids consist of two incompatible parts: an imidazolium-based ionic part as an ion-conducting part and tris(alkyloxy)phenyl parts as insulating parts. Two compounds having octyl and dodecyl chains have been synthesized. Self-assembly of these materials leads to the formation of thermotropic hexagonal columnar liquid crystalline states at room temperature. Anisotropic one-dimensional ionic conductivities have been successfully measured by the cells having comb-shaped gold electrodes. The self-organized columns have been aligned macroscopically in two directions by shearing perpendicular and parallel to the electrodes. The ionic conductivities parallel to the column axis are higher than those perpendicular to the axis. The incorporation of lithium salts in these columnar materials leads to the enhancement of the ionic conductivities and their anisotropy. These materials would be useful for anisotropic transportation of ions at the nanometer level.     

Synthesis and structures of niobium(V) complexes stabilized by linear-linked aryloxide trimers

The preparation and characterization of a series of niobium(V) complexes that incorporate the linear-linked aryloxide trimers 2,6-bis(4,6-dimethylsalicyl)-4-tert-butylphenol [H3(Me-L)] and 2,6-bis(4-methyl-6-tert-butylsalicyl)-4-tert-butylphenol [H3(tBu-L)] are described. The chloride complex [Nb(Me-L)Cl2]2 (1) was prepared in high yield by reaction of NbCl5 with H3(Me-L) in toluene. In contrast, the analogous reaction with H3(tBu-L) gave a mixture of [Nb(tBu-L)Cl2]2 (2) and [Nb(de-tBu-L)Cl2]2 (3a). During the formation of 3a, one of tert-butyl groups at the ortho position in the tBu-L ligand was lost. When the NbCl5/H3(tBu-L) reaction was carried out in acetonitrile, Nb[H(tBu-L)]Cl3(NCMe) (4) was obtained. Heating a solution of 4 in toluene generated 2 and 3a. The isolated complex 4 underwent ligand redistribution in acetonitrile to produce Nb[H(tBu-L)]2Cl(NCMe) (5). Treatment of NbCl5 with Li3(tBu-L) in toluene afforded 2. The chloride ligands in 1 and 2 smoothly reacted with 4 equiv of MeMgI and LiStBu, resulting in [Nb(R-L)Me2]2 [R = Me (6), tBu (7)] and Nb(Me-L)(StBu)2 (8), respectively. A number of the above complexes have been characterized by X-ray crystallography. In the structures of 1, 2, and 6, the R-L ligand is bound to the metal center with a U-coordination mode, while an alternative S-conformation is adopted for 3a and 8. Complexes 4 and 5 contain a bidentate H(tBu-L) diphenoxide-monophenol ligand.     

Seven-membered vibsane-type diterpenes with a 5,10-cis relationship from Viburnum awabuki

New five seven-membered vibsane-type diterpenes named 5-epi-vibsanin C, 5-epi-vibsanin H, 5-epi-vibsanin K, 18-O-methyl-5-epi-vibsanin K and 5-epi-vibsanin E have been isolated from the leaves of Viburnum awabuki (Caplifoliaceae). Their structures have been elucidated by analyses of spectroscopic data and comparison of their spectral data with those of the previously known seven-membered vibsane-type diterpenes. The occurrence of these seven-membered vibsane-type diterpenes with a cis relationship on the C-5 and C-10 positions in nature have been predicted by conformational analysis of vibsanin B, an eleven-membered vibsane-type diterpene. Vibsanin C, 5-epi-vibsanin C and 5-epi-vibsanin H exhibited moderate cytotoxic activities on KB cells.     

A modified method using static head-space gas chromatography for determining the stability constants of 1-alkanol/alpha-cyclodextrin complexation

A modification of the conventional static head-space gas chromatography method (SHSGC method) to determine stability constants for 1-alkanol/alpha-CD inclusion complexes was investigated. The 1 : 1 stability constants determined by this modified SHSGC method are in reasonable agreement with the corresponding values reported previously. The modified SHSGC method precludes the necessity of the calibration curve by the use of Henry's law constant of guest. Consequently, the modified SHSGC method is more advantageous than the conventional SHSGC method because the experimental time required for determination of the stability constant is markedly reduced.     

Complexes of tantalum with triaryloxides: Ligand and solvent effects on formation of hydride derivatives

A family of tantalum compounds supported by the triaryloxide [R-L]³⁻ ligands are reported [H₃(R-L) = 2,6-bis(4-methyl-6-R-salicyl)-4-tert-butylphenol, where R = Me or ^tBu]. The reaction of H₃[Me-L] with TaCl₅ in toluene gave [(Me-L)TaCl₂]₂ (1). The [^tBu-L] analogue [(^tBu-L)TaCl₂]₂ (2) was synthesized via treatment of TaCl₅ with Li₃[^tBu-L]. A THF solution of LiBHEt₃ was added to 1 in toluene to provide [(Me-L)TaCl(THF)]₂ (3), while treatment of 2 with 2 equiv of LiBHEt₃ or potassium in toluene followed by recrystallization from DME resulted in formation of [M(DME)₃][{(^tBu-L)TaCl}₂(μ-Cl)] [M = Li (4a), K (4b)]. When the amount of MBHEt₃ (M = Li, Na, K) was increased to 5 equiv, the analogous reactions in toluene afforded [{(bit-^tBu-L)Ta}₂(μ-H)₃M] [M = Li(THF)₂ (5a), Na(DME)₂ (5b), K(DME)₂ (5c)]. During the course of the reaction, the methylene CH activation of the ligand took place. Dissolution of 5a in DME produced [{(bit-^tBu-L)Ta}₂(μ-H)₃Li(DME)₂] (6), indicating that the coordinated THF molecules are labile. When the 2/LiBHEt₃ reaction was carried out in THF, the ring opening of THF occurred to yield [(^tBu-L)Ta(OBuⁿ)₂]₂ (7) along with a trace amount of [Li(THF)₄][{(^tBu-L)TaCl}₂(μ-OBuⁿ)] (8). Treatment of 2 with potassium hydride in DME yielded [{(^tBu-L)TaCl₂K(DME)₂}₂(μ-OCH₂CH₂O)] (9), in which the ethane-1,2-diolate ligand arose from partial C-O bond rupture of DME. The X-ray crystal structures of 2, 3, 4, 5a, 6, 7, and 9 are described.