Studies on antiulcer drugs. V. Synthesis and antiulcer activity of aralkylbenzazoles.

A series of 2-alkylamino-5- or 6-aralkyl-substituted benzazoles were synthesized and tested for histamine H2-receptor antagonist and anti-stress ulcer activities. These new compounds showed little or no histamine H2-receptor antagonist activity in contrast to imidazo[1,2-a]pyridine analogues (I). On antiulcer assay, however, some pyridine derivatives (II) exerted higher activity than the reference compounds, sofalcone, sucralfate and cimetidine. The structure-activity relationships of these compounds are discussed.     

Bildung siliciumorganischer Verbindungen. XXXXVI. Si-fluorierte Carbosilane

Formation of organosilicon compounds. XXXXVI. Si-fluorinated carbosilanes Compounds (1)–(7) (see “Inhaltsübersicht”) are obtained by reaction of carbosilanes containing Si? Cl groups with ZnF₂. The linear compounds (8) and (9) are prepared from ZnF₂ and (Cl₃Si)₂CCl₂, and (Cl₃Si? CCl₂)SiCl₂, respectively, whereas the cyclic compounds are formed by photochemical chlorination. Photochemical chlorination of (3) goes via compounds (13) and (14) (isolation is possible); both of them can be prepared too by reaction of Si? Cl derivatives with ZnF₂. Compounds (16) and (17) are obtained from the corresponding Si? Cl derivatives.     

GC-MS法测定大蒜中的挥发性物质

大蒜(AlliumsatiuvmL.)是多年生草本百合科植物大蒜的鳞茎,按皮的颜色不同可分为紫皮蒜和白皮蒜两种。大蒜原产于意大利的西西里岛,约在两千多年前传入我国。大蒜不仅是极佳的调味食品,而且还有很好的药用功能。近年来,科学家研究证明,大蒜是一种健康食品,有助人体防病保健、延年益寿,是药食兼优的佳品,对人体具有多种药用价值。大蒜具有一种强烈的蒜臭气味,这种特殊的气味由许多复杂的硫化物组成。这类有机硫化物可促进消化,健胃整肠,强化抗菌作用,消肿止痛,改善机体机能的功能,大蒜中还含有乙烷硫代磺酸乙酯和二烯丙基三硫化物等,能阻断强烈致癌物质亚硝胺类在胃部的形成和积累,可预防胃癌、食道癌、肝癌、鼻咽癌的发生。本试验采用"同时蒸馏-萃取方法"(simultaneousdistillationandextraction,SDE)提取白皮和紫皮大蒜的挥发性成分,经GC-MS分析,确定了化合物的化学组成和相对百分含量。     

Triterpenoid saponins from Ilex mamillata C.Y. Wu ex C.J. Tseng

Two new triterpenoid saponins, ilemaminosides A and B (1 and 2) along with six known saponins (3-8) were isolated from 70% ethanolic extract of the leaves of Ilex mamillata C.Y. Wu ex C.J. Tseng. The new saponins were characterised as 3-O-α-L-arabinopyranosyl-ilexgenin B (1) and 3-O-β-D-glucopyranosyl-(1?→?3)-α-L-arabinopyranosyl-ilexgenin B (2). The structures of compounds 1 and 2 were elucidated on the basis of the chemical and spectroscopic methods, and the structures of known compounds were identified by comparison of their spectroscopic data with those reported in the literature. The compounds showed inhibitory activities in anti-inflammatory assay in?vitro with IC(50) values in the range 25.37-38.33?μg?mL(-1).     

Cyclofunctionalisation of epoxyalcohol derivatives. 1. Delivery of functionalised carbon for stereospecific synthesis of dihydrofurans and dihydroxyacids

E-2-(Phenylsulfonyl)vinyl ethers of 2,3-epoxyalcohols are stereospecifically rearranged to 3-(phenylsulfony])-4-(1-hydroxyalkyl)-4,5-dihydrofurans on treatment with LDA. Oxidation of these compounds or the derived des-sulfonyl compounds provides esters or lactones which correspond to regiospecific delivery of -CO₂H or -CH₂CO₂H to C-2, with inversion.     

Studies on antiplatelet agents. I. Synthesis and platelet inhibitory activity of 5-alkyl-2-aryl-4-pyridylimidazoles.

5-Alkyl-2-aryl-4-pyridylimidazoles were synthesized and tested in rat ex vivo platelet aggregation studies. Among these compounds, 2-(2-fluorophenyl)-5-methyl-4-(3-pyridyl)imidazole (25) was most potent, and showed 98% inhibition at a dose of 10 mg/kg (p.o.). 25 had inhibitory activity on cyclooxygenase, thromboxane A2 (TXA2) synthetase, and phosphodiesterase, and also showed inhibited KCl-induced contraction of rat aorta. All compounds have little acute toxicity and appear to be free of adverse effects on the stomach.     

珠子参化学成分分析

从珠子参根茎中分离得到7个化合物. 利用核磁共振、 质谱和红外等手段, 并结合其理化性质, 鉴定了其结构, 它们分别是24(R)-珠子参苷R1, 6-O-[β-D-吡喃葡萄糖基(1→2)-β-D-吡喃葡萄糖基]-20-O-[β-D-吡喃葡萄糖基(1→4)-β-D-吡喃葡萄糖基]-20(S)-原人参三醇、 6″-乙酰基-人参皂苷Rd、 人参皂苷Rf、 竹节参皂苷Ⅳa、 人参皂苷Rd和竹节参皂苷Ⅴ. 其中, 24(R)-珠子参苷R1和6-O-[β-D-吡喃葡萄糖基(1→2)-β-D-吡喃葡萄糖基]-20-O-[β-D-吡喃葡萄糖基(1→4)-β-D-吡喃葡萄糖基]-20(S)-原人参三醇为2个新化合物, 6″-乙酰基-人参皂苷Rd 和人参皂苷Rf为首次从珠子参根茎中得到.     

Studies on the synthesis of heterocyclie compounds. II. Synthesis of 2,2-disubstituted-1,3-benzoxathioles

The condensation of 2-hydroxythiophenol (I) with acetylenic compounds (IIa-g) or halo-genated esters (IV, V, VIa and b) led to the synthesis of 2,2-disubstituted-1,3-benzoxathioles (IIIa-g). The structures of these compounds were established by elemental analysis and by ir and nmr spectra.     

Head-to-tail regioregular oligothiophene-functionalized 9,9'-spirobifluorene derivatives. 1. Synthesis

Two series of novel fully conjugated oligomers, oligothiophene-functionalized 9,9'-spirobifluorene derivatives, have been developed in this contribution. First, four 9,9'-spirobifluorene bromide derivatives (compounds 1a-d) are prepared through various synthetic routes. Oligothiophene derivatives with or without substituents are synthesized through the Grignard and Suzuki coupling reactions. The Negishi coupling reactions between oligothienylzinc chloride and various 9,9'-spirobifluorene bromides with Pd(PPh(3))(4) as catalyst successfully produce the desired compounds, unsubstituted oligothiophene-functionalized 9,9'-spirobifluorene derivatives, compounds 2 to 4a-d. Since the Negishi coupling reactions afford regioregularly head-to-tail (H-T) oligo(4-n-hexylthiophene)-functionalized 9,9'-spirobifluorene derivatives in poor yields, the Suzuki coupling reactions between sodium 4-n-hexylthienyl-2-boronate 8, and various 9,9'-spirobifluorene-based bromides 1a-d and 9-16 are employed to produce highly regioregular head-to-tail oligothiophene-functionalized 9,9'-spirobifluorene derivatives (compounds 5 to 7a-d) in very high yields. We also investigate the effect of solvents on the Suzuki coupling reactions. The structure and purity of all compounds are verified by FT-IR, (1)H and (13)C NMR, MS, and elemental analysis.     

Synthesis of phenoxyacetic acid derivatives as highly potent antagonists of gastrin/cholecystokinin-B receptors. III.

In order to improve the biological characteristics of DA-3934 (5), a novel gastrin/cholecystokinin (CCK)-B receptor antagonist, phenoxyacetic acid derivatives replacing the N-methyl-N-phenylcarbamoylmethyl moiety of 5 with various alkyl chains have been synthesized and their biological activity evaluated. The relationship between the structure of these compounds and their human gastrin receptor binding affinity showed that there should be the optimal size among the various N-alkyl chains. Also a significant increase in the receptor binding affinity was achieved by several compounds. Among those compounds, 2-[3-[3- [N-cyclohexylmethyl-N-[2-(N-methyl- N-phenylcarbamoylmethoxy)phenyl]carbamoylmethyl]ureido]pheny l]acetic acid (22c) and (+/-)-2-[3-[3-[N-[2-(N-methyl-N- phenylcarbamoylmethoxy)phenyl]-N-(3-methylpentyl)carbamoy lmethyl]ureido] phenyl]acetic acid (22h) exhibited high affinity for human gastrin receptors and were also more potent inhibitors in a pentagastrin-induced gastric acid secretion model than the parent compound, 5. The ED50 values of these compounds when administered intraduodenally to rats were 0.12 and 0.63 mg/kg, respectively.     

Electron ionization mass spectra of phosphorus-containing heterocycles. II. 1,2,3,4,4a,5,6,7,8,8a-decahydro-1,3,2-benzodiazaphosphinine 2-oxides

The electron ionization mass spectra of cis- and trans-fused 1,2,3,4,4a,5,6,7,8,8a-decahydro-1,3,2-benzodiazaphosphinine 2-oxides (1-17) were recorded, and the fragmentation pathways were established and compared with those of 1,4,4a,5,6,7,8,8a-octahydro-2H-3,1,2-benzoxazaphosphinine 2-oxides. In general, the mass spectral behaviors of the isomeric compounds were very similar and it was mostly impossible to differentiate them from each other on the basis of the relative abundances of their characteristic fragment ions. The compounds in which R(2) = Ph or OPh exhibited a series of common fragments, e.g. [R(2)H](+), R(2)PONHR(1(3)+), [M-C(3)H(7)](+) and [M-C(4)H(9)](+), the latter two ions being present in the spectra of only two of the derivatives with an N(CH(2)CH(2)Cl)(2) substituent on the P atom. When R(2) = Ph, numerous other alkyl radicals, alkenes and a cycloalkane were also ejected and these compounds also lost NH(2), NH(3), CH(3)N, CH(4)N or CH(3)NH(2). The compounds with an N(CH(2)CH(2)Cl)(2) substituent on the P atom most closely resembled their 3,1,2-O,N,P analogs in respect of the dominant role of this substituent.     

Photochemische Reaktionen. 107. Mitteilung. Zur Photochemie offenkettiger 2,6-bzw. 2,7-Dien-Carbonylverbindungen

The Photochemistry of Open-Chained 2,6- or 2,7-Dien-Carbonyl Compounds On ¹n, π*-excitation (λ > 347 nm) citral (5) and the methyl ketone 10 isomerize to compounds A (7, 19) and B (6, 20) , whereas the phenyl ketone 11 changes into the isomer 24 of type E. Evidence is given that the conversions to A and B may arise from the ³n, π*-state of the 2,6-diene-carbonyl compounds. On ¹n, π*-excitation (λ = 254 nm) 5 and 10 yield the isomers A (7, 19) and D (18, 22) , but no products of type B. Furthermore, conversion of 10 to the isomer 21 of type C is observed. Selective ¹n, π*-excitation (λ = 254 nm) as well as selective ¹n, π*-excitation (λ > 347 nm) of the 2,7-diene-carbonyl compounds 12 and 13 give rise to isomerization to the compounds F (25, 28) , exclusively. The intramolecular [2 + 2]-photocycloadditions are shown to be triplet processes. UV.-irradiation (λ > 280 nm) of compounds F (25, 28) furnishes the isomeric products G (26, 29) which photoisomerize to oxetanes of type H (27, 30).     

Transition-metal-promoted reactions of boron hydrides. 17. Titanium-catalyzed decaborane-olefin hydroborations.

The titanium-catalyzed hydroboration reactions of decaborane with a variety of terminal olefins have been found to result in the exclusive, high-yield formation of monosubstituted decaborane 6-R-B(10)H(13) products, arising from anti-Markovnikov addition of the cage B6-H to the olefin. The titanium-catalyzed reactions are slow, often less than one turnover per hour; however, their high selectivities and yields coupled with the fact that they are simple, one-pot reactions give them significant advantages over the previously reported routes to 6-R-B(10)H(13) compounds. The catalyst also has extended activity with reactions carried out for as long as 13 days, showing little decrease in reactivity, thereby allowing for the production of large amounts of 6-R-B(10)H(13). The titanium-catalyzed reactions of decaborane with the nonconjugated diolefins, 1,5-hexadiene and diallylsilane, were found to give, depending upon reaction conditions and stoichiometries, high yields of either alkenyl-substituted 6-(CH(2)=CH(CH(2))(4))-B(10)H(13) (4) and 6-(CH(2)=CHCH(2)SiMe(2)(CH(2))(3))-B(10)H(13) (5) or linked-cage 6,6'-(CH(2))(6)-(B(10)H(13))(2) (6) and Me(2)Si(6-(CH(2))(3)-B(10)H(13))(2) (7) compounds, respectively. The unique tetra-cage product, Si(6-(CH(2))(3)-B(10)H(13))(4) (8), was obtained by the catalyzed reaction of 4 equiv of decaborane with tetraallylsilane. Sequential use of the titanium catalyst and previously reported platinum catalysts (PtBr(2) or H(2)PtCl(6).6H(2)O with an initiator) provides an efficient pathway to asymmetrically substituted 6-R-9-R'-B(10)H(12) species. The structures of compounds 5, 6, and 8, as well as a platinum derivative, (PSH(+))(2)-commo-Pt-[nido-7-Pt-8-(n-C(8)H(17))B(10)H(11)](2)(2-), of 6-(n-octyl)decaborane have been established by single-crystal crystallographic determinations.     

The mutagenic constituents of Rubia tinctorum.

Twenty compounds were isolated from the roots of Rubia tinctorum which are used as a commercial source of madder color. Among these compounds, mollugin (1), 1-hydroxy-2-methylanthraquinone (2), 2-ethoxymethylanthraquinone(11), rubiadin (13), 1,3-dihydroxyanthraqunone (14), 7-hydroxy-2-methylanthraquinone (16), lucidin (17), 1-methoxymethylanthraquinone (18) and lucidin-3-O-primeveroside (19) showed mutagenicity with Salmonella typhimurium TA 100 and/or TA 98. Since the mutagenic compounds isolated are anthraquinone derivatives with the exception of compound 1, structure-mutagenicity relationships of the anthraquinones were also studied. The results suggested that the greatest activity is exhibited by 1,3-dihydroxyanthraquinones possessing methyl or hydroxylmethyl group on carbon 2.     

Degenerate two-photon absorption spectra in azoaromatic compounds.

A systematic study of the degenerate two-photon absorption (2PA) spectra of seven azoaromatic compounds in dimethyl sulfoxide solution is reported, which employed the Z-scan technique with femtosecond laser pulses from the bottom of the azo compound absorption bands up to 1100 nm. The 2PA peaks for pseudostilbene-type azo compounds (Disperse Orange (DO) 3, Disperse Red (DR) 13, DR1, DR19, and DR19-Cl) were observed at twice the peak wavelength of the linear absorption. However, such peaks were not observed for other azo compounds (PAMINO and DIAMINO) because of the symmetry of these molecules. A resonance enhancement of the 2PA cross-section was observed for all compounds. The 2PA peak and the nonlinear resonance enhancement behavior could be adjusted with a model based on perturbation theory. Such knowledge can be a guideline to the understanding of the 2PA process in azoaromatic compounds.     

Entzündungshemmende wirkstoffe. XI. Ringschlußreaktion an 5-phenyl-2-thiobiuret

The reaction of 5-phenyl-2-thiobiuret (1) with α-chlorocarbonyl compounds 2 leads to the structure type of N-phenyl-N¹-(thiazolyl)urea (3). The new compounds exhibit particularly antiinflammatory, anthelminthic, and trichomonacidal activity.     

GPC analysis of model compounds. I. Phenyl- and benzo-substituted aromatic compounds

A series of 36 compounds of known structure was used in a study to elucidate the mechanism of separation of gel-permeation chromatography (GPC). The various molecular dimensions were defined and measured for these compounds. The elution volume for these compounds was determined by GPC under specified and controlled conditions. The relationships between elution volume and molecular dimension were investigated using computer-based statistical analysis for the entire set of compounds and manual simultaneous equations for smaller sets of compounds. It was found that, as increasingly more molecular dimensions are considered, (1) the importance of the maximum molecular dimension A_p′ (the only dimension considered by many investigators) significantly decreases and (2) a significantly better prediction of the elution volume of these compounds could be made.     

Agents for the treatment of overactive detrusor. III. Synthesis and structure-activity relationships of N-(4-amino-2-butynyl)acetamide derivatives.

A series of N-(4-amino-2-butynyl)acetamides were synthesized and examined for their inhibitory activity on detrusor contraction and mydriatic activity as an index of anticholinergic side effect. Among those compounds synthesized, (+)-2-cyclohexyl-N-(4-dimethylamino-2-butynyl)-2-hydroxy-2-phenylacet amide hydrochloride ((+)-13b.HCl), 2-cyclohexyl-2-hydroxy-N-(4-methylamino-2-butynyl)-2-phenylacetamide+ ++ hydrochloride (13c.HCl), N-(4-dimethylamino-2-butynyl)-2,2-diphenyl-2-hydroxyacetamide hydrochloride (14a.HCl), and 2,2-diphenyl-N-(4-ethylamino-2-butynyl)-2-hydroxyacetamide hydrochloride (14b.HCl) showed equipotent inhibitory activity on detrusor contraction to oxybutynin (1) and less mydriatic activity. Further evaluation of these compounds as an agent for the treatment of overactive detrusor has been examined.     

Spectral (u.v.-vis,i.r.MS), electrochemical and metallochromic properties of 2-hydroxy-benzoylhydrazones of acetylpyridines

The synthesis, electronic, infra-red and mass spectra of salicyloylhydrazones of 2-, 3-, and 4-acetylpyridine are reported. Ultraviolet absorption spectra have been applied to determine the dissociation constants which are ranged between 4.0–4.5 (pyridine nitrogen) and 6.2–6.3 (OH group). Infrared spectra show that strong intramolecular H-bonding exists in the solid compounds. Fragmentation of these compounds were found to undergo skeletal rearrangement in addition to either CON or NN simple bond cleavage; pyridine nitrogen position contributes in the paths leading to ions. These aroylhydrazones exhibit polarograms that show several reduction waves, the positions of which change with the pH value. Of the three compounds, 3-pyridyl derivative was the most difficult to reduce. The chelating properties of the compounds towards metal ions were investigated. The 2-acetylpyridine derivative results to be the most adequate ligand, as well as a good preconcentrating agent for metal ions.     

Structural chemistry of polycyclic heteroaromatic compounds. Part 13. Photoelectron spectra and electronic structures of tricyclic hetarenes of the anthracene type.

The ultraviolet photoelectron spectra of two tricyclic heteroaromatic compounds (2,3) that are pi-isoelectronic with anthracene (1) have been recorded and analysed making use of semi-empirical AM1 and PM3, as well as density functional theory (DFT) B3LYP calculations. In compounds 2 and 3, one peripheral benzene ring of compound 1 is substituted by a thiophene ring that is either [b]- or [c]-annellated. In compounds 2 and 3, only small shifts are found for most of the ionization potentials of pi electrons. Since the ionization energies of all occupied pi molecular orbitals of compounds 1-3 could be assigned, a direct comparison of their pi electron energy is possible. Compared with compound 1, the pi-electron system of naphtho[2,3-b]thiophene (2) is stabilized by 0.6 eV, while that of naphtho[2,3-c]thiophene (3) is destabilized by 0.2 eV. [b]-Annellation of the thiophene ring is thus favourable while [c]-annellation is unfavourable.