非螯合型手性双膦/钌催化的不对称氢化反应

对RuCl₃和手性双膦(2S,5S)-2,5-双-(二苯膦)-1,4∶3,6-双脱水-2,5-双去氧-L-艾杜醇(BDPI)催化的不对称氢化反应进行了研究,反应的转化率为100%,光学收率受[双膦]/[RuCl₃]比值的影响较大.在α-乙酰胺基肉桂酸的催化氢化反应中,[双膦]/[RuCl₃]=2.0时e.e.值最大,为68%;对衣糠酸的催化氢化,[双膦]/[RuCl₃]=3时e.e.值最大,为92%.     

Two new compounds from Dendrobium candidum

Two new compounds were isolated from the stems of Dendrobium candidum: (R)-3,4-dihydroxy-5,4',alpha-trimethoxybibenzyl (1), named dendrocandin A; and 4-[2-[(2S,3S)-3-(4-hydroxy-3,5-dimethoxyphenyl)-2-hydroxymethyl-8-methoxy-2,3-dihydrobenzo[1,4]dioxin-6-yl]ethyl]-1-methoxyl benzene (2), dendrocandin B. Five previously known bibenzyls were also identified: 4,4'-dihydroxy-3,5-dimethoxybibenzyl (3), 3,4-dihydroxy-5,4'-dimethoxybibenzyl (4), 3-O-methylgigantol (5), dendrophenol (6), and gigantol (7).     

2,5-Dimethyl-3,4-bis[(2R,5R)-2,5-dimethylphospholano]thiophene: first member of the hetero-DuPHOS family

[reaction: see text] The 2,5-dimethyl-3,4-bis[(2R,5R)-2,5-dimethylphospholano]thiophene (UlluPHOS), a new thiophene-based analogue of (R,R)-1,2-bis(phospholano)benzene (Me-DuPHOS), was synthesized, geometrically and electronically characterized, and employed as ligand of Rh and Ru in some standard hydrogenation reactions of prostereogenic functionalized carbon-carbon and carbon-oxygen double bonds. The synthesis of UlluPHOS is much easier than that provided for Me-DuPHOS. UlluPHOS and Me-DuPHOS display very similar geometries, while the electronic availability of the former is higher than that exhibited by the latter. The Rh and Ru complexes of UlluPHOS produced excellent enantiomeric excesses (98.9-99.5%) in the hydrogenation of N-acetyl-alpha-enamino acids and reaction rates higher than those found when employing the analogous complexes of Me-DuPHOS.     

Studies on the constituents of Broussonetia species VIII. Four new pyrrolidine alkaloids, broussonetines R, S, T, and V and a new pyrroline alkaloid, broussonetine U, from Broussonetia kazinoki Sieb

Four new pyrrolidine alkaloids, broussonetines R, S, T, and V and a new pyrroline alkaloid, broussonetine U were isolated from the branches of Broussonetia kazinoki SIEB. (Moraceae) in low yield. Broussonetines R, S and T were formulated as (2R,3R,4R,5R)-2-hydroxymethyl-3,4-dihydroxy-5-[(1R)-1-hydroxy-3-[6-(4-hydroxybutyl)-cyclohexy-2-on-1(6)-enyllpropyl] pyrrolidine (1), (2R,3R,4R,5R)-2-hydroxymethyl-3,4-dihydroxy-5-[(1R,10S)-1,10,13-trihydroxytridecyl] pyrrolidine (2), (2R,3R,4R,5R)-2-hydroxymethyl-3,4-dihydroxy-5-[(1R,5S)-1,5, 13-trihydroxy-10-oxo-tridecyl] pyrrolidine (3). And broussonetines U and V were proposed to be (2S,3S,4S)-2-hydroxymethyl-3, 4-dihydroxy-5-(9-oxo-13-hydroxytridecyl)-5-pyrroline (4), (2R,3S,4R,5R)-2-hydroxymethyl-3,4-dihydroxy-5-[(E)-9-oxo-13-hydroxy-3-tridecenyl] pyrrolidine (5), respectively, by spectroscopic and chemical methods.     

对甲苯磺酸催化下二乙酰苯与含有羟基的苯甲醛的Aldol缩合反应

以对甲苯磺酸(p-TsOH)作催化剂, 二乙酰苯与含有羟基的苯甲醛发生aldol缩合反应, 合成了3个1,3-双[3-(取代苯基)丙烯酰基]苯衍生物1～3, 3个1,4-双[3-(取代苯基)丙烯酰基]苯衍生物4～6和2个中间体7, 8, 中间体7, 8再与含有羟基的苯甲醛发生aldol反应合成了3个1-[3-(4-羟基苯基)丙烯酰基]-4-[3-(取代苯基)丙烯酰基]苯衍生物9～11, 反应均能在2～6 d内完成, 操作和后处理简便. 以上11个新化合物均未见报道, 其结构经1H NMR, IR, MS和HRMS加以确证.     

Studies on the constituents of Broussonetia species X. Six new alkaloids from Broussonetia kazinoki Sieb.

Six new alkaloids, broussonetines W, X, M1, U1, J3, and J2 (1-6) were isolated from the branches of Broussonetia kazinoki SIEB. (Moraceae) as minor constituents. They were formulated as (2R,3R,4R,5R)-2-hydroxy-methyl-3,4-dihydroxy-5-17-(cyclohexy-2-on-1(6)-enyl)heptyllpyrrolidine (1), (2R,3S,4R,5R)-2-hydroxymethyl-3,4-dihydroxy-5-17-(cyclohexy-2-on-1(6)-enyl)heptyl]pyrrolidine-4-O-beta-D-glucopyranoside (2), (2R,3R,4R,5R)-2-hydroxymethyl-3,4-dihydroxy-5-[(9R)-9,13-dihydroxytridecyl]- pyrrolidine (3), (2S,3S,4S)-2-hydroxymethyl-3,4-dihydroxy-5-(10-oxo-13-hydroxytridecyl)-5- pyrroline (4), (2R)-2-[(IS,2S)-1,2-dihydroxy-8-1(2R,3R,4R,5R)-5-(2-hydroxymethyl-3,4-dihydroxy-1-acetylpyrrolidinyl)loctyl]piperidine (5), (2R)-2-[(1S,2S)-1,2-dihydroxy-8-[(2R,3R, 4R,5R)-5-(2-hydroxymethy]-3,4-dihydroxypyrrolidinyl)]octyl]piperidine (6).     

Chiral Cyclopentane-Based Mimics of D-myo-Inositol 1,4,5-Trisphosphate from D-Glucose

Two routes from D-glucose to chiral, ring-contracted analogs of the second messenger D-myo-inositol 1,4,5-trisphosphate are described. Methyl alpha-D-glucopyranoside was converted by an improved procedure into methyl 4,6-O-(p-methoxybenzylidene)-alpha-D-glucopyranoside (6) and thence into methyl 2-O-benzyl-3,4-bis-O-(p-methoxybenzyl)-alpha-D-gluco-hexodialdopyranoside (1,5) (14) in four steps. In the first ring-contraction method 14 was converted into methyl 2-O-benzyl-6,7-dideoxy-3,4-bis-O-(p-methoxybenzyl)-alpha-D-gluco-hept-6-enopyranoside (1,5) (15), which on sequential treatment with Cp(2)Zr(n-Bu)(2) followed by BF(3).Et(2)O afforded a mixture of (1R,2S,3S,4R,5S)-3-(benzyloxy)-4-hydroxy-1,2-bis[(p-methoxybenzyl)oxy]-5-vinylcyclopentane (16) and its 4S,5R diastereoisomer 17. Removal of the p-methoxybenzyl groups of 16 and subsequent phosphorylation and deprotection afforded the first target compound, (1R,2R,3S,4R,5S)-3-hydroxy-1,2,4-tris(phosphonooxy)-5-vinylcyclopentane (3). In the second route, intermediate 14 was subjected to SmI(2)-mediated ring contraction to give (1R,2S,3S,4R,5S)-3-(benzyloxy)-4-hydroxy-5-(hydroxymethyl)-1,2-bis[(p-methoxybenzyl)oxy]cyclopentane (20). Benzylation of 20 provided (1R,2S,3S,4R,5S)-3-(benzyloxy)-6-[(benzyloxy)methyl]-4-hydroxy-1,2-bis[(p-methoxybenzyl)oxy]cyclopentane (22) and (1R,2S,3S,4R,5S)-3,4-bis(benzyloxy)-5-(hydroxymethyl)-1,2-bis[(p-methoxybenzyl)oxy]cyclopentane (21), which were elaborated to the target trisphosphates (1R,2R,3S,4R,5S)-3-hydroxy-5-(hydroxymethyl)-1,2,4-tris(phosphonooxy)cyclopentane (4) and (1R,2S,3R,4R,5S)-1,2-dihydroxy-3,4-bis(phosphonooxy)-5-[(phosphonooxy)methyl]cyclopentane (5), respectively. Both 3 and 4 mobilized intracellular Ca(2+), but 4 was only a few fold less potent than D-myo-inositol 1,4,5-trisphosphate, demonstrating that effective mimics can be designed that do not bear a six-membered ring.     

Studies on the constituents of Broussonetia species. VII. Four new pyrrolidine alkaloids, broussonetines M, O, P, and Q, as inhibitors of glycosidase, from Broussonetia kazinoki SIEB

Four new pyrrolidine alkaloids, broussonetines M, O, P, and Q, were isolated from the branches of Broussonetia kazinoki SIEB, (Moraceae). Broussonetines M, O, P, and Q were formulated as (2R,3R,4R,5R)-2-hydroxymethyl-3,4-dihydroxy-5-[(10S)-10,13-dihydroxy-tri decyl]pyrrolidine (1), (2R,3R,4R,5R)-2-hydroxymethyl-3,4-dihydroxy-5-[(E)9-oxo-13-hydroxy-3- tridecenyl]pyrrolidine (2), (2R,3R,4R,5R)-2-hydroxymethyl-3,4-dihydroxy-5-[(E)10-oxo-13-hydroxy-3-++ +tridecenyl]pyrrolidine (3), and (2R,3S,4R,5R)-2-hydroxymethyl-3-hydroxy-4-(beta-D-glucopyranosyloxy++ +)-5-[10-oxo-13-(beta-D-glucopyranosyloxy)tridecyl]pyrrolidine (4) respectively, by spectroscopic and chemical methods. 1-4 inhibited beta-glucosidase, beta-galactosidase and beta-mannosidase.     

Selective reduction of 2-

[formula: see text] NaBH4 reduction of 2,5-bis[(4'-(n-alkoxy)benzoyl)oxy]benzaldehydes produces primarily the rearranged phenol, which does not generate liquid crystalline phases when laterally attached to a polymer backbone. Rearrangement is prevented by quenching the intermediate benzyl alkoxide with a weak acid. For example, 2,5-bis[(4'-(methoxy)benzoyl)oxy]benzaldehyde is selectively reduced to 2,5-bis[(4'-(methoxy)benzoyl)oxy]-benzyl alcohol with less than 5% intramolecular transesterification using 2-3 equiv of NaBH4 in the presence of 20-30 equiv of acetic acid (1:10 NaBH4/AcOH).     

C,O-dialkylation of Meldrum's acid: synthesis and reactivity of 1,3,7,7-tetramethyl-4H,10H-6,8,9-trioxa-2-thiabenz[f]azulen-5-one

Reaction of Meldrum's acid with 3,4-bis(chloromethyl)-2,5-dimethylthiophene (1) or 3,4-bis(bromomethyl)-2,5-dimethylthiophene (2) produces the kinetically favored C,O-dialkylation product, 1,3,7,7-tetramethyl-4H,10H-6,8,9-trioxa-2-thiabenz[f]azulen-5-one (4). Recrystallization of 4 from refluxing methanol results in the methanolysis product 5-(4-methoxymethyl-2,5-dimethylthiophen-3-ylmethyl)-2,2-dimethyl[1,3]dioxane-4,6-dione (5). Attempts to isomerize 4 to the thermodynamically favored C,C-dialkylation product, 1,3-dimethyl-5,6-dihydro-4H-cyclopenta[c]thiophene(2-spiro-5)2,2-dimethyl-4,6-dione (8), result in the formation of 1,3-dimethyl-7,8-dihydro-4H-thieno[3,4-c]oxepin-6-one (6). The transformation occurs via a retro-Diels-Alder elimination of acetone followed by hydrolysis and decarboxylation of the resulting ketene. The ketene is trapped by tert-butyl alcohol, furnishing 1,3-dimethyl-6-oxo-7,8-dihydro-4H,6H-thieno[3,4-c]oxepine-7-carboxylic acid tert-butyl ester (7). All compounds are characterized spectroscopically as well as by X-ray crystallography of products 4-7.     

Reaction of 3,4,6-trioxoalkanoic acid esters with 2,4-dinitrophenylhydrazine

Methyl 3,4,6-trioxoalkanoates (3,4-dihydroxy-6-oxo-2,4-alkadienoates) reacted with 2,4-dinitrophenylhydrazine to give methyl 3,6-bis[(2,4-dinitrophenyl)hydrazinylidene]-4-oxoalkanoates or methyl {5-alkyl-2-hydroxy-1-(2,4-dinitroanilino)-3-oxo-2,3-dihydro-1H-pyrrol-2-yl }acetates. Alkyl 3,6-bis[(2,4-dinitrophenyl) hydrazinylidene]-4-oxoalkanoates were also synthesized by reaction of disodium 1-alkoxy-1,6-dioxoalka-2,4-diene-3,4-diolates with 2,4-dinitrophenylhydrazine.     

Synthesis of (−)-(4R,5R)-4,5-bis[di-3′-(2′,6′-dimethoxypyridyl)phosphinomethyl]-2,2-dimethyl-1,3-dioxolane and its application in the Rh-catalyzed asymmetric hydrogenation reactions

The chiral ligand (−)-(4R,5R)-4,5-bis[di-3′-(2′,6′-dimethoxypyridyl)phosphinomethyl]-2,2-dimethyl-1,3-dioxolane 3 [(R,R)-Py*-DIOP] was synthesized via a key intermediate bis[3-(2,6-dimethoxypyridyl)]phosphine-borane 9. The asymmetric hydrogenation of prochiral olefins was investigated using a rhodium catalyst containing 3. For the hydrogenation of amidoacrylic acids, enols and itaconic acid, while the enantioselectivity of [Rh-(R,R)-Py*-DIOP] was similar to that of [Rh-(R,R)-DIOP] the absolute configurations of the products from the two catalyst systems were found to be opposite.     

In vitro cytotoxicity activity on several cancer cell lines of acridone alkaloids and N-phenylethyl-benzamide derivatives from Swinglea glutinosa (Bl.) Merr

The methanol extract from the stems and fruits of Swinglea glutinosa (Rutaceae) afforded 11 known acridone alkaloids and three N-phenylethyl-benzamide derivatives, glycocitrine-IV, 1,3,5-trihydroxy-4-methoxy-10-methyl-2,8-bis(3-methylbut-2-enyl)acridin-9(10H)-one, 1,3,5- trihydroxy-2,8-bis(3-methylbut-2-enyl)-10-methyl-9-acridone, citbrasine, citrusinine-II, citrusinine-I, 5-dihydroxyacronycine, pyranofoline, 3,4-dihydro-3,5,8-trihydroxy-6-methoxy-2,2,7-trimethyl-2H-pyrano[2,3-a]acridin-12(7H)-one, 2,3-dihydro-4,9-dihydroxy-2-(2-hydroxy-propan-2-yl)-11-methoxy-10-methylfuro[3,2-b]acridin-5(10H)-one, bis-5-hydroxyacronycine, N-(2-{4-[(3,7-dimethylocta-2,6-dien-1-yl)oxy]phenyl}ethyl)benzamide, N-(2-{4-[(3,7-dimethyl-4-acethyl-octa-2,6-dien-1-yl)oxy]phenyl}ethyl)benzamide, and severine acetate. All compounds isolated were examined for their activity against three cancer cell lines: human lung carcinoma (COR-L23), human breast adenocarcinoma (MCF7), human melanoma (C32), and normal human fetal lung cell line, MRC-5. The acridones tested exhibited weak cytotoxicity but the amides showed moderate nonselective cytotoxic activity.     

Reactions of 1,4-bis(tetrazole)benzenes: formation of long chain alkyl halides

The reactions of 1,4-bis[2-(tributylstannyl)tetrazol-5-yl]benzene with α,ω-dibromoalkanes were carried out in order to synthesise pendant alkyl halide derivatives of the parent bis-tetrazole. This led to the formation of several alkyl halide derivatives, substituted variously at N1 or N2 on the tetrazole ring. The crystal structures of 1,4-bis[(2-(4-bromobutyl)tetrazol-5-yl)]benzene (2-N,2-N′), 1,4-bis[(2-(4-bromobutyl)tetrazol-5-yl)]benzene (1-N,2-N′) and 1,4-bis[(2-(8-bromooctyl)tetrazol-5-yl)]benzene (2-N,2-N′) are reported. Further discussion involves the structure of 1,4-bis[2-(6-bromohexyl)-2H-tetrazol-5-yl]benzene (2-N,2-N′) previously reported.     

On the syntheses and some reactions of bis- and tris(methylthio)thiophenes

Reaction between various thienyllithium derivatives and dimethyl disulfide has been used for the preparation of 2,5-, 2,3-, and 3,4-bis(methylthio)thiophenes, as well as 2,3,4- and 2,3,5-tris(methylthio)thiophenes. Bromination of (methylthio)thiophenes with N-bromosuccinimide was found to be most convenient for the preparation of brominated (methylthio)thiophenes such as 3-bromo-2,5-bis(methylthio)- and 5-bromo-2,3-bis(methylthio)thiophene, 3,4-dibromo-2,5-bis(methylthio)-, 2,5-dibromo-3,4-bis(methylthio)- and 2,3-dibromo-4,5-bis(methylthio)thiophene as well as 3-bromo-2,4,5-tris(methylthio)thiophene. The reaction of methylthio substituted thienyllithium derivatives with methyl chloroformate was used for the syntheses of methyl methylthio substituted thiophenecarboxylates and using 1/3 of an equivalent for the direct preparation of methylthio substituted 3-thienylcarbinols as tris[2,4,5-tris(methylthio)-3-thienyl]carbinol.     

Three new megastigmane glucopyranosides from the Cardamine komarovii

Three new megastigmane glucopyranosides, komaroveside A [(3S,4R,5Z,7E)-3,4-dihydroxy-5,7-megastigmadien-9-one-3-O-β-D-glucopyranoside] (1), komaroveside B [(3S,4S,5S,6R,7E)-5,6-epoxy-3,4-dihydroxy-7-megastigmen-9-one-3-O-β-D-glucopyranoside] (2) and komaroveside C [(3S,4S,5S,6R,7E,9S)-5,6-epoxy-3,4,9-trihydroxy-7-megastigmen-3-O-β-D-glucopyranoside] (3) were isolated, together with eight known compounds, from Cardamine komarovii. The identification of these compounds and the elucidation of their structures were based on 1D- and 2D-NMR spectral data analysis. The isolated compounds were tested for their cytotoxicity against four human tumor cell lines (A549, SK-OV-3, SK-MEL-2, HCT15) in vitro using the sulforhodamine B bioassay.     

Highly diastereoselective alkylation of vicinal dianions of chiral succinic acid derivatives: a new general strategy to (R)-β-arylmethyl-γ-butyrolactones

The vicinal dianions derived from chiral succinic acid derivatives, 1,4-bis[(4R,5S)-3,4-dimethyl-2-oxo-5-phenylimidazolidin-1-yl]butane-1,4-dione and 1,4-bis[(4S,5R)-3,4-dimethyl-2-oxo-5-phenylimidazolidin-1-yl]butane-1,4-dione react with arylmethyl bromides with high diastereo- and regio-selectivity to provide the corresponding chiral α-arylmethylated succinic acid derivatives; the (R)-products are converted into (R)-β-arylmethyl-γ-butyrolactones and (R)-α-arylmethyl-γ-butyrolactones.     

Synthesis of indan-based unusual alpha-amino acid derivatives under phase-transfer catalysis conditions

Conformationally constrained cyclic alpha-amino acid derivatives were synthesized under solid-liquid phase-transfer catalysis conditions. This methodology involves the bis-alkylation of ethyl isocyanoacetate with various alpha,alpha'-dibromo-o-xylene derivatives [alpha,alpha'-dibromo-o-xylene 5, 2,3-bis(bromomethyl)-1, 4-dimethoxybenzene 6, 1,2-bis(bromomethyl)-4,5-dibromobenzene 7, 2, 3-bis(bromomethyl)naphthalene 8, 1,8-bis(bromomethyl)-naphthalene 9, 6,7-bis(bromomethyl)-2,2-dimethyl-1H-phenalene-1,3(2H)-dione 10, 2, 3-bis(bromomethyl)-1,4-anthraquinone 11, 6, 7-bis(bromomethyl)quinoxaline 12, 3,4-bis(bromomethyl)furan 13, 1,2, 4,5-tetrakis(bromomethyl)benzene 28, and hexakis(bromomethyl)benzene 30] using potassium carbonate as a base and tetrabutylammonium hydrogensulfate as a phase-transfer catalyst to give corresponding isonitrile derivatives, which upon hydrolysis with HCl in ethanol gave amino esters. Using this method electron-deficient as well as electron-rich and halogen-substituted indan-based alpha-amino acids were prepared. The preparation of bis-indan as well as tris-indan alpha-amino esters is also described.     

Synthesis and characterization of novel fluorophosphazene-derived cobaltacyclopentadienyl metallacycles: reagents for assembly of aryl-bridged fluorophosphazenes

Reaction of (beta-phenylethynyl)pentafluorocyclotriphosphazene, F5P3N3C identical with CPh, with in situ generated eta5-(MeOC(O)C5H4)Co(PPh3)2 resulted in the formation of two isomers of cobaltacyclopentadienylmetallacycles, (eta(5)-carbomethoxycyclopentadienyl)(triphenylphosphine)-2,5-bis(pentafluorocyclotriphosphazenyl)-3,4-diphenyl cobaltacyclopentadiene (1) and (eta5-carbomethoxycyclopentadienyl)(triphenylphosphine)-2,4-bis(pentafluorocyclotriphosphazenyl)-3,5-diphenyl cobaltacyclopentadiene (2), along with the sandwich compound [eta5-carbomethoxycyclopentadienyl]-[eta4-1,3-bis(pentafluorocyclotriphosphazenyl)-2,4-diphenylcyclobutadiene]cobalt (3). Formation of cobaltacyclopentadienylmetallacycles or cyclobutadienylmetallocene having two fluorophosphazene units on vicinal carbon atoms of the rings was not observed in this reaction. Reaction of 1 with diphenylacetylene resulted in the formation of a novel aryl-bridged fluorophosphazene, 1,4-bis(pentafluorocyclotriphosphazenyl)-2,3,5,6-tetraphenyl benzene (4), and the conversion of cobaltametallacycle to the sandwich compound, [eta5-(MeOC(O)C5H4]Co(eta4-C4Ph4) (5). Reaction of 1 with phenylacetylene resulted in the formation of aryl-bridged fluorophosphazene, 1,4-bis(pentafluorophosphazenyl)-2,3,5,-triphenyl benzene (6). New compounds 1-4 were structurally characterized. In compound 1, the two fluorophosphazene units were oriented in gauche form with respect to each other. However, in compounds 2 and 3, they were eclipsed to each other, and in compound 4, they were oriented anti to each other.     

Novel octulosonic acid derivatives in the composite Smallanthus sonchifolius

Two novel octulosonic acid derivatives with a 6,8-dioxabicyclo[3.2.1]octane skeleton that are major water-soluble phenolic compounds were found in the roots of Smallanthus sonchifolius. The structures of these compounds were determined to be (1R,2S,3S,4R,5S,7R)-4-hydroxy-7-hydroxymethyl-3-[3-(3,4-dihydroxyphenyl)-1-oxo-2-propenyloxy]-6,8-dioxabicyclo[3.2.1]octan-5-carboxylic acid (4-O-caffeoyl-2,7-anhydro-d-glycero-β-d-galacto-oct-2-ulopyranosonic acid) and (1R,2S,3R,4R,5S,7R)-2,4-dihydroxy-7-hydroxymethyl-2,3-bis[3-(3,4-dihydroxyphenyl)-1-oxo-2-propenyloxy]-6,8-dioxabicyclo[3.2.1]octan-5-carboxylic acid (4,5-di-O-caffeoyl-2,7-anhydro-d-glycero-β-d-galacto-oct-2-ulopyranosonic acid) by MS, NMR and CD spectral analyses.