ALBERT

Beschreibung: Two different synthetic concepts led to the formation of 17, 19 , and 29 , the first structural isomeric benzobis[1,3]oxathiins. Hetero- Diels Alder reactions of diethyl mesoxylate 14 and the open valence isomers of the benzobisthietes 12 and 18 yielded the linear benzobis[1,3]oxathiin 17 and its angular isomer 22 , respectively. The isomeric angular system 29 could be obtained by a twofold O , S -acetalization reaction of the dihydroxydisulfanyl compound 27 and acetone ( 28 ).

Beschreibung: A one-pot four-component synthesis of thieno[2,3- d ]pyrimidin-4-amines via sequential Gewald /cyclocondensation reactions is described. 2-Aminothiophene-3-carbonitriles obtained from the Gewald reaction between cyclic ketones, malononitrile, and sulfur underwent a condensation cyclization reaction with benzonitriles under solvent-free conditions to afford the title compounds in excellent yields.

Beschreibung: Bioassay-guided fractionation of an AcOEt-soluble fraction of the liquid fermentation of an endophytic fungus Hypoxylon sp. BCRC 12F0687 associated with the root of Taiwanese Ilex formosana (Aquifoliaceae) resulted in the isolation of two new compounds, i.e. , one benzenoid, hypoxyphenone ( 1 ), and one azaphilone derivative, hypoillexidiol ( 2 ), two metabolites isolated for the first time from natural source, (−)-(3 S )-3-hydroxy-3-methyloxindole ( 3 ) and (+)-vermelone ( 4 ), along with twelve previously identified compounds, 5 – 16 . Their structures were determined through in-depth spectroscopic and mass-spectrometric analyses. The effects of some isolates on the inhibition of NO and IL-6 production in lipopolysaccharide-activated RAW 264.7 murine macrophages were evaluated. Of the isolates, 2 and 3 exhibited potent anti-NO production activity, with IC 50 values of 17.5±1.8 and 24.7±1.6 μ M , respectively, compared to that of quercetin, an iNOS inhibitor with an IC 50 value of 35.9±1.7 μ M . Compounds 2, 4, 5 , and 12 also showed moderate inhibition of IL-6 production, with IC 50 values ranging from 27.2±1.8 to 35.3±5.8 μ M . This is the first report on an oxindole metabolite from the genus Hypoxylon.

Beschreibung: One novel p -terphenyl compound, named vialisyl A ( 1 ), was isolated from the fruiting bodies of Thelephora vialis , together with six known compounds, ganbajunin B ( 2 ), phenylacetic acid ( 3 ), a mixture of ganbajunins D ( 4 ) and E ( 5 ), and vialinins A ( 6 ) and B ( 7 ). Their structures were established by extensive analysis of spectroscopic data (including 1 H- and 13 C-NMR, HSQC, HMBC, 2D-INADEQUATE) as well as by comparison with literature reports.

Beschreibung: This work explores the self-disproportionation of enantiomers (SDE) via achiral, gravity-driven column chromatography as typically used in laboratory settings for the purpose of enantiomeric enrichment using N -(1-phenylethyl)acetamide (PEA) as a case study. The major finding of this work is the very large magnitude of the SDE for PEA across a variety of conditions and broad range of starting ee values, thereby facilitating a simple, reliable, and predictable means of obtaining enantiomerically pure samples. For example, starting with a sample of PEA of ee as low as 28%, a single column run yielded an enantiomerically pure sample (〉99.9% ee) from the first fractions and a significantly enantiomerically depleted sample (〈17% ee) from the final fractions. An assessment of SDE via achiral, gravity-driven column chromatography was also rendered with regard to the differing objectives that workers might target – a large magnitude of the SDE, obtaining an optimum sample of desired ee, or preparative-scale separation of the excess enantiomer. Overall, it can be considered that the SDE phenomenon via achiral, gravity-driven column chromatography – readily applicable in the usual laboratory settings – is a simple and convenient method for enantiomeric enrichment with a high degree of proficiency. Advantages of SDE via achiral, gravity-driven column chromatography over conventional fractional recrystallization for the enantiomeric enrichment of amides/amines, and applicable also to many other classes of compounds as well, are discussed.

Beschreibung: Four possible stereoisomers of a model compound of highly O-bearing bisabolane sesquiterpenes were synthesized and their NMR spectra were compared. Starting from isopulegol, allylic oxidation and Grignard reaction afforded a mixture of alcohols at C(8), which was separated. After metathesis reaction, both α - and β -epoxides were obtained via non-stereoselective epoxidation, while VO(O i Pr) 3 -catalyzed epoxidation afforded a single diastereoisomer selectively. NMR Spectra of twelve synthesized compounds, four stereoisomers of acetates, isobutyrates, and tiglates, were measured. A difference between C(8 α )- and C(8 β )-acyloxy isomers was observed in the δ -values of H C(8) in CDCl 3 . Within the 8 β -acyloxy compounds, the α - and the β -epoxides were distinguished by either the J -value of H C(8) or the chemical shift of CH 2 (9). Within the 8 α -acyloxy compounds, two epoxide isomers were distinguished by the J -value of H C(10) in C 6 D 6 or in CD 3 OD.

Beschreibung: Two new aryl-tetralin lignan glycosides, linderanosides A and B ( 1 and 2 , resp.), and a new dihydrobenzofuran neolignan glycoside, linderanoside C ( 3 ), together with five known lignan derivatives ( 4 – 8 ) were isolated from the trunk of Lindera glauca. The structures of these new compounds were determined through spectroscopic analyses, including extensive 2D-NMR data and acid hydrolysis. The absolute configurations of the compounds were clarified by circular dichroism (CD) spectroscopic studies. Compounds 1 – 8 were evaluated for their cytotoxicity against A549 (non-small cell lung adenocarcinoma), SK-OV-3 (ovarian cancer cells), A498 (human kidney epithelial cells), and HCT-15 (colon cancer cells) human tumor cell lines using sulforhodamine B assays in vitro.

Beschreibung: A one-pot three-component reaction of ethyl acetoacetate, AcONH 4 , and different aldehydes has been successfully performed in the presence of ionic liquids (ILs) possessing a (MeO) 2 PO counterion. The impact of electronic and steric effects of the substituents of aromatic aldehydes, as well as the influence of different anions of ILs on the product yield, have been investigated. The application of dimethyl phosphate ILs in the synthesis of Hantzsch 1,4-dihydropyridines presents a simple method for obtaining structurally diverse products in moderate to high yields without using any additional catalyst.

Beschreibung: Four new iridoids, incarvoids D–F ( 1 – 3 , resp.) and incarvoid B 9- O - β - D -glucopyranoside ( 4 ), and one new monoterpenoid, argutoid B ( 5 ), along with 14 known compounds, were isolated from Rhododendron microphyton. Their structures were established by comprehensive 1D- and 2D-NMR spectroscopic analysis.

Beschreibung: The straightforward synthesis of a novel benzocyclotrimer is herein presented. The syn -product is characterized by an electron-rich rigid aromatic cavity and a flexible electron-rich aromatic pocket. The molecule is a potential scaffold for supramolecular applications.

Beschreibung: Systematic phytochemical investigation on heat-processed Epimedium koreanum led to the isolation of 13 flavonoids, including five new prenyl-flavonol glycosides, koreanosides A–E ( 1 – 5 , resp.). Their structures were elucidated on the basis of detailed analysis of the 1D- and 2D-NMR spectroscopic data and chemical reactions. Apigenin ( 11 ) exhibited moderate anti-HIV-1 activity with an EC 50 value of 12.8±3.27 μg/ml.

Beschreibung: A stereospecific synthesis of (2 S ) - 3-(2,4,5-trifluorophenyl)propane-1,2-diol from D -mannitol has been developed. The reaction of 2,3- O -isopropylidene- D -glyceraldehyde with 2,4,5-trifluorophenylmagnesium bromide gave [(4 R )-2,2-dimethyl-1,3-dioxolan-4-yl](2,4,5-trifluorophenyl)methanol in 65% yield as a mixture of diastereoisomers (1 : 1). The Ph 3 P catalyzed reaction of the latter with C 2 Cl 6 followed by reduction with Pd/C-catalyzed hydrogenation gave (2 S )-3-(2,4,5-trifluorophenyl)propane-1,2-diol with 〉99% ee and 65% yield.

Beschreibung: Total syntheses of iso-cladospolide B ( 1 ) and the 12-membered macrolactone (6 S ,12 R )-6-hydroxy-12-methyloxacyclododecane-2,5-dione ( 2 ), a non-natural product, were achieved from a common intermediate starting from commercially available 1,9-nonane diol.

Beschreibung: ‘One-pot’ AcONa-catalyzed transformation of salicylaldehydes, malononitrile and 4-hydroxy-1-methylquinolin-2(1 H )-one in the presence of a minimal quantity of EtOH results in fast (3 min) and efficient formation of unknown 2-amino-4-(2-hydroxyaryl)-6-methyl-5-oxo-5,6-dihydro-4 H -pyrano[3,2- c ]quinoline-3-carbonitriles in 85–98% yields, which are potential pharmaceutical agents for treating disorders responsive to the induction of apoptosis, antiproliferation, or vascular disruption. This efficient ‘on-solvent’ approach to the 4 H -pyrano[3,2- c ]quinoline scaffold represents a novel synthetic concept for multicomponent reaction (MCR) strategy and allows to combine the synthetic virtues of conventional MCR with ecological benefits and convenience of facile ‘on-solvent’ procedure.

Beschreibung: A phytochemical investigation of the BuOH-soluble fraction of the EtOH extract from the stems of Glycosmis pentaphylla resulted in the isolation of three new phenolic glycosides, glycopentosides D–F ( 1 – 3 , resp.). Their structures were determined by using spectroscopic analysis including UV, 1 H- and 13 C-NMR, DEPT, COSY, ROESY, HMBC, HSQC, HR-ESI-MS, and acid hydrolysis.

Beschreibung: A new and facile method for the preparation of single-walled carbon nanotubes (SWCNTs) decorated with Cu nanoparticles (CuNPs) formed on a double-stranded DNA template in aqueous solution has been developed. A specially designed synthetic DNA sequence, containing a single-stranded domain for the dispersion of carbon nanotubes and double-stranded domains for the selective growth of CuNPs, was utilized. The final SWCNT/CuNP hybrids were characterized using fluorescence spectroscopy and transmission electron microscopy. The analyses clearly demonstrated the selective formation of uniform CuNPs on the carbon nanotube scaffold.

Beschreibung: Carbene transfer to appropriate substrates is a highly versatile tool for the construction of carbon frameworks with increased functional and structural complexity. In this study, some novel cyclopropane derivatives were synthesized via carbenoid reactions and their further reactivities were investigated. (1 E )-Buta-1,3-dien-1-yl acetate was reacted with four different diazocarbonyl compounds, ethyl diazoacetate, dimethyl diazomalonate, 1-diazo-1-phenylpropan-2-one, and methyl (3 E )-2-diazo-4-phenylbut-3-enoate, in the presence of two catalysts. All synthesized substituted cyclopropanes were obtained chemoselectively with respect to less-hindered C C bonds. Under the applied conditions, while cyclopropanes 7a and 7d underwent further reactions, cyclopropanes 7b and 7c were stable enough. Cyclopropanes 7a and an additional equivalent of ethyl diazoacetate yielded polyfunctionalized cyclohexenes. Cyclopropanes from methyl (3 E )-2-diazo-4-phenylbut-3-enoate yielded polyfunctionalyzed cycloheptadiene isomers by Cope rearrangement.

Beschreibung: The first concise synthesis of the bidesmosidic oleanolic acid saponins 1 – 3 isolated from Fadogia ancylantha (Makoni tea) have been accomplished through a ‘one-pot sequential glycosylation’ strategy with two glycosyl 1-(trichloroacetimidate)s as glycosyl donors. The synthesized natural products 1 – 3 were then evaluated for their inhibitory activities against α -glucosidase, α -amylase, and lipase. Among the assayed compounds 1 – 3 , compound 1 showed strong α -glucosidase and α -amylase inhibition, with IC 50 values of 160 and 180 μ M , respectively. Moreover, compounds 2 and 3 showed strong inhibition against α -glucosidase and lipase, with the respective IC 50 values of 170 and 190 μ M , and 190 and 200 μ M .

Beschreibung: One new cyclopropyl-triterpenoid ( 1 ), along with four known constituents including octacosan-1-ol ( 2 ), pentacosanoic acid ( 3 ), β -sitosterol ( 4 ), and β -sitosterol 3- O - β - D -glucopyranoside ( 5 ) were isolated from the aerial parts of Ochradenus arabicus for the first time. These compounds were isolated by repeated column chromatography followed by further purification through recycling HPLC. The structure of the new secondary metabolite 1 was established on the basis of UV, IR, 1D- ( 1 H- and 13 C-) and 2D-NMR (HMBC and HSQC), and MS spectral data. The molecular mass was determined by HR-MS, and hence the molecular formula was deduced. The configurations of stereogenic centers in the molecule were assigned by NOESY experiments, along with biogenetic considerations. The structures of the known compounds were confirmed by comparison of their physical and spectroscopic data with those reported in literature.

Beschreibung: Two novel organic amide alkaloids, 4-[( E )- p -coumaroylamino]butan-1-ol ( 1 ) and 4-[( Z )- p -coumaroylamino]butan-1-ol ( 2 ), together with a rare pyridoindole alkaloid, hippophamide ( 3 ), were isolated from the seed residue of Hippophae rhamnoides Linn . subsp. sinensis Rousi . Their structures were determined by spectroscopic means. The results show that compounds 1 and 2 are ( E / Z ) - isomers, compound 3 , a pyridoindole alkaloid concerted with γ -lactam ring.

Beschreibung: An efficient multi-component synthesis of highly functionalized 2,2′-bifurans and 2-(thiophen-2-yl)furans is described. A mixture of furan- or thiophene-2-carbonyl chloride, an isocyanide, and a dialkyl acetylenedicarboxylate undergoes a smooth addition reaction in dry CH 2 Cl 2 at ambient temperature to produce 2-amino-5-(4-chlorofuran-2-yl)furan-3,4-dicarboxylates and 2-amino-5-(4-chlorothiophen-2-yl)furan-3,4-dicarboxylates. A single-crystal X-ray-analysis of a derivative conclusively confirms the structure of these 2,2′-bifurans and 2-(thiophen-2-yl)furans. A novel electrophilic aromatic substitution reaction can justify the formation of the Cl-substituted furan or thiophene rings.

Beschreibung: One new lactone, cyclopentanepyrone A ( 1 ), and two new monoterpenoids, gardeterpenone A ( 2 ) and jasminoside V ( 3 ), were isolated from the fruits of Gardenia jasminoides var. radicans , along with four known monoterpenoids, 4 – 7 , which were isolated from this plant for the first time. The structures of the isolates were elucidated by extensive spectroscopic studies, including UV, IR, 1D- and 2D-NMR, ESI-MS, HR-ESI-MS, and CD experiments.

Beschreibung: A concise and facile method for the synthesis of heterocyclic compounds with N O tether was introduced. The two important steps of the synthesis are a Mitsunobu reaction and C H activation. The Mitsunobu protocol allows to form the N O moiety in the molecule, while subsequent C H activation leads to heterocycles.

Beschreibung: New calixarene-based dendrimers, containing calix[4]arene as the core and different generations of Fréchet -type poly(benzyl ether) dendrons as building blocks, which possess either Br-atoms or COO t Bu groups at their surface were synthesized and presented herein for the first time. The new calix[4]arene-cored dendritic macromolecules were fully characterized and found to prefer strictly the cone conformation.

Beschreibung: 3-Alkyl-6-amino-1,4-dihydro-4-{[(1,2,3-triazol-4-yl)methoxy]phenyl}pyrano[2,3- c ]pyrazole-5-carbonitrile derivatives were synthesized through a one-pot five-component condensation reaction.

Beschreibung: Three new pentacyclic triterpenoids, named centellasaponins G, H, and F ( 1 – 3 , resp.), together with four known compounds, 4 – 7 , were isolated from the whole plants of Centella asiatica. Their structures were elucidated on the basis of chemical and spectral analysis, including 1D- and 2D-NMR and HR-MS experiments, and by comparison with literature data.

Beschreibung: Three novel limonoids, 2,3-dideacetylxyloccensin S ( 1 ), 30-deacetylxyloccensin W ( 2 ), and 7-hydroxy-21 β -methoxy-3-oxo-24,25,26,27-tetranortirucalla-1,14-diene-23(21)-lactone ( 3 ), were isolated from the seeds of the Chinese mangrove, Xylocarpus granatum. The structures were elucidated on the basis of 1D- and 2D-NMR (including 1 H- and 13 C-NMR, DEPT, 1 H, 1 H-COSY, HSQC, HMBC, and NOESY) data and confirmed by HR-MS.

Beschreibung: A new dimeric secoiridoid glycoside, trivially named oleferrugine B ( 1 ), has been isolated from the AcOEt-soluble part of the MeOH extract of leaves of Olea ferruginea Royle . The structure of the isolated compound was established on the basis of ESI-MS fragmentation patterns, and 1D- and 2D-NMR techniques, including 1 H- and 13 C-NMR, HSQC, 1 H, 1 H-COSY, HMBC, and NOESY experiments, and by comparison with literature data.

Beschreibung: Two new biflavonoids, 14″- O -methyldihydrodaphnodorin B ( 1 ) and 14″- O -methyldaphnodorin J ( 2 ), along with 16 known compounds, i.e. , dihydrodaphnodorin B ( 3 ), daphnodorin J ( 4 ), 3″-epidihydrodaphnodorin B ( 5 ), daphnodorin B ( 6 ), neochamaejasmin B ( 7 ), sikokianin B ( 8 ), (−)-syringaresinol ( 9 ), (−)-syringaresinol 4- O - β - D -glucopyranoside ( 10 ), (+)-nortrachelogenin ( 11 ), (−)-lariciresinol ( 12 ), (−)-pinoresinol ( 13 ), syringin ( 14 ), syringinoside ( 15 ), daphnoretin ( 16 ), phorbol 13-acetate ( 17 ), and methyl paraben ( 18 ) were isolated from the roots of Diplomorpha canescens ( Meisn.) C.A. Meyer . The structures were determined on the basis of spectroscopic data.

Beschreibung: By further chemical investigation of South China Sea gorgonian Menella kanisa , five new highly oxygenated guaiane lactones, menverins H–L ( 1 – 5 , resp.), were obtained. Their structures were established by employing spectroscopic methods, computer modeling, and comparison of their data with those of related metabolites.

Beschreibung: Two new diterpenoids, named paecilomycine A ( 1 ) and paecilomycine B ( 2 ), including a novel skeleton with a five-membered lactone ring, together with three known labdane diterpenoids, rel -(1 R ,3 S ,4a S ,5 R ,8a S )-5-[(3 E )-4-carboxy-3-methylbut-3-en-1-yl]decahydro-3-hydroxy-1,4a-dimethyl-6-methylidenenaphthalene-1-carboxylic acid ( 3 ), botryosphaerin E ( 4 ), and agathic acid ( 5 ), were isolated from solid culture of the insect pathogenic fungi strain Paecilomyces sp. The structures of all compounds were established on the basis of comprehensive spectroscopic studies. The relative configurations of 1 and 2 were determined by single-crystal X-ray diffraction analyses.

Beschreibung: Using various chromatographic methods, three new megastigmane glycosides, docynicasides A-C ( 1 – 3 ) and ten known, (6 S ,9 R )-vomifoliol 9- O - β -D-xylopyranosyl-(1″ 6′)- O - β -D-glucopyranoside ( 4 ), hyperin ( 5 ), quercitrin ( 6 ), quercetin 3- α -L-arabinofuranoside ( 7 ), naringenin 7- O - β -D-glucopyranoside ( 8 ), phloridzin ( 9 ), phloretin 2′- O - β -D-xylopyranosyl-(1 6)- β -D-glucopyranoside ( 10 ), pinosylvin 3- O - β -D-glucopyranoside ( 11 ), tormentic acid ( 12 ), and chlorogenic acid methyl ester ( 13 ) were isolated from the fruits of Docynia indica . Their chemical structures were elucidated by physical and chemical methods. All the isolated compounds were evaluated for the inhibitory activity on nitric oxide production in LPS-stimulated BV2 cells. As the results, compounds 3 – 5 showed significant inhibitory activity on LPS-stimulated NO production in BV2 cells with the IC 50 values ranging from 21.0 to 29.3 μM. This article is protected by copyright. All rights reserved.

Beschreibung: For the preparation of well-defined water-soluble C 60 polymers, several C 60 -PEG conjugates were prepared from a C 60 bis-carboxylic acid derivative and mono-disperse NH 2 -PEGs (NH 2 -EG n , n = 4 - 36) via amide conjugation. When the relatively long PEGs (EG n , n ≥ 12) were employed, the C 60 -PEG conjugates became completely water-soluble by forming micelle-like structure shown by the data of surface tension, DLS, and cryoTEM. Interestingly, these water-soluble C 60 -PEG conjugates (C 60 (EG n ) 2, n = 12 - 36) showed reversible thermoresponse to form larger aggregates (c.a. 1 μ m by DLS) at higher temperatures. The temperature for the aggregation was related to the lengths of PEGs attached to C 60 ; 29 °C (C 60 (EG n ) 2 , n = 12), 51 °C (n = 20), and 72 °C (n = 36). This thermoresponse was speculated to occur by dehydration of well-organized PEG chains in the micelle-type structure of mono-disperse C 60 -PEG caused by gauche -to- anti conformational change of PEG anchors. This thermoresponse of well-defined amphiphilic C 60 -PEG conjugates indicates potential applications in areas such as temperature sensors and thermoresponsive materials. This article is protected by copyright. All rights reserved.

Beschreibung: Suzuki-Miyaura coupling of aroyl chlorides and arylboronic acids has been carried out efficiently in the presence of Pd(II)-salen@MWCNTs as an air-moisture stable precatalyst. The influence of various parameters such as solvent, temperature, and base on the reaction system were studied. Furthermore, the catalyst can be easily recovered quantitatively by simple filtration and reused for three consecutive runs without significant loss of its activity This article is protected by copyright. All rights reserved.

Beschreibung: Here we asked the question whether fluorescence labelled small molecule agonists of the α 7 nicotinic acetylcholine receptor (nAChR) might be identified to enhance receptor studies. Enantiomerically pure 3-amino-quinuclidines appended with fluorophores at the 3-amino group were synthesized and tested by electrophysiology on human α 7 nAChR in Xenopus oocytes, uncovering ( R )-4 and ( R )-9 as the first examples of fluorescent α 7 nAChR agonists. These molecules elegantly incorporate the fluorescent reporter group as part of the pharmacophore itself and provide a new class of tool compounds for the study of these ligand gated ion channels. This article is protected by copyright. All rights reserved.

Beschreibung: Low-coordinate organoCr(III) complexes supported by the silylamido ligand –N(SiMe 3 )DIPP, (DIPP = 2,6-diisopropylphenyl) are ethylene polymerization catalyst precursors without the need of additional co-catalyst. The reaction of CrCl 3 (THF) 3 with 3 or 2 equiv. of LiN(SiMe 3 )DIPP yields either a four-membered cyclometalated Cr complex or Cr[N(SiMe 3 )DIPP] 2 Cl, respectively, with no trace of Cr[N(SiMe 3 )DIPP] 3 . Addition of 1 equiv. of LiN(SiMe 3 )DIPP to Cr[N(SiMe 3 )DIPP] 2 Cl also leads to the four-membered metallacycle, which upon heating transforms to a new six-membered Cr metallacycle, likely via a σ -bond metathesis step. Cr[N(SiMe 3 )DIPP] 2 Cl can be readily converted to bis(amido)Cr(III) vinyl and alkyl complexes Cr[N(SiMe 3 )DIPP] 2 R (R = vinyl, benzyl, methyl). All of these structurally characterized low-coordinate Cr(III) complexes with a Cr–C bond initiate the polymerization of ethylene in the absence activators or cocatalysts, producing ultra-high molecular weight polyethylene. This article is protected by copyright. All rights reserved.

Beschreibung: Acrolein, methacrolein, methylvinylketone, ethylvinylketone, 3-methyl-3-en-2-one, and divinylketone were coordinated to a cationic cyclopentadienyl ruthenium(II) Lewis acid incorporating the electron-poor bidentate BIPHOP–F ligand. Analysis by NOESY and ROESY NMR techniques allowed the determination of conformations of enals and enones present in solution in CD 2 Cl 2 . The results were compared to solid state structures and to the facial selectivities of catalytic asymmetric Diels–Alder reactions with cyclopentadiene. X-Ray structures of four Ru-enal and Ru-enone complexes show the α , β -unsaturated carbonyl compounds to adopt an anti-s-trans conformation. In solution, enals assume both anti-s-trans and anti-s-cis conformations. An additional conformation, syn-s-trans , is present in enone complexes. Enantioface selectivity in the cycloaddition reactions differs for enals and enones. Reaction products indicate enals to react exclusively in the anti-s-trans conformation whereas with enones, the major product results from the syn-s-trans conformation. The alkene in s-cis conformations, while present in solution, is shielded and cannot undergo cycloaddition. A syn-s-trans conformation is found in the solid state of the bulky 6,6-dimethyl cyclohexanone-Ru(II) complex. The X-ray structure of divinyl ketone is unique in that the Ru(II) center binds the enone via a η 2 bond to one of the alkene moieties. In solution coordination to Ru-carbonyl oxygen is adopted. A comparison of facial preference is also made to the corresponding indenyl Lewis acids. This article is protected by copyright. All rights reserved.

Beschreibung: One of the compounds suggested to be responsible for the cyanobacterial dominance over competing green algae is identified. Evidence is provided on the molecular, chemical level that the iron chelator anachelin from the cyanobacterium Anabaena cylindrica promotes both the growth of cyanobacteria and reduces the growth of competing chlorophytes. These results illustrate a molecular strategy of addressing two challenges (nutrient availability and algal competition) by one molecule. Such strategies could be implied in harmful algal blooms in marine and freshwater environments. This article is protected by copyright. All rights reserved.

Beschreibung: Three new compounds, trilepisflavene (1) , trilepisdepsidone (2) and daturadiol stearate (3) , together with nine known compounds, 2-hydroxy-4-[(4-hydroxy-2-methoxy-6-methylbenzoyl)oxy]-6-methylbenzoic acid (4) , lichexanthone (5) , naringenin (6) , 3’,4’,5,7-tetrahydroxyflavanone (7) , 2-hydroxybenzoic acid (8) , methyl 2,4-dihydroxy-6-methylbenzoate (9) , β -amyrine (10) , eurothridiol palmitate (11) , and β -sitosterol (12) , were isolated from the AcOEt extract of the twigs and the roots of Trilepisium madagascariense . Acetylation of eurothridiol palmitate was carried out and a new acetylated derivative (13) obtained. The structures of the isolated and acetylated compounds were elucidated on the basis of spectroscopic analysis. Antimicrobial activity of all these compounds was evaluated using Mueller Hinton Broth (MHB) and Mueller Hinton Agar (MHA) method. Trilepisdepsidone , 2-hydroxy-4-[(4-hydroxy-2-methoxy-6-methylbenzoyl)oxy]-6-methylbenzoic acid, 3’,4’,5,7-tetrahydroxyflavanone and naringenin exhibited moderate to weak antimicrobial activity. This article is protected by copyright. All rights reserved.

Beschreibung: The stereoselective total synthesis of (+)-petromyroxol, isolated from the water conditioned with larval sea lampreyhas has been accomplished employing the cross metathesis, tandem Sharpless asymmetric dihydroxylation/S N 2 cyclization and regioselective ring opening of epoxide as the key steps. This article is protected by copyright. All rights reserved.

Beschreibung: In the presence of ammonium iodide as catalyst and m -chloroperbenzoic acid as oxidant, the Se–Se bond cleavage of diselenides undergoes smoothly. The in situ generated reactive electrophilic selenium species reacts with alkenes quickly and a series of β -hydroxy selenides are prepared in good yields. This new catalytic method for synthesis of β -hydroxy selenides is a stereospecific anti addition, which occurs with a Markovnikov orientation. This article is protected by copyright. All rights reserved.

Beschreibung: Alkenes possessing four different carbon-linked substituents are the main structural motif of many biologically active compounds. The derivatives of (2 E )-3-(3-methoxyphenyl)-2-methylpent-2-enoic acid (( E )-2c) are suitable precursors for the synthesis of Tapentadol , a novel centrally acting analgesic. It was found that the Ni-carbometallation reaction of disubstituted alkyne 8 with CO 2 and an Et 2 Zn allows for efficient and practical preparation of ( E )-2c as a single ( E )-regioisomer in 89% of isolated yield. The influence of the size of the aliphatic substituent of alkyne and the steric hindrance of the organozinc reagent on stereochemical course of the carbometallation reaction was evaluated. Finally, air stable Ni(dme)Cl 2 was proposed as an alternative to widely used Ni(cod) 2 catalyst. This article is protected by copyright. All rights reserved.

Beschreibung: Under mild conditions, an efficient and rapid S-allylation of thiols with cyclic MBH bromides with no need of a transition metal-catalyst or an expensive additive, is described herein. Treatment of the MBH bromides with various thiols or ethane-1,2-dithiol in the presence of Et 3 N, regioselectively affords the corresponding 2-alkyl(or aryl) thiomethyl-2-cyclohexenones or the perhydro benzo[1,4]dithiepinone, respectively, in moderate to good yields (40-73%). The reaction is rapid and carried out in THF at room temperature. This article is protected by copyright. All rights reserved.

Beschreibung: A succession of new isolongifolenone oxime derivatives have been designed and synthesized. The structures of these compounds were identified by IR, 1 H NMR, 13 C NMR, mass spectra and elemental analysis. The bioassays of antibacterial, antifungal and insecticidal activity were carried out. The in vitro antibacterial and antifungal activities were evaluated by the disk diffusion method, and the minimum inhibitory concentration (MIC) was determined by microdilution method. While insecticidal activity was tested by spraying method or straw impregnation method. The results of bioassays showed that compound 3f was more active in resisting all the tested bacterial and fungus when in comparison to the standard drug amoxicillin at the lowest concentration of 31.3 μ g/mL. Compound 4 synthesized by beckmann rearrangement reaction of isolongifone oxime, exerted moderate insecticidal activity against soybean aphid. Furthermore, Compound 3m exhibited more effective in killing armyworms than the standard drug flucycloxuron at the concentration of 0.5 mg/L. This article is protected by copyright. All rights reserved.

Beschreibung: Two new indole alkaloid derivatives (1, 2), together with six known indole alkaloids (3-8) were isolated from the 70% ethanolic-H 2 O extract of the stem of Nauclea officinalis . Their structures were determined on the basis of extensive analyses of spectroscopic data (IR, MS, 1D and 2D NMR). All the isolates were evaluated for their anti-inflammatory activities on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW264.7, and all the compounds showed significant inhibitory activities with IC 50 values of 0.82, 6.45, 9.75, 1.34, 3.40, 2.69, 1.58, and 1.96 μM, compared to the positive drug control group aminoguanidine with IC 50 value of 1.80 μM, compound 1 had the most significant activity, especially. This article is protected by copyright. All rights reserved.

Beschreibung: Irisin is a recently discovered protein hormone with a conserved sequence among vertebrates and with putative functions in the regulation of adipose tissue and bone metabolism. We report the first chemical synthesis using two sequential KAHA ligations to give milligram quantities of unlabeled and fluorescence labeled irisin protein. The synthetic proteins were utilized in cell binding assays, which indicated the expected binding characteristics to stromal cells of white adipose tissue. These studies strongly imply the presence of a specific irisin receptor and provide a path to its identification with synthetic irisin. This article is protected by copyright. All rights reserved.

Beschreibung: While lentil ( Lens culinaris ) seeds are phytochemically well characterized, very little is known about secondary metabolites from lentil roots. Our research on lentil roots led to isolation of five phenolic compounds and five group B soyasaponins. Their structures were established using NMR spectroscopy and mass spectrometry. Four phenolics have not been hitherto described in the literature: 4- O -β-D-glucopyranosyl-2-methoxybenzoic acid, (α S )-4,4′-di- O -β-D-glucopyranosyl-α,2′-dihydroxydihydrochalcone, (α S )-4′- O -β-D-glucopyranosyl-α,2′,4-trihydroxydihydrochalcone and keto -2-hydroxy-glycitein. The DPPH ∙ radical scavenging activity of the purified phenolic compounds was additionally evaluated. This article is protected by copyright. All rights reserved.

Beschreibung: The occurrence of bifurcate hydrogen bonds C A r -H∙∙∙O=C in the structure of (diaryl)-tetrahydrofuranones was experimentally demonstrated using different methods and techniques. The consistent increasing spin-spin coupling constants 1 J C -H of the ortho -protons and low field shift of v C =O in IR spectra of 2,2-(diaryl)tetrahydrofuran-3( 2H )-ones relative to their 5,5-diaryl counterparts, as well as pronounced dependence of the ortho -C-H protons chemical shifts on the temperature and solvent polarity along with X-ray diffraction analysis data unambiguously point to the existence of weak C A r -H∙∙∙O=C hydrogen bonds in these molecules. This article is protected by copyright. All rights reserved.

Beschreibung: Valorization of CO 2 , an abundant C1 synthon, into platform chemicals is of growing interest. In this context a key reaction is the cycloaddition of CO 2 to epoxides to form carbonates. A series of organocatalysts for this reaction, based on imidazolium salts modified with a styrene functional group and a second variable functional group, were prepared and characterized. Both the ionic salts, and ionic polymers derived from the salts, were evaluated in this reaction. In general, the monomers perform slightly better than the polymers, however, the latter are considerably more convenient to use. Of the catalysts studied, the ionic polystyrene imidazolium salt with an ammonium functionality shows highest activity, tolerates a range of epoxides, and can be recycled multiple times without loss of activity. This article is protected by copyright. All rights reserved.

Beschreibung: Two new C-glucosyl chromones named gileadensides A ( 1 ) and B ( 2 ) were isolated from the resin of Commiphora gileadensis (L.) C. Chr. The structures of the two new natural products were elucidated based on 1D ( 1 H and 13 C NMR) and 2D NMR (COSY, HSQC, and HMBC) spectroscopic techniques and mass spectromentry (ESIMS). Gileadensides A ( 1 ) and B ( 2 ) were evaluated for their anticancer activity and induced a 76.4% and 70.5% growth inhibition of the breast cancer cell line (MDA MB231) at a concentration of 100 μ M. Both compounds were also evaluated for their DPPH antioxidant, urease enzyme and α -glucosidase enzyme inhibition activities. Gileadensides A ( 1 ) and B ( 2 ) displayed good urease enzyme inhibition activities (62 and 55% respectively) as well as antioxidant activity in which gileadenside A ( 1 ) had a value of 60% inhibition while gileadenside B ( 2 ) demonstrated a more potent antioxidant activity with 80% inhibition. This article is protected by copyright. All rights reserved.

Beschreibung: The general ‘on-solvent’ PASE approach was found to medicinally relevant 4 H ,5 H -pyrano[4,3- b ]pyran-5-one and 4,6-dihydro-5 H -pyrano[3,2- c ]pyridine-5-one scaffolds. Ammonium acetate catalyzed multicomponent reaction of aldehydes and two different C-H acids in small amount of ethanol results in fast (3-15 min) and efficient formation of scaffolds, promising for many diverse oriented medical applications. This article is protected by copyright. All rights reserved.

Beschreibung: Three new abietane-type diterpenoids, 7 β -acetoxy-12-methoxyabieta-8,11,13-trien-6 α ,11-diol ( 1 ), 7 α -acetoxy-12-methoxyabieta-8,11,13-trien-6 α ,11-diol ( 2 ), and 6 α -acetoxy-12-methoxyabieta-8,11,13-trien-7 α ,11-diol ( 3 ), as well as two known abietane-type diterpenoids, 12-methoxyabieta-8,11,13-trien-6α,7β,11-triol ( 4 ) and 6α-acetoxy-12-methoxyabieta-8,11,13-trien-7β,11-diol ( 5 ), were isolated from the methanol extract of the bark of Cryptomeria japonica . Their structures were determined by analysis of spectroscopic data and comparison of NMR data with those of related metabolites. This article is protected by copyright. All rights reserved.

Beschreibung: With the number of students undertaking a PhD increasing and the nature of the working environment for these students changing, opportunities and problems inherent to this particular way of educating students are evolving. Challenges and difficulties that may arise during a PhD are considered and the ways potential problems can be avoided by PhD student and supervisor are discussed. This article is protected by copyright. All rights reserved.

Beschreibung: A new C -glycosyl flavone containing a 3-keto sugar, isocassiaoccidentalin B (1), was isolated from whole Cassia nomame ( Sieb .) Honda plants, along with eleven known compounds, including two flavonoids (2 and 3), five flavonoid glycosides (4 – 8), two chalcones (9 and 10) and two phenylpropanoids (11 and 12). The chemical structures of each of the compounds were determined via 1D-, 2D-NMR, and ESI-MS spectroscopy. Among these, compounds 2, 3, 7, and 8 were found to be the most potent in inhibiting nitric oxide release. Compounds 1, 2, 4, 8, 9 and 10 showed significant free radical scavenging activity. This article is protected by copyright. All rights reserved.

Beschreibung: Eight phenylspirodrimane-type analogues, including five new compounds, named stachartins A-E ( 1 , 3 , 6 - 8 ), were isolated from cultures of the tin mine tailings-associated fungus Stachybotrys chartarum . Their structures were elucidated by spectroscopic methods including extensive 2D-NMR techniques. This article is protected by copyright. All rights reserved.

Beschreibung: Considering the frightening high level of mortality from cancer, studies of anticancer agents are vital nowadays. The 24 thioderivatives of 2-alkyl(aryl)-quinazolin-4(3 H )-thiones and 20 of [1,2,4]triazolo[1,5- c ]quinazoline-2-thiones were synthesized and evaluated for preliminary in vitro anticancer activity with subsequent in silico QSAR analysis. The substance 18 had the best results inhibiting growth of eight cancer cell lines: CCRF-CEM of leukemia; SF-539, SNB-75 and U251 of CNS cancer; 786, RXF393 and UO-31 of renal cancer, and MDA-MB-231/ATCC of breast cancer (-31.50% – 47.41% of cell growth) with low procancer effect. Calculated QSAR-models for CCRF-CEM of leukemia, T-47D, HS 578T of breast cancer and mean cell growth demonstrated good rate of anticancer activity prediction ( r 2 = 0.7-0.8, Q 2 LOO = 0.5-0.7). This article is protected by copyright. All rights reserved.

Beschreibung: Periplocain A (2), a new naphthalene derivative together with four known compounds: 2-ethylhexyl benzoate (1), quercetin-3- O - α - l -rhamnopyranoside (3), quercetin-3- O - β - d -glucopyranoside (4), and quercetin-3-(6- O - α - l -rhamnopyranosyl- β - d -glucopyranoside) (5) were isolated from the AcOEt fraction of the aerial parts of Periploca aphylla (Asclepiadaceae). Their structures were established by multiple spectroscopic methods in addition to HRESIMS and comparison with literature data. This article is protected by copyright. All rights reserved.

Beschreibung: Treatment of several Diels–Alder adducts of cyclopropenecarboxylates and 1,3-diarylisobenzofurans with a strong acid triggers a skeletal rearrangement resulting in 4,8b-dihydro-3a H -indeno[1,2- b ]furans. This article is protected by copyright. All rights reserved.

Beschreibung: Two new highly oxidized formamidobisabolene sesquiterpenes ( 1 and 2 ), together with seven known related analogues ( 3-9 ), were isolated from a Hainan sponge Axinyssa variabilis . Their structures were determined by extensive 1D & 2D-NMR and MS spectra analyses, and by comparison of their spectroscopic data with those of the related model compounds. The plausible biosynthetic relationship of compounds 1 - 9 have also been described. This article is protected by copyright. All rights reserved.

Beschreibung: A one-pot four-component synthesis of 6-aryl-6 H -dibenzo[ e , i ][1,3,7,2]oxadiazaborecin-8(7 H )-ones is described. Heating a mixture of isatoic anhydride and a benzylamine afforded the corresponding anthranilamide derivative, which was condensed with a 2-hydroxybenzaldehyde and an arylboronic acid under solvent-free conditions to produce bridgehead bicyclo[4.4.0]boron heterocycles in good to excellent yields. Single-crystal X-ray analysis conclusively confirms the structures of the obtained bridgehead bicyclic 6–6 heterocyclic compounds. This article is protected by copyright. All rights reserved.

Beschreibung: Phytochemical investigation of the seeds of Alpinia katsumadai (Zingiberaceae) led to the isolation and identification of six new diarylheptanoid derivatives, katsumains D–G ( 1 – 4 ), 3-(acetyloxy)-alpinikatin ( 5 ), and 5-(acetyloxy)alpinikatin ( 6 ). The structures of 1 – 6 were elucidated by spectroscopic data analysis including 1D- and 2D-NMR experiments.

Beschreibung: The object of this study is the interaction of the cyclic anhydride 2 of (18 α ,19 β )-19-hydroxy-2,3-secooleanane-2,3,28-trioic acid 28,19-lactone ( 1 ) with primary and secondary amines. It was shown that the products of steric control (the corresponding 2-amino-2-oxo-3-oic acids=2-amides) were formed solely upon the opening of the anhydride cycle by secondary amines ( Scheme 2 ), whereas the interaction with primary amines yielded a mixture of isomeric amides ( Scheme 10 ). In the latter case, the solvent provided a noticeable effect on the reaction selectivity, which was demonstrated in the case of 4-methoxybenzylamine. The interaction between the resulting 3-amides and oxalyl chloride yielded the corresponding cyclic imides, whereas under these conditions, 2-amides formed spiropyrrolidinetriones ( Scheme 4 ).

Beschreibung: Two novel indole alkaloids with plumeran skeleton, N -benzoyl-12-demethoxycylindrocarine and N -cinnamoyl-12-demethoxycylindrocarine ( 1 and 2 , resp.), were isolated from the MeOH extract of the stem bark of Aspidosperma cylindrocarpon Müll . Arg . These compounds were obtained by high-speed counter-current chromatography, and their structures were elucidated on the basis of their NMR (1D and 2D) data. They were tested in vitro against chloroquine-resistant strains of Plasmodium falciparum , and only 2 showed a weak activity ( IC 50 127.97 ng/ml with respect to the standard drug). Several other known compounds, comprising steroids, flavonoids, the rarely found atraric acid, as well as the previously reported alkaloid 3 , were also isolated by conventional chromatographic techniques.

Beschreibung: Two new spirostanol saponins, namely elephanosides G and H ( 1 and 2 , resp.) were isolated from the leaves of Yucca elephantipes (Agavaceae), together with the two known furostanol saponins 3 and 4 and the six known flavonoid O - and C -glycosides 5 – 10 . The new structures were elucidated as (3 β ,25 S )-spirost-5-en-3-yl O - β - D -glucopyranosyl-(1→3)- O - β - D -glucopyranosyl-(1→4)- β - D -galactopyranoside ( 1 ) and (3 β ,5 β ,25 R )-3-[(2- O - β - D -glucopyranosyl- β - D -galactopyranosyl)oxy]spirostan-12-one ( 2 ) on the basis of detailed spectroscopic analysis and acidic hydrolysis.

Beschreibung: The chemoselectivity in the reaction of 2-diazo-3-oxo-3-phenylpropanal ( 1 ) with aldehydes and ketones in the presence of Et 3 N was investigated. The results indicate that 1 reacts with aromatic aldehydes with weak electron-donating substituents and cyclic ketones under formation of 6-phenyl-4 H -1,3-dioxin-4-one derivatives. However, it reacts with aromatic aldehydes with electron-withdrawing substituents to yield 1,3-diaryl-3-hydroxypropan-1-ones, accompanied by chalcone derivatives in some cases. It did not react with linear ketones, aliphatic aldehydes, and aromatic aldehydes with strong electron-donating substituents. A mechanism for the formation of 1,3-diaryl-3-hydroxypropan-1-ones and chalcone derivatives is proposed. We also tried to react 1 with other unsaturated compounds, including various olefins and nitriles, and cumulated unsaturated compounds, such as N , N′ -dialkylcarbodiimines, phenyl isocyanate, isothiocyanate, and CS 2 . Only with N , N′ -dialkylcarbodiimines, the expected cycloaddition took place.

Beschreibung: When treated with LiN i Pr 2 (LDA) at −78°, 1-[(methylsulfanyl)methyl]-2-[(1 Z ,3 E )-4-phenylbuta-1,3-dien-1-yl]benzene easily cyclized to form benzocycloheptenyl anion, which successively underwent intramolecular nucleophilic substitution to give a cyclopropanaphthalene. Similar LDA-mediated cyclization also occurred for 4-phenyl- or 4-methyl-substituted 1-[2-(methoxymethyl)phenyl]buta-1,3-dienes to furnish the corresponding benzocycloheptenes and cyclopropanaphthalenes. A 4- tert -butyl analog also underwent LDA-mediated cyclization to give a benzocycloheptene, but not a cyclopropanaphthalene.

Beschreibung: Three new isomeric biisoflavonoids, dapholidins A–C ( 1 – 3 , resp.), have been isolated from the AcOEt-soluble fraction of the MeOH-soluble extract of the roots of Daphne oleoides , along with the known compounds daphwazirin ( 4 ), daphnetin 8- O - β - D -glucopyranoside ( 5 ), daphnin ( 6 ), daphneticin 4″- O - β - D -glucopyranoside ( 7 ), and 6,7-dihydroxy-3-methoxy-8-[2-oxo-2 H -1-benzopyran-7-( O - β - D -glucopyranosyl)-8-yl]-2 H -1-benzopyran-2-one ( 8 ). The structures of the new compounds were determined by spectroscopic analyses, including 1D- and 2D-NMR.

Beschreibung: Two spiroheterocyclic 2 H -azirin-3-amines, 1f and 1g , were shown to be useful synthons for the dipeptides N -(4-aminotetrahydro-2 H -pyran-4-yl)prolinate (Thp-Pro) and the corresponding thiopyran derivative, Tht-Pro, respectively. By coupling of 4-bromobenzoic acid with 1f or 1g and saponification, followed by repeating the coupling and saponification steps, oligopeptides of type 4-BrBz-(Thp-Pro) n -OMe and 4-BrBz-(Tht-Pro) n -OMe were prepared, and their conformations were evaluated in solution by NMR techniques and in the crystalline state by X-ray crystallography. All of these sterically highly congested oligopeptides adopt fairly rigid helical conformations. It is interesting to note that the hexapeptide with Thp forms a 3 10 -helix, whereas the Tht analog has a β -bend ribbon spiral confirmation.

Beschreibung: Two new naphthoquinones, (2 R )-6,8-dihydroxy- α -dunnione ( 1 ), 6,8-dihydroxy-2,7-dimethoxy-3-(1,1-dimethylprop-2-enyl)-1,4-naphthoquinone ( 2 ), together with three known compounds, (2 R )-6,8-dihydroxy-7-methoxy- α -dunnione ( 3 ), nevadensin ( 4 ), and lysioside C ( 5 ), were isolated from the whole plant of Lysionotus pauciflorus. Their structures were established by spectroscopic methods. Hydroxylated naphthoquinones are reported to occur in a Lysionotus species for the first time. The cytotoxic activities of compounds 1 – 3 were evaluated in vitro against a panel of tumor cell lines.

Beschreibung: The three-component reaction of aniline, benzaldehyde, and dienophiles such as 2,3-dihydrofuran, ethyl vinyl ether, 2,3-dihydropyran, and cyclopentadiene can be promoted by ionic liquids like imidazolium salts and guanidinium salts under thermal as well as microwave conditions. The chemical yield as well as the diastereoselectivity of the Povarov reaction strongly depend on the ionic liquid employed. The guanidinium salts can be recycled and reused several times without loss of reactivity.

Beschreibung: One new triterpenoid, (3 β ,11 α ,19 β )-3-(butanoyloxy)-11-hydroxytaraxast-20(30)-ene-23,28-dioic acid (clerodendrumic acid; 1 ) was isolated from the hexane extract of the leaves of Clerodendrum glabrum var. glabrum along with heptadecanoic acid ( 2 ). The structure of the new compound was elucidated by interpretation of its NMR (1D and 2D), MS, and IR data. Combined fractions C and D from the column chromatography of the hexane extract exhibited significant antifungal activities (average MIC of 0.10 mg/ml) against Candida albicans and Cryptococcus neoformans. C. albicans was relatively resistant to clerodendrumic acid ( 1 ; MIC 125 μg/ml) and was resistant to heptadecanoic acid ( 2 ; MIC 188 μg/ml). Both compounds had low antibacterial activities against two Gram -positive and two Gram -negative bacteria with average MIC values of 157 and 172 μg/ml, respectively. Compounds 1 and 2 were relatively nontoxic against monkey kidney Vero cells in vitro with IC 50 values of 202.6 and 108.4 μg/ml, respectively.

Beschreibung: Beginning early in the 19th century, developments in crystallography, optics, and chemistry in France set the stage for the discovery of molecular chirality by Louis Pasteur in 1848. He found that the crystallization of the sodium ammonium salt of ‘ paratartaric acid ’, a mysterious ‘ isomer ’ of natural (+)-tartaric acid (TA), produced two different crystal types that were non-superimposable mirror-image forms of each other. He separated the two types and found their optical rotations in solution opposite in direction and equal in absolute magnitude. This led him to conclude that paratartaric acid is a combination of two mirror-image molecule types of TA that are ‘ dissymmetric ’, an existing term he adapted to the connotation of today's ‘ chiral ’. In 1857, he found that the two enantiomers of TA were metabolized by a microorganism at drastically different rates, and thereby discovered biological enantioselectivity. In 1886, Italian chemist Arnaldo Piutti discovered D -asparagine and found that it tasted intensely sweet, in contrast to the known L -asparagine which had no taste. This was the discovery of stereoselectivity at biological receptors. As a result of advances in stereoselective synthesis and enantioselective chromatography during the last decades of the 20th century, in the 1990s the importance of molecular chirality in drug action and disposition began to receive serious attention from drug-regulatory authorities and the pharmaceutical industry, the overall result of which has been the near-complete disappearance of racemic drugs as newly introduced pharmaceuticals.

Beschreibung: The four new cerebrosides 1 – 4 possessing a unique C 18 9-methylsphinga-4,8-dienine-related moiety and a cyclic octapeptide, 5 , possessing alternating proline and glycine moietes were isolated from the Tuber indicum fermentation mycelium. Their structures were established on the basis of a spectroscopic analysis including NMR and HR-ESI-MS, as well as an acidic methanolysis experiment. To the best of our knowledge, the cerebrosides identified in the present study are quite different from those isolated from Tuber indicum fruiting bodies. Additionally, it was the first time that a cyclic peptide was isolated from the Tuber genus.

Beschreibung: Three fluorescent turn-on probes containing 3,6-dichloro-9 H -carbazole as carbazyl part have been designed and synthesized. Among studied anions F − , AcO − , H 2 PO , Cl − , Br − and I − , AcO − showed the strongest binding ability with all probes. The strong basic anions, such as AcO − , H 2 PO , and F − , induced a significant red-shift in absorption and a concomitant increase in fluorescent emission of the probes caused by photoinduced electron transfer (PET). The determination limit of probe 3 ( Scheme 1 ) toward AcO − is 3.0×10 −7   M . 1 H-NMR Titration experiments shed light on the nature of the interaction between the probes and the anions. Theoretical investigation further illustrated the possible binding mode in these host guest interactions and the roles of molecular frontier orbitals in molecular interplay.

Beschreibung: This Part 4 continues a general presentation of the principles of stereochemistry with special reference to medicinal compounds and their interactions with biological systems. Here, we discuss and illustrate two major aspects of conformational isomerism, namely a ) the concept of torsional isomerism about single bonds, and b ) the intertwined conformational and configurational aspects of the stereochemistry of cyclic systems. The review begins with a brief reminder of the history and thermodynamics of conformational isomerism, and goes on to explain and illustrate the conventions and graphical representations used for conformers. Examples are then examined, beginning with ethane, the simplest one, and building up to more complex cases, documenting the attractive or repulsive role of substituents. A similar approach is applied when dealing with cyclic systems, although here the presentation necessarily takes into account configurational aspects specific to cyclic systems. The pharmacological implications of the concepts discussed here will be presented in Part 6.

Beschreibung: A new eremophilane sesquiterpene, (2 β )-2-deoxo-2-methoxytessaric acid ( 1 ), and two new eudesmane sesquiterpenes, (3 β ,10 α )-3-methoxyleudesma-4,11(13)-dien-12-oic acid ( 2 ) and (3 α ,4 β ,8 α )-4-(acetyloxy)-3-(2,3-dihydroxy)-2-methyl-1-oxobutoxy-8-hydroxyeudesm-7(11)-eno-12,8-lactone ( 3 ), along with the ten known compounds 4 – 13 were isolated from the aerial parts of Laggera pterodonta. The structures of the new compounds were elucidated by spectroscopic analyses, including 2D-NMR data.

Beschreibung: A simple synthesis of 2-hydrazinylidene-3-hydroxy-4 H -furo[3,2- c ]pyran-4-ones is described. A mixture of (isocyanoimino)(triphenyl)phosphorane, an aromatic aldehyde, and dehydroacetic acid (=3-acetyl-2-hydroxy-6-methyl-4 H -pyran-4-one) undergo a 1 : 1 : 1 addition reaction under mild conditions to afford the title compounds in excellent yields.

Beschreibung: A linear synthesis of the major oxepane fragment of zoapatanol, showing the induction of uterine contractions, and cervical dilation and uterine bleeding (by the concentrated zoapatle tea) in early human pregnancy, isolated from the leaves of Mexican zoapatle plant Montanoa tomentosa , is described from known intermediate involving Sharpless asymmetric epoxidation, bis-epoxide opening reaction with Corey Chaykovsky reagent, ring-closing metathesis reaction, and Horner Wadsworth Emmons olefination reaction as key steps.

Beschreibung: Total synthesis of biologically interesting natural and unnatural pyranoflavones has been accomplished starting from readily available 2,4-dihydroxyacetophenone or 2,4-dihydroxy-6-methoxyacetophenone in three steps, i.e. , benzopyran formation, condensation, and cyclization reaction.

Beschreibung: On treatment of 3-amino-5-aryl-1 H -pyrazoles 1 with dialkyl dicyanofumarates (=( E )-but-2-enedioates) 4 in boiling 1,2-dichloroethane, two competitive reactions occurred leading to 3-aryl-5-cyano-6,7-dihydro-6-oxo-1 H -pyrazolo[3,4- b ]pyridine-4-carboxylates 10 and 7-amino-2-arylpyrazolo[1,5- a ]pyrimidine-5,6-dicarboxylates 11 . In DMF at room temperature, as well as at 100°, only compounds 10 were isolated. The formation of the major products of type 10 was rationalized via Michael addition of 1 as a C ( 4 )-nucleophile onto 4 , followed by HCN elimination and lactamization. On the other hand, the minor products 11 result from a Michael addition of 1 onto 4 via the NH 2 group, and subsequent HCN elimination and cyclization. The structures of the products have been established by X-ray crystallography.

Beschreibung: A phytochemical investigation of the MeOH extract of Valeriana fauriei Briq . roots resulted in the isolation of two new sesquiterpenes, isovalerianin A (=(1 β ,4 Z ,6 β ,8 α )-8-(acetyloxy)-1,10-dihydroxy-6,11-cyclogermacr-4-en-15-al= rel -(1 R ,2 Z ,6 S ,7 R ,9 R ,10 S )-9-(acetyloxy)-6,7-dihydroxy-7,11,11-trimethylbicyclo[8.1.0]undec-2-ene-3-carboxaldehyde; 1 ) and valerianin C (=(2 α ,3 α ,6 α ,8 α )-3-(acetyloxy)-2,4,8-trihydroxyguai-1(10)-ene-12,6-lactone= rel -(3 R ,3a S ,4 R ,7 S ,8 S ,9 R ,9a R ,9b R )-8-(acetyloxy)-3a,4,5,7,8,9,9a,9b- octahydro-4,7,9-trihydroxy-3,6,9-trimethylazuleno[4,5- b ]furan-2(3 H )-one; 2 ), together with six known compounds, i.e. , camphor, methyl 4-hydroxybenzoate, 2-methoxybenzoic acid, benzoic acid, quercetin, and kaempferol. The structures of the compounds were established by detailed spectral analysis and comparison with previously reported data.

Beschreibung: 2,3-Dihydro-4 H -thiopyrano[2,3- b ]pyridin-4-ones 4 were prepared by a three-step sequence from commercially available 2-chloropyridine ( 1 ). Thus, successive treatment of 1 with i Pr 2 NLi (LDA) and α , β -unsaturated aldehydes gave 1-(2-chloropyridin-3-yl)alk-2-en-1-ols 2 , which were oxidized with MnO 2 to 1-(2-chloropyridin-3-yl)alk-2-en-1-ones 3 . The reactions of 3 with NaSH⋅ n H 2 O proceeded smoothly at 0° in DMF to provide the desired thiopyranopyridinones. Similarly, 2,3-dihydro-4 H -thiopyrano[2,3- c ]pyridin-4-ones 8 and 2,3-dihydro-4 H -thiopyrano[3,2- c ]pyridin-4-ones 12 were obtained starting from 3-chloropyridine ( 5 ) and 4-chloropyridine ( 9 ), respectively.

Beschreibung: Three new ent -kaurane diterpenoids, (4 α )-19-nor- ent -kaurane-4,16,17-triol ( 1 ), (4 α ,16 α )-17-(acetyloxy)-19-nor- ent -kaurane-4,16 - diol ( 2 ), and 17-hydroxy- ent -kaur-15-en-19-al ( 3 ), together with 11 known compounds, were isolated from the stem bark of Annona squamosa L. The structures of 1 – 3 were identified by analysis of their spectroscopic data. All compounds were evaluated for cytotoxic activity against human lung cancer (95-D) and ovarian cancer (A2780) cell lines, and compounds 3, 5, 7, 11 – 14 exhibited promising antiproliferative activities with IC 50 values ranging from 0.38 to 34.66 μ M .

Beschreibung: Two new triazoles, chrysotriazoles A and B ( 1 and 2 , resp.), along with two known quinazolinones, 3 and 4 , two known 2-(4-hydroxyphenyl)acetamides, 5 and 6 , and two known N -(4-hydroxystyryl)formamides, 7 and 8 , were isolated and identified from the culture extract of Penicillium chrysogenum EN-118, an endophytic fungus obtained from the marine brown alga Sargassum pallidium. The structures of the isolated compounds were elucidated by NMR-spectroscopic analysis, and that of compound 1 was confirmed by X-ray crystallographic analysis of its p -bromobenzoate derivative. Compounds 4, 5 , and 7 showed moderate cytotoxicities against Du145, A-549, and HeLa cell lines.

Beschreibung: The reaction of N , N -bis(diphenylphosphino)naphthalen-1-amine ( 1 ) with [M(CO) 6 ] (M=Cr, Mo, W; 1 : 1 molar ratio) afforded cis -[M(CO) 4 ( 1 )] 2 (M=Cr), 3 (M=Mo), and 4 (M=W). Compounds 2 – 4 were identified and characterized by elemental analysis and multinuclear NMR ( 1 H-, 13 C-, and 31 P-NMR) and IR spectroscopy. A crystal-structure determination of complex 3 was carried out.

Beschreibung: Phytochemical investigation of the whole herbs of Aconitum tanguticum ( Maxim .) Stapf var. trichocarpum Hand.-Mazz . led to the isolation of one heteratisine-hetidine-type bis-diterpenoid alkaloid, trichocarpidine ( 1 ), three hetidine-hetisine type bis-diterpenoid alkaloids, trichocarpinine A–C ( 2 – 4 , resp.), together with nine known compounds. Their structures were elucidated by spectroscopic analyses.

Beschreibung: Four metal-ion-binding nucleosides, viz. 2,6-bis(1-methylhydrazinyl)-9-( β - D -ribofuranosyl)-9 H -purine ( 2a ) and its N -acetylated derivative, 2b , 2,4-bis(3,5-dimethyl - 1 H -pyrazol-1-yl)-5-( β - D -ribofuranosyl)pyrimidine ( 3 ), and 2,4-bis(1-methylhydrazinyl)-5-( β - D -ribofuranosyl)pyrimidine ( 4 ) have been synthesized. The ability of these nucleosides and the previously prepared 2,6-bis(3,5-dimethyl - 1 H -pyrazol-1-yl)-9-( β - D -ribofuranosyl)-9 H -purine to form Pd 2+ - and Hg 2+ -mediated complexes with uridine has been studied by 1 H-NMR spectroscopy. To obtain additional support for the interpretation of the NMR data, comparative measurements on the ternary-complex formation between pyridine-2,6-dicarboxamide ( 5 ), pyrimidine nucleosides, and K 2 PdCl 4 were carried out.

Beschreibung: Organotin complexes 1 – 6 of the general formula [SnR 2 L] and [(SnR 3 ) 2 L] (L=phenanthrenequinone dioximato – a bidentate ligand, R=Me, Bu, and Ph) were synthesized by the reaction of the sodium salt of the ligand H 2 L (prepared in situ with MeONa) and SnR 2 Cl 2 /SnR 3 Cl in 1 : 1 and 1 : 2 molar ratios. The physical and spectral properties of the newly synthesized complexes 1 – 6 are described. DFT and HF Calculations were performed to confirm the proposed structures.

Beschreibung: The 3-allyl-2-methylquinazolin-4(3 H )-one ( 1 ), a model functionalized terminal olefin, was submitted to hydroformylation and reductive amination under optimized reaction conditions. The catalytic carbonylation of 1 in the presence of Rh catalysts complexed with phosphorus ligands under different reaction conditions afforded a mixture of 2-methyl-4-oxoquinazoline-3(4 H )-butanal ( 2 ) and α ,2-dimethyl-4-oxoquinazoline-3(4 H )-propanal ( 3 ) as products of ‘linear’ and ‘branched’ hydroformylation, respectively ( Scheme 2 ). The hydroaminomethylation of quinazolinone 1 with arylhydrazine derivatives gave the expected mixture of [(arylhydrazinyl)alkyl]quinazolinones 5 and 6 , besides a small amount of 2 and 3 ( Scheme 3 ). The tandem hydroformylation/reductive amination reaction of 1 with different amines gave the quinazolinone derivatives 7 – 10 . Compound 10 was used to prepare the chalcones 11a and 11b and pyrazoloquinazolinones 12a and 12b ( Scheme 4 ).

Beschreibung: A stereoselective total synthesis of a naturally occurring cytotoxic styryl lactone, crassalactone A ( 1 ), has been accomplished. The synthesis involves (−)-diisopropyl D -tartrate as the starting material, and the stereoselective additions of Grignard reagent and MeNO 2 to two chiral aldehyde intermediates as the key steps.

Beschreibung: Two new norfumiquinazolines, cottoquinazolines E and F ( 1 and 2 , resp.), together with pyripyropene A ( 3 ), were isolated from the fungus Neosartorya fischeri NRRL 181. The structures of the new isolates were established by spectroscopic methods, including UV, IR, HR-ESI-MS, and extensive 1D- and 2D-NMR techniques. To the best of our knowledge, this is the first report on norfumiquinazolines and pyripyropenes produced by the genus Neosartorya.

Beschreibung: Copper-exchanged tungstophosphoric acid (Cu-TPA) is found to catalyze efficiently the coupling of propargyl alcohol (prop-2-yn-1-ol) with (arylmethylidene)malononitriles to afford the corresponding 2,3,4,5-tetrahydro-4-methylidenefuran derivatives in good yields and with high selectivity. The catalyst is recycled and reused for three-to-four subsequent runs with a minimal decrease of activity.

Beschreibung: Two new furanoflavonoids, retamasins A and B ( 1 and 2 , resp.), along with five known flavonoids, 3 – 7 , were isolated from the aerial parts of Retama raetam. Their structures were determined on the basis of extensive spectroscopic (IR, MS, and 1D- and 2D-NMR) analyses and by comparison with the literature data. This is the first report of the isolation of new furanoflavonoids 1 and 2 from Retama genus, while compounds 3, 5 , and 6 were found for the first time from R. raetam. Antioxidant and anti-inflammatory activities of the isolated compounds were also evaluated. Compounds 2, 3 , and 5 – 7 exhibited potent inhibitions of iNOS activity with IC 50 values of 2.9, 5.0, 3.1, 1.2, and 4.8 μg/ml, respectively. All compounds inhibited NF- κ B except 1 and 5 . Compound 6 was most active in inhibiting iNOS and NF- κ B activity, as well as in decreasing oxidative stress.

Beschreibung: An efficient synthesis for polysubstituted benzenes was successfully developed by the reaction of ninhydrin (=2,2-dihydroxyindane-1,3-dione), malononitrile (=propanedinitrile), and alkylidenemalononitrile. The method involves vinylogous Michael addition of alkylidenemalononitrile to 2-(1,3-dioxo-1 H -inden-2(3 H )-ylidene)malononitrile, which formed by condensation of malononitrile and ninhydrin in the presence of Et 3 N, and the alcoholic solvent has participated in the reaction as a reagent. The method has the advantages of good yields and of not requiring a metal catalyst. The structures were confirmed spectroscopically (IR, 1 H- and 13 C-NMR, and EI-MS) and by elemental analyses, and, in the case of 2c , by X-ray crystallography. A plausible mechanism for this reaction is proposed ( Scheme ).

Beschreibung: A straightforward strategy for the stereoselective synthesis of (+)-bovidic acid has been developed in eleven steps with an overall yield of 8.85%. The synthesis started from commercially available nonanal, and the key reactions involved were Sharpless asymmetric dihydroxylation, Grignard reaction, and Corey Bakshi Shibata reduction.

Beschreibung: Five new triterpenoid saponins, oleiferosides I–M ( 1 – 5 , resp.) were isolated from the roots of Camellia oleifera Abel . Their structures were elucidated by a combination of 1D- and 2D-NMR spectroscopy, mass spectrometry, and chemical methods. All the compounds were identified as oleanane-type saponins with sugar moieties linked to C(3) of the aglycone. In addition, cytotoxic activities of these saponins were evaluated against four human tumor cell lines (A549, B16, BEL-7402, and MCF-7) by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) in vitro assay. All of the compounds showed significant cytotoxic activities against the tested cell lines.

Beschreibung: Dihetaryl thioketones react with thiocarbonyl ylides to give 1,3-dithiolanes in high yields. No competitive side reactions of the thiocarbonyl ylides were observed, evidencing the ‘superdipolarophilic’ character of this less-known group of thioketones. Depending on the type of substituents present in both the thiocarbonyl ylide and the thioketone, formal [3+2] cycloadditions occur with complete regioselectivity or with formation of a mixture of both regioisomers. Regioselective formation of the sterically more crowded 1,3-dithiolanes is explained via a mechanism involving stabilized 1,5-biradicals. In systems with less-efficient radical stabilization, e.g. , in the case of adamantanethione S -methanide, substantial violation of the regioselectivity was observed as a result of steric hindrance.

Beschreibung: Eight heterocycles have been prepared in a one-pot reaction manner based the on Hantzsch dihydropyridine synthesis. The synthesis afforded seven dihydropyridines (DHP) and one unexpected 1,3-oxazin-6-one. Their structures were confirmed based on NMR spectroscopy and mass spectrometry. The obtained products have been evaluated for their cytotoxicity against eight cancer cell lines and one normal cell line. Two halogenated DHPs ( 7 and 8 ) displayed cytotoxicity towards all the nine tested cancer cell lines with IC 50 values from 4.10 μ M to 58.90 μ M while others showed selective activities. DHPs ( 7 and 8 ) bearing a methyl group at C(2) and C(6) as well as a halogenated substituent at C(4’) were more anti-proliferative than the others. This article is protected by copyright. All rights reserved.

Beschreibung: Five new triterpenoid saponins, including 3- O - β -D-galactopyranosyl-(1 2)-[ β -D-xylopyranosyl-(1 3)]- β -D-glucuronopyranosyl quillaic acid 28- O - β -D-glucopyranosyl-(1 3)- β -D-xylopyranosyl-(1 4)- α -L-rhamnopyranosyl-(1 2)-[ β -D-xylopyranosyl-(1 3)-(4- O -acetyl)- β -D-quinovopyranosyl-(1 4)]- β -D-fucopyranoside (1), 3- O - β -D-galactopyranosyl-(1 2)-[ β -D-xylopyranosyl-(1 3)]- β -D-glucuronopyranosyl quillaic acid 28- O -(6- O -acetyl)- β -D-glucopyranosyl-(1 3)-[ β -D-xylopyranosyl-(1 4)]- α -L-rhamnopyranosyl-(1 2)-[ β -D-xylopyranosyl-(1 3)-(4- O -acetyl)- β -D-quinovopyranosyl-(1 4)]- β -D-fucopyranoside (2), 3- O - β -D-galactopyranosyl-(1 2)-[ β -D-xylopyranosyl-(1 3)]- β -D-glucuronopyranosyl quillaic acid 28- O - β -D-xylopyranosyl-(1 4)- α -L-rhamnopyranosyl-(1 2)-[ β -D-xylopyranosyl-(1 3)-(4- O -acetyl)- β -D-quinovopyranosyl-(1 4)]- β -D-fucopyranoside (3), 3- O - β -D-galactopyranosyl-(1 2)-[ β -D-xylopyranosyl-(1 3)]- β -D-glucuronopyranosyl quillaic acid 28- O - β -D-glucopyranosyl-(1 3)- β -D-xylopyranosyl-(1 4)- α -L-rhamnopyranosyl-(1 2)-[(4- O -acetyl)- β -D-quinovopyranosyl-(1 4)]- β -D-fucopyranoside (4), 3- O - β -D-galactopyranosyl-(1 2)-[ β -D-xylopyranosyl-(1 3)]- β -D-glucuronopyranosyl quillaic acid 28- O -(6- O -acetyl)- β -D-glucopyranosyl-(1 3)-[ β -D-xylopyranosyl-(1 4)]- α -L-rhamnopyranosyl-(1 2)-[(4- O -acetyl)- β -D-quinovopyranosyl-(1 4)]- β -D-fucopyranoside (5) together with two known congeners, saponariosides A (6) and B (7) were isolated from the roots of Saponaria officinalis L. Their structures were elucidated by extensive spectroscopic methods, including 1D- ( 1 H, 13 C) and 2D-NMR (DQF-COSY, TOCSY, HSQC and HMBC) experiments, HR-ESI-MS and acid hydrolysis. This article is protected by copyright. All rights reserved.