ALBERT

Beschreibung: Three new flavonoids, 5,6,7,8,3′,4′-hexamethoxyhomoflavone ( 1 ), 5,6,7,8,4′-pentamethoxyhomoflavone ( 2 ) and 3,6,7,8,2′,5′-hexamethoxyflavone ( 3 ) were isolated from the peels of mature fruits of Citrus unshiu Marcow (Rutaceae), together with the three known compounds 6,7,8,4′-tetramethoxyflavone (=6,7,8-trimethoxy-2-(4-methoxyphenyl)-4 H -1-benzopyran-4-one), 3,5,7,8,2′,5′-hexamethoxyflavone (=2-(2,5-dimethoxyphenyl)-3,5,7,8-tetramethoxy-4 H -1-benzopyran-4-one), and scopoletin (=7-hydroxy-6-methoxy-2 H -1-benzopyran-2-one) of which the former two have never been isolated from natural resources, although they have been reported as synthetic compounds. The structures of 1 – 3 were elucidated on the basis of spectroscopic evidence, including 1D- and 2D-NMR analysis.

Beschreibung: Since deregulation of the tyrosine-kinase receptor c-Met is implicated in several human cancers and is an attractive target for small-molecule-drug discovery, we report herein the synthesis of 2,3,4,5-tetrahydro-8-[1-(quinolin-6-ylmethyl)-1 H -1,2,3-triazolo[4,5- b ]pyrazin-6-yl]-1 H -pyrido[4,3- b ]indoles 4a – 4c and 2,3,4,5-tetrahydro-8-[3-(quinolin-6-ylmethyl)-1,2,4-triazolo[4,3- b ]pyridazin-6-yl]-1 H -pyrido[4,3-b]indoles 5a – 5c . These indole derivatives demonstrated inhibition of c-Met kinase activity. Concurrently, five key intermediates were synthesized. These compounds could be prepared in good yields.

Beschreibung: The hitherto unreported, highly functionalized 1 H -pyrazole-3-carboxylates 3 have been synthesized in good yields via a one-pot three-component domino reaction of phenylhydrazines, dialkyl acetylenedicarboxylates, and ninhydrin under mild conditions for the first time. No co-catalyst or activator is required for this multicomponent reaction, and the reaction is, from an experimental point of view, simple to perform ( Scheme 1 ). The structures of compounds 3 were corroborated spectroscopically (IR, 1 H- and 13 C-NMR, and EI-MS) and by elemental analyses. A plausible mechanism for this type of cyclization/addition reaction is proposed ( Scheme 2 ).

Beschreibung: Five new tetranortriterpenoids, toonaciliatones B–F ( 1 – 5 , resp.), together with four known compounds, dihydrocedrelone ( 6 ), cedrelone ( 7 ), 6 α -acetoxyazadirone ( 8 ), and 6 α -acetoxy-14 β ,15 β -epoxyazadirone ( 9 ), were isolated from the seeds of Toona ciliata. Their structures were elucidated by spectroscopic methods, including 1D- and 2D-NMR spectroscopy.

Beschreibung: Eleven new triterpenoids, named mesendanins K–U ( 1 – 11 , resp.), together with seven known analogs, were isolated from the leaves and twigs of Melia toosendan. Their structures were elucidated on the basis of extensive spectroscopic analysis.

Beschreibung: Taking the regio- and chemoselectivities of our iron complex precursors with pyridine core in aerobic oxidations into account, we envisioned a more effective influence on catalytic properties by the introduction of different substituents in 4-position of the pyridine moiety. The synthesis of these novel 4-substituted (pyridine-2,6-diyl)dipropanoic acids 4 is described. Analogously to the unsubstituted derivative, ligands 4 reacted with Fe(ClO 4 ) 3 to form trinuclear Fe 3 ( μ 3 -O) complexes 3 , which were tested in the aerobic Gif -type oxidation of α -pinene to myrtenol, verbenone, myrtenal, and pinene oxide. The electronic nature of the substituents was found to slightly effect the ratio of allylic oxidation/epoxidation, whereas its influence on the oxidation preference of secondary to primary C H bonds is negligible as compared to the unsubstituted complex.

Beschreibung: A convergent and efficient total synthesis of stagonolide C ( 1 ), a phytotoxic metabolite, was achieved ( Schemes 2 and 3 ) The synthesis exploited the high configuration control in the Prins cyclization along with alkene rearrangement and ring-closing metathesis as key steps.

Beschreibung: Two new cembranoids, yalongenes A ( 1 ) and B ( 2 ), were isolated from the South China Sea soft coral Sarcophyton trocheliophorum Marenzeller . Their structures were elucidated by detailed spectroscopic analysis (IR, MS, and NMR) and by comparison with a related model compound. Yalongenes 1 and 2 were evaluated for their cytoprotective effects on SH-SY5Y cell injury induced by H 2 O 2 in vitro , and the result showed that only compound 1 had a significant cytoprotective activity at the concentration of 1 μ M .

Beschreibung: Two new pentacyclic triterpenoids, named centelloside D ( 1 ) and centelloside E ( 9 ), together with the seven known compounds 2 – 8 , were isolated from the whole plants of Centella asiatica. Compound 5 was reported for the first time from this genus. Their structures were elucidated on the basis of chemical and spectral analysis, including 1 D - and 2 D -NMR, and HR-MS experiments, and by comparison with literature data. Compounds 1 – 4, 6 , and 8 did not show any cytotoxicity against L929 (mouse embryonic fibroblast).

Beschreibung: Various new C 2 -symmetric bidentate ligands, bearing phosphorus, nitrogen, and sulfur, were obtained in an efficient manner, starting from (±)- trans -3-methylidenecyclopropane-1,2-dicarboxylic acid ( Feist 's acid; (±)- trans - 3 ). The structures of the new bidentate ligands, di( tert- butyl) (±)-[( trans -3-methylidenecyclopropane-1,2-diyl)dimethanediyl]biscarbamate ((±)- 9 ), (±)-( trans -3-methyldienecyclopropane-1,2-diyl)dimethanaminium dichloride ((±)- 10 ), (±)- S , S′- [( trans -3-methylidenecyclopropane-1,2-diyl)dimethanediyl] diethanethioate ((±)- 11 ), and (±)-[( trans -3-methylidenecyclopropane-1,2-diyl)dimethanediyl]bis(diphenylphosphane) ((±)- 12 ), were fully characterized by standard spectroscopic techniques. These new classes of C 2 -symmetric bidentate ligands have the potential to be used in asymmetric catalysis.

Beschreibung: A formal synthesis of (−)-cephalotaxine ( 1 ) by means of a highly stereoselective radical carboazidation process is reported. The synthesis begins with the protected ( S )-cyclopent-2-en-1-ol derivative 10 and uses the concept of self-reproduction of a stereogenic center ( Schemes 5 and 6 ). For this purpose, the double bond adjacent to the initial chiral center in 10 is converted into an acetonide after stereoselective dihydroxylation. The initial alcohol function is used to build an exocyclic methylene group suitable for the carboazidation process 8 → 7 (Scheme 7). Finally the protected diol moiety is converted back to an alkene ( 14 → 15 → 6 ) and used for the formation of ring B via a Heck reaction ( 6 →(−)- 16 ; Scheme 8 ).

Beschreibung: The 1,2-bis[(diarylphosphino)ethynyl]benzene derivatives 1a (R=Ph) and 1b (R= o -tolyl) undergo 1,1-carboboration at one of their acetylene units upon treatment with (C 6 F 5 ) 3 B at elevated temperature to give the products 5a and 5b , respectively. At room temperature, we observed the formation of the corresponding phosphireniumborate zwitterions, 7a and 7b , respectively, which may be intermediates of the 1,1-carboboration reactions. The reaction of the more bulky 1,2-bis[(dimesitylphosphino)ethynyl]benzene 1c with (C 6 F 5 ) 3 B takes a different course. At 110°, we observed the complete conversion to the benzopentafulvene derivative 8 which is probably formed in a typical carbocation rearrangement sequence after the initial (C 6 F 5 ) 3 B Lewis acid-addition step. The compounds 5a, 5b, 7b , and 8 were characterized by X-ray crystal-structure analyses.

Beschreibung: Backbone alkylation has been shown to result in a dramatic reduction in the conformational space that is sterically accessible to α -amino acid residues in peptides. By extension, the presence of geminal dialkyl substituents at backbone atoms also restricts available conformational space for β and γ residues. Five peptides containing the achiral β 2,2 -disubstituted β- amino acid residue, 1-(aminomethyl)cyclohexanecarboxylic acid ( β 2,2 Ac 6 c), have been structurally characterized in crystals by X-ray diffraction. The tripeptide Boc-Aib- β 2,2 Ac 6 c-Aib-OMe ( 1 ) adopts a novel fold stabilized by two intramolecular H-bonds (C 11 and C 9 ) of opposite directionality. The tetrapeptide Boc-[Aib- β 2,2 Ac 6 c] 2 -OMe ( 2 ) and pentapeptide Boc-[Aib- β 2,2 Ac 6 c] 2 -Aib-OMe ( 3 ) form short stretches of a hybrid αβ C 11 helix stabilized by two and three intramolecular H-bonds, respectively. The structure of the dipeptide Boc-Aib- β 2,2 Ac 6 c-OMe ( 5 ) does not reveal any intramolecular H-bond. The aggregation pattern in the crystal provides an example of an extended conformation of the β 2,2 Ac 6 c residue, forming a ‘polar sheet’ like H-bond. The protected derivative Ac- β 2,2 Ac 6 c-NHMe ( 4 ) adopts a locally folded gauche conformation about the C β C α bonds ( θ =−55.7°). Of the seven examples of β 2,2 Ac 6 c residues reported here, six adopt gauche conformations, a feature which promotes local folding when incorporated into peptides. A comparison between the conformational properties of β 2,2 Ac 6 c and β 3,3 Ac 6 c residues, in peptides, is presented. Backbone torsional parameters of H-bonded αβ / βα turns are derived from the structures presented in this study and earlier reports.

Beschreibung: Alkylation reactions of nickel(II) complex 6 derived from glycine and 2-[(1-benzyl- L -prolyl)amino]benzophenone (BPBP) were studied under phase-transfer-catalysis (PTC) conditions. The goal of this work was to find an alternative suitable solvent for these reactions to replace the commonly used CH 2 Cl 2 which leads to the formation of several by-products, thus lowering the yield of target compounds. We demonstrate that 1,2-dichloroethane is a markedly better solvent providing higher yields (75–99%) of the desired products 10 with 36–88% diastereoisomer purity ( Scheme 3 and Table ). Furthermore, we show that the stereochemical outcome of these PTC reactions (kinetic control) can be easily improved to 〉95% de by treatment of the PTC products with MeONa/MeOH. The scope of these reactions includes alkylations with methyl iodide as well as activated halides such as benzyl, allyl or propargyl, bromides and most notably ethyl 2-bromoacetate ( Table ).

Beschreibung: The total synthesis of gymnopusin ( 2 ) is described. The originally assigned structure for gymnopusin 1a was found to be incorrect by total synthesis using the Directed ortho -Metalation (D o M) Cross-Coupling Directed remote Metalation (DreM) sequence, a demonstrable key strategy for the regioselective construction of the 9-phenanthrol core. The revised structure of gymnopusin ( 2 ) was confirmed by synthesis by adopting the same strategy but involving a key remote anionic Fries- rearrangement step. Both routes highlight methodologies and concepts which may be of value in the regiocontrolled synthesis of phenanthrenoids specifically and in complex polycyclic aromatics in general.

Beschreibung: Unnatural amino acids extend the pharmacological formulator's toolkit. Strategies to prepare unnatural amino acid derivatives using Lewis acid-activated allylsilane reactions are few. In this regard, we examined the utility of allylsilanes bearing an amino acid substituent in the reaction. Diastereoselective addition of methyl 2-( N -PG-amino)-3-(trimethylsilyl)pent-4-enoate and methyl ( E )-2-( N -PG-amino)-3-(trimethylsilyl)hex-4-enoate (PG=protecting group), 2 and 13 , respectively, to aromatic acetals in the presence of Lewis acids is described. Of those examined, TiCl 4 was found to be the most effective Lewis acid for promoting the addition. At least 1 equiv. of TiCl 4 was required to achieve high yields, whereas 2 equiv. of BF 3 ⋅OEt 2 were required for comparable outcomes. Excellent selectivity (〉99% syn / anti ) and high yield (up to 89%) were obtained with halo-substituted aromatic acetals, while more electron-rich electrophiles led to both lower yields and diastereoselectivities.

Beschreibung: A straightforward synthesis of orthogonally protected nucleoproline (Nup) amino acids and their coupling to oligomers are described. A key step is the attachment of alkynylated nucleobases to Fmoc-protected 4-azidoproline (Fmoc-Azp-OH) by a Cu-catalyzed 1,3-dipolar cycloaddition (‘click reaction’). The developed protocol allows preparation of the nucleoprolines in scales of 〉30 g. Solid-phase peptide synthesis proved to be straightforward with these Nup amino acids. The resulting oligonucleoproline peptides adopt defined helices, are very well H 2 O soluble, and show comparable cell-penetrating properties as recently reported α -nucleoalanine peptides.

Beschreibung: A diversity-oriented method to synthesize ( E )-azastilbenes having an intramolecular B N coordination bond from alkynyl(triaryl)borates and azaaromatic halides is described. The obtained π -conjugated compounds exhibit an intense blue fluorescence and a high electron affinity, indicating their potential to be used as n-type light-emitting materials.

Beschreibung: A versatile method for the synthesis of enantiomerically pure isoxazolidine monomers for the synthesis of β 3 -oligopeptides via α -keto acid hydroxylamine (KAHA) ligation is presented. This one-pot synthetic method utilizes in situ generated nitrones bearing gulose-derived chiral auxiliaries for the asymmetric 1,3-dipolar cycloaddition with methyl 2-methoxyacrylate. The resulting enantiomerically pure isoxazolidine monomers bearing diverse side chains (proteinogenic and non-proteinogenic) can be synthesized in either configuration ( like - and unlike -configured). The scalable and enantioselective synthesis of the isoxazolidine monomers enables the use of the synthesis of β 3 -oligopeptides via iterative α -keto acid hydroxylamine (KAHA) ligation.

Beschreibung: Glycosylation of decan-1-ol ( 2 ), (±)-decan-2-ol ( 3 ), and (±)-methyl 3-hydroxydecanoate ( 4 ) with L - rhamnose peracetate 5 to produce rhamnosides (=6-deoxymannosides) 6, 7 , and 8 in the presence of Lewis acids BF 3 ⋅Et 2 O, Sc(OTf) 3 , InBr 3 , and Bi(OTf) 3 was studied ( Table 1 ). While the strong Lewis acids BF 3 ⋅Et 2 O and Sc(OTf) 3 were effective as glycosylation promoters, they had to be used in excess; however, glycosylation required careful control of reaction times and temperatures, and these Lewis acids produced impurities in addition to the desired glycosides. Enantiomerically pure rhamnosides ( R )- 1 and ( S )- 1 ( Fig. ) were obtained from L - rhamnose peracetate 5 and (±)-benzyl 3-hydroxydecanoate ( 9 ) via the diastereoisomeric rhamnosides 10 ( Table 2 ; Scheme 3 ). The much weaker Lewis acids InBr 3 and Bi(OTfl) 3 produced purer products in high yield under a wider range of conditions (higher temperatures), and were effective glycosylation promoters even when used catalytically (〈10% catalyst; Table 2 ). We refer to these Lewis acids as ‘minimally competent Lewis acids’ ( cf. Scheme 4 ).

Beschreibung: β -Amino acids are key structural elements in unnatural peptides, peptidomimetics, and many other physiologically active compounds. In view of their importance, we have developed an efficient synthetic route that provides highly enantiomerically enriched ( R )- and ( S )-H- β 2 -h t Leu-OH via highly diastereo- and regioselective addition of tert -butyl radical to enantiomerically pure N -fumaroyloxazolidinones, followed by removal of the chiral auxiliary, Curtius rearrangement, ester hydrolysis, and catalytic hydrogenolysis.

Beschreibung: A set of ten C 1 -symmetric chiral bicyclo[2.2.2]octa-2,5-dienes (bod*) 2 ( Fig. 1 ) were tested as ligands in Rh-catalyzed arylation reactions. The 1,4-addition of arylboronic acids to cyclohex-2-en-1-one, cyclopent-2-en-1-one, and tert -butyl cinnamate proceeded smoothly with excellent enantioselectivities (up to 99% ee; Tables 1 – 3 ). The challenging 1,2-addition of triphenylboroxine to N -[(4-nitrophenyl)sulfonyl]imines yielded the product in high yield and in good enantioselectivity (up to 92% ee; Table 4 ). Generally, the use of C 1 -symmetric chiral bod* ligands bearing bulky substituents resulted in lower enantioselectivities, whereas several electron-poor and electron-rich bod* ligands gave higher enantioselectivities than the benchmark ligands reported in literature.

Beschreibung: We describe efficient and flexible enantioselective syntheses of the active enantiomers of the pheromones of pine sawflies, including the species Diprion jingyuanensis , their homologs and, stereoisomers, as well as those identified from the Chinese species Diprion jingyuanensis, i.e. , 126 . A total of 48 compounds, including acetates 78 – 101 and propanoates 102 – 125 , have been synthesized. Our general approach towards these compounds originated from the commercially available chirons diethyl ( S )- and ( R )-malates, as well as ethyl ( R )-3-hydroxybutanoate. The Seebach asymmetric methylation was employed in a key step to control additional configuration.

Beschreibung: A convergent synthesis of an analogue of (1 α )-1,25-dihydroxyvitamin D 3 ( 1b ) with a C 7 side chain at C(12), i.e. , of 5 ( Fig. ), is described. A key step of the synthesis is the assembly of the triene system by a Pd II -catalyzed ring closure of an enol triflate (‘bottom’ fragment) followed by coupling of the resulting Pd II intermediate with an alkenylboronate (‘upper’ fragment) ( Scheme 2 ). The synthetic strategy allows isotopic labelling at the end of the synthesis.

Beschreibung: γ -Halocarbanions, short-lived intermediates, add to electron-deficient double bonds of aldehydes, Michael acceptors, and imines to form anionic adducts that enter intramolecular 1,5-substitution to form five-membered rings of tetrahydrofurans, cyclopentanes, and pyrrolidines, respectively. Although the γ -halocarbanions can be generated by simple deprotonation of appropriate precursors, a wealth of other methods based on Lewis acid-catalyzed opening of cyclopropanes with formation of dipolar species utilizes a similar mechanistic scheme. In our review, we analyze kinetic relations of elementary processes in the multistep transformations, and demonstrate how structural factors influence the mechanisms and selectivity of the reaction.

Beschreibung: A bottom-up strategy was used for the synthesis of cross-linked copolymers containing the organocatalyst N -{(1 R )-2′-{[(4-ethylphenyl)sulfonyl]amino}[1,1′-binaphthalen]-2-yl}- D -prolinamide derived from 2 ( Scheme 1 ). The polymer-bound catalyst 5b containing 1% of divinylbenzene as cross-linker showed higher catalyst activity in the aldol reaction between cyclohexanone and 4-nitrobenzaldehyde than 5a and 5c . Remarkably, the reaction in the presence of 5b was carried out under solvent-free, mild conditions, achieving up to 93% ee ( Table 1 ). The polymer-bound catalyst 5b was recovered by filtration and re-used up to seven times without detrimental effects on the achieved diastereo- and enantioselectivities ( Table 2 ). The catalytic procedure with polymer 5b was extended to the aldol reaction under solvent-free conditions of other ketones, including functionalized ones, and different aromatic aldehydes ( Table 3 ). In some cases, the addition of a small amount of H 2 O was required to give the best results (up to 95% ee). Under these reaction conditions, the cross-aldol reaction between aldehydes proceeded in moderate yield and diastereo- and enantioselectivity ( Scheme 2 ).

Beschreibung: Experimental values for a number of organolithium equilibria in THF solution expressed as p K values are compared with computational results at several theory levels. Solvation effects are considered only by coordination of lithium with two THF molecules. Best results are obtained with the hybrid density-functional method mPW1PW91, which gives satisfactory results over a range of almost 40 p K units, but explicit thermal corrections to 25° are required.

Beschreibung: A new three-step synthetic pathway to generate polycyclic annulated hydantoins via rarely investigated heterocyclic imines is described. This procedure includes a one-pot reaction forming imines as precursor structures ( e.g., Asinger reaction), followed by an Ugi reaction to build up a bisamide structure that allows a ring-closing reaction to the targeted hydantoins via substitution. This pathway leads to a multiplicity of substances with a potential pharmacological activity.

Beschreibung: A total synthesis of aliskiren ( 20 ) was accomplished. A key in our synthesis was to use the symmetric trans-cisoid-trans- bis-lactone 1 as a precursor. It was expediently prepared by three different routes ( Scheme 2 ). Appending the end groups and functional group transformations completed the synthesis ( Scheme 3 ).

Beschreibung: The Morita Baylis Hillman ( MBH ) reactions of (4 S ,5 R ,7 R ,8 R )- and (4 R ,5 R ,7 R ,8 R )-4-hydroxy-7,8-dimethoxy-7,8-dimethyl-6,9-dioxaspiro[4.5]dec-2-en-1-ones ( 2 and 3 , resp.) with aldehydes using various catalysts were studied. A combination of Bu 3 P/phenol in THF was found being optimum conditions giving the corresponding MBH adducts with high diastereoisomeric ratios. After separation, each stereomerically pure isomer of the MBH adducts was subjected to hydrolysis employing 1% aq. CF 3 COOH (TFA) in a water bath of an ultrasonic cleaner to afford the corresponding polyhydroxylated cyclopentenones in good yields.

Beschreibung: Aryl epoxides undergo rearrangement and oxidative cleavage when reacted with in situ prepared hydroxy- λ 3 -iodane complexes. The presence of H 2 O plays a decisive role in steering the reaction path. A mechanistic scheme is proposed that accounts for the observed chemoselectivities.

Beschreibung: A detailed investigation of the reactions of PhSO 2 CF 2 H and PhSO 2 CH 2 F with ( E )-chalcone (=( E )-1,3-diphenylprop-2-en-1-one) at low temperatures revealed that these two reactions were kinetically controlled, and the ratios of 1,2- vs. 1,4-adducts, which did not change much over time at these temperatures, reflect the relative rates of the two reaction pathways. The controlled experiments of converting the PhSO 2 CF 2 - and PhSO 2 CHF-substituted 1,2-adducts to 1,4-adducts showed that these isomerizations are not favored due to the low stability and hard-soft nature of PhSO 2 CF and PhSO 2 CHF − anions. Moreover, taking advantage of the remarkable stability and softness of (PhSO 2 ) 2 CF − anion, an efficient thermodynamically controlled isomerization of (PhSO 2 ) 2 CF-substituted 1,2-adduct to 1,4-adduct was achieved for the first time.

Beschreibung: We report on a new three-color FRET system consisting of three fluorescent dyes, i.e. , of a carbostyril (=quinolin-2(1 H )-one)-derived donor D, a (bathophenanthroline)ruthenium complex as a relay chromophore A 1 , and a Cy dye as A 2 (FRET= Förster resonance-energy-transfer) ( cf. Fig. 1 ). With their widely matching spectroscopic properties ( cf. Fig. 2 ), the combination of these dyes yielded excellent FRET efficiencies. Furthermore, fluorescence lifetime measurements revealed that the long fluorescence lifetime of the Ru complex was transferred to the Cy dye offering the possibility to measure the whole system in a time-resolved mode. The FRET system was established on double-stranded DNA ( cf. Fig. 3 ) but it should also be generally applicable to other biomolecules.

Beschreibung: Eremosides A–C ( 1 – 3 ), three new iridoid glucosides, were isolated from the AcOEt-soluble fraction of the EtOH extract of the whole plant of Eremostachys loasifolia , along with buddlejoside B ( 4 ), 10- O -benzoylcatalpol ( 5 ), and pakiside A ( 6 ) reported for the first time from this species. The structures of these compounds were elucidated by spectroscopic data including 2D-NMR, FAB-MS, ESI-MS, as well as by acid and basic hydrolyses.

Beschreibung: A convenient synthis for 4-substituted and 3,4-disubstituted 1,7-naphthyridine-2(1 H )-thiones 7 has been developed. The method is based on the electrocyclic reaction of 4-(1-arylalk-1-enyl)-3-isothiocyanatopyridines 6 , generated in situ by the treatment of the respective isocyanides 5 with S 8 in the presence of a catalytic amount of selenium. The isocyanides 5 can be easily prepared from commercially available pyridin-3-amine by conventional organic reactions.

Beschreibung: The three-component reaction of isocyanides 1 , carbodiimides 2 , and trimethylsilyl azide ( 3 ) occurs at room temperature, and the produced 1,5-disubstituted 1 H -tetrazole derivatives 4 are formed in 81–98% yields ( Scheme 1, Table ). The reaction proceeds smoothly and cleanly under mild conditions, and no side reactions are observed.

Beschreibung: Four caffeoylquinic acid (CQA) derivatives, 5- O -caffeoylquinic acid ( 1 ), 3,5-di- O -caffeoylquinic acid ( 3 ), 4,5-di- O -caffeoylquinic acid ( 4 ), and 3,4,5-tri- O -caffeoylquinic acid ( 5 ), have been isolated from Artemisia herba-alba growing wild in Algeria, using the on-line HPLC DAD DPPH radical-scavenging detection technique as guidance. In the course of the purification work, the non-frequent ( E )-2-( β - D -glucopyranosyloxy)-4-methoxycinnamic acid ( 2 ) has also been isolated. The CQAs showed fair-to-good antioxidant activities determined by the DPPH . scavenging assay. The structures of the five isolated compounds were determined by spectroscopic methods. The on-line HPLC DAD DPPH technique allowed for a rapid pinpointing of antioxidants in the studied plant, accomplishing the facile guided isolation of the target molecules. Algerian A. herba-alba could be an interesting source of natural antioxidants that deserve further work.

Beschreibung: A new prenylated isoflavonoid, flemiphilippinin G ( 1 ), and a new flavonol glycoside, flemiphilippininside ( 2 ), along with eleven known isoflavonoids were obtained from the roots of Flemingia philippinensis ( Merr. et Rolfe) Li . Their structures were elucidated on the basis of spectroscopic data. The in vitro cytotoxicities of compounds 1 – 13 against MCF-7, A549, and Hep-G2 cell lines were determined by using the MTT (=3-(4,5-dimethylthazol-2-yl)-2,5-diphenyl-2 H -tetrazolium bromide) colorimetric assay, and their antioxidant activities were evaluated by ferric-reducing antioxidant power (FRAP) method. Compound 1 exhibited significant cytotoxicity against all the tested cell lines with IC 50 values of 4.8–7.3 μ M , and compound 2 was found to be inactive. Both compounds 1 and 2 showed weak antioxidant activities with FRAP values of 110±15 and 124±16 μmol/g, respectively.

Beschreibung: The attempted ethenylation at C(2) of 2-unsubstituted 1 H -imidazole N -oxides with ethyl acrylate (=prop-2-enoate) in the presence of Pd(OAc) 2 does not occur. In contrast to the other aromatic N -oxides, the [2+3] cycloaddition of imidazole N -oxides predominates, and 3-hydroxyacrylates, isomeric with the cycloadducts, are key products for the subsequent reaction. The final products were identified as dehydrated 2+1 adducts of 1 H -imidazole N- oxide and ethyl acrylate. The role of the catalyst is limited to the dehydration of the intermediate 3-hydroxypropanoates to give 1 H -imidazol-2-yl-substituted acrylates.

Beschreibung: A new method for the efficient synthesis of aldehydes, ketones, and oxophosphonates from various types of amines (primary and secondary) and aminophosphonates via oxidative deamination by nicotinium dichromate (=3-carboxypyridinium dichromate; NDC) is described.

Beschreibung: Chemical investigation of the aerial part of Leonurus heterophyllus led to the isolation and characterization of the seven labdane-type diterpenoids 1 – 7 , including six new ones, 1 – 6 . Compounds 4 and 5 were isolated as a C(15) epimer pair. The determination of the structures and relative configurations of the new compounds were mainly based on 1D- and 2D-NMR spectroscopic methods, and comparison of their NMR data with related compounds. The structure of compound 7 was confirmed by X-ray crystallographic analysis.

Beschreibung: Chemical examination of the MeOH extract of Plectranthus bishopianus Benth ., a rare and endangered plant, resulted in isolation of a new abietane diterpene, 6 β -hydroxy-7 α -methoxyroyleanone ( 1 ), along with two more diterpenoids, 6,7-dehydroroyleanone, and 6 β ,7 α -dihydroxyroyleanone, a triterpene oleanolic acid, and two sterols, β -sistosterol and stigmasterol. The structures of the isolated compounds were elucidated on the basis of spectroscopic data and also by comparison with authentic samples.

Beschreibung: Five new compounds, i.e. , the three new norlignans metasequirins G–I ( 1 – 3 ) and the two new phenylpropanoids 7-(3-ethoxy-5-methoxyphenyl)propane-7,8,9-triol (=1-(3-ethoxy-5-methoxyphenyl)propane-1,2,3-triol; 4 ) and 7-(3-hydroxy-5-methoxyphenyl)propane-7,8,9-triol (=1-(3-hydroxy-5-methoxy-phenyl)propane-1,2,3-triol; 5 ), were isolated from the branches and stems of Metasequoia glyptostroboides Hu et Cheng . Their structures were elucidated by physical, chemical, and spectroscopic methods, including 1D- and 2D-NMR and HR-ESI-MS. The cytotoxicites of the five compounds were tested against A549 and Colo 205 cell lines by the MTT method.

Beschreibung: The four new sesquiterpenoids 1 – 4 , and the new 2-(2-phenylethyl)-4 H -chromen-4-one (=2-(2-phenylethyl)-4 H -1-benzopyran-4-one) derivative 5 , together with the two known sesquiterpenoids 6 and 7 , the five known chromenones 8 – 12 , and 1-hydroxy-1,5-diphenylpentan-3-one ( 13 ), were isolated from a 70% MeOH extract of Aquilaria malaccensis agarwood chips. Their structures were elucidated on the basis of comprehensive spectral analyses and comparison with literature data.

Beschreibung: An efficient and organocatalyzed asymmetric reaction of phenacyl halides with coumarin-based dihydrobenzothiazoles was developed to afford cis- 2,3-disubstituted 3,4-dihydro-2 H -benzothiazines. This method provides a one-step and highly diastereoselective route to a wide variety of coumarin-based 3,4-dihydro-2 H -benzothiazines using the cheap and commercially available Cinchona alkaloid quinine hydrochloride.

Beschreibung: A convergent approach to dibenzodioxocinones was explored, thereby racemic penicillide ((±)- 1a ) could be obtained in 13 steps in 4.2% overall yield, based on 5-amino-2-methylphenol ( 5 ) ( Schemes 2–4 ).

Beschreibung: The reaction of the ‘oximato’-ligand precursor A ( Fig. 1 ) and metal salts with KCN gave two mononuclear complexes [ML(CN)(H 2 O) n ](ClO 4 ) ( 1 and 2 ; L={ N -(hydroxy- κO )- α -oxo- N′ -[(pyridin-2-yl- κN )methyl[1,1′-biphenyl]-4-ethanimidamidato- κN′ }; M=Co II ( 1 ), Cu II ( 2 ); n =2 for Co II , n =0 for Cu II ; Figs. 2 and 3 ). The new cyano-bridged pentanuclear ‘oximato’ complexes [{ML(H 2 O) n (NC)} 4 M 1 (H 2 O) x ](ClO 4 ) 2 ( 3 – 6 ) and trinuclear complexes [{ML(H 2 O) n (NC)} 2 M 1 L](ClO 4 ) ( 7 – 10 ) ([M 1 =Mn II , Cu II ; x =2 for Mn II , x =0 for Cu II ] were synthesized from mononuclear complexes and characterized by elemental analyses, magnetic susceptibility, molar conductance, and IR and thermal analysis. The four [ML(CN)(H 2 O) n ] + moieties are connected by a metal(II) ion in the pentanuclear complexe 3 – 6 , each one involving four cyano bridging ligands ( Fig. 4 ). The central metal ion displays a square-planar or octahedral geometry, with the cyano bridging ligands forming the equatorial plane. The axial positions are occupied by two aqua ligands in the case of the central Mn-atom. The two [ML(CN)(H 2 O) n ] + moieties and an ‘oximato’ ligand are connected by a metal(II) ion in the trinuclear complexes 7 – 10 , each one involving two cyano bridging ligands ( Fig. 5 ). The central metal ions display a distorted square-pyramidal geometry, with two cyano bridging ligands and the donor atoms of the tridentate ‘oximato’ ligand. Moreover catalytic activities of the complexes for the disproportionation of hydrogen peroxide (H 2 O 2 ) were also investigated in the presence of 1 H -imidazole. The synthesized homopolynuclear Cu II complexes 6 and 10 displayed eficiency in disproportion reactions of H 2 O 2 producing H 2 O and dioxygen thus showing catalase-like activity.

Beschreibung: We report on a new three-color FRET system consisting of three fluorescent dyes, i.e. , of a carbostyril (=quinolin-2(1 H )-one)-derived donor D, a (bathophenanthroline)ruthenium complex as a relay chromophore A 1 , and a Cy dye as A 2 (FRET= Förster resonance-energy-transfer) ( cf. Fig. 1 ). With their widely matching spectroscopic properties ( cf. Fig. 2 ), the combination of these dyes yielded excellent FRET efficiencies. Furthermore, fluorescence lifetime measurements revealed that the long fluorescence lifetime of the Ru complex was transferred to the Cy dye offering the possibility to measure the whole system in a time-resolved mode. The FRET system was established on double-stranded DNA ( cf. Fig. 3 ) but it should also be generally applicable to other biomolecules.

Beschreibung: Four caffeoylquinic acid (CQA) derivatives, 5- O -caffeoylquinic acid ( 1 ), 3,5-di- O -caffeoylquinic acid ( 3 ), 4,5-di- O -caffeoylquinic acid ( 4 ), and 3,4,5-tri- O -caffeoylquinic acid ( 5 ), have been isolated from Artemisia herba-alba growing wild in Algeria, using the on-line HPLC DAD DPPH radical-scavenging detection technique as guidance. In the course of the purification work, the non-frequent ( E )-2-( β - D -glucopyranosyloxy)-4-methoxycinnamic acid ( 2 ) has also been isolated. The CQAs showed fair-to-good antioxidant activities determined by the DPPH . scavenging assay. The structures of the five isolated compounds were determined by spectroscopic methods. The on-line HPLC DAD DPPH technique allowed for a rapid pinpointing of antioxidants in the studied plant, accomplishing the facile guided isolation of the target molecules. Algerian A. herba-alba could be an interesting source of natural antioxidants that deserve further work.

Beschreibung: Eremosides A–C ( 1 – 3 ), three new iridoid glucosides, were isolated from the AcOEt-soluble fraction of the EtOH extract of the whole plant of Eremostachys loasifolia , along with buddlejoside B ( 4 ), 10- O -benzoylcatalpol ( 5 ), and pakiside A ( 6 ) reported for the first time from this species. The structures of these compounds were elucidated by spectroscopic data including 2D-NMR, FAB-MS, ESI-MS, as well as by acid and basic hydrolyses.

Beschreibung: A convenient synthis for 4-substituted and 3,4-disubstituted 1,7-naphthyridine-2(1 H )-thiones 7 has been developed. The method is based on the electrocyclic reaction of 4-(1-arylalk-1-enyl)-3-isothiocyanatopyridines 6 , generated in situ by the treatment of the respective isocyanides 5 with S 8 in the presence of a catalytic amount of selenium. The isocyanides 5 can be easily prepared from commercially available pyridin-3-amine by conventional organic reactions.

Beschreibung: Chemical investigation of the aerial part of Leonurus heterophyllus led to the isolation and characterization of the seven labdane-type diterpenoids 1 – 7 , including six new ones, 1 – 6 . Compounds 4 and 5 were isolated as a C(15) epimer pair. The determination of the structures and relative configurations of the new compounds were mainly based on 1D- and 2D-NMR spectroscopic methods, and comparison of their NMR data with related compounds. The structure of compound 7 was confirmed by X-ray crystallographic analysis.

Beschreibung: Five new compounds, i.e. , the three new norlignans metasequirins G–I ( 1 – 3 ) and the two new phenylpropanoids 7-(3-ethoxy-5-methoxyphenyl)propane-7,8,9-triol (=1-(3-ethoxy-5-methoxyphenyl)propane-1,2,3-triol; 4 ) and 7-(3-hydroxy-5-methoxyphenyl)propane-7,8,9-triol (=1-(3-hydroxy-5-methoxy-phenyl)propane-1,2,3-triol; 5 ), were isolated from the branches and stems of Metasequoia glyptostroboides Hu et Cheng . Their structures were elucidated by physical, chemical, and spectroscopic methods, including 1D- and 2D-NMR and HR-ESI-MS. The cytotoxicites of the five compounds were tested against A549 and Colo 205 cell lines by the MTT method.

Beschreibung: A new method for the efficient synthesis of aldehydes, ketones, and oxophosphonates from various types of amines (primary and secondary) and aminophosphonates via oxidative deamination by nicotinium dichromate (=3-carboxypyridinium dichromate; NDC) is described.

Beschreibung: A new prenylated isoflavonoid, flemiphilippinin G ( 1 ), and a new flavonol glycoside, flemiphilippininside ( 2 ), along with eleven known isoflavonoids were obtained from the roots of Flemingia philippinensis ( Merr. et Rolfe) Li . Their structures were elucidated on the basis of spectroscopic data. The in vitro cytotoxicities of compounds 1 – 13 against MCF-7, A549, and Hep-G2 cell lines were determined by using the MTT (=3-(4,5-dimethylthazol-2-yl)-2,5-diphenyl-2 H -tetrazolium bromide) colorimetric assay, and their antioxidant activities were evaluated by ferric-reducing antioxidant power (FRAP) method. Compound 1 exhibited significant cytotoxicity against all the tested cell lines with IC 50 values of 4.8–7.3 μ M , and compound 2 was found to be inactive. Both compounds 1 and 2 showed weak antioxidant activities with FRAP values of 110±15 and 124±16 μmol/g, respectively.

Beschreibung: The four new sesquiterpenoids 1 – 4 , and the new 2-(2-phenylethyl)-4 H -chromen-4-one (=2-(2-phenylethyl)-4 H -1-benzopyran-4-one) derivative 5 , together with the two known sesquiterpenoids 6 and 7 , the five known chromenones 8 – 12 , and 1-hydroxy-1,5-diphenylpentan-3-one ( 13 ), were isolated from a 70% MeOH extract of Aquilaria malaccensis agarwood chips. Their structures were elucidated on the basis of comprehensive spectral analyses and comparison with literature data.

Beschreibung: Chemical examination of the MeOH extract of Plectranthus bishopianus Benth ., a rare and endangered plant, resulted in isolation of a new abietane diterpene, 6 β -hydroxy-7 α -methoxyroyleanone ( 1 ), along with two more diterpenoids, 6,7-dehydroroyleanone, and 6 β ,7 α -dihydroxyroyleanone, a triterpene oleanolic acid, and two sterols, β -sistosterol and stigmasterol. The structures of the isolated compounds were elucidated on the basis of spectroscopic data and also by comparison with authentic samples.

Beschreibung: The reaction of the ‘oximato’-ligand precursor A ( Fig. 1 ) and metal salts with KCN gave two mononuclear complexes [ML(CN)(H 2 O) n ](ClO 4 ) ( 1 and 2 ; L={ N -(hydroxy- κO )- α -oxo- N′ -[(pyridin-2-yl- κN )methyl[1,1′-biphenyl]-4-ethanimidamidato- κN′ }; M=Co II ( 1 ), Cu II ( 2 ); n =2 for Co II , n =0 for Cu II ; Figs. 2 and 3 ). The new cyano-bridged pentanuclear ‘oximato’ complexes [{ML(H 2 O) n (NC)} 4 M 1 (H 2 O) x ](ClO 4 ) 2 ( 3 – 6 ) and trinuclear complexes [{ML(H 2 O) n (NC)} 2 M 1 L](ClO 4 ) ( 7 – 10 ) ([M 1 =Mn II , Cu II ; x =2 for Mn II , x =0 for Cu II ] were synthesized from mononuclear complexes and characterized by elemental analyses, magnetic susceptibility, molar conductance, and IR and thermal analysis. The four [ML(CN)(H 2 O) n ] + moieties are connected by a metal(II) ion in the pentanuclear complexe 3 – 6 , each one involving four cyano bridging ligands ( Fig. 4 ). The central metal ion displays a square-planar or octahedral geometry, with the cyano bridging ligands forming the equatorial plane. The axial positions are occupied by two aqua ligands in the case of the central Mn-atom. The two [ML(CN)(H 2 O) n ] + moieties and an ‘oximato’ ligand are connected by a metal(II) ion in the trinuclear complexes 7 – 10 , each one involving two cyano bridging ligands ( Fig. 5 ). The central metal ions display a distorted square-pyramidal geometry, with two cyano bridging ligands and the donor atoms of the tridentate ‘oximato’ ligand. Moreover catalytic activities of the complexes for the disproportionation of hydrogen peroxide (H 2 O 2 ) were also investigated in the presence of 1 H -imidazole. The synthesized homopolynuclear Cu II complexes 6 and 10 displayed eficiency in disproportion reactions of H 2 O 2 producing H 2 O and dioxygen thus showing catalase-like activity.

Beschreibung: The attempted ethenylation at C(2) of 2-unsubstituted 1 H -imidazole N -oxides with ethyl acrylate (=prop-2-enoate) in the presence of Pd(OAc) 2 does not occur. In contrast to the other aromatic N -oxides, the [2+3] cycloaddition of imidazole N -oxides predominates, and 3-hydroxyacrylates, isomeric with the cycloadducts, are key products for the subsequent reaction. The final products were identified as dehydrated 2+1 adducts of 1 H -imidazole N- oxide and ethyl acrylate. The role of the catalyst is limited to the dehydration of the intermediate 3-hydroxypropanoates to give 1 H -imidazol-2-yl-substituted acrylates.

Beschreibung: An efficient and organocatalyzed asymmetric reaction of phenacyl halides with coumarin-based dihydrobenzothiazoles was developed to afford cis- 2,3-disubstituted 3,4-dihydro-2 H -benzothiazines. This method provides a one-step and highly diastereoselective route to a wide variety of coumarin-based 3,4-dihydro-2 H -benzothiazines using the cheap and commercially available Cinchona alkaloid quinine hydrochloride.

Beschreibung: The three-component reaction of isocyanides 1 , carbodiimides 2 , and trimethylsilyl azide ( 3 ) occurs at room temperature, and the produced 1,5-disubstituted 1 H -tetrazole derivatives 4 are formed in 81–98% yields ( Scheme 1, Table ). The reaction proceeds smoothly and cleanly under mild conditions, and no side reactions are observed.

Beschreibung: A convergent approach to dibenzodioxocinones was explored, thereby racemic penicillide ((±)- 1a ) could be obtained in 13 steps in 4.2% overall yield, based on 5-amino-2-methylphenol ( 5 ) ( Schemes 2–4 ).

Beschreibung: Reverse micelles (RM) were formed in heptane/CHCl 3 with a surfactant carrying the triallylammonium (=triprop-2-en-1-ylammonium) head group ( Scheme ). Photo-cross-linking with dithiothreitol (= rel -(2 R ,3 R )-1,4-dimercaptobutane-2,3-diol; DTT) captured the RMs and afforded organic, soluble nanoparticles in a one-step reaction. Similar to dendrimers, the cross-linked reverse micelles could encapsulate palladium nanoparticles within their hydrophilic cores and protect them in catalytic reactions. Good to excellent yields were obtained in the Heck coupling of a range of alkyl acrylates (=alkyl prop-2-enoates) and iodobenzenes ( Tables 1 and 2 ). The catalytic activity of the palladium nanoparticles was maintained in several repeated runs.

Beschreibung: A new cyclopeptide, cyclozanthoxylane A ( 1 ), the lignans cis - and trans -methylpluviatolide, the flavonoid isoquercitrin, along with a mixture of benzoic and cinnamic acid derivatives, were isolated from the MeOH extract of the leaves of Zanthoxylum rigidum (Rutaceae). The structures of the compounds were determined on the basis of 1D- and 2D-NMR, and MS analysis. It is the first time that a natural cyclic peptide has been isolated from the genus Zanthoxylum.

Beschreibung: Nicotinamide adenine dinucleotide (oxidized form, free acid, NAD + ) was utilized as an auxiliary for polar alignment of gallic acid (=3,4,5-trihydroxybenzoic acid, GA) in the crystalline molecular complex NAD + ⋅(GA) 2 ⋅(H 2 O) 5 . In this adduct, NAD + takes up a novel U-shaped conformation accepting a GA molecule to give rise to a pincer-type π -complex. With the assistance of further GA molecules, these pincer assemblies build up infinite donor acceptor π -stacks in the crystal. An extended network of H-bonds among the multitude of pertinent active functional groups and the water molecules supports the crystal structure. These findings may imply noteworthy material properties, in particular nonlinear optical effects, and might also serve to trigger inspiring biochemical connections to be made. The crystal structure of anhydrous GA is also reported, which is centrosymmetric and non-polar.

Beschreibung: Two new cycloheptapeptides, tunicyclins F and G, were isolated from the roots of Psammosilene tunicoides. Their chemical structures were elucidated by extensive analysis of 1D- and 2D-NMR, as well as HR-ESI-MS data. Tunicyclin G contains an unusual α , β -dehydrotryptophan (Δ Z -Trp) residue, which mainly occurs in the cyclic peptides from marine sponge and bacteria.

Beschreibung: 2′- C -Methylnucleosides are known to exhibit antiviral activity against Hepatitis C virus. Since the inhibitory activity depends on their intracellular conversion to 5′-triphosphates, dosing as appropriately protected 5′-phosphates or 5′-phosphorothioates appears attractive. For this purpose, four potential pro-drugs of 2′- C -methylguanosine, i.e. , 3′,5′-cyclic phosphorothioate of 2′- C -methylguanosine and 2′- C , O 6 -dimethylguanosine, 1 and 2 , respectively, the S -[(pivaloyloxy)methyl] ester of 2′- C , O 6 -dimethylguanosine 3′,5′-cyclic phosphorothioate and the O -methyl ester of 2′- C , O 6 -dimethylguanosine 3′,5′-cyclic phosphate, 3 and 4 , respectively, have been prepared.

Beschreibung: Two new natural compounds, (1 R ,2 E )-2-(6-hydroxyhexylidene)cyclopropyl- β - D -glucopyranoside ( 1 ) and (6 E )-6-[(2 R )-2-( β - D -glucopyranosyloxy)cyclopropylidene]hexanoic acid ( 2 ), glucosides of a very rare methylidenecyclopropane alcohol, as well as two known glycosides of phenolic acids, namely 4- O - β - D -glucopyranosylcaffeic acid ( 3 ) and ( E )-4- O - β - D -glucopyranosylcoumaric acid ( 4 ), and methyl α -fructofuranoside ( 5 ) were isolated for the first time from the rhizomes of the tree fern Metaxya rostrata C. Presl . The structures were elucidated on the basis of detailed spectroscopic data analysis, and the structure of 1 was additionally confirmed by X-ray crystal-structure analysis.

Beschreibung: A synthesis of cis -3-aryl-3a,8b-dihydro-3a,8b-dihydroxy-1-phenylindeno[1,2- c ]pyrazol-4(1 H )-ones in good yields from the sequential reaction between benzaldehydes, phenylhydrazine, and indan-1,2,3-trione in MeCN is described ( Scheme 1 ).

Beschreibung: The three new 3- O -methylquercetin glucosides 1 – 3 , together with three known congeners and 3- O -methylquercetin, were isolated from the fern Ophioglossum pedunculosum (quercetin=2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxy-4 H -1-benzopyran-4-one). The new compounds were identified on the basis of spectroscopic analysis as 5′-isoprenyl-3- O -methylquercetin 4′,7-di- β - D -glucopyranoside ( 1 ), 3- O -methylquercetin 4′- β - D -glucopyranoside 7-[ O-β - D -glucopyranosyl-(1→2) -β - D -glucopyranoside] ( 2 ), and 3- O -methylquercetin 7-[ O-β - D -glucopyranosyl-(1→2) -β - D -glucopyranoside] ( 3 ). The effect of the isolated compounds on lipopolysaccharide (LPS)-induced NO production was evaluated. The inhibitory activity of 3- O -methylquercetin derivatives decreased markedly with the increasing number of glucosyl groups in the structures.

Beschreibung: A new polyketide metabolite, the twelve-membered macrolide 1 , isolated from the endophytic fungal strain Cladosporium tenuissimum LR 463 of Maytenus hookeri , whose structure had been determined as (6 R ,12 S )-6-hydroxy-12-methyl-1-oxacyclododecane-2,5-dione, was synthesized for the first time by a convergent strategy via Yamaguchi esterification of 2 with 3 and ring-closing metathesis (RCM) to afford the cyclic ester 1 that was eventually transformed to the target molecule. However, the total synthesis revealed that the assigned structure of the natural product is not correct.

Beschreibung: A simple and efficient stereoselective total synthesis of (+)-umuravumbolide ( 1b ) and (−)-deacetylumuravumbolide ( 1a ) starting from commercially available pentanal is described. The synthesis involves Sharpless asymmetric epoxidation, Jacobsen 's hydrolytic kinetic resolution (HKR), and the Yamaguchi oxirane opening as key steps ( Scheme 2 ).

Beschreibung: The stereoselective total synthesis of a naturally occurring bioactive diarylheptanoid, (3 R ,6 E )-1,7-bis(4-hydroxyphenyl)hept-6-en-3-ol, has been accomplished starting from 4-hydroxybenzaldehyde through two different approaches involving Wittig olefination, hydrolytic kinetic resolution of a racemic epoxide, and olefin cross-metathesis reaction as the key steps.

Beschreibung: A novel straightforward synthesis of 3-(1 H -tetrazol-5-yl)coumarins (=3-(1 H -tetrazol-5-yl)-2 H -1-benzopyran-2-ones) 6 via domino Knoevenagel condensation, Pinner reaction, and 1,3-dipolar cycloaddition of substituted salicylaldehydes (=2-hydroxybenzaldehydes), malononitrile (propanedinitrile), and sodium azide in H 2 O is reported ( Scheme 1 and Table 2 ). This general protocol provides a wide variety of 3-(1 H -tetrazol-5-yl)coumarins in good yields under mild reaction conditions.

Beschreibung: Five novel pyrazole-coupled glucosides, 1,5-diaryl-1 H -pyrazol-3-yl 2,3,4,6-tetra- O -acetyl- β - D -glucopyranosides 5a – 5e , were synthesized by the phase-transfer catalytic reaction of 1,5-diaryl-1 H -pyrazol-3-ols 4a – 4e with acetobromo- α - D -glucose in H 2 O/CHCl 3 under alkaline conditions, using Bu 4 N + Br − as catalyst. Then, glucosides 5a – 5c were deacetylated in a solution of Na 2 CO 3 /MeOH to yield the 1,5-diaryl-3-( β - D -glucopyranosyloxy)-1 H -pyrazoles 6a – 6c . Their structures were characterized by 1 H, 1 H-COSY, 1 H-, 13 C-, and 19 F-NMR spectroscopy, as well as elemental analysis. The structures of 5d and 6c were also determined by single-crystal X-ray diffraction analysis. A preliminary in vitro bioassay indicated that compounds 4e and 5d exhibited excellent-to-medium fungicidal activity against Sclerotinia sclerotiorum at the dosage of 10 μg/ml.

Beschreibung: The AcOEt-soluble part of a MeOH extract from the whole plant of Erigeron bonariensis yielded two new rare-class octulosonic acid derivatives, rel -methyl (1 R ,2 S ,3 S ,5 R )-3-( trans -caffeoyloxy)-7-[( trans -caffeoyloxy)methyl]-2-hydroxy-6,8-dioxabicyclo[3.2.1]octane-5-carboxylate ( 1 ) and 5,8-di[ O - trans -caffeoyl]-3-deoxy- β - D - gluco -oct-2-ulopyranosonosyl 4,8-di[ O - trans -caffeoyl]-3-deoxy- β - D - gluco -oct-2-ulopyranosidonic acid ( 2 ) along with a cyclohexanecarboxylic acid derivative, (1 α ,3 β ,4 β ,5 β )-1,4-di-3,5-dihydroxy-bis( trans -caffeoyloxy)cyclohexanecarboxylic acid ( 3 ). The structures of these compounds were elucidated through ESI-MS, and 1D- and 2D-NMR spectroscopic techniques including 1 H- and 13 C-NMR, HMQC or HSQC, and HMBC experiments.

Beschreibung: The electrochemical oxidation of catechol (=benzene-1,2-diol; 1a ) and some of its derivatives in H 2 O/MeCN 1 : 1 containing benzoylacetonitrile (= β -oxobenzenepropanenitrile; 3 ) as a nucleophile was studied by cyclic voltammetry and controlled-potential coulometry. The voltammetric data showed that electrochemically generated o -benzoquinones (=cyclohexa-3,5-diene-1,2-diones) from catechol ( 1a ) and 3-methylcatechol ( 1b ) participate in a Michael -addition reaction with 3 to form the corresponding 5,6-dihydroxybenzofuran-3-carbonitrile 8 ( Scheme 1 ). In this work, we report an efficient one-pot method with high atom economy for the synthesis of new substituted 5,6-dihydroxybenzofuran-3-carbonitriles in an undivided cell under ambient conditions.

Beschreibung: Two new and a known N -( O -carbamoylglucopyranosyl)ansamitocins were isolated from Actinosynnema pretiosum ssp. auranticum ATCC 31565. The known N -(4- O- carbamoyl- β - D -glucopyranosyl)- N -demethylansamitocin P 2 (=ACGP-2; 1 ) was assigned according to 1D- and 2D-NMR data, and the two new compounds were identified as N -(6- O- carbamoyl- β - D -glucopyranosyl)- N -demethylansamitocin P 2 (=ACGP-2′; 2 ) and N -(4- O- carbamoyl- β - D -glucopyranosyl)- N -demethylansamitocin P 1 (=ACGP-1; 3 ) on the basis of spectroscopic data interpretation including 2D-NMR and tandem MS analysis.

Beschreibung: Eight new and eight known 2-(2-phenylethyl)chromone (=2-(2-phenylethyl)-4 H -1-benzopyran-4-one) derivatives, i.e. , 1 – 8 and 9 – 16 , respectively, together with the two known sesquiterpenoids 17 and 18 were isolated from a 70% MeOH extract of Aquilaria malaccensis (AM) agarwood chips. Their structures were determined based on extensive spectroscopic analysis and comparison with reported data.

Beschreibung: Two novel diterpene dimers with a bismagdalenic acid skeleton, bisyinshanic acids A and B ( 1 and 2 , resp.), along with eight known diterpenoids ( 3 – 10 ), were isolated from the roots of Euphorbia yinshanica. Their structures were elucidated on the basis of spectroscopic evidence.

Beschreibung: The six new germacrane-type sesquiterpenoid lactones 1 – 6 were isolated from the CHCl 3 extract of Eupatorium lindleyanum DC. The structures of these compounds were determined by spectroscopic analyses, including interpretation of 1D- and 2D-NMR spectra. Compounds 1 – 6 were tested for cytotoxicity against NB4 and K562 leukemia cell lines, showing that 2 and 5 possess potent cytotoxicity ( Table 3 ).

Beschreibung: Two new neolignans, syripinnalignins A and B ( 1 and 2 , resp.), were isolated from the 95% EtOH extract of the stem of Syringa pinnatifolia Hemsl . var. alashanensis. The structures of 1 and 2 were elucidated by spectroscopic methods, including UV, IR, HR-ESI-MS, and extensive 1D- and 2D-NMR techniques.

Beschreibung: Three or four aromatic rings interconnected by acetylene bridges form a stiff conjugated system with sufficient conformational freedom to make it useful to link together the two strands of a DNA clamp. Upon targeting a ssDNA, the conformational flexibility allows better stacking of the linker to the underlying non-planar base triplet in the formed triplex. This type of triplexes has a substantially higher thermal melting temperature which can be further improved by inserting locked nucleic acids (LNAs) in the Hoogsteen part of the clamp. An extremely high sensitivity to mismatches is observed in an octamer triplex when placed in the middle of the sequence.

Beschreibung: A new ursene-type triterpene, (3 β )-30-norurs-11-en-3-ol ( 1 ), was isolated from the MeOH extract of the roots of Alhagi camelorum. Its structure was elucidated on the basis of extensive spectroscopic investigations by 1D- and 2D-NMR studies. In addition, 1 was evaluated for antifungal activities. Its application on prepared cultures of two fungi, i.e., Aspergillus niger and Saccharomyces cerevisiae , showed noticeable antifungal activity, suggesting that 1 could be used as a new promising agent in antifungal drug formulations.

Beschreibung: The one-pot synthesis of 4-aryl-1,4-dihydro-2-thioxo-2 H -3,1-benzoxazine-4-acetic acid derivatives 2 was achieved in good yields by the reaction of aryl(2-isothiocyanatophenyl)methanones 1 with lithium enolates of acetates and tertiary acetamides. (2 E )-1-(2-Isothiocyanatophenyl)-3-phenylprop-2-en-1-one ( 3 ) gave 1,4-dihydro-4-[(1 E )-2-phenylethenyl]-2-thioxo-2 H -3,1-benzoxazine-4-acetic acid derivatives 4 in good yields as well.

Beschreibung: An internal historical point of view is presented on the discovery and development of both methyl jasmonate and its saturated analogue Hedione ® . A discussion of the synthetic approaches performed during the last decade, and structure activity relationships of analogous structures are also presented.

Beschreibung: Enantiomerically pure bis-heterocycles containing a ( S )-proline moiety have been prepared starting from ( S )- N -benzylprolinehydrazide ( 2b ). The reactions with isothiocyanates or butyl isocyanate in refluxing MeOH led to the corresponding thiosemicarbazide 5 and semicarbazide 9 with a N -benzylprolinoyl residue. The structure of the tert -butyl derivative 5d was established by X-ray crystallography. Base-catalyzed cyclization of 5 and 9 led to ( S )-3-(pyrrolidin-2-yl)-1 H -1,2,4-triazole-5(4 H )-thiones 6 and the corresponding 5(4 H )-one 8 , respectively, whereas, in concentrated H 2 SO 4 , compounds 5 undergo cyclization to give ( S )-5-amino-2-(pyrrolidin-2-yl)-1,3,4-thiadiazoles 7 . Furthermore, 2b reacted with hexane-2,5-dione in boiling i PrOH to yield the ( S )- N -(2,5-dimethylpyrrol-1-yl)prolinamide 10 . In the case of the bis-heterocycle 8 , treatment with HCOONH 4 and Pd/C in MeOH gave the debenzylated product 12 .

Beschreibung: New dichromophoric cyanine dyes based on benzothiazol-2-amines as push pull systems were synthesized in two series of disperse and cationic forms (see 4 in Scheme 1 and 5 in Scheme 2 , resp.). Their thermal stabilities, UV/VIS, fluorescence, and solvatochromic behavior, which are important parameters in push pull systems, were also studied.

Beschreibung: Two new natural taxanes were isolated from the heartwood of Taxus cuspidata. The structures were established as rel -(2 α ,5 α ,7 β ,9 α ,10 β ,12 α )-7,9-bis(acetyloxy)-2-(benzoyloxy)-11,12-epoxy-1,5-dihydroxy-10-[(hydroxyacetyl)oxy]tax-4(20)-en-13-one ( 1 ), and (2 α ,5 α ,10 β ,14 β )-taxa-4(20),11-diene-2,5,10,14-tetrol 2-acetate ( 2 ) on the basis of spectroscopic analysis.

Beschreibung: Two new oleanane-type triterpene saponins, afrocyclamins A and B ( 1 and 2 , resp.), were isolated from a MeOH extract of the roots of Cyclamen africanum Boiss . & Reuter , together with three known triterpenoid saponins, lysikokianoside, deglucocyclamin I, and its dicrotalic acid derivative. The structures were elucidated, on the basis of 1D- and 2D-NMR experiments and mass spectrometry as (3 β ,20 β )-13,28-epoxy-16-oxo-3-{ O - β - D -xylopyranosyl-(1→2)- O - β - D -glucopyranosyl-(1→4)- O -[ β - D -glucopyranosyl-(1→2)]- α - L -arabinopyranosyl}oxy}oleanan-29-al ( 1 ) and (3 β ,16 α ,20 β )-16,28,29-trihydroxy-olean-12-en-3-yl O -4- O -(4-carboxy-3-hydroxy-3-methyl-1-oxobutyl)- β - D -xylopyranosyl-(1→2)- O - β - D -glucopyranosyl-(1→4)- O -[ β - D -glucopyranosyl-(1→2)]- α - L -arabinopyranoside ( 2 ).

Beschreibung: TADDOL (= α , α , α′ , α′ -Tetraaryl-1,3-dioxolane-4,5-dimethanol) and the corresponding dichloride are converted to TADDAMINs (=(4 S ,5 S )-2,2, N , N′ -tetramethyl- α , α , α′ , α′ -tetraphenyl-1,3-dioxolan-4,5-dimethanamines) ( Scheme 2 ) and ureas, 12 – 15 , and to TADDOP derivatives with seven-membered O P O ester rings ( Schemes 3 and 4 ). Cl/P-Replacement via the Michaelis Arbuzov reaction ( Scheme 7 ) on mono- and dichlorides, derived from TADDOL, are described. It was not possible to obtain phosphines with the P-atom attached to the benzhydrylic C-atom of the TADDOL skeleton ( Schemes 6 and 7 ). The X-ray crystal structures ( Figs. 1 and 2 ) of ten of the more than 30 new TADDOL derivatives are discussed. Full experimental details are presented.

Beschreibung: A brief overview is presented of the field of organocatalysis using chiral H-bond donors, chiral Brønsted acids, and chiral counter-anions ( Fig. 1 ). The role of TADDOLs (= α , α , α′ , α′ -tetraaryl-1,3-dioxolane-4,5-dimethanols) as H-bond donors and the importance of an intramolecular H-bond for acidity enhancement are discussed. Crystal structures of TADDOLs and of their N-, S-, and P-analogs ( Figs. 2 and 3 ) point the way to proposals of mechanistic models for the action of TADDOLs as organocatalysts ( Scheme 1 ). Simple experimental two-step procedures for the preparation of the hitherto strongest known TADDOL-derived acids, the bicyclic phosphoric acids ( 2 in Scheme 2 ) and of a phosphoric-trifluorosulfonic imide ( 9 in Scheme 4 ), are disclosed. The mechanism of sulfinamide formation in reactions of TADDAMIN with trifluoro-sulfonylating reagents is discussed ( Scheme 3 ). p K a Measurements of TADDOLs and analogs in DMSO (reported in the literature; Fig. 5 ) and in MeO(CH 2 ) 2 OH/H 2 O (described herein; Fig. 6 ) provide information about further possible applications of this type of compounds as strong chiral Brønsted acids in organocatalysis.

Beschreibung: A new synthesis of (Aib-Pro) n oligopeptides ( n =2, 3, and 4) via azirine coupling by using the dipeptide synthon methyl N -(2,2-dimethyl-2 H -azirin-3-yl)- L -prolinate ( 1b ; Fig. 1 ) is presented. The most important feature of the employed protocol is that no activation of the acid component is necessary, i.e. , no additional reagents are required, and the coupling reaction is performed under mild conditions at room temperature. As an attempt to provide an answer to the question of the preferred conformation of the prepared molecules, we carried out experiments by using NMR techniques and X-ray crystallography. For example, in the case of the hexapeptide 11 , it was possible to compare the conformations in the crystalline state and in solution. After the selective hydrolysis of the methyl ester p -BrBz-(Aib-Pro) 4 -OMe ( 13 ) under basic conditions, the corresponding octapeptide acid was obtained, which was then converted into the octapeptide amide p -BrBz-(Aib-Pro) 4 -NHC 6 H 13 ( 15 ) by using standard coupling conditions and activating reagents (HOBt/TBTU/DIEA) of the peptide synthesis. The conformation of this compound, as well as those of the tetrapeptides 14 and 18 , was also established by X-ray crystallography and in solution by NMR techniques. In the crystalline state, a β -bend ribbon structure is the preferred conformation, and similar conformations are formed in solution.

Beschreibung: Two new epimeric chlorinated withaphysalins, rel -(4 β ,5 β ,6 α ,18 S ,22 R )- and rel -(4 β ,5 β ,6 α ,18 R ,22 R )-6-chloro-18,20-epoxy-18-ethoxy-4,5-dihydroxy-1-oxowitha-2,24-diene-26,22-lactone ( 1 and 2 resp.), together with the new rel -(4 β ,5 β ,6 α ,18 R ,22 R )-6-chloro-18,20-epoxy-4,5-dihydroxy-18-methoxy-1-oxowitha-2,24-diene-26,22-lactone ( 3 ) and rel -(3 β ,4 β ,5 β ,6 β ,18 R ,22 R )-5,6:18,20-diepoxy-3,18-diethoxy-4-hydroxy-1-oxowith-24-ene-26,22-lactone ( 4 ) were isolated from the leaves of Acnistus arborescens and named withaphysalins T–W, respectively. The final structures and the complete 1 H- and 13 C-NMR assignments of the three chlorowithaphysalins 1 – 3 were performed by means of HR-ESI-MS and 1D- and 2D-NMR experiments, including COSY, HSQC, and HMBC, beside comparison with spectral data of analogous compounds from the literature. The structure of 4 was also confirmed by means of a single-crystal X-ray diffraction analysis.

Beschreibung: A novel 30-nortriterpenoid saponin, (3 β )-3-hydroxy-30-noroleana-12,20(29)-dien-28-oic acid 3-( β - D -glucopyranosiduronic acid 6-methyl ester) ( 1 ), and a known compound, (3 β )-oleanolic acid 3-( β - D -glucopyranosiduronic acid 6-methyl ester) ( 2 ), were isolated from the aerial parts of Wedelia chinensis. The structures were established by their spectral data including 1 H- and 13 C-NMR, 1 H, 1 H-COSY, HMBC, HSQC, NOESY, and HR-FAB-MS data.

Beschreibung: Four new diketopiperazine alkaloids, rel -(8 R )-9-hydroxy-8-methoxy-18- epi -fumitremorgin C ( 1 ), rel -(8 S )-19,20-dihydro-9,20-dihydroxy-8-methoxy-9,18-di- epi -fumitremorgin C ( 2 ), rel -(8 S ,19 S )-19,20-dihydro-9,19,20-trihydroxy-8-methoxy-9- epi -fumitremorgin C ( 3 ), and (3 S ,8 S ,9 S ,18 S )-8,9-dihydroxyspirotryprostatin A ( 4 ), together with the eight known compounds 5 – 12 , were isolated from the endophytic fungus Aspergillus fumigatus. The structures of the new compounds were determined by extensive spectroscopic methods including HR-ESI-MS, NMR, and CD experiments. Compound 12 showed weak inhibitory activity in vitro against the release of β- glucuronidase in rat polymorphonuclear leukocytes induced by the platelet-activating factor. None of the twelve compounds exhibited detectable cytotoxic activities toward five human tumor cell lines (HCT-8, Bel-7402, BGC-823, A549, and A2780) in the MTT assay.

Beschreibung: A successful aza- Michael addition of arylamines to a conjugated enone, acryloylferrocene, has been achieved by ultrasonic irradiation of the mixture of these reactants and the catalyst, i.e. , montmorillonite K-10. This solvent-free reaction, yielding ferrocene containing Mannich bases, 3-(arylamino)-1-ferrocenylpropan-1-ones, considered as valuable precursors in organic synthesis, has been performed by using a simple ultrasonic cleaner. Among 17 synthesized β -amino ketones, three were new ones, and these were fully characterized by spectroscopic means. X-Ray crystallographic analysis of three of these crystalline products enabled the insight into the conformational details of these compounds. All compounds were evaluated for their antibacterial activities against six Gram -positive and five Gram -negative strains in a microdilution assay. The observed promising antibacterial activity (with a MIC value of 25 μg/ml ( ca. 0.07 μmol/ml) as the best result for almost all tested compounds against Micrococcus flavus ) seems not only to be compound but also bacterial species-specific.

Beschreibung: A new polyprenylated xanthone (=9 H -xanthen-9-one) and a new polyprenylated benzophenone, namely oblongifolixanthone A ( 1 ) and garciniagifolone A ( 2 ), were isolated from the bark of Garcinia oblongifolia , together with five known compounds including the four xanthones 3 – 5 and 7 and a benzophenone 6 . The structures of 1 and 2 were established by detailed analysis of their spectroscopic data, especially 1D- and 2D-NMR spectra and HR-ESI-MS data. All these compounds were assayed for their cytotoxic activities against three human tumor cell lines (HeLa, SGC7901, and HepG2). The 1,3,6,7-tetrahydroxy-9 H -xanthen-9-one ( 3 ) was inactive, and the other compounds showed weak to moderate activity.

Beschreibung: A new simple carbazole alkaloid, 4-(7-hydroxy-3-methoxy-6-methyl-9 H -carbazol-4-yl)but-3-en-2-one ( 1 ), and two new dimeric carbazole alkaloids, bisglybomine B ( 2 ) and biscarbalexine A ( 3 ), together with seven known alkaloids, were isolated from the stems of Glycosmis pentaphylla. Their structures were elucidated by spectroscopic methods, especially 2D-NMR techniques.

Beschreibung: A new megastigmane palmitate, 9-oxomegastigm-5(13)-ene-2 β -palmitate ( 1 ), and a new oleanane triterpenoid, (3 β )-3,23,28-trihydroxyolean-12-en-11-one ( 2 ), together with three known oleanane-type triterpenoids, β -amyrin ( 3 ), erythrodiol ( 4 ), and (3 β )-olean-12-ene-3,23,28-triol ( 5 ), were isolated from the aerial parts of Aster yomena (Asteraceae). Their structures were identified based on 1D- and 2D-NMR analysis, including 1 H, 1 H-COSY, HSQC, HMBC, and NOESY techniques.