Inseparable Mixture Research Articles

ChemInform Abstract: Palladium‐Catalyzed Synthesis of Quino[2,3‐a]carbazoles and Indolo[2,3‐a]carbazoles via Intramolecular ortho‐Arylation.

AbstractThe presence of electron‐withdrawing groups on the chloroquinoline‐3‐carbaldehyde moiety provides inseparable mixtures of the corresponding products in low yields.

Cyclohexane-fused octahydroquinolizine alkaloids from Myrioneuron faberi with activity against hepatitis C virus.

Investigation of the alkaloids from Myrioneuron faberi, a plant unique to China, gave four pairs of enantiomers (1-4). (±)-β-Myrifabral A (1) and (±)-α-myrifabral A (2) formed an inseparable mixture of anomers (cluster A), as did (±)-β-myrifabral B (3) and (±)-α-myrifabral B (4) (cluster B). Their structures were determined by X-ray diffraction and NMR analysis. Compounds 1-4 possessed novel cyclohexane-fused octahydroquinolizine skeletons and represent the first quinolizidine alkaloids from the genus Myrioneuron. The epimers of cluster A (1 and 2) were modified and separated. In vitro, clusters A and B and their derivatives inhibited replication of hepatitis C virus (HCV, IC50 0.9 to 4.7 μM) with cytotoxicity lower than that of telaprevir.

Characterisation of triterpenes and new phenolic lipids in Cameroonian propolis

Chemical investigation of a sample of propolis originating from North-Western Cameroon led to the isolation of thirteen alk(en)ylphenols (1–13) (inseparable mixture) along with α-amyrin (14), β-amyrin (15), lupeol (16), cycloartenol (17), mangiferonic acid (18), ambonic acid (19), mangiferolic acid (20), ambolic acid (21), isomangiferolic acid (22) and nine alk(en)ylresorcinols (23–31) (inseparable mixture). All compounds were identified following analysis of their spectroscopic data and comparison with previously published reports. Compounds (8), (12), (13) and (30) are new natural products. GC–MS analysis carried out on the alk(en)ylphenol and alk(en)ylresorcinol mixtures (dimethyl disulphide trimethylsilyl derivatives) revealed the presence of saturated and mono-unsaturated compounds with side chain lengths ranging from C11 to C19 and C15 to C19, respectively. The position of the double bond in mono-unsaturated derivatives was established from the characteristic fragments resulting from the cleavage of the bond between the two methylthio-substituted carbons. The most abundant compound in each mixture was 3-(12′Z-heptadecenyl)-phenol (10) and 5-(12′Z-heptadecenyl)-resorcinol (29). This study is the first to report the presence of triterpenes (except for lupeol) and phenolic lipids, including eighteen compounds previously unreported in bee glue, in an African sample.

Enzymatic oxidative dimerization of silymarin flavonolignans

• C C linked dimers of silybin A and B, silydianin and silychristin were prepared. • Oxidative dimerization of the flavonolignans was done by T. versicolor laccase. • All dimers exhibited improved DPPH radical scavenging compared to their monomers. • The first reaction and the first derivative of silydianin were reported. • Laccase oxidation helps to understand an antioxidation mechanism of flavonoids. Dimerization of phenolic compounds can potentially enhance their biological (antioxidant) activity. We present here the selective oxidative dimerization of several flavonolignans from Silybum marianum seed extract, namely, silybin A ( 1a ), silybin B ( 1b ), silychristin ( 3 ), and silydianin ( 4 ) catalyzed by a laccase from Trametes versicolor . Selective benzylation of C-7 OH group of both silybins ensured the priority of the dimerization reaction, avoiding thus polymerization. C C homodimers connected via E-rings of silybin A and B and silydianin dimers were successfully isolated after respective debenzylation. On the contrary, dimerization of 7- O -benzyl silychristin afforded a complex, inseparable mixture of the products. All isolated flavonolignan dimers exhibited significantly improved 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity compared to their monomers and, therefore, seem to be promising for further biological studies.

Nickel(II) Benzimidazolin-2-ylidene Complexes with Thioether-Functionalized Side Chains as Catalysts for Suzuki–Miyaura Cross-Coupling

Four bis(benzimidazolin-2-ylidene) nickel(II) complexes featuring thioether moieties in the side chain have been synthesized by reactions of the respective benzimidazolium salts with nickel(II) acetate in molten tetrabutylammonium bromide as an ionic liquid. All complexes were obtained as inseparable mixtures of trans-syn and trans-anti rotamers, as evidenced by NMR spectroscopy. For one of the complexes, X-ray diffraction confirmed the square-planar coordination geometry. The catalytic activity of all complexes for Suzuki–Miyaura cross-coupling was examined. Under the optimized conditions, both aryl bromides and aryl chlorides were successfully coupled in the presence of triphenylphosphine as additive. Yields ranged from good to moderate for electron-deficient aryl halides, while electron-rich aryl halides were found to be unreactive.

ChemInform Abstract: Ligand Bite Angle‐Dependent Palladium‐Catalyzed Cyclization of Propargylic Carbonates to 2‐Alkynyl Azacycles or Cyclic Dienamides.

AbstractThe cyclization products are obtained as inseparable mixtures.

Banchromene and other secondary metabolites from the endophytic fungus Fusarium sp. obtained from Piper guineense inhibit the motility of phytopathogenic Plasmopara viticola zoospores

A new chromene, (S)-banchromene (1), together with seven known compounds, ergosterol, beauvericin (2), fusaproliferin (3), radicinin (4), poly(3-hydroxybutyric acid) (PHB, 5), N-methylpyrrolidone and an inseparable mixture of isochromene derivatives 6a, 6b, were isolated from a culture of Fusarium sp. strain CAMKT24b1, an endophytic fungus from the leaves and twigs of Piper guineense (Piperaceae). The structures of these metabolites were elucidated on the basis of their spectroscopic data; the absolute configuration of 1 was determined by ab initio-calculation of the optical rotation. In tests with the zoospores of the grapevine downy mildew pathogen Plasmopara viticola, compounds 1–4 showed moderate to high levels of motility-impairing activity at concentrations as low as 2.5μg/mL. Compound 2 was the most active, exhibiting both motility-halting and lytic activities. Furthermore, compounds 2 and 3 displayed significant cytotoxic activity against brine shrimp larvae (Artemia salina) at 10μg/mL. This is the first report on motility inhibitory and lytic activities of metabolites from an endophytic Fusarium species against the zoospores of the downy mildew pathogen P. viticola.

Four new ginkgolic acids from Ginkgo biloba

Four new compounds, 2-hydroxy-6-(12′-hydroxyheptadec-13′(E)-en-1-yl)benzoic acid (1), 2-hydroxy-6-(13′-hydroxyheptadec-11′(E)-en-1-yl)benzoic acid (2), 2-hydroxy-6-(10′-hydroxypentadec-11′(E)-en-1-yl)benzoic acid (3), and 2-hydroxy-6-(11′-hydroxypentadec-9′(E)-en-1-yl)benzoic acid (4) were isolated from the leaves of Ginkgo biloba and the structures of new ginkgolic acids were deduced on the basis of spectroscopic methods and chemical means. Compounds 1 and 2, and 3 and 4 examined as an inseparable mixture of hydroxyl and double bond positional isomers, were ultimately defined by total synthesis. Compounds 1–4 showed moderate lipid droplets accumulation inhibitory activity on mouse pre-adipocyte cell line, MC3T3-G2/PA6.

Nitrous Oxide Reduction-Coupled Alkene-Alkene Coupling Catalyzed By Metalloporphyrin

Metalloporphyrins are of great interest as versatile catalysts, e.g. for oxidation, cyclopropanation and aziridination and so on. These catalysts have been extensively investigated mainly as model compounds for active site of peroxidases and cytochrome P450, i.e., natural oxidation catalysts. Molecular oxygen, peroxides and other various oxidants have been examined for the oxidants.1 We also have shown that the oxidation of alkanes, alkenes, and aromatics and N-carbonyl cyclic amines is efficiently catalyzed by ruthenium porphyrins with heteroaromatic N-oxides as oxidants.2 We therefore considered other molecules having N-O bond could be oxidant for metalloporphyrin catalysts. Nitrous oxide (N2O) is a physico-chemically CO2-like stable molecule. Huge amounts of N2O are generated as a by-product of industrial processes. N2O itself is a potent contributor to global-warming and an ozone-depleting substance. Here we report N2O reduction-coupled alkene coupling reaction catalyzed by metalloporphyrin.3 a-Methylstyrene (1a) dimerized to afford 2,3-dimethyl-2,3-diphenylbutane (2a) mainly with NaBH4 in the presence of iron meso-tetraphenylporphyrin chloride (FeIII(TPP)Cl) (1 mol%) under N2O. Addition of OH- or CH3O- enhanced the reaction, resulting complete consumption of 1a (Table). Mn(TPP)Cl, Co(TPP)Cl and Rh(TMP)CH3 also had catalytic activity that was lower than that of Fe(TPP)Cl. The use of 0.05 mol% of Fe(TPP)Cl in the reaction of 1a afforded 2a in 69% yield, i.e., the turnover number reached 1380 or more. The coupling product 2 is considered formed by radical-radical coupling. Methyl methacrylate 1d afforded an isolable head-to-tail coupling product 2d and an inseparable mixture of oligomers, probably due to radical chain reaction. Measurement of the FT-IR of gas phase over the reaction solution showed N2O was completely consumed under the reaction conditions. UV-Vis spectra and EPR spectra of reaction solution under Ar instead of N2O clearly indicated the formation of Fe(I)porphyrin intermediate. Bubbling of N2O into the solution at 20˚C caused the EPR signal to disappear. These results indicate that Fe(I) (TPP) reduces N2O to N2 and O2-, regenerating Fe(III)(TPP). Thus, the reaction enables both N2O consumption and synthesis of coupling products, some of which would be useful for organic synthesis. We proposed a reaction mechanism (Scheme). Since N2O may become the dominant ozone-depleting substance emitted in the 21st century, the reaction system described here might prove useful as a green process to decrease emissions of N2O, perhaps in conjunction with large-scale synthetic applications.@font-face { "ＭＳ 明朝"; }@font-face { "Cambria Math"; }@font-face { "@ＭＳ 明朝"; }@font-face { "AdvOT999035f4"; }p.MsoNormal, li.MsoNormal, div.MsoNormal { margin: 0mm 0mm 0.0001pt; font-size: 10pt; ""; }.MsoChpDefault { font-size: 10pt; }div.WordSection1 { page: WordSection1; }References(1) (a) B. Meunier, A. Robert, G. Pratviel and J. Bernadou, in The Porphyrin Handbook, ed. K. M. Kadish, K. M. Smith and R. Guilard, Academic Press, San Diego, 2000, ch. 31, vol. 4, pp. 119–187; (b) J. T. Groves, K. Shalyaev and J. Lee, in The Porphyrin Handbook, ed. K. M. Kadish, K. M. Smith and R. Guilard, Academic Press, San Diego, 2000, ch. 27, vol. 4, pp. 17–40.(2) R. Ito, N. Umezawa and T. Higuchi, J. Am. Chem. Soc., 2005, 127,834–835, and references therein.(3) S. Saito, H. Ohtake, N. Umezawa, Y. Kobayashi, N. Kato, M. Hirobe, T. Higuchi, Chem. Commun. 2013, 49, 8979-8981.

Synthesis of a cyclic isostere of α-methyl homoserine by a stereoselective acylation–alkylation sequence of a chiral γ-lactam

Starting from a chiral 4-hydroxymethyl pyrrolidin-2-one, an isostere of α-methyl homoserine tethered on a γ-lactam ring was prepared exploiting a stereoselective acylation-methylation sequence, followed by Curtius rearrangement, and structural assignment was confirmed by n.O.e. experiments. By reverting the sequence, the 3-carboxy-3-methyl derivative having the opposite configuration at C-3 was obtained with total stereoselection, but Curtius rearrangement invariably afforded only inseparable mixtures of decomposition products.

Indium-Bridged [1]Ferrocenophanes

Indium-bridged [1]ferrocenophanes ([1]FCPs) and [1.1]ferrocenophanes ([1.1]FCPs) were synthesized from dilithioferrocene species and indium dichlorides. The reaction of Li2fc⋅tmeda (fc = (H4C5)2Fe) and (Mamx)InCl2 (Mamx = 6-(Me2NCH2)-2,4-tBu2C6H2) gave a mixture of the [1]FCP (Mamx)Infc (4(1)), the [1.1]FCP [(Mamx)Infc]2 (4(2)), and oligomers [(Mamx)Infc]n (4(n)). In a similar reaction, employing the enantiomerically pure, planar-chiral (Sp,Sp)-1,1'-dibromo-2,2'-diisopropylferrocene (1) as a precursor for the dilithioferrocene derivative Li2fc(iPr2), equipped with two iPr groups in the α position, gave the inda[1]ferrocenophane 5(1) [(Mamx)Infc(iPr2)] selectively. Species 5(1) underwent ring-opening polymerization to give the polymer 5(n). The reaction between Li2fc(iPr2) and Ar'InCl2 (Ar' = 2-(Me2NCH2)C6H4) gave an inseparable mixture of the [1]FCP Ar'Infc(iPr2) (6(1)) and the [1.1]FCP [Ar'Infc(iPr2)]2 (6(2)). Hydrogenolysis reactions (BP86/TZ2P) of the four inda[1]ferrocenophanes revealed that the structurally most distorted species (5(1)) is also the most strained [1]FCP.

Euryjanicins E–G, poly-phenylalanine, and poly-proline cyclic heptapeptides from the Caribbean sponge Prosuberites laughlini

A new investigation of the active sponge extracts of Prosuberites laughlini collected off the West coast of Puerto Rico has yielded three new cyclic heptapeptides, namely euryjanicins E (1)–G (3), containing multiple phenylalanine and proline residues. In CDCl3 solution, each euryjanicin F (2) and G (3) exists as an inseparable complex mixture of conformational isomers. The molecular structures of 1–3 were elucidated by a combination of chemical degradation, extensive ESI-MS/MSn analyses, and 2D NMR methods. The elucidation of the absolute configuration was achieved by HPLC following analysis of the acid hydrolysates after derivatization with Marfey's reagent. When assayed against the National Cancer Institute 60 tumor cell line panel, the new cyclic peptides did not display significant in vitro cytotoxicity.

Efficient NMR enantiodiscrimination of bridge fluorinated paracyclophanes using lanthanide tris β-diketonate complexes

A selection of amino-substituted 1,1,2,2,9,9,10,10 octafluoro[2.2]paracyclophanes were tested for enantiodiscrimination by 1H and 19F NMR spectroscopy via their interaction with different lanthanide tris β-diketonate chiral shift reagents. The amino-, and the pseudo-ortho di-amino substituted octafluoro[2.2]paracyclophanes, both of which exhibit planar chirality, revealed significant shifts and splittings of various 1H and 19F NMR signals upon the addition of the chiral shift reagents, which allowed the easy determination of the enantiomeric purity. When the chiral shift reagent was added to an inseparable mixture of the (chiral) pseudo-meta, and (achiral) pseudo-para diamino analogues, both the chiral and achiral molecules revealed NMR doubling. In the case of the achiral molecule, this NMR behavior is due to the meso nature of the pseudo-para species.

Hydride Dynamics in Triosmium and Triruthenium Carbonyl Clusters: Synthesis, Reactivity and Dynamics of a Trihydrido Quinoline-4-Carboxaldehyde Triosmium Cluster

An overview of the dynamical processes involving the hydrido ligand in triosmium and triruthenium carbonyl clusters is presented. The relationship between the mechanisms of hydride motions and the other ligands in the cluster are discussed for mono- di- and trihydrido-clusters. In addition, the reactivity of the electron deficient 46e− cluster, (μ-H)(μ3-η2-C9H5N-4-CHO)Os3(CO)9 (1) with hydrogen is reported. The reaction gives two isomeric trihydrido clusters, H(μ-H)2(μ3-η2-C9H5N-4-CHO)Os3(CO)8 (2) and (μ-H)3(μ3-η2-C9H5N-4-CHO)Os3(CO)8 (2′) in low yield along with trace amounts of other hydrido clusters. Reaction of the inseparable mixture of 2 and 2′ with triphenylphosphine at ambient temperatures gives two related addition products H(μ-H)2(μ-η2-C9H5N-4-CHO)Os3(CO)8PPh3 (3) and (μ-H)3(μ-η2-C9H5N-4-CHO)Os3(CO)8PPh3 (3′) in a 5:1 ratio. These results contrast with the previously reported trihydrido-derivatives of triosmium μ3-η2-imidoyl clusters where only analogues of 2 and 3 are obtained. Clusters 2 and 2′ are rigid on the NMR time scale while 3 exhibits dynamical behavior in the temperature range of −50 to +25 °C. Cluster 3′ is stereochemically rigid in this temperature range. The dynamical behavior of 3 involves the exchange of the terminal and bridging hydrides coupled with tripodal motion of the phosphine substituted osmium atom, a process virtually identical to previously reported trihydrides of the μ3-η2-imidoyl triosmium clusters.

ChemInform Abstract: Synthesis of Highly Substituted Tetrahydrofurans by Catalytic Polar‐Radical‐Crossover Cycloadditions of Alkenes and Alkenols.

AbstractThe products are isolated as inseparable mixtures of diastereomers, some also containing traces of additional diastereomers not shown in the scheme.

Opening of the azastibol heterocycle with various acids: Isolation of novel N,C-chelated organoantimony(III) compounds

The reaction of N,C-intramolecularly coordinated organoantimony(III) compound L2SbCl (1) (where L is [2-(2′,6′-i-Pr2C6H3)NCHC6H4]) with one molar equivalent of the K-selectride (K[B(s-Bu)3H]) gave compound LSb{2-[CH2N(2′,6′-i-Pr2C6H3)]C6H4} (2) containing five membered aza-stiba heterocycle. On the contrary, analogical reaction between the organobismuth(III) compound L2BiCl (3) and K-selectride gave only inseparable mixture of products. Reactions of 2 with selected acids HX resulted in the cleavage of the present Sb–N bond and formation of novel N,C-chelated compounds LSb(X){2-[CH2NH(2′,6′-i-Pr2C6H3)]C6H4} (where X = Cl (4), CH3COO (5), CF3COO (6), CF3SO3 (7) or FcCOO (8); Fc = ferrocenyl). Compounds 4–8 were characterized by the help of elemental analysis, electrospray ionization (ESI) mass spectrometry, multinuclear NMR spectroscopy, IR spectroscopy and in the case of 5 by the single-crystal X-ray diffraction analysis. The molecular structures of compounds LSb(X){2-[CH2NH(2′,6′-i-Pr2C6H3)]C6H4}·HX (where X = CF3COO (6a), CF3SO3 (7a)) were determined by the single-crystal X-ray diffraction analysis as well. Compounds 6a and 7a are most probably products of partial hydrolysis of compounds 6 and 7.

Ligand Exchange at a Gold(I) Carbene Complex

Abstract Gold complex [AuCl(NHC)] (NHC=N,N0-dipropylbenzimidazolin-2-ylidene) 1 undergoes facile substitution reactions at the gold(I) center. Treatment of 1 with anionic phenylacetylide or thiophenolate led to the neutral gold complexes 2 and 3, respectively. The cationic gold complexes [Au(NHC)(pyridine)](BF4) [4]BF4 and [Au2(NHC)2(4,4'-bipyridine)](BF4)2 [5](BF4)2 were obtained via abstraction of the chloro ligand from 1 and reaction with the appropriate amine. Reaction of 1 with AgBF4 in the presence of PPh3 instead of an amine led to an inseparable product mixture of the mixed NHC=PPh3 complex [6]BF4, the dicarbene complex [Au(NHC)2]BF4, [7]BF4, and [Au(PPh3)2]BF4, [8]BF4. Crystals of 2 and [6]BF4 were obtained, and X-ray diffraction structure analyses revealed that the gold(I) atoms are coordinated in a linear fashion by the NHC and the co-ligand

ChemInform Abstract: Stereoselective Synthesis of 1,3‐anti Diols by an Ipc‐Mediated Domino Aldol‐Coupling/Reduction Sequence.

AbstractDiols and intermediate boronates are obtained as inseparable mixtures of anti/anti diastereomers whereas excellent anti/syn diastereoselectivity is observed.

Spirostane, furostane and cholestane saponins from Persian leek with antifungal activity

A phytochemical investigation of the seeds of Persian leek afforded the isolation of two new spirostane glycosides, persicosides A (1) and B (2), four new furostane glycosides, isolated as a couple of inseparable mixture, persicosides C1/C2 (3a/3b) and D1/D2 (4a/4b), one cholestane glycoside, persicoside E (5), together with the furostane glycosides ceposides A1/A2 and C1/C2 (6a/6b and 7a/7b), tropeosides A1/A2 and B1/B2 (8a/8b and 9a/9b), and ascalonicoside A1/A2 (10a/10b), already described in white onion, red Tropea onion, and shallot, respectively. Structure elucidation of the compounds was carried out by comprehensive spectroscopic analyses, including 2D NMR spectroscopy and MS spectrometry, and by chemical evidences. The chemical structure of new compounds were identified as (25S)-spirostan-2α,3β,6β-triol 3-O-[β-d-glucopyranosyl-(1→3)] [β-d-xylopyranosyl-(1→2)]-β-d-glucopyranosyl-(1→4)-β-d-galactopyranoside (1), (25S)-spirostan-2α,3β,6β-triol 3-O-[β-d-xylopyranosyl-(1→3)] [α-l-rhamnopyranosyl-(1→2)]-β-d-glucopyranosyl-(1→4)-O-β-d-galactopyranoside (2), furosta-1β,3β,22ξ,26-tetraol 5-en 1-O-β-d-glucopyranosyl (1→3)-β-d-glucopyranosyl (1→2)-β-d-galactopyranosyl 26-O-α-l-rhamnopyranosyl (1→2)-β-d-galactopyranoside (3a,3b), furosta-2α,3β,22ξ,26-tetraol 3-O-β-d-glucopyranosyl (1→3)-β-d-glucopyranosyl (1→2)-β-d-galactopyranosyl 26-O-β-d-glucopyranoside (4a,4b), (22S)-cholesta-1β,3β,16β,22β-tetraol 5-en 1-O-α-l-rhamnopyranosyl 16-O-α-l-rhamnopyranosyl (1→2)-β-d-galactopyranoside (5).Antifungal activity of the isolated compounds was evaluated against the fungal pathogens, Penicillium italicum, Aspergillus niger, Trichoderma harzianum and Botrytis cinerea. Persicosides A and B showed the higher activity on the tested fungi highlighting the positive effect of the spirostane skeleton on the antifungal activity.

The Use of Sodium Chlorite in the Direct Synthesis of Glycidic Amides: Enantiopure Synthesis of Both Enantiomers of Norbalasubramide

Recently, the first direct method for preparing 2,3-epoxyamides (glycidic amides) was disclosed. Now in this letter, the enantiopure synthesis of both enantiomers of norbalasubramide featuring this synthetic method is reported. To this end, chiral <i>N</i>-allyltryptamine <b>12</b> was prepared and transformed into an inseparable mixture of diastereomeric epoxyamides <b>13a</b>/<b>13b</b>, which were submitted to intramolecular cyclization with Cu(OTf)₂ to afford a separable mixture of eight-membered ring lactams <b>14a</b> and <b>14b</b>. Finally, after removal of the protective group and the chiral auxiliary an enantiopure synthesis of the title compounds was completed.