Dimerization of a cell-penetrating peptide leads to enhanced cellular uptake and drug delivery

• Jan Hoyer,
• Ulrich Schatzschneider,
• Michaela Schulz-Siegmund and
• Ines Neundorf

Beilstein J. Org. Chem. 2012, 8, 1788–1797, doi:10.3762/bjoc.8.204

• medium (DMEM), Ham’s F12 (without L-glutamine), OptiMEM, Dulbecco’s phosphate buffered saline (PBS) without calcium and magnesium, fetal bovine serum (FBS), L-glutamine and trypsin/EDTA (all purchased from PAA, Linz, Austria, or Gibco Life Technologies, Karlsruhe, Germany). Cell culture flasks (75 cm2

Synthesis and evaluation of new guanidine-thiourea organocatalyst for the nitro-Michael reaction: Theoretical studies on mechanism and enantioselectivity

• Tatyana E. Shubina,
• Matthias Freund,
• Sebastian Schenker,
• Timothy Clark and
• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2012, 8, 1485–1498, doi:10.3762/bjoc.8.168

• magnesium sulfate. Product 10 was isolated by preparative thin-layer chromatography over silica gel. 1H NMR (300 MHz, DMSO-d6) δ 1.58–1.83 (m, 2H), 2.55–2.82 (m, 2H), 4.05–4.17 (m, 1H), 4.39 (dd, J = 9.3 Hz, J = 12.2 Hz, 1H), 4.71 (dd, J = 3.0 Hz, J = 12.2 Hz, 1H), 5.48 (d, J = 6.4 Hz, 1H), 7.10–7.36 (m, 5H

• with aqueous 20% potassium hydrogen sulfate solution (3 mL) and brine (3 mL). After drying over magnesium sulfate, the organic phase was evaporated and purified by column chromatography over silica gel (petrol ether/ethyl acetate 2:1) to yield 13 (19.00 mg, 76.23 μmol, 54%). 1H NMR (300 MHz, CDCl3) δ

Synthesis of diverse indole libraries on polystyrene resin – Scope and limitations of an organometallic reaction on solid supports

• Kerstin Knepper,
• Sylvia Vanderheiden and
• Stefan Bräse

Beilstein J. Org. Chem. 2012, 8, 1191–1199, doi:10.3762/bjoc.8.132

• after thin-layer chromatography. A slightly higher temperature was optimal for the reaction of (3-methyl-4-nitrophenyl)carboxymethyl-polystyrene (1{i}) with the less active vinyl magnesium bromide 2{a} (Figure 3). In addition to this, we also varied the amount of Grignard reagent for the reaction of 1{h

• , and the filtrate is hydrolyzed with water and subsequently extracted with ethyl acetate three times. After being dried over magnesium sulfate, the solvent is removed under reduced pressure and the residue is purified by column chromatography by using cyclohexane/ethyl acetate, 3:1 as eluent

Screening of ligands for the Ullmann synthesis of electron-rich diaryl ethers

• Nicola Otto and
• Till Opatz

Beilstein J. Org. Chem. 2012, 8, 1105–1111, doi:10.3762/bjoc.8.122

• ). It turned out that caesium carbonate as a base without addition of molecular sieves did not result in any diaryl ether formation, presumably due to the formation of water inactivating the base. With chemical drying agents such as magnesium sulfate, only trace amounts of the product were obtained. In

Toward unidirectional switches: 2-(2-Hydroxyphenyl)pyridine and 2-(2-methoxyphenyl)pyridine derivatives as pH-triggered pivots

• Christina Tepper and
• Gebhard Haberhauer

Beilstein J. Org. Chem. 2012, 8, 977–985, doi:10.3762/bjoc.8.110

• over magnesium sulfate, and the solvent was removed in vacuo. The residue was purified by column chromatography over silica gel (n-hexane/AcOEt 1:1). The product was obtained as a colorless solid (77 mg, 39%). 1H NMR (500 MHz, CDCl3) δ 7.74 (dd, 3JH,H = 7.6 Hz, 4JH,H = 1.9 Hz, 1H, Har), 7.59–7.58 (m

• poured into a dichloromethane/water mixture. The organic layer was separated and dried over magnesium sulfate, and the solvent was removed in vacuo. The product was obtained as a colorless solid (32 mg, 95%). 1H NMR (500 MHz, CDCl3) δ 14.72 (bs, 1H, OH), 7.86 (dd, 3JH,H = 8.0 Hz, 4JH,H = 1.6 Hz, 1H, Har

• afterwards 2-methoxyphenylboronic acid (14 mg, 0.092 mmol) was added and the mixture was heated to 80 °C for 4 h. After cooling to room temperature, water and ethyl acetate were added. The aqueous phase was extracted with ethyl acetate. The organic layers were combined and dried over magnesium sulfate, and

Two-directional synthesis as a tool for diversity-oriented synthesis: Synthesis of alkaloid scaffolds

• Kieron M. G. O’Connell,
• Monica Díaz-Gavilán,
• Warren R. J. D. Galloway and
• David R. Spring

Beilstein J. Org. Chem. 2012, 8, 850–860, doi:10.3762/bjoc.8.95

• intramolecular conjugate addition. Three of these compounds (1–3) were obtained from the corresponding alcohols [19][20] in three steps: Mitsunobu reaction with NH-Boc-tosylate, followed by tosyl deprotection with magnesium, and finally two-directional cross metathesis with ethyl acrylate to install the desired

2-Allylphenyl glycosides as complementary building blocks for oligosaccharide and glycoconjugate synthesis

• Hemali D. Premathilake and
• Alexei V. Demchenko

Beilstein J. Org. Chem. 2012, 8, 597–605, doi:10.3762/bjoc.8.66

• <40 °C. CH2Cl2 and ClCH2CH2Cl were distilled from CaH2, directly prior to application. Anhydrous DMF (EM Science) was used as received. Methanol was dried by heating under reflux with magnesium methoxide, distilled and stored under argon. Pyridine and acetonitrile were dried by heating under reflux

Volatile organic compounds produced by the phytopathogenic bacterium Xanthomonas campestris pv. vesicatoria 85-10

• Teresa Weise,
• Marco Kai,
• Anja Gummesson,
• Armin Troeger,
• Stephan von Reuß,
• Silvia Piepenborn,
• Francine Kosterka,
• Martin Sklorz,
• Ralf Zimmermann,
• Wittko Francke and
• Birgit Piechulla

Beilstein J. Org. Chem. 2012, 8, 579–596, doi:10.3762/bjoc.8.65

• dried over magnesium sulfate. The solvent was removed in vacuo, and the residue was submitted to flash chromatography (silica; cyclohexane/ethyl acetate 40:1) yielding 2.44 g (29.8 mmol, 83%) of 2-benzyloxypent-3-yne (A). A solution of 2.70 g (15.5 mmol) of A in 50 mL dry THF was cooled to −78 °C and

• aqueous solution of ammonium chloride was added. After separation, the aqueous layer was extracted with three portions of diethyl ether at 50 mL each. The combined organic solutions were washed with brine and dried over magnesium sulfate. The solvent was removed in vacuo, and the residue was submitted to

A ferrocene redox-active triazolium macrocycle that binds and senses chloride

• Nicholas G. White and
• Paul D. Beer

Beilstein J. Org. Chem. 2012, 8, 246–252, doi:10.3762/bjoc.8.25

• organic fractions were dried (magnesium sulfate), taken to dryness under reduced pressure and then purified by column chromatography (silica, gradient: 3% methanol in dichloromethane) to give 3 as an orange powder. Yield: 0.065 g (54%). 1H NMR (CDCl3) δ 7.44 (s, 2H, trz-H), 5.06 (s, 4H, Fc-CH2-trz), 4.15

Efficient oxidation of oleanolic acid derivatives using magnesium bis(monoperoxyphthalate) hexahydrate (MMPP): A convenient 2-step procedure towards 12-oxo-28-carboxylic acid derivatives

• Jorge A. R. Salvador,
• Vânia M. Moreira,
• Rui M. A. Pinto,
• Ana S. Leal and
• José A. Paixão

Beilstein J. Org. Chem. 2012, 8, 164–169, doi:10.3762/bjoc.8.17

• /bjoc.8.17 Abstract A new, straightforward and high yielding procedure to convert oleanolic acid derivatives into the corresponding δ-hydroxy-γ-lactones, by using the convenient oxidizing agent magnesium bis(monoperoxyphthalate) hexahydrate (MMPP) in refluxing acetonitrile, is reported. In addition, a

• ][24], but weak selectivity and low isolated yields were observed. Alternatively, oxidation reagents such as H2O2 in acetic acid [25][26], the inorganic salt mixture KMnO4/CuSO4 [27], ozone [15][28][29] and m-chloroperoxybenzoic acid (mCPBA) [30][31] have also been reported. Magnesium bis

• dissolved in acetonitrile under reflux, and MMPP (2.0–3.0 equiv) was added to the solution under strong magnetic stirring. After completion of the reaction, the magnesium salts were easily filtered off after evaporation of the acetonitrile and suspension of the resulting white solid in ethyl acetate. We

Fluorescent hexaaryl- and hexa-heteroaryl[3]radialenes: Synthesis, structures, and properties

• Antonio Avellaneda,
• Courtney A. Hollis,
• Xin He and
• Christopher J. Sumby

Beilstein J. Org. Chem. 2012, 8, 71–80, doi:10.3762/bjoc.8.7

• water (40 mL) and extracted with dichloromethane (50 mL) followed by further dichloromethane (5 × 25 mL). The organic extracts were combined, dried over anhydrous magnesium sulfate, and the solvent was evaporated to yield a red–brown oil. Purification via alumina chromatography eluting with 9:1 CH2Cl2

• % w/v, 5 mL). The mixture was extracted with dichloromethane (6 × 10 mL). The organic fractions were combined and washed with 1 M hydrochloric acid solution (20 mL), 1 M sodium thiosulfate solution (20 mL), dried over anhydrous magnesium sulfate and the solvent was evaporated under vacuum to yield a

• mixture was diluted with ethyl acetate (40 mL) and the resultant solution was washed with concentrated ammonia solution (30 mL), water (20 mL) and brine (20 mL). Then, it was dried over anhydrous magnesium sulfate and the solvent evaporated under vacuum to yield 6 as an off-white solid (0.33 g, 90%). Mp

Binding of group 15 and group 16 oxides by a concave host containing an isophthalamide unit

• Jens Eckelmann,
• Vittorio Saggiomo,
• Svenja Fischmann and
• Ulrich Lüning

Beilstein J. Org. Chem. 2012, 8, 11–17, doi:10.3762/bjoc.8.2

• of triethylamine was evaporated under reduced pressure. The residue was dissolved in chloroform (25 mL) and water (25 mL). The water phase was extracted once with chloroform (25 mL), the combined organic layer was dried with magnesium sulfate and evaporated under reduced pressure to yield a yellow

• residue was dissolved in chloroform (25 mL) and water (25 mL). The aqueous phase was extracted with chloroform (25 mL). The organic layers were collected, dried with magnesium sulfate and the solvent was evaporated under reduced pressure. The product was isolated by column chromatography (silica

Functionalization of heterocyclic compounds using polyfunctional magnesium and zinc reagents

• Paul Knochel,
• Matthias A. Schade,
• Sebastian Bernhardt,
• Georg Manolikakes,
• Albrecht Metzger,
• Fabian M. Piller,
• Christoph J. Rohbogner and
• Marc Mosrin

Beilstein J. Org. Chem. 2011, 7, 1261–1277, doi:10.3762/bjoc.7.147

• the most important procedures for the preparation of functionalized organzinc and organomagnesium reagents. In addition, new methods for the preparation of polyfunctional aryl- and heteroaryl zinc- and magnesium compounds, as well as new Pd-catalyzed cross-coupling reactions, are reported herein

• pharmaceutical research. In this review article, we describe the approaches to this problem that use functionalized magnesium and zinc heterocyclic intermediates. Some typical experimental procedures are indicated in each case for the most important methods. New Pd-catalyzed cross-coupling procedures are also

• require the use of transition metal catalysts. The preparation of aryl and heteroaryl zinc derivatives is conveniently achieved by three general procedures: the direct insertion of zinc dust to aryl or heteroaryl iodides or bromides; the direct insertion of magnesium in the presence of Zn(II) salts to

Combined directed ortho-zincation and palladium-catalyzed strategies: Synthesis of 4,n-dimethoxy-substituted benzo[b]furans

• Verónica Guilarte,
• M. Pilar Castroviejo,
• Estela Álvarez and
• Roberto Sanz

Beilstein J. Org. Chem. 2011, 7, 1255–1260, doi:10.3762/bjoc.7.146

• ), the introduction in the last years of new organometallic “ate” complexes [8][9], which combine an alkali metal with either magnesium, zinc, aluminium, or copper, has allowed more selective metallation reactions. The milder reaction conditions required make these deprotonation reactions tolerant to the

Meta-metallation of N,N-dimethylaniline: Contrasting direct sodium-mediated zincation with indirect sodiation-dialkylzinc co-complexation

• David R. Armstrong,
• Liam Balloch,
• Eva Hevia,
• Alan R. Kennedy,
• Robert E. Mulvey,
• Charles T. O'Hara and
• Stuart D. Robertson

Beilstein J. Org. Chem. 2011, 7, 1234–1248, doi:10.3762/bjoc.7.144

• different components. The work of Knochel uncovered a special reactivity and selectivity that can be realised with a mixed lithium halide–magnesium amide complex sometimes labelled a “turbo-Grignard” reagent [8]. It has been proposed that LiCl breaks up the magnesium amide aggregates allowing more soluble

A practical route to tertiary diarylmethylamides or -carbamates from imines, organozinc reagents and acyl chlorides or chloroformates

• Erwan Le Gall,
• Antoine Pignon and
• Thierry Martens

Beilstein J. Org. Chem. 2011, 7, 997–1002, doi:10.3762/bjoc.7.112

• imine/carbonyl-containing compound mixture and the resulting mixture was stirred at rt for 30 min. The solution was poured into a sat. NH4Cl solution (100 mL), extracted with diethyl ether (2 × 75 mL) and the combined organic fractions were dried with magnesium sulfate, filtrated and then concentrated

Synthesis of novel 5-alkyl/aryl/heteroaryl substituted diethyl 3,4-dihydro-2H-pyrrole-4,4-dicarboxylates by aziridine ring expansion of 2-[(aziridin-1-yl)-1-alkyl/aryl/heteroaryl-methylene]malonic acid diethyl esters

• Satish S. More,
• T. Krishna Mohan,
• Y. Sateesh Kumar,
• U. K. Syam Kumar and
• Navin B. Patel

Beilstein J. Org. Chem. 2011, 7, 831–838, doi:10.3762/bjoc.7.95

• -chloromethylene)malonates 19. The chloro alkenyl malonates 19 were synthesized in two steps from diethyl malonate and acid chlorides. The acylation of diethyl malonate was carried out with various acyl chlorides in the presence of anhydrous magnesium chloride and triethylamine, as per the reaction conditions

An overview of the key routes to the best selling 5-membered ring heterocyclic pharmaceuticals

• Marcus Baumann,
• Ian R. Baxendale,
• Steven V. Ley and
• Nikzad Nikbin

Beilstein J. Org. Chem. 2011, 7, 442–495, doi:10.3762/bjoc.7.57

• chloride 89 are added concurrently from two different sides of the reactor to stop these reagents reacting with each other. This method of adding the reagents circumvents the necessity to isolate the magnesium salt of the indole and increases the yield from 50 to 82%. The carbonyl group of the proline side

Oxidative allylic rearrangement of cycloalkenols: Formal total synthesis of enantiomerically pure trisporic acid B

• Silke Dubberke,
• Muhammad Abbas and
• Bernhard Westermann

Beilstein J. Org. Chem. 2011, 7, 421–425, doi:10.3762/bjoc.7.54

• cyclohexenone (+)-7, which is the key building block in our synthesis, was the incorporation of a C2 unit into β-ketoester (−)-1c (Scheme 3). This was achieved by adding ethynyl magnesium bromide in THF at room temperature. The cyclohexenol (+)-6 can be isolated in 79% yield with a diastereomeric ratio of 96:4

• -dimethylcyclohex-3-ene-1-carboxylate (6). To a solution of (−)-1c (0.50 g, 2.75 mmol) in THF (5 mL), was added dropwise over a period of 30 min ethynyl magnesium bromide (0.5 M in THF; 9.05 mL, 4.53 mmol) at 20 °C. Stirring at this temperature was continued for 1 h, and then the reaction mixture was quenched by

Anion–π interactions influence pK_a values

• Christopher J. Cadman and
• Anna K. Croft

Beilstein J. Org. Chem. 2011, 7, 320–328, doi:10.3762/bjoc.7.42

• heated (110 °C, 19–43 h, Table 4) then left to cool and extracted twice with diethyl ether (25 cm3) and water (25 cm3), and once with brine (25 cm3). The extracts were dried with magnesium sulfate. The products (1–5) were isolated by column chromatography on silica gel with hexane/ethyl acetate as the

Reciprocal polyhedra and the Euler relationship: cage hydrocarbons, C_nH_n and closo-boranes [B_xH_x]²⁻

• Michael J. McGlinchey and
• Henning Hopf

Beilstein J. Org. Chem. 2011, 7, 222–233, doi:10.3762/bjoc.7.30

• by sodium- or magnesium-mediated dehalogenation of the appropriate REX3 precursor, where R is a very bulky alkyl or aryl group, and X is chlorine or bromine [38][39]. The hexatellurium cation, [Te6]4+, is also trigonal prismatic [40][41]. Similarly, the inorganic cubane analogues R8E8, where E = Si

Photocycloaddition of aromatic and aliphatic aldehydes to isoxazoles: Cycloaddition reactivity and stability studies

• Axel G. Griesbeck,
• Marco Franke,
• Jörg Neudörfl and
• Hidehiro Kotaka

Beilstein J. Org. Chem. 2011, 7, 127–134, doi:10.3762/bjoc.7.18

• , extracted two times with chloroform, dried over magnesium sulfate and filtered. The solvent was evaporated and the residual oil distilled (170 °C) to give 23.01 g (72%) of 3 as a colorless oil. 13C NMR (75.5 MHz, CDCl3): 204.8 (2C, Cq), 190.1 (1C, Cq), 104.5 (1C, Cq), 61.4 (1C, CH), 28.4 (2C, CH3), 23.0 (1C

• organic layers were neutralized with aqueous sodium hydroxide. The organic solution was then washed two times with water, dried over magnesium sulfate, filtered and evaporated. The resulting solid was recrystallized twice from ethanol to yield 6.34 g (41%) of 4 as colorless crystals. 13C NMR (75.5 MHz

• hydrochloride (5.56 g, 80 mmol), potassium carbonate (5.53 g, 40 mmol), ethanol (40 mL) and water (40 mL) was stirred at rt for 15 h. The solid was filtered, washed with water and extracted three times with ether. The combined organic layers were dried over magnesium sulfate, filtered and the solvent was

Redox-active tetrathiafulvalene and dithiolene compounds derived from allylic 1,4-diol rearrangement products of disubstituted 1,3-dithiole derivatives

• Filipe Vilela,
• Peter J. Skabara,
• Christopher R. Mason,
• Thomas D. J. Westgate,
• Asun Luquin,
• Simon J. Coles and
• Michael B. Hursthouse

Beilstein J. Org. Chem. 2010, 6, 1002–1014, doi:10.3762/bjoc.6.113

• ) and re-extracted with dichloromethane or ethyl acetate (3 × 100 cm3). The combined extracts were dried over magnesium sulfate and the solvent removed under reduced pressure. All compounds were purified by column chromatography (silica). 4,6-Diphenyl-4,6-dihydro-[1,3]dithiolo[4,5-c]furan-2-thione (5

• ), dried over magnesium sulfate and filtered. The solvent was removed under reduced pressure to yield a straw-coloured solid which was purified by recrystallisation from dichloromethane and petroleum ether 40/60, to give 26 as straw needles, 0.145 g, 89%, mp 118–124 °C; EI+ MS (M+) 306; Accurate mass

• added and the reaction stirred at room temperature for 16 h, during which time a white precipitate formed. The mixture was added to water (50 ml) and extracted with dichloromethane (3 × 100 ml). The combined organic extracts were dried over magnesium sulfate, filtered, and the solvent was removed under

Chain stopper engineering for hydrogen bonded supramolecular polymers

• Thomas Pinault,
• Bruno Andrioletti and
• Laurent Bouteiller

Beilstein J. Org. Chem. 2010, 6, 869–875, doi:10.3762/bjoc.6.102

• mmol) in dry THF (100 mL) was then added, and the solution heated under reflux for 24 h. After cooling, ice was slowly added and the solvent evaporated. Chloroform (200 mL) was added and the organic phase washed successively with brine (300 mL) and water (2 × 300 mL), dried over magnesium sulfate and

• over magnesium sulfate and concentrated. Silica gel column chromatography (ethyl acetate/dichloromethane and then ethyl acetate) followed by recrystallization from pentane afforded 0.66 g of a white solid (57%). 1H NMR (200 MHz, DMSO-d6): δ (ppm) = 7.42/7.17 (2d, 4H, Ar-H), 3.21 (m, 6H, N-CH2), 2.15 (s

Novel 2-(ω-phosphonooxy-2-oxaalkyl)acrylate monomers for self-etching self-priming one part adhesive

• Joachim E. Klee and
• Uwe Lehmann

Beilstein J. Org. Chem. 2010, 6, 766–772, doi:10.3762/bjoc.6.95

• ) 1,2-ethanediol. After stirring for 12 h at room temperature, the solution was washed successively with 1 × 200 mL water, 2 × 250 mL of an aqueous sodium carbonate solution (25 wt %) and 1 × 200 mL water. The organic layer was dried over magnesium sulfate and filtered. After the evaporation of the

• . The layers were separated and the aqueous layer was washed with 2 × 100 mL diethyl ether. The aqueous layer was reduced in volume to 100 mL and extracted with 4 × 100 mL dichloromethane. The combined organic extracts were dried over magnesium sulfate, filtered and evaporated to yield 19 g of a yellow