An improved synthesis of adefovir and related analogues

• David J. Jones,
• Eileen M. O’Leary and
• Timothy P. O’Sullivan

Beilstein J. Org. Chem. 2019, 15, 801–810, doi:10.3762/bjoc.15.77

• Sciences, Cork Institute of Technology, Cork, Ireland 10.3762/bjoc.15.77 Abstract An improved synthesis of the antiviral drug adefovir is presented. Problems associated with current routes to adefovir include capricious yields and a reliance on problematic reagents and solvents, such as magnesium tert

• studies [35][37][38][39]. While it was demonstrated that magnesium tert-butoxide (MTB) is the optimum base for this transformation (Scheme 1), it is not without drawbacks. MTB is expensive and hydrolyses on storage when exposed to moisture. The yield for the reaction is often inconsistent, being highly

• dependent on the quality of the MTB employed. The reaction does not proceed to completion when a stoichiometric amount of the base is used and up to 3.0 equivalents may be required in order to ensure complete consumption of the starting alcohol. The resultant magnesium salts are highly deliquescent and form

Synthesis of the aglycon of scorzodihydrostilbenes B and D

• Katja Weimann and
• Manfred Braun

Beilstein J. Org. Chem. 2019, 15, 610–616, doi:10.3762/bjoc.15.56

• brine and dried with magnesium sulfate. The solvent was removed in a rotary evaporator and the crude product (1.08 g) was purified by column chromatography (silica gel; ethyl acetate/n-hexane, 1:4 to 1:2) to give 91 mg (14%) of pure glycoside 12 as a colorless syrup. 1H NMR (CDCl3, 600 MHz) δ 2.04 (s

Syntheses and chemical properties of β-nicotinamide riboside and its analogues and derivatives

• Mikhail V. Makarov and
• Marie E. Migaud

Beilstein J. Org. Chem. 2019, 15, 401–430, doi:10.3762/bjoc.15.36

• order to manipulate the NAD+ pathway in mammalian cells and tissues. The key step in the synthesis of the NMN analogues 39–41 is the activation of the 5′-hydroxy group of the NRH acetonide 42 with a Grignard reagent, to produce the corresponding magnesium alkoxide. As illustrated by the synthesis of the

Study on the regioselectivity of the N-ethylation reaction of N-benzyl-4-oxo-1,4-dihydroquinoline-3-carboxamide

• Pedro N. Batalha,
• Luana da S. M. Forezi,
• Maria Clara R. Freitas,
• Nathalia M. de C. Tolentino,
• Ednilsom Orestes,
• José Walkimar de M. Carneiro,
• Fernanda da C. S. Boechat and
• Maria Cecília B. V. de Souza

Beilstein J. Org. Chem. 2019, 15, 388–400, doi:10.3762/bjoc.15.35

• carboxamide group, may contribute to enhance the bioactivity. This fact could be explained by the coplanarity induced by the C-4 carbonyl hydrogen bond interactions with biological targets [3] or complexation with physiological metal cations such as magnesium and zinc [23]. Besides the derivatives 3a and 3b

Mechanistic studies of an L-proline-catalyzed pyridazine formation involving a Diels–Alder reaction with inverse electron demand

• Anne Schnell,
• J. Alexander Willms,
• S. Nozinovic and
• Marianne Engeser

Beilstein J. Org. Chem. 2019, 15, 30–43, doi:10.3762/bjoc.15.3

• organic layer was washed with brine and dried over magnesium sulfate. The solvents were evaporated and the remaining solid was dissolved in 4.4 mL acetic acid at 0 °C. The mixture was stirred while a solution of sodium nitrite (839 mg, 12.17 mmol, 7.4 equiv) in 1 mL of deionized water was added dropwise

• . The mixture was stirred for another 3 h, after the solution of sodium nitrite had been added. 55 mL dichloromethane were added and the organic layer was washed twice with saturated sodium hydrogen carbonate solution and dried over magnesium sulfate. The solvents were evaporated and 340 mg of a pink

Thermophilic phosphoribosyltransferases Thermus thermophilus HB27 in nucleotide synthesis

• Ilja V. Fateev,
• Ekaterina V. Sinitsina,
• Aiguzel U. Bikanasova,
• Maria A. Kostromina,
• Elena S. Tuzova,
• Larisa V. Esipova,
• Tatiana I. Muravyova,
• Alexei L. Kayushin,
• Irina D. Konstantinova and
• Roman S. Esipov

Beilstein J. Org. Chem. 2018, 14, 3098–3105, doi:10.3762/bjoc.14.289

• (1.1 unit/mg) is observed at 60 °C. The activity at 36 °C is 5% from the maximal one and at 90 °C it is 3% from the maximal one. It is interesting, that TthAPRT shows its maximal activity at 75 °C. The influence of the magnesium ion concentration on the TthHPRT activity is nonlinear. The activity

• increases rapidly while the magnesium chloride concentration increases from 0 to 1 mM (Figure 4). Further increasing of the concentration (up to 5 mM) does not increase the activity significantly. Since the reaction rate increases rapidly with increasing the magnesium chloride concentration to values

• equivalent to the concentration of 5-phosphoribosyl-α-1-pyrophosphate (1 mM), it can be assumed that the presence of magnesium ions promotes the proper spatial orientation of the substrate. The reaction also proceeds in the absence of magnesium ions in solution. A similar dependence is observed for TthAPRT

Nucleofugal behavior of a β-shielded α-cyanovinyl carbanion

• Rudolf Knorr and
• Barbara Schmidt

Beilstein J. Org. Chem. 2018, 14, 3018–3024, doi:10.3762/bjoc.14.281

• °C; the subsequent cleavage reaction of the generated magnesium alkoxide 14b was very slow at rt, creating 2MgBr (Scheme 3) in the presence of t-BuCH=O (4) and therefrom 7 together with only a small amount of 1. This almost clean production of 7 agrees with the versatile [5] reactions of H2C=C(CN

• ; this provided a first evidence for the retro-addition process with an alkenylmetal intermediate. These fissions were slow in case of the magnesium alkoxide but rapid for the lithium or potassium alkoxides at ambient temperatures. (iii) The alternative trapping [3] of the carbonyl component by means of

Domino ring-opening–ring-closing enyne metathesis vs enyne metathesis of norbornene derivatives with alkynyl side chains. Construction of condensed polycarbocycles

• Ritabrata Datta and
• Subrata Ghosh

Beilstein J. Org. Chem. 2018, 14, 2708–2714, doi:10.3762/bjoc.14.248

• (G-II) was used. The norbornene derivative 7a was first chosen for investigating ROM–RCEYM. Compound 7a was prepared in the following way (Scheme 3). Reaction of the known lactol 5 [33] with propargyl magnesium bromide afforded the diol 6 in 88% yield (For detailed experimental procedures and

Microwave-assisted synthesis of biologically relevant steroidal 17-exo-pyrazol-5'-ones from a norpregnene precursor by a side-chain elongation/heterocyclization sequence

• Gergő Mótyán,
• László Mérai,
• Márton Attila Kiss,
• Zsuzsanna Schelz,
• Izabella Sinka,
• István Zupkó and
• Éva Frank

Beilstein J. Org. Chem. 2018, 14, 2589–2596, doi:10.3762/bjoc.14.236

• magnesium enolate of malonic acid half ester, prepared in situ from potassium methyl malonate, MgCl2 and triethylamine in acetonitrile, was added [24][25]. The acylation of magnesium methyl malonate by the preformed imidazole 3 led to the desired bifunctional starting material 4 in good yield (79

• magnesium enolate. Although the presence of a C16–C17 double bond as in 4' is assumed to be beneficial for a P45017α-inhibitory effect, further transformations of this compound were abandoned because of the insufficient yield and its potential tendency to react with monosubstituted hydrazines – not only

Practical tetrafluoroethylene fragment installation through a coupling reaction of (1,1,2,2-tetrafluorobut-3-en-1-yl)zinc bromide with various electrophiles

• Ken Tamamoto,
• Shigeyuki Yamada and
• Tsutomu Konno

Beilstein J. Org. Chem. 2018, 14, 2375–2383, doi:10.3762/bjoc.14.213

• that possesses higher thermal stability than the corresponding organolithium or -magnesium species due to the almost covalent C–Zn bond [29][30]. Moreover, organozinc reagents can be easily transformed to the “reactive” species, through a transmetallation process with a transition metal (e.g., Pd or Cu

• tetrafluoroethyllithium [12][25] and -magnesium species [22][23]. The synthetic uses of 2-Zn as a promising tetrafluorinating agent were tested in several reactions. First, we demonstrated a typical C–C bond formation reaction. Treating freshly prepared 2-Zn (ca. 0.70 M in DMF) with 5.0 equiv of iodobenzene (3a) in the

Novel photochemical reactions of carbocyclic diazodiketones without elimination of nitrogen – a suitable way to N-hydrazonation of C–H-bonds

• Liudmila L. Rodina,
• Xenia V. Azarova,
• Jury J. Medvedev,
• Dmitrij V. Semenok and
• Valerij A. Nikolaev

Beilstein J. Org. Chem. 2018, 14, 2250–2258, doi:10.3762/bjoc.14.200

• for up to 6.5 h (control of the reacted diazodiketone 1 by TLC). Thereupon the reaction mixture was dried over magnesium sulfate, the solvent completely distilled off in vacuum and the residue separated by column chromatography (SiO2, eluent: petroleum ether → petroleum ether/acetone 8:1) to give the

• disappearance of diazodiketone 1a (control by TLC). Then the reaction mixture was dried with magnesium sulfate and the solvent distilled off in vacuum. The obtained residue was dissolved in 25 ml of anhydrous Et2O, cooled to −75 to −78 °C. The precipitated resinous matter was separated by decantation and the

• glutaric acid. Photolysis of diazodiketone 1b (with MeOH). A solution of diazodiketone 1b (141 mg, 0.75 mmol) in 10 ml of THF/CH3OH 200:1 was irradiated for 55 min in a quartz reactor (λ > 210 nm). Then the reaction mixture was dried with magnesium sulfate and the solvent and excess of CH3OH were

Studies towards the synthesis of hyperireflexolide A

• G. Hari Mangeswara Rao

Beilstein J. Org. Chem. 2018, 14, 2106–2111, doi:10.3762/bjoc.14.185

• dichloroethane (1,2-DCE) were distilled over phosphorous pentoxide and stored over 4 Å molecular sieves. Acetone was distilled over anhydrous K2CO3. Methanol was refluxed and distilled over magnesium turnings and stored over 4 Å molecular sieves. Distilled water was used for aqueous reactions and aqueous work-up

Oligonucleotide analogues with cationic backbone linkages

• Melissa Meng and
• Christian Ducho

Beilstein J. Org. Chem. 2018, 14, 1293–1308, doi:10.3762/bjoc.14.111

• ≈25 °C for the according hybridization with DNA was observed [40]. In addition, the cationic dimer 11 was shown to bind more tightly to native RNA and DNA strands in the presence of magnesium chloride [40]. For the cationic T-oligomer 18, Letsinger and co-workers reported a strongly reduced absorbance

Rhodium-catalyzed C–H functionalization of heteroarenes using indoleBX hypervalent iodine reagents

• Erwann Grenet,
• Ashis Das,
• Paola Caramenti and
• Jérôme Waser

Beilstein J. Org. Chem. 2018, 14, 1208–1214, doi:10.3762/bjoc.14.102

• separated and the aqueous layer was extracted twice with DCM (5 mL). The organic layers were combined, dried over magnesium sulfate dehydrate, filtered and concentrated under reduced pressure. The crude residue was purified by preparative TLC using DCM/MeOH to afford the pure desired compound. Bioactive

Cobalt-catalyzed directed C–H alkenylation of pivalophenone N–H imine with alkenyl phosphates

• Wengang Xu and
• Naohiko Yoshikai

Beilstein J. Org. Chem. 2018, 14, 709–715, doi:10.3762/bjoc.14.60

• cycle illustrated in Scheme 5. An alkylcobalt species A, generated from the cobalt precatalyst and the Grignard reagent, would undergo cyclometalation of magnesium alkylidene amide 1·MgX, generated from imine 1 and the Grignard reagent, to give a cobaltacycle species B while liberating an alkane R–H

Biocatalytic synthesis of the Green Note trans-2-hexenal in a continuous-flow microreactor

• Morten M. C. H. van Schie,
• Tiago Pedroso de Almeida,
• Gabriele Laudadio,
• Florian Tieves,
• Elena Fernández-Fueyo,
• Timothy Noël,
• Isabel W. C. E. Arends and
• Frank Hollmann

Beilstein J. Org. Chem. 2018, 14, 697–703, doi:10.3762/bjoc.14.58

• magnesium sulphate and analysed on a CP-wax 52 CB GC column (50 m × 0.53 m × 2 µm) (GC method: 60 °C for 3 min; 30 °C/min to 105 °C; 105 °C for 7 min; 30 °C/min to 250 °C; 250 °C for 1 minute). Dodecane (5 mM) was added as standard. Work-up semi-preparative scale The reaction mixture was directly collected

Enzyme-free genetic copying of DNA and RNA sequences

• Marilyne Sosson and
• Clemens Richert

Beilstein J. Org. Chem. 2018, 14, 603–617, doi:10.3762/bjoc.14.47

• aqueous media, hydrolysis of activated nucleotides is all but unavoidable, and hydrolytic deactivation becomes more likely when significant concentrations of magnesium ions are present [31]. High initial concentrations of monomers are usually used to compensate for this problem (0.1 M solutions are not

• dimethylaminopyridine [61]. With aminoterminal primers, in situ activation and organocatalysis with 1-methylimidazole in a magnesium-free buffer had led to encouraging results, even at submillimolar nucleotide concentration [62]. So, starting from a primer extension reaction with an RNA-system that gave less than 1

Gram-scale preparation of negative-type liquid crystals with a CF₂CF₂-carbocycle unit via an improved short-step synthetic protocol

• Tatsuya Kumon,
• Shohei Hashishita,
• Takumi Kida,
• Shigeyuki Yamada,
• Takashi Ishihara and
• Tsutomu Konno

Beilstein J. Org. Chem. 2018, 14, 148–154, doi:10.3762/bjoc.14.10

• leads to the formation of the corresponding magnesium acetal Int-D, (ii) the alkoxide attacks another ester carbonyl moiety in the molecule to form the corresponding 5-membered ring acetal intermediate (Int-E) [15][16][17], after which immediate hydrolysis leads to the exclusive formation of the

• chloride with the γ-keto ester 6 furnishes the corresponding magnesium alkoxide Int-F, which can be easily converted to the 5-membered ring intermediate, Int-G, as already discussed in the reaction of 7→6 (Figure 2b). However, the reaction at a higher temperature may lead to the elimination of MeOMgCl

• addition reaction, a Michael addition reaction, giving rise to the corresponding magnesium enolate Int-L. The subsequent hydrolysis of Int-L then leads to the γ-hydroxyketone 8a', which easily tautomerizes into the more stable 5-membered hemiacetal 8a. From the above insight into the reaction mechanism, if

Reactivity of bromoselenophenes in palladium-catalyzed direct arylations

• Aymen Skhiri,
• Ridha Ben Salem,
• Jean-François Soulé and
• Henri Doucet

Beilstein J. Org. Chem. 2017, 13, 2862–2868, doi:10.3762/bjoc.13.278

• to room temperature and stirred during 20 h. After addition of water, the extraction was carried out with diethyl ether. Then, the organic phase was dried over magnesium sulphate. Finally, evaporation of the solvent and purification on silica gel afforded the 5-bromo-2-arylselenophenes 15–17. Eluents

Preparation and isolation of isobenzofuran

• Morten K. Peters and
• Rainer Herges

Beilstein J. Org. Chem. 2017, 13, 2659–2662, doi:10.3762/bjoc.13.263

• hydrogen carbonate solution and filtered over Celite. The aqueous phase was extracted three times with dichloromethane. The combined organic layers were dried over magnesium sulfate and the solvent was removed under reduced pressure. The crude product was purified by column chromatography on silica gel

• and then twice with water. The combined organic layers were dried over magnesium sulfate and the solvent was removed under reduced pressure. The crude product was purified by column chromatography on silica gel (cyclohexane/ethyl acetate 8:2, Rf 0.92). The solvent was carefully evaporated at 20 °C. A

Exploring mechanochemistry to turn organic bio-relevant molecules into metal-organic frameworks: a short review

• Vânia André,
• Sílvia Quaresma,
• João Luís Ferreira da Silva and
• M. Teresa Duarte

Beilstein J. Org. Chem. 2017, 13, 2416–2427, doi:10.3762/bjoc.13.239

• biomedical applications [128]. Having in mind the synthesis of BioMOFs involving the excipient magnesium oxide initially proposed by Byrn et al. [129], Chow et al. and Friščić et al. developed new BioMOFs by LAG, grinding together MgO with the non-steroidal anti-inflammatory drugs (NSAIDS) ibuprofen (S and

• RS-forms), salicylic acid [130] and naproxen using water as the grinding liquid [7]. With naproxen, LAG was also used to screen for hydrated forms of magnesium–naproxen by systematically varying the fraction of water in the LAG experiments [7]. Low, intermediate and high amounts of water as grinding

• ) fragment of the crystal structure of a mechanochemically obtained magnesium–ibuprofen complex; d) fragment of the crystal structure of a mechanochemically obtained magnesium–salicylate complex; e) screening for different hydrated forms of magnesium–naproxen BioMOFs by systematically varying the quantity of

Solvent-free and room temperature synthesis of 3-arylquinolines from different anilines and styrene oxide in the presence of Al₂O₃/MeSO₃H

• Hashem Sharghi,
• Mahdi Aberi,
• Mohsen Khataminejad and
• Pezhman Shiri

Beilstein J. Org. Chem. 2017, 13, 1977–1981, doi:10.3762/bjoc.13.193

• solution was dried over magnesium sulfate; the solvent was evaporated to give the crude product, which was purified by silica gel column chromatography employing n-hexane/ethyl acetate (10:1) as eluent. Investigation of the reusability of Al2O3. Synthesis of 3-arylquinolines from anilines and styrene oxide

Oxidative dehydrogenation of C–C and C–N bonds: A convenient approach to access diverse (dihydro)heteroaromatic compounds

• Santanu Hati,
• Ulrike Holzgrabe and
• Subhabrata Sen

Beilstein J. Org. Chem. 2017, 13, 1670–1692, doi:10.3762/bjoc.13.162

• -tetrahydroquinazolines which underwent oxidative dehydrogenation in the presence of magnesium iodide (that generates iodine) to afford the aromatic quinazoline 80 in excellent yield. Zhou et al. [90] reported a similar example in the presence of catalytic ferrous chloride and molecular oxygen for the synthesis of

• . Magnesium iodide-catalyzed synthesis of quinazolines. Ferrous chloride-catalyzed aerobic dehydrogenation of 1,2,3,4-tetrahydroquinolines. Cu(I)-catalyzed oxidative aromatization of indoles. Putative mechanism of the transformation. Oxidative dehydrogenation of pyrimidinones and pyrimidines. Putative

Chemical systems, chemical contiguity and the emergence of life

• Terrence P. Kee and
• Pierre-Alain Monnard

Beilstein J. Org. Chem. 2017, 13, 1551–1563, doi:10.3762/bjoc.13.155

• protocellular „metabolism“. Inspired by the non-enzymatic, template-directed RNA polymerization in bulk aqueous solutions [7] (the synthesis of a RNA using a primer/template system and magnesium ions as catalysts), the Szostak group [21][82] has demonstrated that RNA could be synthesized within mixed vesicles

• , Chen et al. [87] established that an inorganic catalyst itself, magnesium ions, could be delivered to non-functional hammerhead ribozymes with consequent induction of activity (self-cleavage). The enzymatic reactions were conducted within vesicles formed by long chained fatty acids, such as

Effect of uridine protecting groups on the diastereoselectivity of uridine-derived aldehyde 5’-alkynylation

• Raja Ben Othman,
• Mickaël J. Fer,
• Laurent Le Corre,
• Sandrine Calvet-Vitale and
• Christine Gravier-Pelletier

Beilstein J. Org. Chem. 2017, 13, 1533–1541, doi:10.3762/bjoc.13.153

• triisopropylsilyl group. The addition of triethylsilylacetylide magnesium bromide gave a 5’R /5’S ratio of 5:95 (Table 2, entries 9 and 10). To determine if R3 was able to influence this ratio, we also tested trimethylsilylacetylmagnesium bromide (Table 2, entry 11) and triisopropylsilylacetylmagnesium bromide