Natural phenolic metabolites with anti-angiogenic properties – a review from the chemical point of view

• Qiu Sun,
• Jörg Heilmann and
• Burkhard König

Beilstein J. Org. Chem. 2015, 11, 249–264, doi:10.3762/bjoc.11.28

• concentrations in many fruits and vegetables, resulting in a continuous and long-term intake of such plant phenols. Consequently, their beneficial and protective impact on unbalanced angiogenic processes has been intensively discussed [7][8]. In the last decade, many excellent review articles summarized the

• , epigallocatechin-3-O-gallate, xanthohumol, (2S)-7,2’,4’-trihydroxy-5-methoxy-8-dimethylallylflavanone and genistein. Other compounds belong to the group of simple phenols (4-hydroxybenzyl alcohol), hydrolysable tannins (ellagic acid), stilbenoids (resveratrol) and diarylheptanoids (curcumin). In addition

• , acylphloroglucinols, quinolone-substituted phenols and 4-amino-2-sulfanylphenol derivatives are discussed. Some important aspects of the described pharmacological activities of the compounds are summarized in Table 3. Review 4-Hydroxybenzyl alcohol 4-Hydroxybenzyl alcohol (HBA, 1) (Figure 1) is a well-known phenolic

Cross-dehydrogenative coupling for the intermolecular C–O bond formation

• Igor B. Krylov,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2015, 11, 92–146, doi:10.3762/bjoc.11.13

• /CH-reagent was 1:1 for aromatic OH-reagents and 5:1 for aliphatic alcohols. Different organic and inorganic bases were used depending on the structures of substrates. The cross-dehydrogenative coupling of phenols and arenes 61 with a directing group containing a pyridine N-oxide moiety occurs in the

• quinone 116 afforded esters 117. This method was also applied to the synthesis of esters 117a–c from amino alcohols (Scheme 25) [115][116]. Different conditions were proposed for the cross-dehydrogenative C–O coupling of aldehydes with alcohols and phenols catalyzed by N-heterocyclic carbenes (118, 129

• works, the oxidative coupling of alcohols, aldehydes, or formamides with 1,3-dicarbonyl compounds or phenols was accomplished in the presence of tert-butyl hydroperoxide and copper salts (Table 5). In most cases, the range of phenols applicable to the coupling is limited to 2-acylphenols. However, 2

Recent advances in the electrochemical construction of heterocycles

• Robert Francke

Beilstein J. Org. Chem. 2014, 10, 2858–2873, doi:10.3762/bjoc.10.303

• of 2,3-dihydrobenzofuran structures 43 via double-mediatory Wacker-type cyclization of alkenyl phenols 42 [61]. Pd(OAc)2 was used to catalyze the cyclization while TEMPO served as redox mediator for the electrochemical regeneration of the catalytically active Pd(II) species. In contrast to

• phenols [78][79], they could observe the formation of spiropentacyclic scaffold 76 (Scheme 29) as byproduct of the electrolysis of 2,4-dimethylphenol (72) [80]. Later it turned out that compound 73 (a dehydrotetramer of 72) is the actual electrolysis product, which reacted to 76 via thermal rearrangement

• ). Electrosynthesis of 39 as part of the total synthesis of alkaloids 40 and 41. Wacker-type cyclization of alkenyl phenols 42. Cathodic synthesis of indol derivatives. Fluoride mediated anodic cyclization of α-(phenylthio)acetamides. Synthesis of 2-substituted benzoxazoles from Schiff bases. Synthesis of euglobal

A small azide-modified thiazole-based reporter molecule for fluorescence and mass spectrometric detection

• Stefanie Wolfram,
• Hendryk Würfel,
• Stefanie H. Habenicht,
• Christine Lembke,
• Phillipp Richter,
• Eckhard Birckner,
• Rainer Beckert and
• Georg Pohnert

Beilstein J. Org. Chem. 2014, 10, 2470–2479, doi:10.3762/bjoc.10.258

• . Derivatization with dansyl chloride is used for labeling of primary and secondary amines or phenols resulting in enhanced ESI signals and shifted retention times of labeled polar analytes in reversed-phase LC [27]. For comparison with BPT (1) we also introduced bromine into the aromatic system of DNS (8) to

Oligomerization of optically active N-(4-hydroxyphenyl)mandelamide in the presence of β-cyclodextrin and the minor role of chirality

• Helmut Ritter,
• Antonia Stöhr and
• Philippe Favresse

Beilstein J. Org. Chem. 2014, 10, 2361–2366, doi:10.3762/bjoc.10.246

• the oligomerization of substituted electron-rich phenols in the presence of oxidizing agents [3][4]. In addition to that, N,N'-bis(salicylidene)ethylenediamine-iron(II) (iron(II)-salen) represents an alternative catalyst for oxidative coupling reactions of phenol derivatives [5]. The use of β

Facile synthesis of 1-alkoxy-1H-benzo- and 7-azabenzotriazoles from peptide coupling agents, mechanistic studies, and synthetic applications

• Mahesh K. Lakshman,
• Manish K. Singh,
• Mukesh Kumar,
• Raghu Ram Chamala,
• Vijayender R. Yedulla,
• Domenick Wagner,
• Evan Leung,
• Lijia Yang,
• Asha Matin and
• Sadia Ahmad

Beilstein J. Org. Chem. 2014, 10, 1919–1932, doi:10.3762/bjoc.10.200

• , entry 16), indicating the potential use of this reagent as a tosylating agent for phenols. The outcome in the phenol reaction may be linked to the potential reaction pathway, an aspect that is described below. However, because phenoxide is a softer nucleophile as compared to alkoxide, we had to consider

• tosylate, which is consistent with this mechanism. This reaction also shows that Bt-OTs (and At-OTs) could serve as tosylating agents for phenols as well. Further, the utilities of this reaction, as well as some of the products have been explored. In this vein, acyclic nucleoside-like compounds containing

Supercritical carbon dioxide: a solvent like no other

• Jocelyn Peach and
• Julian Eastoe

Beilstein J. Org. Chem. 2014, 10, 1878–1895, doi:10.3762/bjoc.10.196

• was significantly less pronounced than those seen in water-in-oil systems [94]. AOT surfactant organogels have also been induced in isooctane through the addition of trace levels of para-substituted phenols (p-ethylphenol and p-methylphenol, Figure 8), with reports of vast viscosity enhancements up to

• hydrotropic salts and phenols to microemulsions can lead to positive viscosity builds in both water-in-oil and water-in-carbon dioxide systems as observed by Eastoe et al. and John et al. [40][94][104] Emerging areas using supercritical CO2 Bicontinuous and lamellar phases, lamellar liquid crystals and foams

Atherton–Todd reaction: mechanism, scope and applications

• Stéphanie S. Le Corre,
• Mathieu Berchel,
• Hélène Couthon-Gourvès,
• Jean-Pierre Haelters and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2014, 10, 1166–1196, doi:10.3762/bjoc.10.117

Synthesis of zearalenone-16-β,D-glucoside and zearalenone-16-sulfate: A tale of protecting resorcylic acid lactones for regiocontrolled conjugation

• Hannes Mikula,
• Julia Weber,
• Dennis Svatunek,
• Philipp Skrinjar,
• Gerhard Adam,
• Rudolf Krska,
• Christian Hametner and
• Johannes Fröhlich

Beilstein J. Org. Chem. 2014, 10, 1129–1134, doi:10.3762/bjoc.10.112

• be formed by rearrangement of 11 when activated in the presence of a weak acceptor (Scheme 2B) [31][32][33][34]. Königs–Knorr glucosylation, which in general is most frequently used for the glucosylation of phenols, using commercially available bromo sugar 13 activated by silver(I) salts or under

Olefin cross metathesis based de novo synthesis of a partially protected L-amicetose and a fully protected L-cinerulose derivative

• Bernd Schmidt and
• Sylvia Hauke

Beilstein J. Org. Chem. 2014, 10, 1023–1031, doi:10.3762/bjoc.10.102

• decomposition to isomerization active species. This phenomenon has often been observed for second generation catalysts [53]. For these reasons, phenol was used as a rate accelerating additive. Phenols are believed to coordinate to the Ru and stabilize the catalytically active 14-electron species, resulting in a

A convenient enantioselective decarboxylative aldol reaction to access chiral α-hydroxy esters using β-keto acids

• Zhiqiang Duan,
• Jianlin Han,
• Ping Qian,
• Zirui Zhang,
• Yi Wang and
• Yi Pan

Beilstein J. Org. Chem. 2014, 10, 969–974, doi:10.3762/bjoc.10.95

• one point-binding aldehydes and two-point binding β-keto acids under mild reaction conditions. The lack of strong Lewis acids or very basic intermediates enabled it to tolerate functionalities that would normally be incompatible with ester enolates, for instance, hydroxy groups, phenols, enolizable

Unusual polymorphism in new bent-shaped liquid crystals based on biphenyl as a central molecular core

• Anna Kovářová,
• Svatopluk Světlík,
• Václav Kozmík,
• Jiří Svoboda,
• Vladimíra Novotná,
• Damian Pociecha,
• Ewa Gorecka and
• Natalia Podoliak

Beilstein J. Org. Chem. 2014, 10, 794–807, doi:10.3762/bjoc.10.75

• compatible with the applied reaction conditions, thus, we switched to the benzyl protection of the hydroxy group (acid 1b and 2). The requested lengthening arms for the synthesis of materials of series I–III involved two-ring phenols 3–5 and substituted benzoic acids 6a–c (Figure 1). For the preparation of

• series of materials IV–VI, we utilized lengthening arms of phenols 7a–c and two-ring acids 8–10. All intermediates were obtained previously by known methods [47][48][49]. The bent-shaped liquid crystals I–III were synthesized in three steps (Scheme 1). The protected acids 1a,b were esterified with

• phenols 3–5 in the presence of N,N'-dicyclohexylcarbodiimide (DCC) and 4-dimethylaminopyridine (DMAP) to yield esters 11–13 (Scheme 1). The methoxycarbonyl group in 11 was subsequently removed by means of aq. ammonia and the benzyl group in 12 and 13 by a palladium-catalysed transfer-hydrogenation. The

Visible-light photoredox catalysis enabled bromination of phenols and alkenes

• Yating Zhao,
• Zhe Li,
• Chao Yang,
• Run Lin and
• Wujiong Xia

Beilstein J. Org. Chem. 2014, 10, 622–627, doi:10.3762/bjoc.10.53

• of phenols and alkenes has been developed utilizing visible light-induced photoredox catalysis. The bromine was generated in situ from the oxidation of Br− by Ru(bpy)33+, both of which resulted from the oxidative quenching process. Keywords: alkenes; bromination; phenols; photoredox catalyst

• phenols. The typical approaches include direct electrophilic halogenation by using molecular bromine or N-bromosuccinimide (NBS) [6][7][8], organometallic catalyst-promoted bromination [9][10][11][12], and the oxidative bromination of phenols [13][14][15]. Nevertheless, most of the methods suffer from

• several drawbacks such as toxic reagents, harsh conditions, low yields, and low chemo- and regioselectivity. Hence, the development of an environmentally friendly methodology for the bromination of phenols with high chemoselectivity under mild and operationally simple conditions is still appealing

New sesquiterpene hydroquinones from the Caribbean sponge Aka coralliphagum

• Qun Göthel and
• Matthias Köck

Beilstein J. Org. Chem. 2014, 10, 613–621, doi:10.3762/bjoc.10.52

• halenaquinol sulfate from the marine sponge Xestospongia sapra [14]. In the course of our investigation on the sponge Aka coralliphagum, we isolated a number of compounds containing sulfated phenols. These sulfated metabolites are labile [5], and easily loose the sulfate ester groups by hydrolysis in water [15

Diversity-oriented synthesis of dihydrobenzoxazepinones by coupling the Ugi multicomponent reaction with a Mitsunobu cyclization

• Lisa Moni,
• Luca Banfi,
• Andrea Basso,
• Alice Brambilla and
• Renata Riva

Beilstein J. Org. Chem. 2014, 10, 209–212, doi:10.3762/bjoc.10.16

• reactions [2], especially the intramolecular Mitsunobu reaction of alcohols with phenols or sulfonamides. By exploiting a single post-MCR transformation (the Mitsunobu reaction) it is possible to obtain several diverse heterocyclic scaffolds by installing the two additional groups in any of the four

3-Pyridinols and 5-pyrimidinols: Tailor-made for use in synergistic radical-trapping co-antioxidant systems

• Luca Valgimigli,
• Daniele Bartolomei,
• Riccardo Amorati,
• Evan Haidasz,
• Jason J. Hanthorn,
• Susheel J. Nara,
• Johan Brinkhorst and
• Derek A. Pratt

Beilstein J. Org. Chem. 2013, 9, 2781–2792, doi:10.3762/bjoc.9.313

• stronger O–H bonds than equivalently substituted phenols, but possess similar reactivities toward autoxidation chain-carrying peroxyl radicals. These attributes suggest that 3-pyridinols and 5-pyrimidinols will be particularly effectiveco-antioxidants when used in combination with more common, but less

• reactive phenols to regenerate them from their corresponding aryloxyl radicals. The present investigations were carried out in chlorobenzene and acetonitrile in order to provide some insight into the medium dependence of the synergism and the results, considered with some from our earlier work, prompt a

• phenolic antioxidants, but which are equally efficacious as the 3-pyridinol/5-pyrimidinol antioxidants alone at higher loadings. Keywords: antioxidants; autoxidation; free radical; phenols; 3-pyridinols; 5-pyrimidinols; Introduction Radical-trapping (chain-breaking) antioxidants are arguably the most

Halogenated volatiles from the fungus Geniculosporium and the actinomycete Streptomyces chartreusis

• Tao Wang,
• Patrick Rabe,
• Christian A. Citron and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2013, 9, 2767–2777, doi:10.3762/bjoc.9.311

• ) [25] or the trichlorinated phenols 20–22 (Figure 5) [26]. The biological function of 4b and 10b in Geniculosporium is unknown, but the antibiotic activity of the related compound drosophilin A towards bacteria is well known [27]. A iodinated volatile from Streptomyces chartreusis During the course of

Stereoselectively fluorinated N-heterocycles: a brief survey

• Xiang-Guo Hu and
• Luke Hunter

Beilstein J. Org. Chem. 2013, 9, 2696–2708, doi:10.3762/bjoc.9.306

• to be successfully achieved. One such reagent, PhenoFluor (45, Figure 12), was originally developed by Ritter and co-workers for the direct fluorination of phenols [56]. Recent work showed that 45 can also be used to effect late-stage fluorination of hydroxy groups within complex molecular

New developments in gold-catalyzed manipulation of inactivated alkenes

• Michel Chiarucci and
• Marco Bandini

Beilstein J. Org. Chem. 2013, 9, 2586–2614, doi:10.3762/bjoc.9.294

• process for the formation of new C–O bonds. In this direction numerous examples of metal and Brønsted-acid catalyzed condensations of alcohols, phenols and carboxylic acids to inactivated olefins have been reported [16]. Interestingly, He and co-workers compared the catalytic attitude of TfOH and

• works, Yang and He reported on the Ph3PAuOTf assisted Markovnikov-like addition of phenols and carboxylic acids to C=C under mild reaction conditions (Scheme 1) [27]. Electron-rich and electron-poor phenols reacted smoothly in toluene (85 °C) with only 1 mol % of catalyst loading (Scheme 1a). Contrarily

• , carboxylic acids required a higher loading of catalyst (5 mol %), but an acceptable yield was obtained even when sterically demanding 2-methylpropionic acid was employed as the nucleophile (Scheme 1b). Li and co-workers exploited the [Au(III)]-catalyzed addition of phenols and naphthols to conjugated dienes

Ambient gold-catalyzed O-vinylation of cyclic 1,3-diketone: A vinyl ether synthesis

• Yumeng Xi,
• Boliang Dong and
• Xiaodong Shi

Beilstein J. Org. Chem. 2013, 9, 2537–2543, doi:10.3762/bjoc.9.288

• vinyl ether synthesis using gold has been reported to date [17]. Nevertheless, there have been examples regarding the intermolecular addition of carboxylic acids [19][20], phenols [21][22] as well as phosphoric acids [23][24][25] to alkynes. In this context, we report a gold(I)-catalyzed O-vinylation of

Flexible synthesis of anthracycline aglycone mimics via domino carbopalladation reactions

• Markus Leibeling and
• Daniel B. Werz

Beilstein J. Org. Chem. 2013, 9, 2194–2201, doi:10.3762/bjoc.9.258

• oxidative procedures provided only the mono-oxidized products in trace amounts [40][41][42]. The oxidation of phenyl-substituted silanes to respective phenols is difficult [43][44]. However, literature precedence revealed that benzyl-substituted silane 13c or electron-deficient silane 13d [43][45] should be

Gold(I)-catalyzed hydroarylation reaction of aryl (3-iodoprop-2-yn-1-yl) ethers: synthesis of 3-iodo-2H-chromene derivatives

• Pablo Morán-Poladura,
• Eduardo Rubio and
• José M. González

Beilstein J. Org. Chem. 2013, 9, 2120–2128, doi:10.3762/bjoc.9.249

• Starting materials 1 were obtained from the corresponding phenols through a two steps synthetic route. General procedure for the propargylation of phenols To a suspension or solution of the corresponding phenol (1 equiv; 5 mmol) in DMF (20 mL), potassium carbonate was added (2 equiv; 10 mmol) followed by

• ethers from phenols and chiral non-racemic propargylic alcohols (S)-(−)-3-butyn-2-ol (5 mmol; commercially available, 464007 Sigma-Aldrich) was dissolved in THF (25 mL) in a flame dried round bottom flask, under nitrogen atmosphere, and the corresponding phenol (1.05 equiv, 5.25 mmol) and

Acid, silver, and solvent-free gold-catalyzed hydrophenoxylation of internal alkynes

• Marcia E. Richard,
• Daniel V. Fraccica,
• Kevin J. Garcia,
• Erica J. Miller,
• Rosa M. Ciccarelli,
• Erin C. Holahan,
• Victoria L. Resh,
• Aakash Shah,
• Peter M. Findeis and
• Robert A. Stockland Jr.

Beilstein J. Org. Chem. 2013, 9, 2002–2008, doi:10.3762/bjoc.9.235

• compounds have been synthesized and investigated as single-component catalysts for the hydrophenoxylation of unactivated internal alkynes. Both carbene and phosphine-ligated compounds were screened as part of this work, and the most efficient catalysts contained either JohnPhos or IPr/SIPr. Phenols bearing

• successfully functionalized. Despite the intense interest in this chemistry the addition of phenols to internal alkenes has rarely been investigated [1][5]. Recently, Sahoo reported the hydrophenoxylation of alkynes using a multicomponent catalyst comprised of AuCl3, JohnPhos as the supporting ligand, and

• gold catalyst in these reactions is proposed to occur through a protodeauration reaction between the arylgold compounds and the phenols. The observation of tert-butylbenzene in the reaction mixture supports this proposal. Furthermore, to probe whether or not simple chlorogold-coordination compounds

Gold(I)-catalysed one-pot synthesis of chromans using allylic alcohols and phenols

• Eloi Coutant,
• Paul C. Young,
• Graeme Barker and
• Ai-Lan Lee

Beilstein J. Org. Chem. 2013, 9, 1797–1806, doi:10.3762/bjoc.9.209

• Eloi Coutant Paul C. Young Graeme Barker Ai-Lan Lee Institute of Chemical Sciences, Heriot-Watt University, Edinburgh, EH14 1LP, United Kingdom 10.3762/bjoc.9.209 Abstract A gold(I)-catalysed reaction of allylic alcohols and phenols produces chromans regioselectively via a one-pot Friedel–Crafts

• structural motifs found in a variety of important biologically active natural products such as vitamin E and flavanoids [1][2][3][4][5]. One approach towards chromans [6][7][8][9][10][11][12], which is biosynthetically inspired, is the Friedel–Crafts allylation [13] of phenols followed by cyclisation of the

• dehydrative coupling strategy) [15][16]. To this end, the use of molybdenum catalyst CpMoCl(CO)3 together with an oxidant, o-chloranil, has been documented to catalyse the reaction of allylic alcohols with phenols to form chromans [17][18]. Strong and superacids have also been utilised in the synthesis of

A Lewis acid-promoted Pinner reaction

• Dominik Pfaff,
• Gregor Nemecek and
• Joachim Podlech

Beilstein J. Org. Chem. 2013, 9, 1572–1577, doi:10.3762/bjoc.9.179

• possible. Phenols are not acylated under these reaction conditions. The method has been used for the first total synthesis of the natural product monaspilosin. In the reaction of benzyl alcohols variable amounts of amides are formed in a Ritter-type side reaction. Keywords: carbonitriles; carboxylic

• highly chemoselective; phenols were not acylated by these conditions and were re-isolated with high yields (Table 2, entries 12–14). In this context we tested 4-(2-hydroxyethyl)phenol (53) containing an aliphatic and a phenolic hydroxy function in the reaction with acetonitrile and benzyl cyanide