Stereoselective total synthesis and structural revision of the diacetylenic diol natural products strongylodiols H and I

• Pamarthi Gangadhar,
• Sayini Ramakrishna,
• Ponneri Venkateswarlu and
• Pabbaraja Srihari

Beilstein J. Org. Chem. 2018, 14, 2313–2320, doi:10.3762/bjoc.14.206

• concentrations [11]. There have been few contributions on the total synthesis of strongylodiols [12][13] employing alkynylation of an unsaturated aliphatic aldehyde catalyzed by Trost’s pro-phenol ligand [12][14], β-elimination of epoxy chloride [15], Noyori’s asymmetric reduction of ynones [16], diyne addition

The enzymes of microbial nicotine metabolism

• Paul F. Fitzpatrick

Beilstein J. Org. Chem. 2018, 14, 2295–2307, doi:10.3762/bjoc.14.204

• been cloned and characterized [10]. DHPH contains FAD and requires NADH and oxygen [41], and the sequence of the protein is similar to that of salicylate hydroxylase, although the sequence identity is only 21%. This allowed identification of the enzyme as a flavin-dependent phenol hydroxylase, a

Calix[6]arene-based atropoisomeric pseudo[2]rotaxanes

• Carmine Gaeta,
• Carmen Talotta and
• Placido Neri

Beilstein J. Org. Chem. 2018, 14, 2112–2124, doi:10.3762/bjoc.14.186

• two respective proximal aromatic rings are oriented syn, as in the cone conformation. In contrast, a Δδ value of 0.3 or less is attributable to an anti-orientation between the phenol rings, as in alternate conformations. The de Mendoza’s “13C NMR single rule” [30][31], is focused on the 13C NMR

• chemical shift of the ArCH2Ar methylene C, which is 30–33 ppm for the syn-orientation of the proximal phenol rings and typically 36–39 ppm with anti-positioned phenol rings as in alternate conformations. As exemplified above, the calix[6]arene macrocycle has been widely used as wheel for the assembly of

• ). Differently, in the DFT-optimized structure of 2+11,2,3-alt atropoisomer (Figure 7, right), the stabilization of the 2+11,2,3-alt atropoisomer was brought, principally by two H-bonding interactions between the ammonium group of 2+ and the oxygen atoms of anti-oriented phenol rings of 1 with an average N···O

Functionalization of graphene: does the organic chemistry matter?

• Artur Kasprzak,
• Agnieszka Zuchowska and
• Magdalena Poplawska

Beilstein J. Org. Chem. 2018, 14, 2018–2026, doi:10.3762/bjoc.14.177

• ) radical addition, (d) formation of phenol, (e) adsorption of phenol onto the graphene sheet. Acknowledgements This work was financially supported by the National Science Centre (Poland) through the grant OPUS No. 2016/21/B/ST5/01774. Artur Kasprzak acknowledges Foundation for Polish Science (FNP) for the

Chiral bisoxazoline ligands designed to stabilize bimetallic complexes

• Deepankar Das,
• Rudrajit Mal,
• Nisha Mittal,
• Zhengbo Zhu,
• Thomas J. Emge and
• Daniel Seidel

Beilstein J. Org. Chem. 2018, 14, 2002–2011, doi:10.3762/bjoc.14.175

• , Florida 32611, USA 10.3762/bjoc.14.175 Abstract Chiral bisoxazoline ligands containing naphthyridine, pyridazine, pyrazole, and phenol bridging units were prepared and shown to form bimetallic complexes with various metal salts. X-ray crystal structures of bis-nickel naphthyridine-bridged, bis-zinc

• available. This led to the selection of naphthyridine, pyridazine, pyrazole, and phenol building blocks. We opted to connect these linkers to oxazolines via amide bonds. The reasoning for this was twofold. Firstly, this should provide ligands with significantly improved stabilities over for instance imine

• contrast, a distorted square pyramidal binding mode is observed for Zn(2). Phenol-bridged bisoxazoline ligands. Ligands incorporating naphthyridine, pyridazine and pyrazole linkers discussed thus far bridge two metal atoms by attachment to two different nitrogen donor atoms. As a result, metal∙∙∙metal

Cationic cobalt-catalyzed [1,3]-rearrangement of N-alkoxycarbonyloxyanilines

• Itaru Nakamura,
• Mao Owada,
• Takeru Jo and
• Masahiro Terada

Beilstein J. Org. Chem. 2018, 14, 1972–1979, doi:10.3762/bjoc.14.172

• 30 °C followed by hydrogenative cleavage of the Cbz group afforded the phenol 4h-18O, of which the oxygen-18 content was 64% (Scheme 3b). The result clearly indicates that the rearrangement of the CbzO group in the presence of cationic cobalt catalysts proceeds in a concerted [1,3]-manner [18][19][20

Synthesis of spirocyclic scaffolds using hypervalent iodine reagents

• Fateh V. Singh,
• Priyanka B. Kole,
• Saeesh R. Mangaonkar and
• Samata E. Shetgaonkar

Beilstein J. Org. Chem. 2018, 14, 1778–1805, doi:10.3762/bjoc.14.152

• -hydroxyaryl)cyclobutanols 18 to spirolactones 19 in good yields (Scheme 4). The reaction was initiated with formation of an intermediate 20 by the oxidation of the phenolic hydroxy group of 18, which rearranged to compound 21. Furthermore, water attacks the ketone moiety of 21 to form para-substituted phenol

• (Scheme 8). Probably, the iodine(III) species was generated in situ as the active catalytic species that was playing the key role for the dearomatization of phenol. In addition, a similar reaction was also achieved by using various PIFA analogues as catalyst directly in the presence of 1.5 equivalents of

• using PIDA (15) as an electrophile at −40 °C for 10–15 minutes (Scheme 39). This is an example of an ortho-oxidative phenol dearomatization reaction wherein there is the formation of the steriogenic center at the spiro-ring junction. This approach provides an easy and direct method for the construction

The phenyl vinyl ether–methanol complex: a model system for quantum chemistry benchmarking

• Dominic Bernhard,
• Fabian Dietrich,
• Mariyam Fatima,
• Cristóbal Pérez,
• Hannes C. Gottschalk,
• Axel Wuttke,
• Ricardo A. Mata,
• Martin A. Suhm,
• Melanie Schnell and
• Markus Gerhards

Beilstein J. Org. Chem. 2018, 14, 1642–1654, doi:10.3762/bjoc.14.140

• acceptor sites. An extensive study on diphenoxyethane–water clusters was performed by the Zwier group [13][14][15] including studies in the excited S1 and S2 states. Concerning aggregates of aromatic ethers with alcohols, there is a work of Pietraperzia et al. [16] on the anisole–phenol complex in which an

Anomeric modification of carbohydrates using the Mitsunobu reaction

• Julia Hain,
• Patrick Rollin,
• Werner Klaffke and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2018, 14, 1619–1636, doi:10.3762/bjoc.14.138

•  8) were converted into the respective unprotected phenyl glycosides 44 and 45 with phenol in just one step in moderate to good yields. Recently, the scope of this synthetic approach was expanded by the Lindhorst group employing D-mannose and hydroxyazobenzene 46 for the synthesis of the

• reaction with phenol to stereoselectively achieve the respective β-mannoside 82 in good yield (Scheme 14) [60]. This stereo-differentiating effect of isopropylidene protecting groups was also observed in other cases with D-mannopyranose [46][61]. It might be used as a key to a reliable approach to

Metal-free formal synthesis of phenoxazine

• Gabriella Kervefors,
• Antonia Becker,
• Chandan Dey and
• Berit Olofsson

Beilstein J. Org. Chem. 2018, 14, 1491–1497, doi:10.3762/bjoc.14.126

• a high-yielding O-arylation of a phenol with an unsymmetrical diaryliodonium salt to provide an ortho-disubstituted diaryl ether. This species was cyclized to acetylphenoxazine in moderate yield. The overall yield in the three-step sequence is 72% based on recovered diaryl ether. An interesting

• , unusually stable iodine(III) intermediate in the O-arylation was observed by NMR and could be converted to the product upon longer reaction time. Keywords: arylation; cyclization; diaryl ether; diaryliodonium salt; phenol; Introduction Phenoxazine (1) is a tricyclic compound consisting of an oxazine ring

• illustrated, either employing 2-iodophenol (4) and 2-acetamido-substituted salt 5 (route A) or N-functionalized phenol 6 with 2-iodophenyl salt 7 (route B). In route A, the chemoselective transfer of the 2-amido aryl group over the other aryl group would require a quite electron-rich dummy group or the use of

Recent applications of chiral calixarenes in asymmetric catalysis

• Mustafa Durmaz,
• Erkan Halay and
• Selahattin Bozkurt

Beilstein J. Org. Chem. 2018, 14, 1389–1412, doi:10.3762/bjoc.14.117

• asymmetric Michael addition reaction of thiophenol could be catalyzed by inherently chiral calixarenes bearing amino alcohol/phenol structure [47][48]. In order to see the effect of the diarylmethanol moiety, Shirakawa and Shimizu used 43 (Figure 6) as organocatalyst in the Michael addition reaction between

• analogue 68 bearing the same bifunctional pattern was also prepared from p-tert-butylphenol and used for comparison (Scheme 19). When monomeric analog 68 was used as a catalyst alone or in the presence of p-tert-butylphenol/phenol as acidic additives, lower yield and enantioselectivity were observed. These

Design and biological characterization of novel cell-penetrating peptides preferentially targeting cell nuclei and subnuclear regions

• Anja Gronewold,
• Mareike Horn and
• Ines Neundorf

Beilstein J. Org. Chem. 2018, 14, 1378–1388, doi:10.3762/bjoc.14.116

• , MCF-7 200,000 cells per well) and grown to 70–80% confluency. Then, cells were treated with 400 μL of peptide solutions dissolved in serum-free medium for the appropriate time at 4 °C or 37 °C. Afterwards, the cells were washed twice with PBS and detached with Trypsin-EDTA 1× in PBS without phenol red

Novel unit B cryptophycin analogues as payloads for targeted therapy

• Eduard Figueras,
• Adina Borbély,
• Mohamed Ismail,
• Marcel Frese and
• Norbert Sewald

Beilstein J. Org. Chem. 2018, 14, 1281–1286, doi:10.3762/bjoc.14.109

• preparation of the two different spacers that were later connected to the phenol. Starting from triethylene glycol (3) or 2-allyloxyethanol (7) tosylations and nucleophilic displacements by azide or iodide substitution provided 6 and 9 in good yields. O-Alkylation of Boc-protected 3-chlorinated D-tyrosine 10

A survey of chiral hypervalent iodine reagents in asymmetric synthesis

• Soumen Ghosh,
• Suman Pradhan and
• Indranil Chatterjee

Beilstein J. Org. Chem. 2018, 14, 1244–1262, doi:10.3762/bjoc.14.107

• (Scheme 5). Later, this dearomatization strategy was further reinvestigated by the Ishihara group using a new chiral iodine precatalyst 10 derived from a chiral 2-aminoalcohol [39]. Its application in the oxidative dearomatization of phenol 33 and the subsequent reaction of the so-obtained dienes 34 with

• phenol dearomatization, leading to the formation of cyclodimerization products 43 with high enantioselectivity (up to 94% ee, Scheme 8 lower part). Alkene functionalization Nearly simultaneously to Ishihara’s work, Fujita et al. reported on the modification of their previously synthesized non C2

Rapid transformation of sulfinate salts into sulfonates promoted by a hypervalent iodine(III) reagent

• Elsa Deruer,
• Vincent Hamel,
• Samuel Blais and
• Sylvain Canesi

Beilstein J. Org. Chem. 2018, 14, 1203–1207, doi:10.3762/bjoc.14.101

• solvent and appears to be selective for phenols; only two primary alcohol examples were produced in 63–67% yield in the presence of a strong base. A radical pathway from the alkoxide species was proposed by the authors as an explanation for the phenol selectivity under weakly basic conditions in the

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

Fluorocyclisation via I(I)/I(III) catalysis: a concise route to fluorinated oxazolines

• Felix Scheidt,
• Christian Thiehoff,
• Gülay Yilmaz,
• Stephanie Meyer,
• Constantin G. Daniliuc,
• Gerald Kehr and
• Ryan Gilmour

Beilstein J. Org. Chem. 2018, 14, 1021–1027, doi:10.3762/bjoc.14.88

• which contains a free phenol moiety, were also tolerated (69% and 65% yield, respectively), as was the highly deactivated pentafluorophenyl analogue 2j (48%). To briefly explore the effect of chain length on efficiency, the cyclisation of N-(but-3-en-1-yl)benzamide and N-(pent-4-en-1-yl)benzamide was

2-Iodo-N-isopropyl-5-methoxybenzamide as a highly reactive and environmentally benign catalyst for alcohol oxidation

• Takayuki Yakura,
• Tomoya Fujiwara,
• Akihiro Yamada and
• Hisanori Nambu

Beilstein J. Org. Chem. 2018, 14, 971–978, doi:10.3762/bjoc.14.82

• of the iodobenzamides depends on the ortho-relationship of the iodine atom to the amide group. Therefore, we then investigated N-isopropyl-2-iodobenzamides that have an additional functional group on the benzene ring. Based on the results of our studies on phenol oxidation [60][62] and Ishihara’s [52

• 14a with 4-iodophenoxyacetic acid (23); the results showed excellent reactivity for phenol oxidations [60][61][62][63][64]. When 14a was oxidized with 23, the reaction was very slow and yielded only 23% of 15a and 75% of recovered 14a even after 48 h (Table 1, entry 9) [68]. Since the 5-methoxy

Mechanochemistry of nucleosides, nucleotides and related materials

• Olga Eguaogie,
• Joseph S. Vyle,
• Patrick F. Conlon,
• Manuela A. Gîlea and
• Yipei Liang

Beilstein J. Org. Chem. 2018, 14, 955–970, doi:10.3762/bjoc.14.81

• reported in 1957. More recently, RNA was extracted from both Gram-negative and Gram-positive bacteria by hand grinding in a mortar with phenol under cooling with liquid nitrogen [71] . The reproducibility of studies requiring arduous mechanochemical operations to be performed by hand lead to the rapid

On the design principles of peptide–drug conjugates for targeted drug delivery to the malignant tumor site

• Eirinaios I. Vrettos,
• Gábor Mező and
• Andreas G. Tzakos

Beilstein J. Org. Chem. 2018, 14, 930–954, doi:10.3762/bjoc.14.80

Mannich base-connected syntheses mediated by ortho-quinone methides

• Petra Barta,
• Ferenc Fülöp and
• István Szatmári

Beilstein J. Org. Chem. 2018, 14, 560–575, doi:10.3762/bjoc.14.43

• mechanism of the formation of phenolic Mannich bases is similar to that discussed above for the synthesis of amidoalkylnaphthols. First, the phenol component reacts with the aldehyde to form the o-QM intermediate, which reacts in a nucleophilic addition step with the amine component, resulting in

Stimuli-responsive oligonucleotides in prodrug-based approaches for gene silencing

• Françoise Debart,
• Christelle Dupouy and
• Jean-Jacques Vasseur

Beilstein J. Org. Chem. 2018, 14, 436–469, doi:10.3762/bjoc.14.32

• the reaction between a phosphorothioate derivative and 2-bromo-4’-hydroxyacetophenone to produce a phosphate protected with a thioether-enol phosphotriester, phenol substituted (TEEP, Scheme 19) [77]. The TEEP modification was introduced into “active sites” of 8–17 and 10–23 DNAzymes with good yields

Synthetic and semi-synthetic approaches to unprotected N-glycan oxazolines

• Antony J. Fairbanks

Beilstein J. Org. Chem. 2018, 14, 416–429, doi:10.3762/bjoc.14.30

• degradation. The original procedure [82] for the isolation of SGP first involved deproteinization by treatment with 90% phenol and washing with Et2O, and then repeated purification by size exclusion chromatography (SEC, Sephadex G-50, followed by Sephadex G-25) from which sialic acid positive fractions were

• published which have made the isolation process easier and improved the yield. Firstly a significantly shortened procedure [83] followed the phenol treatment with a single purification by SEC (Sephadex G-50), and then filtration through graphitized carbon cartridges. Subsequently an even better method was

• developed [84] which avoided the treatment with phenol and all SEC purification steps (Scheme 9). In this process the egg yolks were first stirred with water and then freeze dried to give egg yolk powder. This powder was washed successively with diethyl ether and then 70% aqueous acetone. The solid was then

Progress in copper-catalyzed trifluoromethylation

• Guan-bao Li,
• Chao Zhang,
• Chun Song and
• Yu-dao Ma

Beilstein J. Org. Chem. 2018, 14, 155–181, doi:10.3762/bjoc.14.11

• . Although phenols were widely used building blocks in bioactive compounds, only a few examples introducing a CF3 have been reported. In 2015, the group of Hamashima [52] achieved a direct C–H trifluoromethylation of phenol derivatives with high regioselectivity. The CF3 was selectively incorporated into the

• group of Liu. Trifluoromethylation of terminal alkenes reported by the group of Wang. Trifluoromethylation of tetrahydroisoquinoline derivatives reported by Li and the proposed mechanism. Trifluoromethylation of phenol derivatives reported by the group of Hamashima. Trifluoromethylation of hydrazones

Acid-catalyzed ring-opening reactions of a cyclopropanated 3-aza-2-oxabicyclo[2.2.1]hept-5-ene with alcohols

• Katrina Tait,
• Alysia Horvath,
• Nicolas Blanchard and
• William Tam

Beilstein J. Org. Chem. 2017, 13, 2888–2894, doi:10.3762/bjoc.13.281

• of product 26l (Table 3, entry 12, preparation of compound 26l from 23a and t-BuOH with PPTS was already published in reference [20]). When the aromatic alcohol phenol was investigated as a nucleophile, no reaction occurred though no starting material was recovered (Table 3, entry 13). Although in