A versatile route to polythiophenes with functional pendant groups using alkyne chemistry

• Xiao Huang,
• Li Yang,
• Rikard Emanuelsson,
• Jonas Bergquist,
• Maria Strømme,
• Martin Sjödin and
• Adolf Gogoll

Beilstein J. Org. Chem. 2016, 12, 2682–2688, doi:10.3762/bjoc.12.265

• carbon of the pendant group precursors, with yields of 61% (9), 82% (10) and 65% (12), respectively. Methylation of bipyridyl intermediate 10 by methyl iodide produced viologen derivative 11 after exchanging the iodide for the PF6− anion. For the methylation step drying of both the reactants 10 and

Interactions between cyclodextrins and cellular components: Towards greener medical applications?

• Loïc Leclercq

Beilstein J. Org. Chem. 2016, 12, 2644–2662, doi:10.3762/bjoc.12.261

• correlation between the percentages of cholesterol extraction and the methylation degree of the CDs. This effect was clearly independent of the membrane composition. The expression levels of ABCA1 and ABCG1, as well as the cholesterol efflux to ApoA-I and HDL, were reduced due to cholesterol-methylated β-CD

A direct method for the N-tetraalkylation of azamacrocycles

• Andrew J. Counsell,
• Angus T. Jones,
• Matthew H. Todd and
• Peter J. Rutledge

Beilstein J. Org. Chem. 2016, 12, 2457–2461, doi:10.3762/bjoc.12.239

• ][30], the simplest N-tetraalkyl cyclam derivative, this class of compounds has been extensively investigated [2]. While the N-tetramethyl derivative is readily accessed by treating cyclam with formaldehyde and formic acid [29], this transformation (the Eschweiler–Clarke methylation) [31] is not

Elongated and substituted triazine-based tricarboxylic acid linkers for MOFs

• Arne Klinkebiel,
• Ole Beyer,
• Barbara Malawko and
• Ulrich Lüning

Beilstein J. Org. Chem. 2016, 12, 2267–2273, doi:10.3762/bjoc.12.219

• ). In order to synthesize the respective methoxy compound 5c, commercially available 3-hydroxybenzoic acid (10) was used as starting material (Figure 6). Bromination introduced a bromine atom into the 4 position (11) [19], then the phenol was turned into its methyl ether. This methylation can be

• ” methylation [25] could find a remedy. Steric repulsion between ortho-hydrogen atoms in benzene-1,3,5-tribenzoic acid (BTB) leads to a non-planar structure (left). The exchange of CH units by nitrogen atoms in the central six-membered ring allows a planar structure: 1,3,5-triazine-2,4,6-tribenzoic acid (TATB

Isosorbide and dimethyl carbonate: a green match

• Fabio Aricò and
• Pietro Tundo

Beilstein J. Org. Chem. 2016, 12, 2256–2266, doi:10.3762/bjoc.12.218

• other noxious methylating agents in methylation reactions [24][25][26][27][28][29][30][31][32][33][34][35]. The reactions between the bio-based chemicals D-sorbitol or isosorbide and DMC, are very appealing as they encompass the preparation, as well as the transformation of a renewable resource into

• ) that has potential application as green solvent substitute of high boiling polar solvents. Recently DMI has also appeared as component in the formulation of deodorants [87]. Methylation of isosorbide has been investigated both at reflux and in autoclave conditions via DMC chemistry. It should be

• mentioned that generally methylation of secondary alcohols via DMC chemistry requires high temperatures (>150 °C) and was never obtained in high yield due to the formation of elimination products [88]. However, isosorbide, which incorporates in its backbone secondary hydroxy groups, was quantitatively

A new and expeditious synthesis of all enantiomerically pure stereoisomers of rosaprostol, an antiulcer drug

• Wiesława Perlikowska,
• Remigiusz Żurawiński and
• Marian Mikołajczyk

Beilstein J. Org. Chem. 2016, 12, 2234–2239, doi:10.3762/bjoc.12.215

• at C-5. In fact, 1a and 1c were obtained through a two-step sequence starting with the methylation of (−)-1a and (+)-1c followed by a one-pot Mitsunobu esterification–hydrolysis as shown in Scheme 6. In detail, treatment of rosaprostols (−)-1a and (+)-1c with diazomethane gave the corresponding

Evidence for an iterative module in chain elongation on the azalomycin polyketide synthase

• Hui Hong,
• Yuhui Sun,
• Yongjun Zhou,
• Emily Stephens,
• Markiyan Samborskyy and
• Peter F. Leadlay

Beilstein J. Org. Chem. 2016, 12, 2164–2172, doi:10.3762/bjoc.12.206

• replaced by the apramycin resistance cassette aac(3)IV [57] using RedET recombineering of pYJ2 in E. coli to generate BAC clone pML1. Tri-parental mating was used [58] to introduce pML1 into E. coli ET12567, a triply methylation-deficient strain that provides higher efficiency of conjugation into many

•  2c and d). Also, it appears that the heterologous host can supply appropriate, as yet unidentified, enzymes to catalyse methylation of the guanidino group and to attach the malonyl sidechain to the hydroxy group at C-23/C-25. Presumably, these are enzymes acting in primary metabolism and therefore

Ionic liquids as transesterification catalysts: applications for the synthesis of linear and cyclic organic carbonates

• Maurizio Selva,
• Alvise Perosa,
• Sandro Guidi and
• Lisa Cattelan

Beilstein J. Org. Chem. 2016, 12, 1911–1924, doi:10.3762/bjoc.12.181

• , P; n = 4, 6, 8, Ph), obtained by the methylation of trialkylphosphines or -amines with nontoxic DMC (Scheme 3, top) [34][35]. Such methyl carbonate onium salts are versatile platforms as they allow access to a number of ionic liquids via anion-metathesis reactions, which produce only CH3OH and CO2

• organocatalysts offers several practical advantages: (i) the synthesis of [P8881][CH3OCO2] involves a halide-free methylation of a trialkyl phosphine with nontoxic DMC, (ii) acetate and phenolate salt derivatives could be obtained from [P8881][CH3OCO2] through a chlorine-free metathesis with acetic acid and

• carbonates obtained through transesterification using phosphonium salts as catalysts. The transesterification of diethyl oxalate (DEO) with phenol catalyzed by MoO3/SiO2. Transesterification of a triglyceride (TG) with DMC for biodiesel production using KOH as the base catalyst. Top: Green methylation of

From supramolecular chemistry to the nucleosome: studies in biomolecular recognition

• Marcey L. Waters

Beilstein J. Org. Chem. 2016, 12, 1863–1869, doi:10.3762/bjoc.12.175

• thus studied the influence of lysine methylation and the significance of the positive charge in our β-hairpin model systems [23][24], and then moved into studying the actual protein–peptide interaction as well, providing the first definitive evidence that cation–π interactions provided the dominant

Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides

• Franziska Hemmerling and
• Frank Hahn

Beilstein J. Org. Chem. 2016, 12, 1512–1550, doi:10.3762/bjoc.12.148

• mechanism is reminiscent of the formation of a tetrahydropyridine ring by the berberine bridge enzyme in plant alkaloid biosynthesis. It starts with S-adenosyl-L-methionine (SAM)-dependent methylation of the secondary hydroxy group in 81 by the O-methyltransferase Leu14 (Scheme 14a) [71][72][73][74

• lactone that is decarboxylated towards the xanthone [103]. Studies with recombinant AflM and a lack of isolatable intermediates however made it clear that the order of steps in demethylsterigmatocystin (107) formation needs to be carefully re-evaluated [100]. Methylation by an O-methyltransferase and

Synthesis of highly functionalized 2,2'-bipyridines by cyclocondensation of β-ketoenamides – scope and limitations

• Paul Hommes and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2016, 12, 1170–1177, doi:10.3762/bjoc.12.112

• or O-nonaflation led to functionalized pyridine derivatives. Scheme 1 illustrates this sequence with the synthesis of two 2,2´-bipyridine derivatives 4a or 5b that were obtained by employing picolinic acid chloride for the N-acylations followed by O-methylation with methyl iodide or by O-nonaflation

Synthesis of 2-oxindoles via 'transition-metal-free' intramolecular dehydrogenative coupling (IDC) of sp² C–H and sp³ C–H bonds

• Nivesh Kumar,
• Santanu Ghosh,
• Subhajit Bhunia and
• Alakesh Bisai

Beilstein J. Org. Chem. 2016, 12, 1153–1169, doi:10.3762/bjoc.12.111

• methylation can be done in the presence of 1.2 equivalents of KOt-Bu and 1.1 equivalents of methyl iodide. This was accompanied with an oxidative coupling using 1.2 equivalents of KOt-Bu and iodine to afford the desired product in 65% yield (Table 1, entries 1 and 2). Optimization studies in search of

Marine-derived myxobacteria of the suborder Nannocystineae: An underexplored source of structurally intriguing and biologically active metabolites

• Antonio Dávila-Céspedes,
• Peter Hufendiek,
• Max Crüsemann,
• Till F. Schäberle and
• Gabriele M. König

Beilstein J. Org. Chem. 2016, 12, 969–984, doi:10.3762/bjoc.12.96

• miuraenamide A (31) the absolute configuration was determined. Marfey´s method was employed to show that L-alanine and N-methyl-D-tyrosine are present. Furthermore, after acid hydrolysis, methylation and application of modified Mosher´s method the absolute configuration at the oxygen bearing C-9 was deduced as

Muraymycin nucleoside-peptide antibiotics: uridine-derived natural products as lead structures for the development of novel antibacterial agents

• Daniel Wiegmann,
• Stefan Koppermann,
• Marius Wirth,
• Giuliana Niro,
• Kristin Leyerer and
• Christian Ducho

Beilstein J. Org. Chem. 2016, 12, 769–795, doi:10.3762/bjoc.12.77

• followed by an azide reduction, Boc protection, saponification of the ester, peptide coupling with the amino acid 17, oxidative cleavage of the double bond to give 18 and an intramolecular reductive amination in order to construct the seven-membered ring. Methylation with subsequent acidic global

Opportunities and challenges for direct C–H functionalization of piperazines

• Zhishi Ye,
• Kristen E. Gettys and
• Mingji Dai

Beilstein J. Org. Chem. 2016, 12, 702–715, doi:10.3762/bjoc.12.70

• and properties, as the so-called as the “magic methyl effect” [44]. Direct enantioselective α-methylation of piperazines however, has been a great synthetic challenge and an effective method still needs to be developed. O’Brien and co-workers also reported their work towards a solution to this problem

• . As shown in Figure 11, they have tried various reaction conditions to achieve an enantioselective methylation of the α-lithiation intermediate of N-Boc-N’-alkylpiperazines by using different diamines (TMEDA, 21, and 28) as well as the “chiral auxiliary” strategy. While the result is not yet optimal

Elucidation of a masked repeating structure of the O-specific polysaccharide of the halotolerant soil bacteria Azospirillum halopraeferens Au4

• Elena N. Sigida,
• Yuliya P. Fedonenko,
• Alexander S. Shashkov,
• Nikolay P. Arbatsky,
• Evelina L. Zdorovenko,
• Svetlana A. Konnova,
• Vladimir V. Ignatov and
• Yuriy A. Knirel

Beilstein J. Org. Chem. 2016, 12, 636–642, doi:10.3762/bjoc.12.62

• hydrolysis of the lipopolysaccharide isolated by the phenol–water extraction from the halotolerant soil bacteria Azospirillum halopraeferens type strain Au4. The polysaccharide was studied by sugar and methylation analyses, selective cleavages by Smith degradation and solvolysis with trifluoroacetic acid

• -methylglucose, 2,4-di-O-methylrhamnose, 2,4-di-O-methylfucose, 2-O-methylfucose, and 3,4-di-O-methylxylose were identified by GLC–MS of partially methylated alditol acetates derived after methylation of the OPS with MeI followed by hydrolysis and acetylation [14]. Therefore, the OPS contains 3-substituted Rha

• revealed that its reason is a non-stoichiometric side-chain glucosylation and methylation of the main polysaccharide chain but at this stage, a straightforward structure elucidation of the OPS by NMR spectroscopy [16] was complicated. In order to obtain oligosaccharide fragments of the OPS a Smith

Biosynthesis of α-pyrones

• Till F. Schäberle

Beilstein J. Org. Chem. 2016, 12, 571–588, doi:10.3762/bjoc.12.56

• biosynthesis was investigated using various 13C-labeled precursors [55]. Hence, it was concluded that beside four acetate units also two propionate units and one butyrate unit form the backbone, while the O-methylation is S-adenosyl-methionine dependent. Also cyclooxygenase-2 (COX-2) inhibitors are an

• . Cyclization between C-2, C-7 and C-8, C-13, as well as lactonization takes place, resulting in alternariol (17). Subsequently, a methylation and a hydroxylation reaction occur, catalyzed by the respective enzymes. Structures of phenylnannolones and of enterocin, both biosynthesized via polyketide synthase

Interactions between 4-thiothymidine and water-soluble cyclodextrins: Evidence for supramolecular structures in aqueous solutions

• Vito Rizzi,
• Sergio Matera,
• Paola Semeraro,
• Paola Fini and
• Pinalysa Cosma

Beilstein J. Org. Chem. 2016, 12, 549–563, doi:10.3762/bjoc.12.54

• appeared only weakly in DIMEB CD (Figure 5D). This is due to the methylation of the OH moieties. As described in [42], weak absorption bands were detected also in the region of 1100–650 cm−1 and can be related to vibrations of the С–Н bonds and to the glucopyranose rind. Further, in the region of 1400–1150

Regiodefined synthesis of brominated hydroxyanthraquinones related to proisocrinins

• Joyeeta Roy,
• Tanushree Mal,
• Supriti Jana and
• Dipakranjan Mal

Beilstein J. Org. Chem. 2016, 12, 531–536, doi:10.3762/bjoc.12.52

• ][25][26][27][28][29][30]. It was then treated with bromine in AcOH to afford 3,5-dibromoorsellinate 20 in 81% yield [31][32][33]. Subsequent O-methylation of 20 (using CH3I, K2CO3), and benzylic bromination of 21 with NBS followed by lactonization of 22 in a refluxing mixture of dioxane and water

Interactions of cyclodextrins and their derivatives with toxic organophosphorus compounds

• Sophie Letort,
• Sébastien Balieu,
• William Erb,
• Géraldine Gouhier and
• François Estour

Beilstein J. Org. Chem. 2016, 12, 204–228, doi:10.3762/bjoc.12.23

• trend was disclosed by theoretical semi-empirical calculations of parathion-, methyl parathion- and fenitrothion-β-CD complexes [55]. It was shown that the methyl group, adjacent to the nitro function slightly impairs both deep and axial inclusion of fenitrothion into the cavity. The methylation degree

• decrease of the hydrolysis rate of fenitrothion is observed with methylation of β-CD. These unpredictable results revealed that much more complex parameters than the easiness of the guest entry into the (methylated)CD are involved in the hydrolysis. Indeed, the methylation degree could also affect the

• steric hindrance of the secondary rim, resulting in CD geometrical changes with modifications of the complex stability, the orientation and inclusion depth of the pesticide within the cavity. However, the two main parameters to take into account remain the methylation degree and the pesticide inclusion

Determination of formation constants and structural characterization of cyclodextrin inclusion complexes with two phenolic isomers: carvacrol and thymol

• Miriana Kfoury,
• David Landy,
• Steven Ruellan,
• Lizette Auezova,
• Hélène Greige-Gerges and
• Sophie Fourmentin

Beilstein J. Org. Chem. 2016, 12, 29–42, doi:10.3762/bjoc.12.5

• inclusion of 1 inside the cavity. RAMEB gave the most stable inclusion complexes with both 1 and 2. This is due to that the methoxy groups of RAMEB are small and do not lead to a significant steric hindrance and that the methylation of β-CD hydroxy groups increases the hydrophobic character of the cavity

Physical properties and biological activities of hesperetin and naringenin in complex with methylated β-cyclodextrin

• Waratchada Sangpheak,
• Jintawee Kicuntod,
• Roswitha Schuster,
• Thanyada Rungrotmongkol,
• Peter Wolschann,
• Nawee Kungwan,
• Helmut Viernstein,
• Monika Mueller and
• Piamsook Pongsawasdi

Beilstein J. Org. Chem. 2015, 11, 2763–2773, doi:10.3762/bjoc.11.297

• )-glycosidic bonds. It contains a highly hydrophobic central cavity and the hydrophilic outer surface. The 2,6-di-O-methyl-β-cyclodextrin (DM-β-CD), a commercially available β-CD derivative, is obtained by methylation of the hydroxy groups at C2 and C6 of all glucose units, thus having the degree of

• give much difference to these properties. However, in the third part whereby biological activities were examined, the two flavanones complexing with β-CD and DM-β-CD were used since the different degree of methylation might exert significant effect on the result as previously reported [28]. Binding

• . The methyl substitution plays an important role in balancing the CD water solubility and its complexing ability [44]. It was previously reported that increasing the degree of methylation up to an optimum level improves the CD aqueous solubility, and the binding of guests to CDs is increased by

Inclusion complexes of 2-methoxyestradiol with dimethylated and permethylated β-cyclodextrins: models for cyclodextrin–steroid interaction

• Mino R. Caira,
• Susan A. Bourne,
• Halima Samsodien and
• Vincent J. Smith

Beilstein J. Org. Chem. 2015, 11, 2616–2630, doi:10.3762/bjoc.11.281

• . The unique layering that results in the extended crystal structure is shown in Figure 2f, a view along the [010] direction. Methylation of the DIMEB molecule at the 3-position results in fully methylated β-CD (TRIMEB), the second crystalline derivatised CD investigated here for its potential to

• thermal motion that was not amenable to standard anisotropic treatment while the disordered water oxygen atoms did not warrant anisotropic treatment. A minor, but unexpected feature of the DIMEB inclusion complex, was partial methylation of the O3-H hydroxy group of the host glucose ring G1 (s.o.f. = 0.5

• host molecule. This necessitated reduction of the s.o.f. of the latter methyl group from 1.0 to 0.5. The net effect was that despite partial methylation of O3–H on G1, appropriate modelling of disordered residues resulted in retention of the nominal formula for the DIMEB molecule, namely C56H98O35. The

Synthesis of Xenia diterpenoids and related metabolites isolated from marine organisms

• Tatjana Huber,
• Lara Weisheit and
• Thomas Magauer

Beilstein J. Org. Chem. 2015, 11, 2521–2539, doi:10.3762/bjoc.11.273

• isobutene (36), an isomeric mixture of trans- and cis-fused [4.2.0]octanone was obtained (trans-38/cis-39 = 4:1). The more stable cis-bicycle 39 could be obtained by isomerization of trans-38 with base. Acylation with sodium hydride and dimethyl carbonate followed by methylation furnished β-keto ester 40

Recent highlights in biosynthesis research using stable isotopes

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2015, 11, 2493–2508, doi:10.3762/bjoc.11.271

• branched polyketides at the α-position of the growing chain include the usage of different elongation units such as methylmalonyl-CoA, or methylation of the nucleophilic α-position by S-adenosyl methionine (SAM) [21]. Branching in the β-position is less common and proceeds through a β-aldol attack of an