Selective preparation of tetrasubstituted fluoroalkenes by fluorine-directed oxetane ring-opening reactions

• Clément Q. Fontenelle,
• Thibault Thierry,
• Romain Laporte,
• Emmanuel Pfund and
• Thierry Lequeux

Beilstein J. Org. Chem. 2020, 16, 1936–1946, doi:10.3762/bjoc.16.160

• antiviral agents, respectively (Figure 1) [5][6]. The field of acyclonucleotides (ACN) has been explored less, however, the introduction of fluorine atoms showed remarkable effects. The most representative examples are phosphate analogues such as the nucleoside phosphorylase inhibitor III and acyclic

• VIII was observed due to the difficulty of phosphorylation of the substrate by kinases [16]. The first kinase phosphorylation step is generally rate limiting, and the prior introduction of a phosphate or phosphonate function can circumvent this problem. The preparation of diols VIII was realized by

Synthesis, docking study and biological evaluation of ᴅ-fructofuranosyl and ᴅ-tagatofuranosyl sulfones as potential inhibitors of the mycobacterial galactan synthesis targeting the galactofuranosyltransferase GlfT2

• Marek Baráth,
• Jana Jakubčinová,
• Zuzana Konyariková,
• Stanislav Kozmon,
• Katarína Mikušová and
• Maroš Bella

Beilstein J. Org. Chem. 2020, 16, 1853–1862, doi:10.3762/bjoc.16.152

• -acetylglucosaminyltransferase I (GnT-I) reaction transition state [11]. Previously, we have designed 2-thiohexofuranoside skeletons bearing a phosphate group in position 1 by molecular modeling as potential transition state inhibitors of human glycosyltransferase I (GnT-I) [12], the bisubstrate enzyme requiring a metal co

• originally suggested by molecular modeling having the 1-O-phosphate group stabilized by anomeric sulfones on the ᴅ-fructofuranose and ᴅ-tagatofuranose skeleton (1–3, Figure 1). Similarities in the TS structures of GnT-I and GlfT2 prompted us to examine these molecules against GlfT2, a possible target for the

• -up of lipid-linked galactan precursors. The crude enzymes used in the assay allow for in situ synthesis of the acceptor for galactan polymerization, decaprenyl-P-P-GlcNAc-Rha (GL2), from endogenous decaprenyl phosphate and sugar nucleotides UDP-GlcNAc and TDP-Rha supplied in the reaction mixture

One-pot synthesis of oxazolidinones and five-membered cyclic carbonates from epoxides and chlorosulfonyl isocyanate: theoretical evidence for an asynchronous concerted pathway

• Esra Demir,
• Ozlem Sari,
• Yasin Çetinkaya,
• Ufuk Atmaca,
• Safiye Sağ Erdem and
• Murat Çelik

Beilstein J. Org. Chem. 2020, 16, 1805–1819, doi:10.3762/bjoc.16.148

• . Linezolid (3) is the first oxazolidinone drug approved in 2000 by the Food and Drug Administration (FDA) for the treatment of multidrug resistant Gram-positive bacterial infections (Scheme 1) [10]. Cytoxazone is a microbial metabolite exhibiting potent cytokine-modulating activity. Tedizolid phosphate

Nonenzymatic synthesis of anomerically pure, mannosyl-based molecular probes for scramblase identification studies

• Giovanni Picca,
• Markus Probst,
• Simon M. Langenegger,
• Oleg Khorev,
• Peter Bütikofer,
• Anant K. Menon and
• Robert Häner

Beilstein J. Org. Chem. 2020, 16, 1732–1739, doi:10.3762/bjoc.16.145

• . Reports of using phosphoramidite chemistry for the preparation of carbohydrates via the anomeric position are relatively rare [18][19][20][21][22][23]. Alternatively, the H-phosphonate approach has been used to convert carbohydrates into phosphate-linked derivatives at the anomeric center [24][25][26][27

• headgroup and simultaneously introduced the linking phosphate group. Furthermore, we demonstrate a novel, reliable, and efficient way to synthesize the carbohydrate phosphoramidite with a defined configuration at the anomeric position, a strategy that gives access to future molecular probes containing pure

One-pot synthesis of isosorbide from cellulose or lignocellulosic biomass: a challenge?

• Isaline Bonnin,
• Raphaël Mereau,
• Thierry Tassaing and
• Karine De Oliveira Vigier

Beilstein J. Org. Chem. 2020, 16, 1713–1721, doi:10.3762/bjoc.16.143

• isosorbide. The hydrolysis of cellulose to glucose, the first step, is reported using acid catalysts such as H3PO4, H2SO4 and HCl as well as heterogeneous catalysts tungstolitic acid (H4SiW12O40), niobium phosphate, Amberlyst-70 and Dowex-H [1][12]. For the second step (hydrogenation of glucose to sorbitol

• to sorbitol. Several homogeneous catalysts were used such as mineral acids, boron phosphate and heteropolyacids (Scheme 2). Palkovits et al. studied the combination of supported noble metal catalysts based on Pt, Pd and Ru with dilute mineral acids such as phosphoric or sulfuric acid for the

• showed that the acidity is important in the conversion of lignocellulosic biomass to isosorbide and that the acid can react with the metal-supported catalyst. Another study was devoted to the use of boron phosphate for the conversion of cellulose into liquid hydrocarbon C1–C6 over Ru/C [23]. A mixture of

A dynamic combinatorial library for biomimetic recognition of dipeptides in water

• Florian Klepel and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2020, 16, 1588–1595, doi:10.3762/bjoc.16.131

• . The mobile phase was a mixture of water (0.1 % NH4FA, pH 3.2) and acetonitrile. The injection volume was 5 µL. The following gradient was used with a flow rate of 150 µL/min (Table 2). ITC measurements For determination of binding constants ITC was measured in phosphate buffered solutions (pH 7.4, 100

• chromatograms of a reference library for all possible tripeptide dimers ([M + H]+ ions). a) HPLC–MS chromatograms of the dimers (CFC)2 and templates YY and FF. b) Amplification of the peak areas. ITC of YY (30 mM) to a(CFC)2 (1.5 mM) in phosphate buffer (pH 7.4, 100 mM). Continuously varied NMR measurements of

• ). Measured by ITC in phosphate buffer (pH 7.4, 100 mM). Data fitted with a 1:1 model. Solvent gradients for HPLC. Supporting Information Supporting Information File 338: Synthesis, additional data, and NMR spectra. Acknowledgements We would like to thank Dr. Kevin Eckey, Jens Fangmeyer and Prof. Dr. Uwe

Photocatalyzed syntheses of phenanthrenes and their aza-analogues. A review

• Alessandra Del Tito,
• Havall Othman Abdulla,
• Davide Ravelli,
• Stefano Protti and
• Maurizio Fagnoni

Beilstein J. Org. Chem. 2020, 16, 1476–1488, doi:10.3762/bjoc.16.123

• phosphate base (50 mol %). Thus, the latter played a key role in the PCET event which triggered the activation of the N–H bond in 18.1a–d and led to the N-centered radicals 18.2·a–d. Ensuing cyclization onto the pendant aromatic group, followed by rearomatization enabled by molecular oxygen, gave the

Activated carbon as catalyst support: precursors, preparation, modification and characterization

• Melanie Iwanow,
• Tobias Gärtner,
• Volker Sieber and
• Burkhard König

Beilstein J. Org. Chem. 2020, 16, 1188–1202, doi:10.3762/bjoc.16.104

• structures in the carbon source [6]. Diamadopoulos and co-workers observed also the production of smaller surface areas by H3PO4 activation of bagasse and rice husk due to a reaction of the activating reagent with the carbon precursor. Thereby, phosphate esters or polymerization byproducts are formed, which

• forming phosphate esters or polymerization byproducts that bind on the solid carbon matrix [30]. Boehm titrations: Boehm titrations are used for the determination of acidic or basic surface oxygen functional groups of solid materials. The acidic character is caused by carboxyl groups (R–COOH), lactones (R

Fluorinated phenylalanines: synthesis and pharmaceutical applications

• Laila F. Awad and
• Mohammed Salah Ayoup

Beilstein J. Org. Chem. 2020, 16, 1022–1050, doi:10.3762/bjoc.16.91

• able to increase the secretion of insulin by the pancreas that modulates blood sugar level when it is high. Sitagliptin was granted FDA approval in October, 2006 [116]. Retagliptin phosphate: Retagliptin phosphate (184) is under investigation as a DPP-4 inhibitor for treating type-2 diabetes. It is an

Reaction of indoles with aromatic fluoromethyl ketones: an efficient synthesis of trifluoromethyl(indolyl)phenylmethanols using K₂CO₃/n-Bu₄PBr in water

• Thanigaimalai Pillaiyar,
• Masoud Sedaghati and
• Gregor Schnakenburg

Beilstein J. Org. Chem. 2020, 16, 778–790, doi:10.3762/bjoc.16.71

• was reduced to 91% (Table 1, entry 7) and 81% (Table 1, entry 9), respectively, while it was increased to 97% (Table 1, entry 8) in the presence of K2CO3. The reaction in the presence of tripotassium phosphate base (Table 1, entry 10; 89%), dipotassium phosphate base (Table 1, entry 11; 70%) or sodium

Recent advances in Cu-catalyzed C(sp³)–Si and C(sp³)–B bond formation

• Balaram S. Takale,
• Ruchita R. Thakore,
• Elham Etemadi-Davan and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2020, 16, 691–737, doi:10.3762/bjoc.16.67

• reagent (7), to successfully convert benzyl phosphate 6 to benzylic silanes 8. Curiously, the reaction proceeded even in the absence of a ligand, albeit with lower yield (25%; Scheme 3). However, only one example was reported and a more general method for the preparation of alkylsilanes was developed by

Recent advances in photocatalyzed reactions using well-defined copper(I) complexes

• Mingbing Zhong,
• Xavier Pannecoucke,
• Philippe Jubault and
• Thomas Poisson

Beilstein J. Org. Chem. 2020, 16, 451–481, doi:10.3762/bjoc.16.42

• hydrogen phosphate ((R)-BNDHP) under similar reaction conditions and using the same copper catalyst provided the δ-functionalization of the alcohol (Scheme 28). This reaction manifold was applied to a large variety of N-alkoxyphthalimide derivatives using glycine ester derivatives and was also extended to

Oligomeric ricinoleic acid preparation promoted by an efficient and recoverable Brønsted acidic ionic liquid

• Fei You,
• Xing He,
• Song Gao,
• Hong-Ru Li and
• Liang-Nian He

Beilstein J. Org. Chem. 2020, 16, 351–361, doi:10.3762/bjoc.16.34

• sustainable synthesis protocol is urgently needed to make the product really green. In this work, an environment-friendly Brønsted acidic ionic liquid (IL) 1-butanesulfonic acid diazabicyclo[5.4.0]undec-7-ene dihydrogen phosphate ([HSO3-BDBU]H2PO4) was developed as the efficient catalyst for the production of

• that the cation also affected the catalytic activity of the IL. Taking the decrease of acid value as catalytic activity index, the ionic liquid 1-butanesulfonic acid triethylamine dihydrogen phosphate ([HSO3-BNEt3]H2PO4) performed best among the tested ionic liquids in this study (Table 1, entry 8

Potent hemithioindigo-based antimitotics photocontrol the microtubule cytoskeleton in cellulo

• Alexander Sailer,
• Franziska Ermer,
• Yvonne Kraus,
• Rebekkah Bingham,
• Ferdinand H. Lutter,
• Julia Ahlfeld and
• Oliver Thorn-Seshold

Beilstein J. Org. Chem. 2020, 16, 125–134, doi:10.3762/bjoc.16.14

• nonetheless (further discussion in Supporting Information File 1). We found that the photochemical properties of the non-para-hydroxylated control HITub-6 were similar to those of previously reported non-para-hydroxylated HOTubs [18], with satisfactory photoswitching in both DMSO and phosphate-buffered saline

Reversible photoswitching of the DNA-binding properties of styrylquinolizinium derivatives through photochromic [2 + 2] cycloaddition and cycloreversion

• Sarah Kölsch,
• Heiko Ihmels,
• Jochen Mattay,
• Norbert Sewald and
• Brian O. Patrick

Beilstein J. Org. Chem. 2020, 16, 111–124, doi:10.3762/bjoc.16.13

• bands of the electron acceptor-substituted derivative 3d were shifted to even shorter wavelengths. DNA-binding properties The DNA-binding properties of the 2-styrylquinolizinium derivatives 3a–d were investigated by spectrometric titrations of calf thymus DNA (ct DNA) to 3a–d in a phosphate buffered

• –d were further investigated by circular dichroism (CD) and flow linear dichroism (LD) spectroscopy [74][75] in phosphate buffer at different ligand-to-DNA ratios (LDR). The mixtures of compounds 3a–d with ct DNA showed clear induced circular dichroism (ICD) and LD bands in the absorption region of

The interaction between cucurbit[8]uril and baicalein and the effect on baicalein properties

• Xiaodong Zhang,
• Jun Xie,
• Zhiling Xu,
• Zhu Tao and
• Qianjun Zhang

Beilstein J. Org. Chem. 2020, 16, 71–77, doi:10.3762/bjoc.16.9

• being extremely poor, BALE in artificial gastric juice (pH 1.2, hydrochloric acid solution) and artificial intestinal juice (pH 6.8, phosphate buffer solution) can be detected. After 12 h, the degree of release was 11.26% (BALE) and 13.39% (BALE–Q[8]), respectively in artificial gastric juice and 14.49

Synthesis of C-glycosyl phosphonate derivatives of 4-amino-4-deoxy-α-ʟ-arabinose

• Lukáš Kerner and
• Paul Kosma

Beilstein J. Org. Chem. 2020, 16, 9–14, doi:10.3762/bjoc.16.2

• cationic antimicrobial peptides with the negatively charged phosphate and carboxylate groups in LPS domains. Suitable inhibitors intercepting the attachment of Ara4N units to the lipid A and inner core region might restore sensitivity towards the cationic antimicrobial drugs as a novel approach to combat

• and the glycosyl transfer have not been fully explored yet. Previously, Kline and co-workers reported on the synthesis of acetylated 4-azido-arabinose phosphate and uridine diphosphate (UDP) derivatives. In addition, a 4-aminophosphoamidate UDP derivative was also obtained [8]. Whereas these compounds

Synthesis and characterization of bis(4-amino-2-bromo-6-methoxy)azobenzene derivatives

• David Martínez-López,
• Amirhossein Babalhavaeji,
• Diego Sampedro and
• G. Andrew Woolley

Beilstein J. Org. Chem. 2019, 15, 3000–3008, doi:10.3762/bjoc.15.296

• -2401PC, or an Ocean Optics USB4000 diode array spectrophotometer. The temperature was maintained at 22 °C for all measurements (Quantum Northwest temperature controller), and 10 mm or 1.5 mm quartz cuvettes (Hellma Analytics) were used. Samples were prepared in sodium phosphate buffer, pH 7.0, or in DCM

Bacterial terpene biosynthesis: challenges and opportunities for pathway engineering

• Eric J. N. Helfrich,
• Geng-Min Lin,
• Christopher A. Voigt and
• Jon Clardy

Beilstein J. Org. Chem. 2019, 15, 2889–2906, doi:10.3762/bjoc.15.283

• the mechanistic logic of terpene biosynthesis The entry points of terpene biosynthesis are isopentenyl pyrophosphate (IPP, 6) and dimethylallyl pyrophosphate (DMAPP, 7), which are assembled through the 2-C-methyl-ᴅ-erythritol 4-phosphate (MEP) or the mevalonic acid (MVA) pathway. Each pathway uses

• the novel 1-deoxy-ᴅ-xylulose 5-phosphate pathway (nDXP) [145] and the isopentenol utilization pathway (IUP) [146], that bypass (part of) the natural MVA or MEP pathway were designed to circumvent this complex endogenous interaction and regulation (Figure 11a). Lastly, integration of pathways into the

• is divided into two phases, 1) terpene scaffold generation and 2) terpene scaffold functionalization. Representative examples are shown with the modifications installed in the tailoring step highlighted in red. MEP: 2-C-methyl-ᴅ-erythritol 4-phosphate pathway, MVA: mevalonic acid pathway, IPP

Emission and biosynthesis of volatile terpenoids from the plasmodial slime mold Physarum polycephalum

• Xinlu Chen,
• Tobias G. Köllner,
• Wangdan Xiong,
• Guo Wei and
• Feng Chen

Beilstein J. Org. Chem. 2019, 15, 2872–2880, doi:10.3762/bjoc.15.281

• diverse VOCs, terpenoids are the largest group. Terpenoids are biosynthesized from two C5 diphosphate compounds isopentenyl diphosphate (IPP) and its isomer dimethylallyl diphosphate (DMAPP), which are produced by either the mevalonate (MVA) pathway or the methylerythritol phosphate (MEP) pathway [9][10

Palladium-catalyzed synthesis and nucleotide pyrophosphatase inhibition of benzo[4,5]furo[3,2-b]indoles

• Hoang Huy Do,
• Saif Ullah,
• Alexander Villinger,
• Joanna Lecka,
• Jean Sévigny,
• Peter Ehlers,
• Jamshed Iqbal and
• Peter Langer

Beilstein J. Org. Chem. 2019, 15, 2830–2839, doi:10.3762/bjoc.15.276

• was noticed that both five and six-membered rings of the benzofuran moiety were linked via π–π stacked relation with His483. However, the aromatic ring of indole demonstrated π–alkyl bonding by Leu239. The additional π–anion interaction was observed with the phosphate group and benzofuran. The 3D

Design, synthesis and investigation of water-soluble hemi-indigo photoswitches for bioapplications

• Daria V. Berdnikova

Beilstein J. Org. Chem. 2019, 15, 2822–2829, doi:10.3762/bjoc.15.275

• , the photoisomerization quantum yields as well as the half-lifes of the photoinduced forms appeared to be almost independent of the presence of the alkylamino substituent. Interestingly, a comparison with the data obtained for Z-2 in aqueous 10 mM Na-phosphate buffer containing 0.1 M NaCl, pH 7.0 [12

Skeletocutins M–Q: biologically active compounds from the fruiting bodies of the basidiomycete Skeletocutis sp. collected in Africa

• Tian Cheng,
• Clara Chepkirui,
• Cony Decock,
• Josphat C. Matasyoh and
• Marc Stadler

Beilstein J. Org. Chem. 2019, 15, 2782–2789, doi:10.3762/bjoc.15.270

• multidishes. After three days, the confluent monolayers were washed twice with phosphate buffered saline (PBS), and the reaction mixture (450 µL Hanks' buffer at pH 7.2 containing 50 or 100 µM substrate ʟ-Leu-AMC, compounds dissolved in 50 µL DMSO) was added. After being incubated at 23 °C for 30 min, 1 mL

Diversity-oriented synthesis of spirothiazolidinediones and their biological evaluation

• Sambasivarao Kotha,
• Gaddamedi Sreevani,
• Lilya U. Dzhemileva,
• Milyausha M. Yunusbaeva,
• Usein M. Dzhemilev and
• Vladimir A. D’yakonov

Beilstein J. Org. Chem. 2019, 15, 2774–2781, doi:10.3762/bjoc.15.269

• performed by staining cells with 7-AAD (7-aminoactinomycin D, Biolegend) in a similar manner as described in [62]. In brief, after treatment cells were harvested, washed 1–2 times with phosphate-buffered saline (PBS) and centrifuged at 400g for 5 minutes. Cell pellets were resuspended in 200 µL of flow

Safe and highly efficient adaptation of potentially explosive azide chemistry involved in the synthesis of Tamiflu using continuous-flow technology

• Cloudius R. Sagandira and
• Paul Watts

Beilstein J. Org. Chem. 2019, 15, 2577–2589, doi:10.3762/bjoc.15.251

• use of a base in the DPPA procedure was unavoidable as the reaction did not proceed in its absence. This can be understood by considering the DPPA azidating mechanism. The reaction takes place in two discrete steps, the first being phosphate formation followed by azide displacement (Scheme 4) [24]. We