Synthesis and SAR of the antistaphylococcal natural product nematophin from Xenorhabdus nematophila

• Frank Wesche,
• Hélène Adihou,
• Thomas A. Wichelhaus and
• Helge B. Bode

Beilstein J. Org. Chem. 2019, 15, 535–541, doi:10.3762/bjoc.15.47

• aluminium chloride (AlCl3) in DCM to give compounds 14 and 21. Subsequent reduction was achieved with triethylsilane (Et3SiH) in TFA to give 15 and 22. For the synthesis of the primary amine, halides 15 and 22 were converted in a Gabriel synthesis with potassium phthalimide in DMF to the appropriate

• in DMF (c 0.1 M), 25 W, 75 °C, 20 min. Synthesis of azatryptamines (4-azatryptamine (4ATRA) and 1-methyl-4-azatryptamine (1M4ATRA)). i) 5.0 equiv AlCl3, 5.0 equiv chloroacetyl chloride in DCM, overnight, rt 67%; ii) 7.0 equiv Et3SiH in TFA, overnight, rt, 93%; iii) 1.1 equiv potassium phthalimide, in

• %; ii) 7.0 equiv Et3SiH in TFA, overnight, rt, 93%; iii) 1.1 equiv potassium phthalimide, in DMF, 100 °C, 56%; iv) 1.2 equiv NaH, 1.0 equiv MeI in DMF, overnight, rt, 57%; v) 5.0 equiv N2H4·H2O in EtOH, 2 h, 90 °C, 25 W, 92% to quant. Summary of synthesized nematophin derivatives (1–12) and their

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

• , tripivalate, 5-O-myristolate analogues [34], 2′,3′-O-isopropylidene-1,4-dihydronicotinamide riboside [60], and 1,4-dihydronicotinate ribosides [70]. Typically, the reduction with Na2S2O4 is performed under mild basic conditions (e.g., in a medium of aqueous sodium bicarbonate or potassium phosphate dibasic

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

• treated with potassium carbonate followed by a dropwise addition of bromoethane, as the alkylating agent. This synthetic strategy provided exclusively the 1-ethylated product 7 with a good overall yield (80%, Scheme 1). Previous treatment of 5 with potassium carbonate promotes the establishment of an acid

• for the deprotonation reaction using potassium carbonate as a base. These results are in agreement with the analysis of the stability of the conjugate bases due to structural electronic effects. The oxoquinoline conjugate base presents a great stability, since it promotes a greater dispersion of the

• . Procedure for the preparation of N-benzyl-1-ethyl-4-oxo-1,4-dihydroquinoline-3-carboxamide (7) In a round bottom flask, 1.0 g (3,6 mmol) of N-benzyl-4-oxo-1,4-dihydroquinoline-3-carboxamide (5), 1.4 g (10.1 mmol) of potassium carbonate and 10.0 mL of dimethyl sulfoxide (DMSO) were added and stirred at room

Thiol-free chemoenzymatic synthesis of β-ketosulfides

• Adrián A. Heredia,
• Martín G. López-Vidal,
• Marcela Kurina-Sanz,
• Fabricio R. Bisogno and
• Alicia B. Peñéñory

Beilstein J. Org. Chem. 2019, 15, 378–387, doi:10.3762/bjoc.15.34

• Scheme 3, α-chloroacetophenone (1.0 g, 6.47 mmol) was reacted with 1.1 equiv of potassium thioacetate, 1.1 equiv of allyl bromide and 2 equiv of K2CO3 in 5 mL of DMSO. After 24 h, 45 mL of buffer (Tris·HCl 50 mM pH 7.5) were added. Then, KH2PO4 was added in order to reach pH ≈7.5, followed by 200 mg of

• chemoenzymatic synthesis of β-ketosulfides. One-pot two-step preparation of phenacylalkylsulfides. aReaction conditions: i. α-haloketone (0.25 mmol), potassium thioacetate (1.1 equiv), alkyl halide (1.1 equiv) and K2CO3 (2.0 equiv) in 500 µL of DMSO, 5 h at room temperature; ii. 100 mg of CAL-B (Novozyme 435

• ) and 9.5 mL of Tris·HCl buffer (50 mM pH 7.5), 30 °C, 24 h, 250 rpm. bReaction performed using 1.0 g of α-chloroacetophenone, potassium thioacetate (1.1 equiv), alkyl halide (1.1 equiv) and K2CO3 (2.0 equiv) in 5 mL of DMSO, 200 mg of CAL-B and 45 mL of Tris-HCl buffer (50 mM pH 7.5), 24 h at room

Sigmatropic rearrangements of cyclopropenylcarbinol derivatives. Access to diversely substituted alkylidenecyclopropanes

• Guillaume Ernouf,
• Jean-Louis Brayer,
• Christophe Meyer and
• Janine Cossy

Beilstein J. Org. Chem. 2019, 15, 333–350, doi:10.3762/bjoc.15.29

• ketene acetals of (Z)-configuration 57a–l, arising from O-silylation of the corresponding chelated potassium enolates [60], underwent an efficient [3,3]-sigmatropic rearrangement upon warming to room temperature. After an acidic work-up and treatment of the crude carboxylic acids with

Metal-free C–H mercaptalization of benzothiazoles and benzoxazoles using 1,3-propanedithiol as thiol source

• Yan Xiao,
• Bing Jing,
• Xiaoxia Liu,
• Hongyu Xue and
• Yajun Liu

Beilstein J. Org. Chem. 2019, 15, 279–284, doi:10.3762/bjoc.15.24

• potassium hydroxide and DMSO. This novel protocol is featured by direct C–H mercaptalization of heteroarenes and a simple reaction system. Keywords: benzothiazole; benzoxazole; C–H functionalization; mercaptalization; 1,3-propanedithiol; Introduction Both 2-mercaptobenzothiazoles and 2

• -catalyzed C–S coupling reactions [13]. Conventional methods for the synthesis of 2-mercaptobenzoxazoles and 2-mercaptobenzothiazoles include the interaction of 2-aminophenol or 2-haloanilines with carbon disulfide [14][15][16], or potassium ethyl xanthate [17][18] (Scheme 1). In 2017, the Dong group

• 2009, the Daugulis group reported that benzoxazole was converted to 2-mercaptobenzoxazoles in the presence of sulfur and potassium tert-butoxide, but only one example was shown [35]. In 2017, the Lei group reported a copper catalyzed C–H mercaptalization strategy using elementary sulfur as thiol source

Oxidative radical ring-opening/cyclization of cyclopropane derivatives

• Yu Liu,
• Qiao-Lin Wang,
• Zan Chen,
• Cong-Shan Zhou,
• Bi-Quan Xiong,
• Pan-Liang Zhang,
• Chang-An Yang and
• Quan Zhou

Beilstein J. Org. Chem. 2019, 15, 256–278, doi:10.3762/bjoc.15.23

• 2016, the silver-promoted oxidative ring-opening/alkynylation of cyclopropanols 91 with ethynylbenziodoxolones (EBX) 116 had been presented by Li and co-workers (Scheme 29) [109]. Both silver(I) nitrate and potassium persulfate played an important role in this transformation. In 2016, Hu and co-workers

Synthesis of nonracemic hydroxyglutamic acids

• Dorota G. Piotrowska,
• Iwona E. Głowacka,
• Andrzej E. Wróblewski and
• Liwia Lubowiecka

Beilstein J. Org. Chem. 2019, 15, 236–255, doi:10.3762/bjoc.15.22

• electrophilic hydroxylation at C4 When the lithium enolate of dimethyl N-Cbz-L-glutamate 63 was treated with Davis oxaziridine, an inseparable 9:1 mixture of diastereoisomers was formed with (2S,4S)-64 predominating (Scheme 16) [74]. For sodium and potassium enolates diastereoselectivity of the hydroxylation

First synthesis of cryptands with sucrose scaffold

• Patrycja Sokołowska,
• Michał Kowalski and
• Sławomir Jarosz

Beilstein J. Org. Chem. 2019, 15, 210–217, doi:10.3762/bjoc.15.20

• , 19.84; found: C, 58.12; H, 5.67; I, 19.79. Cryptand 11: To a solution of 10 (258 mg, 0.20 mmol) in acetonitrile (7 mL), powdered potassium carbonate (342 mg, 3.227 mmol, 16 equiv) was added, followed by aza-crown 8 (53 mg, 0.20 mmol, 1 equiv), and the mixture was stirred and boiled under reflux for 24 h

• , 27.32. Synthesis of cryptand 23: To a solution of 22 (118 mg, 0.09 mmol) in acetonitrile (15 mL), powdered potassium carbonate (270 mg, 2.55 mmol, 30 equiv) was added, followed by amine 15 (40 mg, 0.09 mmol, 1.1 equiv), and the mixture was stirred and boiled under reflux for 24 h (TLC monitoring

Silanediol versus chlorosilanol: hydrolyses and hydrogen-bonding catalyses with fenchole-based silanes

• Falco Fox,
• Jörg M. Neudörfl and
• Bernd Goldfuss

Beilstein J. Org. Chem. 2019, 15, 167–186, doi:10.3762/bjoc.15.17

• not hydrolyzed by aqueous potassium hydroxide solution [53]. The heterolytic reaction of solid BIFOXSiCl2 (7) in an aqueous KOH solution is negligible (<1% yield, Table 1, Scheme 3 in a) H2O and b) H2O/KOH). The reluctance against hydrolysis of BIFOXSiCl2 (7) can be explained by the hydrophobic aryl

• backbone and the fenchyl groups, which result in a decrease of the solubility of BIFOXSiCl2 (7) in water. Thus, a H2O/THF mixture is used to increase solubility and yields (Table 1, Scheme 3c). While the solubility of BIFOXSiCl2 (7) in H2O/THF greatly increases (clear solution), potassium hydroxide is

• needed as a strong nucleophile to yield BIFOXSi(OH)2 (9) at 20 °C (14% yield, Table 1, Scheme 3d). By increasing the temperature to 50 °C the hydrolysis increases, resulting in 32% yield in H2O/THF and 64% yield in H2O/THF/KOH (Table 1, Scheme 3). At reflux conditions in H2O/THF, but without potassium

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

• shield. Then potassium carbonate (412 mg, 3.31 mmol, 2 equiv) was added and the mixture was refluxed for another 24 h. Hydrazine (587 µL, 9.93 mmol, 6 equiv) was added again and the mixture was refluxed for 1 h. When the mixture had cooled to room temperature 10 mL of dichloromethane were added. The

• , ingredients see below) in 186 mL deionized water was added dropwise to a 0 °C cold stirred solution of cyanuric acid (2.00 g, 15.50 mmol, 1 equiv), sodium hydroxide (1.86 g, 46.49 mmol, 3 equiv), sodium carbonate (2.46 g, 23.24 mmol, 1.5 equiv) and potassium bromide (5.53 g, 46.49 mmol, 3 equiv) in 223 mL

A simple and effective preparation of quercetin pentamethyl ether from quercetin

• Jin Tatsuzaki,
• Tomohiko Ohwada,
• Yuko Otani,
• Reiko Inagi and
• Tsutomu Ishikawa

Beilstein J. Org. Chem. 2018, 14, 3112–3121, doi:10.3762/bjoc.14.291

• carbonyl group at 4 position. Thus, it is generally difficult to synthesize the pentamethyl ether efficiently by conventional methylation. Here, we describe a simple and effective per-O-methylation of quercetin with dimethyl sulfate in potassium (or sodium) hydroxide/dimethyl sulfoxide at room temperature

• potassium carbonate (K2CO3) are generally selected as the solvent and base, acetone can be replaced with dimethylformamide (DMF) if the starting phenol is poorly soluble in acetone. To our knowledge four reactions [37][38][39][40] were found in the literature as successful per-O-methylations of quercetin (2

• . This indicates the difficult methylation of the OH group at 5 position. Therefore, we consider to apply the more strongly basic system of potassium hydroxide (KOH) and dimethyl sulfoxide (DMSO). To a suspension of powdered KOH (9 equiv) in DMSO were successively added quercetin (2) and Me2SO4 (8 equiv

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

• , phenylmethylsulfonyl chloride, magnesium chloride, nickel sulfate, potassium dihydroorthophosphate, Ni-IDA sepharose, 5-phosphoribosyl-α-1-pyrophosphate and all bases (adenine, hypoxanthine, guanine, 2-chloroadenine, etc.) were purchased from Sigma-Aldrich (USA, MO). Bacterial strains: a) E. coli C3030 [MiniF lysY

• , 0.21 mmol) and potassium dihydroorthophosphate (276 mg, 2.03 mmol) were added. The pH of the solution was adjusted to 8.0 by 2 N potassium hydroxide. The pentasodium salt of 5-phosphoribosyl-α-1-pyrophosphate (70 mg, 0.14 mmol) and TthAPRT (5 units) were added, and the reaction mixture was incubated at

• potassium dihydroorthophosphate (276 mg, 2.03 mmol) were added. The pH of the solution was adjusted to 8.0 with 2 N potassium hydroxide. The pentasodium salt of 5-phosphoribosyl-α-1-pyrophosphate (70 mg, 0.14 mmol) and TthHPRT (5 units) were added, and the reaction mixture was incubated at 60 °C for 2 days

Degenerative xanthate transfer to olefins under visible-light photocatalysis

• Atsushi Kaga,
• Xiangyang Wu,
• Joel Yi Jie Lim,
• Hirohito Hayashi,
• Yunpeng Lu,
• Edwin K. L. Yeow and
• Shunsuke Chiba

Beilstein J. Org. Chem. 2018, 14, 3047–3058, doi:10.3762/bjoc.14.283

• chain mechanism was further confirmed by calculating the quantum yield (Φ) because a chain process provides multiple equivalents of product per photon absorbed by the photocatalyst (Φ > 1). The photon flux of blue LED (λmax = 469 nm) was determined using the potassium ferrioxalate actinometer [57][58

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

• attempted recrystallization from methanol. A possible reason for this instability at a temperature far below the boiling point became clear on addition of some solid potassium tert-butoxide (KOt-Bu) to an NMR tube that contained purified 7 in DMSO at rt: After the immediate appearance of a yellow tint, the

• next 1H NMR spectrum revealed that 7 was almost completely transformed into the acrylonitrile derivative 1 (bottom line of Scheme 2). This suggested that the nucleofugal carbanion unit of 2K had escaped from the potassium alkoxide 10 with formation of 2K (yellow tint) and t-BuCH=O, whereupon 2K was

• preponderant product) may be encountered when the deprotonating base is added to the alcohol 13 either too slowly or in a less than stoichiometric amount. For instance (bottom line of Scheme 3), the heterogeneous, slow deprotonation of 13 in THF by the insoluble base potassium hydride (KH) afforded 11 and 1 as

Volatiles from the hypoxylaceous fungi Hypoxylon griseobrunneum and Hypoxylon macrocarpum

• Jan Rinkel,
• Alexander Babczyk,
• Tao Wang,
• Marc Stadler and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2018, 14, 2974–2990, doi:10.3762/bjoc.14.277

• iodine and potassium hydroxide in methanol [39]. The obtained material also showed identical behaviour in the GC–MS analysis to natural 26. Both compounds 25 and 26 are new natural products. Identification of volatiles from Hypoxylon macrocarpum The composition of the headspace extracts from H

Stereodivergent approach in the protected glycal synthesis of L-vancosamine, L-saccharosamine, L-daunosamine and L-ristosamine involving a ring-closing metathesis step

• Pierre-Antoine Nocquet,
• Aurélie Macé,
• Frédéric Legros,
• Jacques Lebreton,
• Gilles Dujardin,
• Sylvain Collet,
• Arnaud Martel,
• Bertrand Carboni and
• François Carreaux

Beilstein J. Org. Chem. 2018, 14, 2949–2955, doi:10.3762/bjoc.14.274

• configuration of the stereogenic center bearing the hydroxy group (Scheme 5). With this in mind, the secondary alcohol 23 was engaged in a Mitsunobu reaction using p-nitrobenzoic acid as nucleophile to afford the expected compound 25. Hydrolysis of the ester was achieved using potassium carbonate in methanol to

An overview on recent advances in the synthesis of sulfonated organic materials, sulfonated silica materials, and sulfonated carbon materials and their catalytic applications in chemical processes

• Hashem Sharghi,
• Pezhman Shiri and
• Mahdi Aberi

Beilstein J. Org. Chem. 2018, 14, 2745–2770, doi:10.3762/bjoc.14.253

• graphite powder (141), potassium persulfate, phosphorus pentoxide, and sulfuric acid was heated at 80 °C for 2 h. The resulted solid was filtered and washed with water, methanol, and ether. Then, the obtained black paste was dried. After mixing the resulting material with sulfuric acid at 0 °C, potassium

Assembly of fully substituted triazolochromenes via a novel multicomponent reaction or mechanochemical synthesis

• Robby Vroemans,
• Yenthel Verhaegen,
• My Tran Thi Dieu and
• Wim Dehaen

Beilstein J. Org. Chem. 2018, 14, 2689–2697, doi:10.3762/bjoc.14.246

• furnished both regioisomers in poor yields since the chromanones 7 and 8 are known to be unstable under the triazolization conditions [36]. Hence, no further attempts were made to improve these yields. Additionally, NH-triazole 9 could be alkylated using benzyl bromide and potassium carbonate in acetone

Novel solid-phase strategy for the synthesis of ligand-targeted fluorescent-labelled chelating peptide conjugates as a theranostic tool for cancer

• Sagnik Sengupta,
• Mena Asha Krishnan,
• Premansh Dudhe,
• Ramesh B. Reddy,
• Bishnubasu Giri,
• Sudeshna Chattopadhyay and
• Venkatesh Chelvam

Beilstein J. Org. Chem. 2018, 14, 2665–2679, doi:10.3762/bjoc.14.244

• . General procedure for the Kaiser test Few resin beads were taken in a test-tube and 2 drops of each of ninhydrin, phenol and 0.1% potassium cyanide solution were added to the test-tube and heated for 2 minutes at 110 °C in a sand bath. The presence of free amine groups was confirmed by the appearance of

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

Quinolines from the cyclocondensation of isatoic anhydride with ethyl acetoacetate: preparation of ethyl 4-hydroxy-2-methylquinoline-3-carboxylate and derivatives

• Nicholas G. Jentsch,
• Jared D. Hume,
• Emily B. Crull,
• Samer M. Beauti,
• Amy H. Pham,
• Julie A. Pigza,
• Jacques J. Kessl and
• Matthew G. Donahue

Beilstein J. Org. Chem. 2018, 14, 2529–2536, doi:10.3762/bjoc.14.229

• in 91% yield. The ethyl ester was then smoothly reduced with DIBAL to the benzyl alcohol. While the in-process analysis (TLC and HPLC) indicated quantitative reduction, the isolated yields from the reductions were only poor to modest despite utilizing standard workup conditions with sodium potassium

Synthesis of a leopolic acid-inspired tetramic acid with antimicrobial activity against multidrug-resistant bacteria

• Luce Mattio,
• Loana Musso,
• Leonardo Scaglioni,
• Andrea Pinto,
• Piera Anna Martino and
• Sabrina Dallavalle

Beilstein J. Org. Chem. 2018, 14, 2482–2487, doi:10.3762/bjoc.14.224

• intermediate 10 by treatment of compound 9 with potassium tert-butoxide (1 M in THF) in THF [24]. The optimisation of reaction conditions, work-up and purification, allowed us to obtain the desired compound in 65% yield. Before removing the PMB group and installing the ureidodipeptide fragment, we needed to

• -alkylation. Moreover, we selected a base containing potassium as a metal cation, which provides a greater electron density to the nucleophilic enolate, thus favouring O-alkylation. Satisfyingly, O-selective alkylation of compound 10 was achieved by deprotonation with KHMDS followed by alkylation with benzyl

Synergistic approach to polycycles through Suzuki–Miyaura cross coupling and metathesis as key steps

• Sambasivarao Kotha,
• Milind Meshram and
• Chandravathi Chakkapalli

Beilstein J. Org. Chem. 2018, 14, 2468–2481, doi:10.3762/bjoc.14.223

• adopting SM coupling and RCM as key steps. In this respect, SM coupling of sulfoximine 65 with potassium vinyltrifluoroborate (66) in the presence of a palladium catalyst produced vinyl sulfoximine derivative 67 (73%). Next, N-alkenylation of sulfoximine 67 was accomplished with Z-vinyl bromide (68) to

Synthesis of eunicellane-type bicycles embedding a 1,3-cyclohexadiene moiety

• Alex Frichert,
• Peter G. Jones and
• Thomas Lindel

Beilstein J. Org. Chem. 2018, 14, 2461–2467, doi:10.3762/bjoc.14.222

• pyridine derivatives was possible on treatment with KOt-Bu at −23 °C, presumably with formation of potassium triflinate [27]. In our case, pyridine was used as solvent and the reaction mixture was heated up to 70 °C. This could allow pyridine itself taking the double role of nucleophile and base, leading