Visible-light-induced addition of carboxymethanide to styrene from monochloroacetic acid

• Kaj M. van Vliet,
• Nicole S. van Leeuwen,
• Albert M. Brouwer and
• Bas de Bruin

Beilstein J. Org. Chem. 2020, 16, 398–408, doi:10.3762/bjoc.16.38

• of radicals with visible light photoredox catalysis. The reductive formation of the carboxymethanide radical could be used for lactone formation with styrene. Benzene was found to be the best solvent for this reaction. However, the reaction is associated with some unsolved problems. The carboxylic

• acid group seems to be advantageous for the activation of monochloroacetic acid, but the apolar solvent in combination with formation of HCl is likely to cause catalyst deactivation/precipitation. This effect is more pronounced if electron-poor styrenes are used. We also found indications that a

Architecture and synthesis of P,N-heterocyclic phosphine ligands

• Wisdom A. Munzeiwa,
• Bernard Omondi and
• Vincent O. Nyamori

Beilstein J. Org. Chem. 2020, 16, 362–383, doi:10.3762/bjoc.16.35

• was obtained by the reaction of ʟ-valinol with in situ-generated indolylacyl chloride. The latter compound was obtained through an oxalic acid-mediated chlorination of carboxylic acid 96 with dimethylformamide as catalyst in dichloromethane. Next, oxazoline derivative 98 was obtained via a

• carbon dioxide and phenyllithium gives the phosphine ferrocene carboxylic acid 152 as the major reagent. Oxidation of the phosphine using hydrogen peroxide generated the phosphine oxide 153. In situ chlorination of the carboxylic acid followed by addition of the chiral amino alcohols gave the phosphoryl

Two antibacterial and PPARα/γ-agonistic unsaturated keto fatty acids from a coral-associated actinomycete of the genus Micrococcus

• Amit Raj Sharma,
• Enjuro Harunari,
• Naoya Oku,
• Nobuyasu Matsuura,
• Agus Trianto and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 297–304, doi:10.3762/bjoc.16.29

• unambiguously determined to be E. α-Keto fatty acids are characterized by the presence of a keto group at the α-position of a carboxylic acid moiety. They are present in all living cells and play crucial roles in biological systems as they are involved in the Krebs cycle and glycolysis [20]. In contrast, keto

Ultrasonic-assisted unusual four-component synthesis of 7-azolylamino-4,5,6,7-tetrahydroazolo[1,5-a]pyrimidines

• Yana I. Sakhno,
• Maryna V. Murlykina,
• Oleksandr I. Zbruyev,
• Anton V. Kozyryev,
• Svetlana V. Shishkina,
• Dmytro Sysoiev,
• Vladimir I. Musatov,
• Sergey M. Desenko and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2020, 16, 281–289, doi:10.3762/bjoc.16.27

• remained stable under refluxing in acetic acid for 60 min, while heating for 120–180 min led to its decomposition. At the same time, compound 4b, after refluxing in acetic acid for ca. 120 min, was converted into 3-cyano-7-(4-methoxyphenyl)-4,7-dihydropyrazolo[1,5-a]pyrimidine-5-carboxylic acid (7, yield

• 35%). The same carboxylic acid 7 was obtained by counter synthesis through a three-component reaction involving 5-aminopyrazole-4-carbonitrile (1a), 4-methoxybenzaldehyde (2b), and pyruvic acid (3a) under heating at reflux in acetic acid for 240 min (yield 28%) or through two-component

• materials (HOAc, refluxing at 118 °C for 240 min) yielded the thermodynamically preferred dihydropyrazolopyrimidine-5-carboxylic acid 7 (Scheme 5). The most probable pathway A (Scheme 6) to compounds 4 includes initial formation of the corresponding azomethines 9 and 10. A similar pathway was previously

Recent developments in photoredox-catalyzed remote ortho and para C–H bond functionalizations

• Rafia Siddiqui and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 248–280, doi:10.3762/bjoc.16.26

• seen in Figure 8, the mechanism of the reaction commences with the deprotonation of the biphenyl carboxylic acid 36, followed by the reaction of 38 with dimethyl dicarbonate (DMDC) to generate compound 39. On the other hand, the photocatalyst is excited by metal–ligand charge transfer, which produces

Synthesis of 3-alkenylindoles through regioselective C–H alkenylation of indoles by a ruthenium nanocatalyst

• Abhijit Paul,
• Debnath Chatterjee,
• Srirupa Banerjee and
• Somnath Yadav

Beilstein J. Org. Chem. 2020, 16, 140–148, doi:10.3762/bjoc.16.16

• different functional groups (Table 2). It was found that the reactions tolerated carboxylic acid, ketone, halogen (Cl, Br, I, and F), aldehyde, amide, primary amine, secondary amine, and phenolic functional groups to a reasonably acceptable extent. Recovery and recyclability of the Ru nanocatalyst The

• -carboxylic acid was anchored to Wang resin and then subjected to the conditions for the alkenylation reaction with 2a using the solid catalyst (3 mg) for 48 h. After that, the reaction mixture was worked up, and the solid product was isolated and subjected to solid-state NMR spectroscopy. The results were

• -anchored indole-5-carboxylic acid was successful during the homogeneous two-phase alkenylation reaction. Subsequently, during its removal from the support under alkaline conditions, N-alkylation occurred through a Michael addition to the acrylate 2a, followed by the formation of the methyl ester of the 5

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

• ] easily. Because the hydroxy group on the carboxylic acid of the baicalin formed a hydrogen bond with the oxygen atoms of Q[8] at the portal, cycle C of baicalin was pushed into the cavity of Q[8]. Therefore, the inclusion model of cucurbit[8] with flavonoid compounds was determined by the structure of

Construction of trisubstituted chromone skeletons carrying electron-withdrawing groups via PhIO-mediated dehydrogenation and its application to the synthesis of frutinone A

• Qiao Li,
• Chen Zhuang,
• Donghua Wang,
• Wei Zhang,
• Rongxuan Jia,
• Fengxia Sun,
• Yilin Zhang and
• Yunfei Du

Beilstein J. Org. Chem. 2019, 15, 2958–2965, doi:10.3762/bjoc.15.291

• = 5.3 nM) properties [90][91][92]. Treating the obtained chromene-3-carboxylate 2l with LiOH [93] led to the formation of the chromene-3-carboxylic acid G. Heating compound G overnight in the presence of AgNO3 and K2S2O8 afforded frutinone A in an isolated yield of 45% (Scheme 5). Conclusion In summary

A green, economical synthesis of β-ketonitriles and trifunctionalized building blocks from esters and lactones

• Daniel P. Pienaar,
• Kamogelo R. Butsi,
• Amanda L. Rousseau and
• Dean Brady

Beilstein J. Org. Chem. 2019, 15, 2930–2935, doi:10.3762/bjoc.15.287

• -substituted carboxylic acid derivatives, in general, from cheap commercially available esters, and as such merited further investigation. We required a green, safe and scalable process for the facile production of O-unprotected hydroxylated β-hydroxynitrile 1 via trifunctionalized β-ketonitrile 2 by a direct

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

• thiotemplated assembly lines, such as type I polyketide synthases (PKS) and nonribosomal peptide synthetases (NRPS), are modular, with each module contributing a distinct fragment to the final product’s core structure – a short-chain carboxylic acid (PKS) or an amino acid (NRPS). The modularly defined template

An improved, scalable synthesis of Notum inhibitor LP-922056 using 1-chloro-1,2-benziodoxol-3-one as a superior electrophilic chlorinating agent

• Nicky J. Willis,
• Elliott D. Bayle,
• George Papageorgiou,
• David Steadman,
• Benjamin N. Atkinson,
• William Mahy and
• Paul V. Fish

Beilstein J. Org. Chem. 2019, 15, 2790–2797, doi:10.3762/bjoc.15.271

• contains an essential carboxylic acid and acids tend to have low passive brain penetration [8][9][10][11][12]. We are investigating the role of Notum in modulating Wnt signalling in the central nervous system (CNS) [13] and wished to establish if 1 would serve as a peripherally restricted control compound

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

• difference being the absence of one maleic anhydride moiety, which was replaced by a dicarboxylic acid motif and an olefinic bond between position C-3 (δ = 124.5 ppm) and C-4 (δ = 148.9 ppm). Resonances for the carbon atoms of the carboxylic acid moieties occurred at δ = 176.8 ppm (C-1) and 172.0 ppm (C-23

• acid motif at one end of the chain. The three carboxylic acid functions of the molecule had resonances at δ = 174.5 (C-1), 173.8 (C-23), and 167.8 ppm (C-24) in the 13C NMR spectrum. The HMBC correlations between H2-2 and C-1/3/4/23 as well as H-5 and C-3/24 and the COSY correlations between H2-2 and H

Nanangenines: drimane sesquiterpenoids as the dominant metabolite cohort of a novel Australian fungus, Aspergillus nanangensis

• Heather J. Lacey,
• Cameron L. M. Gilchrist,
• Andrew Crombie,
• John A. Kalaitzis,
• Daniel Vuong,
• Peter J. Rutledge,
• Peter Turner,
• John I. Pitt,
• Ernest Lacey,
• Yit-Heng Chooi and
• Andrew M. Piggott

Beilstein J. Org. Chem. 2019, 15, 2631–2643, doi:10.3762/bjoc.15.256

• dehydrogenase could oxidise the alcohol (at C-11 or C-12) to an aldehyde. Depending on whether C-11 or C-12 formed an aldehyde, further oxidation of the aldehyde to a carboxylic acid and condensation with the γ-OH group would afford the butyrolactone ring in nanagenines A–E and isonanagenines B/D, respectively

A new approach to silicon rhodamines by Suzuki–Miyaura coupling – scope and limitations

• Thines Kanagasundaram,
• Antje Timmermann,
• Carsten S. Kramer and
• Klaus Kopka

Beilstein J. Org. Chem. 2019, 15, 2569–2576, doi:10.3762/bjoc.15.250

• conditions applied for the cross coupling of the triflate were similar to those published by Calitree and Detty for the coupling of the triflates derived from the O, S, Se, and Te-xanthones 16 with various phenylboroxines (bearing nitro, carboxylic acid, methyl and methoxy substituents) [29]. Here yields of

• reaction could be a valuable approach to silicon rhodamines. Thus, we aimed at the optimization of coupling conditions as well as evaluation of the best boron compounds for coupling. Since carboxylic acid-substituted dyes like compound 17 (X = Si, R = COOH) can be easily coupled to tumor binding vectors

Combining the Ugi-azide multicomponent reaction and rhodium(III)-catalyzed annulation for the synthesis of tetrazole-isoquinolone/pyridone hybrids

• Gerardo M. Ojeda,
• Prabhat Ranjan,
• Pavel Fedoseev,
• Lisandra Amable,
• Upendra K. Sharma,
• Daniel G. Rivera and
• Erik V. Van der Eycken

Beilstein J. Org. Chem. 2019, 15, 2447–2457, doi:10.3762/bjoc.15.237

• variety of pharmacological and antimicrobial properties [5][6], including analgesic, antihypertensive, anti-inflammatory, anticancer, antifungal and antimalarial activity (Figure 1). A key feature of the tetrazole ring is its bioisosteric character with the carboxylic acid and amide functional groups

• steps without purification of the intermediates. In this strategy, three different diversity sites could be generated, i.e., those derived from the isocyano and aldehyde components and a third one from the carboxylic acid used in the last acylation step. We sought to incorporate aryl or vinyl carboxylic

• carboxylic acid (2.0 mmol, 1.0 equiv) and TEA (10 mmol, 5.0 equiv, 1.39 mL) were added and the mixture was cooled to 0 °C. Then, HBTU (2.0 mmol, 1.0 equiv) was added portion-wise and the mixture allowed to slowly reach rt. Then DMAP (0.2 mmol, 10 mol %) was added and the reaction developed for 72 hours. The

Sugar-derived oxazolone pseudotetrapeptide as γ-turn inducer and anion-selective transporter

• Sachin S. Burade,
• Sushil V. Pawar,
• Tanmoy Saha,
• Navanath Kumbhar,
• Amol S. Kotmale,
• Manzoor Ahmad,
• Pinaki Talukdar and
• Dilip D. Dhavale

Beilstein J. Org. Chem. 2019, 15, 2419–2427, doi:10.3762/bjoc.15.234

• 2b. The influx of Cl‒ ion by these transporters were monitored using EYPC-LUVslucigenin. Additionally, compound 9, which has a free amino group and a free carboxylic acid group, was also subjected to the Cl‒ transport study. The Cl– sensitive dye lucigenin, was entrapped within the lipid vesicles and

Mono- and bithiophene-substituted diarylethene photoswitches with emissive open or closed forms

• A. Lennart Schleper,
• Mariano L. Bossi,
• Vladimir N. Belov and
• Stefan W. Hell

Beilstein J. Org. Chem. 2019, 15, 2344–2354, doi:10.3762/bjoc.15.227

• , substitution of fluorine and/or the addition of nucleophiles to the electron-poor double bond take place. Therefore, tert-butyl protection is required for carboxylates present in diarylethenes with “oxidized” benzothiophene units and perfluorocyclopentene rings. Photoswitches containing the free carboxylic

• acid residues benefit from solubility in aqueous buffers and the presence of a reactive group required for further modifications. The methyl groups were cleaved using 1 M aq NaOH, and the product SyTh2-H was isolated by preparative HPLC in 84% yield (see Scheme 4). As shown in Figure S2 (see Supporting

Thermal stability of N-heterocycle-stabilized iodanes – a systematic investigation

• Andreas Boelke,
• Yulia A. Vlasenko,
• Mekhman S. Yusubov,
• Boris J. Nachtsheim and
• Pavel S. Postnikov

Beilstein J. Org. Chem. 2019, 15, 2311–2318, doi:10.3762/bjoc.15.223

• extensively, the chemical design of the stabilizing donor ligand L2 has not been investigated as intensive. In general, carboxylic acid derivatives, ethers or free alcohols are utilized to stabilize the hypervalent iodine center by an oxygen–iodine bond or through dative oxygen–iodine interactions in (pseudo

Recent advances in transition-metal-catalyzed incorporation of fluorine-containing groups

• Xiaowei Li,
• Xiaolin Shi,
• Xiangqian Li and
• Dayong Shi

Beilstein J. Org. Chem. 2019, 15, 2213–2270, doi:10.3762/bjoc.15.218

• ’-dCF3bpy)PF6 (1) undergoes photoexcitation with visible light to form the highly oxidizing excited state ·Ir(III) 2. Then, SET from copper carboxylate 4, derived from carboxylic acid 3 with the Cu(II) catalyst to ·Ir(III) 2 provides Cu(III) carboxylate 5, or in the dissociated form, a carboxyl radical and

Cyclopropanation–ring expansion of 3-chloroindoles with α-halodiazoacetates: novel synthesis of 4-quinolone-3-carboxylic acid and norfloxacin

• Sara Peeters,
• Linn Neerbye Berntsen,
• Pål Rongved and
• Tore Bonge-Hansen

Beilstein J. Org. Chem. 2019, 15, 2156–2160, doi:10.3762/bjoc.15.212

• indoline cyclopropane intermediate and elimination of HX. The 4-quinolone-3-carboxylic acid scaffold (Figure 1) is regarded as a privileged scaffold in medicinal chemistry, due to the frequent appearance of this structural subunit in many commercial drugs [16][17][18][19][20][21], and a large variety of

• ethyl group and yields quinolone (6) after tautomerization. Standard hydrolysis (LiOH, H2O/THF) of ester 6 gave the 4-quinolone-3-carboxylic acid (7) in 87% yield (not shown). Quinolones, and fluoroquinolones (FQs) in particular, are among the most commonly prescribed antibiotics in the world [34

Characterization of two new degradation products of atorvastatin calcium formed upon treatment with strong acids

• Jürgen Krauß,
• Monika Klimt,
• Markus Luber,
• Peter Mayer and
• Franz Bracher

Beilstein J. Org. Chem. 2019, 15, 2085–2091, doi:10.3762/bjoc.15.206

• dehydration of the δ-hydroxy group and some epimers resulting from acid-catalyzed isomerization reactions. In contrast, Vukkum et al. [13] describe, besides lactones 2 and 3, an α,β-unsaturated carboxylic acid 4. Treatment under more drastic conditions (6 M HCl, reflux, 3 h) was reported to result mainly in

• hydrolysis of the anilide moiety to give carboxylic acid 5 [16][17] (Figure 1). Here we report on the results of our investigations on the decomposition of atorvastatin calcium (1) under strongly acid conditions. Results and Discussion Stress tests Since the lability of atorvastatin towards moderately acidic

• treatment with acids: lactone 2, dehydrated lactone 3, α,β-unsaturated carboxylic acid 4, and carboxylic acid 5 (resulting from postulated anilide hydrolysis). Top: Molecular structure of artefact 6. Shown here is the molecular structure of one of three independent molecules in 6 drawn at the 50% ellipsoid

A review of the total syntheses of triptolide

• Xiang Zhang,
• Zaozao Xiao and
• Hongtao Xu

Beilstein J. Org. Chem. 2019, 15, 1984–1995, doi:10.3762/bjoc.15.194

• corresponding carboxylic acid followed by hydrogenolysis with H2/Pd-C led in spontaneous lactonization to give the key butenolide 66. Oxidation of 66 with CrO3/AcOH–H2O, followed by saponification and reduction afforded known benzyl alcohol 46 (19% from 66). Then, phenol 46 was converted to the corresponding

Application of chiral 2-isoxazoline for the synthesis of syn-1,3-diol analogs

• Juanjuan Feng,
• Tianyu Li,
• Jiaxin Zhang and
• Peng Jiao

Beilstein J. Org. Chem. 2019, 15, 1840–1847, doi:10.3762/bjoc.15.179

• subjected to silica gel chromatography. Compound 4 was used to determine the stereoselectivity of the cycloaddition step as well as for oxidation. Oxidation of the 2-isoxazoline 4 with Jones’ reagent gave a complicated mixture, in which the desired carboxylic acid was not observed (Scheme 2). The stepwise

• chromophore facilitating HPLC analysis. Afterwards, we tried oxidations once again. After removal of THP from 6, the resulting compound 6' was subjected to oxidation with various reagents (Scheme 4) [53][54][55]. The expected carboxylic acid or aldehyde was not observed, which further verified the intolerance

• NaIO4 yielded the carboxylic acid 14 in 86% yield [70], which was reacted with Boc2O to get the tert-butyl ester 15 [26][43][71]. The ee of 15 was determined as 74%. The racemic sample of 15 was prepared from racemic diethyl malate following known methods [26][27]. Finally, K2CO3-catalyzed methanolysis

Metal-free mechanochemical oxidations in Ertalyte^® jars

• Andrea Porcheddu,
• Francesco Delogu,
• Lidia De Luca,
• Claudia Fattuoni and
• Evelina Colacino

Beilstein J. Org. Chem. 2019, 15, 1786–1794, doi:10.3762/bjoc.15.172

• carboxylic acid derivatives were observed in any sample. Similar results were obtained for alcohols containing an aliphatic carbon ring in their backbone, such as cyclohexylmethanol (5a). Interestingly, the oxidation reaction of benzylic alcohols proceeded smoothly to completeness in about 10 minutes even

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

• which is finally easily removed [11]. Among three-carbon chirons related to Garner’s aldehyde derivatives of N-(1-phenylethyl)aziridine-2-carboxylic acid 5–8 (Figure 2) play an important role in asymmetric synthesis as they function as a chiral synthon combined with a chiral auxiliary [(R)- or (S)-1

• (1-phenylethyl)aziridine-2-carboxylic acid and its derivatives till the beginning of 2019. The usefulness of any chiron depends on its availability and to some extent on versatility of the protective groups. In case of the 1-phenylethyl group its removal at any stage of synthesis is not limited to a