Copper-catalysed alkylation of heterocyclic acceptors with organometallic reagents

• Yafei Guo and
• Syuzanna R. Harutyunyan

Beilstein J. Org. Chem. 2020, 16, 1006–1021, doi:10.3762/bjoc.16.90

• alkenylaluminium and alkylaluminium reagents to the β-substituted unsaturated conjugated lactams 25 was utilized (Scheme 7B) [32]. Chiral lactones are yet another interesting class of heterocyclic substrates that have attracted great attention because of their usefulness in both organic synthesis and medicinal

• chemistry. The copper-catalysed ACA of organozinc reagents to 5,6-dihydro-2-pyranone is one of the best methods to obtain chiral lactones. During the past two decades, the research groups of Chan, Hoveyda (who applied an approach depending on the trapping by an aldehyde), Mauduit, and Wang reported a

• variety of methods employing the chiral ligands L9–L13 that, in combination with copper, efficiently catalysed the ACA of diethylzinc to 5,6-dihydro-2-pyranone (Scheme 8), providing access to chiral β-substituted lactones with high enantioselectivity and conversion [33][34][35][36][37]. Although the

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

• scope of this silicon addition to unsaturated lactones using copper catalysis together with NHC ligand L16. The ligand used previously to great advantage by the Hoveyda and Oestreich groups for conjugate additions did not yield high ees for these substrates. The authors designed a new NHC possessing

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

• Daniel P. Pienaar Kamogelo R. Butsi Amanda L. Rousseau Dean Brady Molecular Sciences Institute, School of Chemistry, University of the Witwatersrand, PO Wits 2050, Johannesburg, South Africa 10.3762/bjoc.15.287 Abstract The acylation of the acetonitrile anion with lactones and esters in ethereal

• solvents was successfully exploited using inexpensive KOt-Bu to obtain a variety of β-ketonitriles and trifunctionalized building blocks, including useful O-unprotected diols. It was discovered that lactones react to produce the corresponding derivatized cyclic hemiketals. Furthermore, the addition of a

• preparation of trifunctionalized building blocks (hydroxylated β-ketonitriles) and valuable β-ketonitriles (including enolizable compounds) in modest to good yields from lactones and esters. We are currently investigating novel applications of diols 1 and 8, as well as the application of this methodology for

A review of asymmetric synthetic organic electrochemistry and electrocatalysis: concepts, applications, recent developments and future directions

• Munmun Ghosh,
• Valmik S. Shinde and
• Magnus Rueping

Beilstein J. Org. Chem. 2019, 15, 2710–2746, doi:10.3762/bjoc.15.264

• lactonization of diols 51. However, in this method instead of a chiral base, they used 1-azaspiro[5.5]undecane N-oxyl 52 as a radical mediator for modifying the electrodes which resulted in optically active lactones 53 with enantiopurity of up to 99% (conditions B, Scheme 20) [52]. Chiral medium In this section

• 66 (Scheme 26). Galvanostatic electrolysis of 66 in an undivided cell using a catalytic amount of 67 resulted in the corresponding lactones 68 in moderate yields and good stereoselectivities. The stereoselectivity was proposed to be controlled through the preferential formation of transition state A

• over B after reaction of the enolates of 66 with chiral iodoarene 67. Steric factors restrict the formation of transition state B, and the reaction preferentially proceeds via transition state A to stereoselectively form the lactones [62]. Chiral catalysts Achieving enantiocontrol in electrochemical

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

• File 1) yielded ten drimane metabolites shown in Figure 1: one trihydroxylated drimane sesquiterpenoid lactone, nanangenine A (1), four drimane lactones bearing C6/C8 acyl chains, nanangenines B, C, D and E (2, 4, 5 and 6), two acylated drimanes bearing isomeric lactones, isonanangenines B and D (3 and

• Our investigations into unique Australian microbial biodiversity have led to discovery of a family of drimane sesquiterpenoids, the nanangenines, which serve as key chemotaxonomic markers for the novel fungal species, A. nanangensis. Although related drimane sesquiterpenoid lactones have been found in

An overview of the cycloaddition chemistry of fulvenes and emerging applications

• Ellen Swan,
• Kirsten Platts and
• Anton Blencowe

Beilstein J. Org. Chem. 2019, 15, 2113–2132, doi:10.3762/bjoc.15.209

• the formation of several different products, although predominantly enol lactones [47][50][51][52] (Scheme 3). Highly reactive intermediates formed during these reactions (Scheme 3) have only been observed spectroscopically at low temperatures (−55 °C) [52]. Heptafulvenes also undergo reactions with

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

Isolation and characterisation of irinans, androstane-type withanolides from Physalis peruviana L.

• Annika Stein,
• Dave Compera,
• Bianka Karge,
• Mark Brönstrup and
• Jakob Franke

Beilstein J. Org. Chem. 2019, 15, 2003–2012, doi:10.3762/bjoc.15.196

• Withanolides are steroidal lactones widespread in Nightshade plants with often potent antiproliferative activities. Additionally, the structural diversity of this compound class holds much potential for the discovery of novel biological activity. Here, we report two newly characterised withanolides, named

• research. An important example is Withania somnifera, also known as ashwaghanda or Indian ginseng, which has been used in Ayurvedic medicine to treat a large variety of ailments [1]. Extensive studies revealed withanolides, a class of steroidal lactones, to be primarily responsible for the medicinal

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

• -catalyzed lactonization, and iii) construction of the epoxides by a newly developed methodology. The synthesis commenced from the alkylation of tetralone 22 with 3-(2-iodoethyl)dihydrofuran-2(3H)-one (23) to give diastereomeric lactones that subsequently reacted with dimethylamine to afford a 1:1 mixture of

Archangelolide: A sesquiterpene lactone with immunobiological potential from Laserpitium archangelica

• Silvie Rimpelová,
• Michal Jurášek,
• Lucie Peterková,
• Jiří Bejček,
• Vojtěch Spiwok,
• Miloš Majdl,
• Michal Jirásko,
• Miloš Buděšínský,
• Juraj Harmatha,
• Eva Kmoníčková,
• Pavel Drašar and
• Tomáš Ruml

Beilstein J. Org. Chem. 2019, 15, 1933–1944, doi:10.3762/bjoc.15.189

• Sciences of the Czech Republic, Flemingovo náměstí 2, 166 10 Prague 6, Czech Republic Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, v.v.i., 14220 Prague 4, Czech Republic 10.3762/bjoc.15.189 Abstract Sesquiterpene lactones are secondary plant metabolites with sundry

• studied by us and others, there are only scarce reports on the biological activity of archangelolide. Here we present the preparation of its fluorescent derivative based on a dansyl moiety using azide–alkyne Huisgen cycloaddition having obtained the two sesquiterpene lactones from the seeds of Laserpitium

• fluorescent conjugate; sarco/endoplasmic reticulum calcium ATPase; sesquiterpene lactone; trilobolide analogue; Introduction Sesquiterpene lactones (SLs) have been attracting interest already for some time due to the plethora of biological effects they elicit. Various SLs show anticancer, antimicrobial

Vicinal difunctionalization of alkenes by four-component radical cascade reaction of xanthogenates, alkenes, CO, and sulfonyl oxime ethers

• Shuhei Sumino,
• Takahide Fukuyama,
• Mika Sasano,
• Ilhyong Ryu,
• Antoine Jacquet,
• Frédéric Robert and
• Yannick Landais

Beilstein J. Org. Chem. 2019, 15, 1822–1828, doi:10.3762/bjoc.15.176

• reaction using xanthogenates, alkenes, and sulfonyl oxime ethers (Scheme 1, reaction 1) [21][22]. The reaction proceeds efficiently to provide good yields of α-alkoxyimino esters, potential precursors of lactams, lactones and β-keto esters. Since the three-component radical reaction involving alkyl halides

Mechanochemical synthesis of poly(trimethylene carbonate)s: an example of rate acceleration

• Sora Park and
• Jeung Gon Kim

Beilstein J. Org. Chem. 2019, 15, 963–970, doi:10.3762/bjoc.15.93

• biomedical applications [24]. The amidine base 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) is one of the best studied and most popular organocatalysts for ring-opening polymerizations of cyclic carbonates and lactones [25][26][27]. In contrast to the high activity of lactone polymerization, cyclic carbonate

Synthesis of 2H-furo[2,3-c]pyrazole ring systems through silver(I) ion-mediated ring-closure reaction

• Vaida Milišiūnaitė,
• Rūta Paulavičiūtė,
• Eglė Arbačiauskienė,
• Vytas Martynaitis,
• Wolfgang Holzer and
• Algirdas Šačkus

Beilstein J. Org. Chem. 2019, 15, 679–684, doi:10.3762/bjoc.15.62

• AgOTf efficiently catalyzed the intramolecular cyclization of phenoxyethynyl diols into 2,3-unsaturated lactones [38]. In our case, the addition of 10 mol % chloro(triphenylphosphine)gold(I) improved the yield of product 4a to 69% (Table 1, entry 4). However the best results were obtained when AgOTf was

Reusable and highly enantioselective water-soluble Ru(II)-Amm-Pheox catalyst for intramolecular cyclopropanation of diazo compounds

• Hamada S. A. Mandour,
• Yoko Nakagawa,
• Masaya Tone,
• Hayato Inoue,
• Nansalmaa Otog,
• Ikuhide Fujisawa,
• Soda Chanthamath and
• Seiji Iwasa

Beilstein J. Org. Chem. 2019, 15, 357–363, doi:10.3762/bjoc.15.31

• proceeded smoothly at room temperature, affording the corresponding bicyclic cyclopropane ring-fused lactones and lactams in high yields (up to 99%) with excellent enantioselectivities (up to 99% ee). After screening of various catalysts, the Ru(II)-Amm-Pheox complex having an ammonium group proved to be

• intramolecular cyclopropanation of a variety of diazo compounds such as diazoacetates and diazoacetamides in a biphasic medium. Diazoacetates were tested in our catalytic system because they are widely used for intramolecular cyclopropanation reactions and also the resulted lactones are widely distributed in

Regioselective addition of Grignard reagents to N-acylpyrazinium salts: synthesis of substituted 1,2-dihydropyrazines and Δ⁵-2-oxopiperazines

• Valentine R. St. Hilaire,
• William E. Hopkins,
• Yenteeo S. Miller,
• Srinivasa R. Dandepally and
• Alfred L. Williams

Beilstein J. Org. Chem. 2019, 15, 72–78, doi:10.3762/bjoc.15.8

• nucleophilic addition of bis(trimethylsilyl)ketene acetals to pyrazines activated with methyl chloroformate was found to afford polycyclic γ-lactones in moderate yields [3][10][11]. The work by Garduño-Alva and co-workers demonstrated that these TMS-ketene acetals can be regioselectively added to substituted N

• -triflate pyrazinium salts to also generate γ-lactones [12]. Grignard reagents have been used as nucleophiles on a variety of N-acyl-activated pyridines in the production of natural products and biologically active small molecules [13][14][15][16][17][18][19][20]. To our surprise, there are no reports on

Ring-closing-metathesis-based synthesis of annellated coumarins from 8-allylcoumarins

• Christiane Schultze and
• Bernd Schmidt

Beilstein J. Org. Chem. 2018, 14, 2991–2998, doi:10.3762/bjoc.14.278

• , we investigated the synthesis of coumarins with annellated unsaturated lactones starting from the same 8-allylcoumarins 8 (Scheme 1). For the synthesis of oxepin-2-one-annellated coumarins 13 compounds 8 were first converted to the corresponding acrylates 12 with acryloyl chloride (Table 3). RCM of

N-Acylated amino acid methyl esters from marine Roseobacter group bacteria

• Hilke Bruns,
• Lisa Ziesche,
• Nargis Khakin Taniwal,
• Laura Wolter,
• Thorsten Brinkhoff,
• Jennifer Herrmann,
• Rolf Müller and
• Stefan Schulz

Beilstein J. Org. Chem. 2018, 14, 2964–2973, doi:10.3762/bjoc.14.276

• Roseobacter group (Rhodobacteraceae) are important members of many marine ecosystems. Similar to other Gram-negative bacteria many roseobacters produce N-acylhomoserine lactones (AHLs) for communication by quorum sensing systems. AHLs regulate different traits like cell differentiation or antibiotic

• derivatives; 2-aminobutyric acid; homoserine lactones; natural products; quorum sensing; Introduction The identification and structural elucidation of naturally occurring compounds traditionally requires isolation and NMR investigation as key method to detect novel compounds and new structural classes

• habitats with a broad metabolic potential [4][5][6][7]. Especially attached-living roseobacters produce diverse secondary metabolites, e.g., N-acylhomoserine lactones (AHLs) that the bacteria use for communication by quorum sensing [8][9][10]. AHLs are extensively investigated because of the broad

Copolymerization of epoxides with cyclic anhydrides catalyzed by dinuclear cobalt complexes

• Yo Hiranoi and
• Koji Nakano

Beilstein J. Org. Chem. 2018, 14, 2779–2788, doi:10.3762/bjoc.14.255

• (ROP) of lactones and cyclic diesters [5][6][7][8][9][10]. In contrast to the step-growth polymerization, the ROP does not give any small molecule byproducts and proceeds under mild conditions. In addition, high molecular weight polyesters with narrow polydispersity can be prepared even at a low

• monomer conversion. A variety of lactones and cyclic diesters, such as ε-caprolactone, β-propiolactone, lactic acid (LA), and glycolide have been used for the ROP. However, the employable monomers are rather limited, which restricts the range of polymer properties. In view of the aforementioned, the

Synthesis of a tyrosinase inhibitor by consecutive ethenolysis and cross-metathesis of crude cashew nutshell liquid

• Jacqueline Pollini,
• Valentina Bragoni and
• Lukas J. Gooßen

Beilstein J. Org. Chem. 2018, 14, 2737–2744, doi:10.3762/bjoc.14.252

• ]. A limited number of derivatizations of anacardic acid are reported by now, including the synthesis of lactones [18][19][20], sulfonamides [21] or hydrazones [22], typically bioactive compounds though with low commercial value. However, several studies suggest that anacardic acid and its derivatives

Ring-opening metathesis of some strained bicyclic systems; stereocontrolled access to diolefinated saturated heterocycles with multiple stereogenic centers

• Zsanett Benke,
• Melinda Nonn,
• Márton Kardos,
• Santos Fustero and
• Loránd Kiss

Beilstein J. Org. Chem. 2018, 14, 2698–2707, doi:10.3762/bjoc.14.247

• functionalized derivatives such as bicyclic lactones, γ-lactams or isoxazolines, derived from various cyclodienes and to evaluate their chemical behavior under Ru-catalyzed ring-opening conditions (Scheme 2). First, the ring opening of racemic bicyclic γ-lactone (±)-3 (derived from cyclodiene 1 via β-lactam

• that unsaturated bicyclic β-lactams (±)-2 and (±)-8, bearing the fused four-membered and six-membered ring system, have a lower ring strain than bicyclic, unsaturated γ-lactones (±)-3, (±)-4 and (±)-9. Because of their higher constraint, the latter compounds underwent ring opening providing the

• corresponding monocyclic, dialkenylated amino lactones, albeit with modest yields (Scheme 5); (for relevant literature date for the ROM for various cyclic systems with ring strain see ref. [27][28][29]. We continued our ring-opening investigations with other model derivatives possessing a larger ring system

Non-native autoinducer analogs capable of modulating the SdiA quorum sensing receptor in Salmonella enterica serovar Typhimurium

• Matthew J. Styles and
• Helen E. Blackwell

Beilstein J. Org. Chem. 2018, 14, 2651–2664, doi:10.3762/bjoc.14.243

• sub-libraries consisted of substituted phenylacetanoyl homoserine lactones (PHLs), phenylpropionyl homoserine lactones (PPHLs), and phenoxyacetyl homoserine lactones (POHLs), many of which we have previously found to be highly active in a range of LuxR-type receptors as both agonists and competitive

• antagonists [45][47][48][51][56]. The Q and R sub-libraries contain a related group of substituted benzoyl homoserine lactones (BHLs) [56]. Sub-library S probed the effects of branched alkyl groups on the acyl tail [56]. The F sub-library contained a variety of AHL analogs with alternative, often hydrolysis

• derivatives (thiolactones F8 and F5 vs lactones A1 and A3) and the PHL-type derivatives (thiolactones F11 and F12 vs lactones C14 and C24) were nearly an order of magnitude more potent. As thiolactone hydrolysis can occur more slowly than lactone hydrolysis in the AHL scaffold [53], these compounds may find

Targeting the Pseudomonas quinolone signal quorum sensing system for the discovery of novel anti-infective pathoblockers

• Christian Schütz and
• Martin Empting

Beilstein J. Org. Chem. 2018, 14, 2627–2645, doi:10.3762/bjoc.14.241

• actually autoinducers (AIs) and, hence, have an agonistic activity toward their receptor, a positive feedback loop is created. In P. aeruginosa three different chemotypes of AIs have been identified, to date: alkyl homoserine lactones (AHLs) used by the las and rhl systems, alkylquinolones (AQs) used by

Pathoblockers or antivirulence drugs as a new option for the treatment of bacterial infections

• Matthew B. Calvert,
• Varsha R. Jumde and
• Alexander Titz

Beilstein J. Org. Chem. 2018, 14, 2607–2617, doi:10.3762/bjoc.14.239

• Gram-positive bacteria. While Gram-positive bacteria often use peptides as signal molecules, Gram-negative bacteria employ N-acylhomoserine lactones (AHLs) with subtle differences in their chemical structure, as well as other types of autoinducers (Figure 5). Interestingly, the signaling molecule

Impact of Pseudomonas aeruginosa quorum sensing signaling molecules on adhesion and inflammatory markers in endothelial cells

• Carmen Curutiu,
• Florin Iordache,
• Veronica Lazar,
• Aurelia Magdalena Pisoschi,
• Aneta Pop,
• Mariana Carmen Chifiriuc and
• Alina Maria Hoban

Beilstein J. Org. Chem. 2018, 14, 2580–2588, doi:10.3762/bjoc.14.235

• infections. P. aeruginosa produce two types of quorum-sensing signaling molecules (QSSMs): N-acylhomoserine lactones (AHL) and 2-alkyl-4-quinolone (PQS) derivatives. The AHLs molecules described so far in P. aeruginosa belong at two quorum sensing (QS) systems: las and rhl systems whose autoinducer (AI

• of the disease. Recent studies have found that the QS molecules interact with eukaryotic cells and modulate also host immune response [9]. But, although the roles of the N-acylhomoserine lactones in the modulation of immune response have been well studied, the results obtained until now were

Recent advances in hypervalent iodine(III)-catalyzed functionalization of alkenes

• Xiang Li,
• Pinhong Chen and
• Guosheng Liu

Beilstein J. Org. Chem. 2018, 14, 1813–1825, doi:10.3762/bjoc.14.154

• sulfonyl- and phoshoryloxylactonization of alkenoic acids 11 with additional nucleophiles (Scheme 4, bottom) [50], in which a bisamide chiral precatalyst was applied [51]. This reaction provides an efficient access to various interesting enantioenriched γ-lactones through a tandem sequence in acceptable