Navigating and expanding the roadmap of natural product genome mining tools

• Friederike Biermann,
• Sebastian L. Wenski and
• Eric J. N. Helfrich

Beilstein J. Org. Chem. 2022, 18, 1656–1671, doi:10.3762/bjoc.18.178

• bioinformatic analysis of (meta-)genomes to identify gene clusters involved in the biosynthesis of NPs [3]. NPs have been shown to act as signaling metabolites (e.g., acylhomoserine lactones (1) [6]), siderophores (e.g., pyoverdines (2) [7]), virulence factors (e.g., malleicyprol (3) [8][9][10]), toxins (e.g

Rhodium-catalyzed intramolecular reductive aldol-type cyclization: Application for the synthesis of a chiral necic acid lactone

• Motoyuki Isoda,
• Kazuyuki Sato,
• Kenta Kameda,
• Kana Wakabayashi,
• Ryota Sato,
• Hideki Minami,
• Yukiko Karuo,
• Atsushi Tarui,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2022, 18, 1642–1648, doi:10.3762/bjoc.18.176

• , the synthesis of necic acid lactones such as monocrotalic acid is rare (Figure 2). Consequently, we attempted to apply the rhodium-catalyzed intramolecular reductive aldol-type reaction to the synthesis of a chiral necic acid lactone that is a part of structural component of monocrotaline. According

Synthesis of (−)-halichonic acid and (−)-halichonic acid B

• Keith P. Reber and
• Emma L. Niner

Beilstein J. Org. Chem. 2022, 18, 1629–1635, doi:10.3762/bjoc.18.174

• system found in this natural product. However, we were intrigued that a competing cyclization process also formed isomeric lactones 9 and 10 in 8% yield and 11% yield, respectively. 1H NMR analysis confirmed that compounds 9 and 10 were both trans-fused 6/5 bicycles based on the magnitude of the vicinal

• difference in the 13C NMR chemical shift of the C7-methyl group, which appears at δ = 20.7 in (−)-2 and δ = 14.5 in 11. Discussion Rationalizing the outcome of the aza-Prins reaction leading to the formation of ethyl ester 8 and isomeric lactones 9 and 10 (Scheme 2) provides an interesting exercise in

• hydrolyzed under basic conditions (Scheme 2) to form the enantiomer of halichonic acid B ((−)-2). It is interesting to note that halichonic acid B exists exclusively as an open-chain 4-hydroxycarboxylic acid even though the corresponding γ-lactones typically form spontaneously. Indeed, no lactone formation

Vicinal ketoesters – key intermediates in the total synthesis of natural products

• Marc Paul Beller and
• Ulrich Koert

Beilstein J. Org. Chem. 2022, 18, 1236–1248, doi:10.3762/bjoc.18.129

• alcohol 56, which was dehydroxylated to the diastereomeric cations VIII and IX. Friedel–Crafts reaction gave diastereomeric lactones 57 and 58. The major diastereomer 58 could be converted to the complex polyphenol (−)-hopeanol (59) in seven further steps. (+)-Camptothecin In the formal synthesis of the

New azodyrecins identified by a genome mining-directed reactivity-based screening

• Atina Rizkiya Choirunnisa,
• Kuga Arima,
• Yo Abe,
• Noritaka Kagaya,
• Kei Kudo,
• Hikaru Suenaga,
• Junko Hashimoto,
• Manabu Fujie,
• Noriyuki Satoh,
• Kazuo Shin-ya,
• Kenichi Matsuda and
• Toshiyuki Wakimoto

Beilstein J. Org. Chem. 2022, 18, 1017–1025, doi:10.3762/bjoc.18.102

• alcohols [24], methoxides [23][25][26], carboxylic acids [27], amides [28], ketones [29][30], an exo-olefin [31], and lactones [32]. Elucidating the mechanisms of structural diversification is essential when considering the synthesis of unnatural azoxides by a synthetic biology-based approach. However

First example of organocatalysis by cathodic N-heterocyclic carbene generation and accumulation using a divided electrochemical flow cell

• Daniele Rocco,
• Ana A. Folgueiras-Amador,
• Richard C. D. Brown and
• Marta Feroci

Beilstein J. Org. Chem. 2022, 18, 979–990, doi:10.3762/bjoc.18.98

• and cis γ-butyrolactones were easily separated by column chromatography. Increasing the applied charge from 0.5 F (Table 2, entry 1) to 1.0 F (Table 2, entry 2) improved the yield of both cis (2a) and trans (2b) lactones by approximately three fold. Instead, with a charge of 2.0 F the yield of 2a

Terpenoids from Glechoma hederacea var. longituba and their biological activities

• Dong Hyun Kim,
• Song Lim Ham,
• Zahra Khan,
• Sun Yeou Kim,
• Sang Un Choi,
• Chung Sub Kim and
• Kang Ro Lee

Beilstein J. Org. Chem. 2022, 18, 555–566, doi:10.3762/bjoc.18.58

• distributed in Korea, Japan, and China. This plant has been used as Korean traditional medicine for treating asthma, bronchitis, cholelithiasis, colds, and inflammation [1][2]. Previous studies have shown that G. hederacea var. longituba contains phytochemicals such as monoterpenoids, sesquiterpene lactones

Efficient and regioselective synthesis of dihydroxy-substituted 2-aminocyclooctane-1-carboxylic acid and its bicyclic derivatives

• İlknur Polat,
• Selçuk Eşsiz,
• Uğur Bozkaya and
• Emine Salamci

Beilstein J. Org. Chem. 2022, 18, 77–85, doi:10.3762/bjoc.18.7

• -functional theory (DFT) computations were used to explain the reaction mechanism for the ring opening of the epoxide and the formation of five-membered lactones. The stereochemistry of the synthesized compounds was determined by 1D and 2D NMR spectroscopy. The configuration of methyl 6-hydroxy-9-oxo-8

A two-phase bromination process using tetraalkylammonium hydroxide for the practical synthesis of α-bromolactones from lactones

• Yuki Yamamoto,
• Akihiro Tabuchi,
• Kazumi Hosono,
• Takanori Ochi,
• Kento Yamazaki,
• Shintaro Kodama,
• Akihiro Nomoto and
• Akiya Ogawa

Beilstein J. Org. Chem. 2021, 17, 2906–2914, doi:10.3762/bjoc.17.198

• Kawai Building, 8-15,4-Chome, Nihonbashi-Honchou, Chuo-Ku, Tokyo 103-0023, Japan 10.3762/bjoc.17.198 Abstract A simple and efficient method for α-brominating lactones that affords α-bromolactones under mild conditions using tetraalkylammonium hydroxide (R4N+OH−) as a base was developed. Lactones are

• ring-opened with Br2 and a substoichiometric amount of PBr3, leading to good yields of the corresponding α-bromocarboxylic acids. Subsequent intramolecular cyclization over 1 h using a two-phase system (H2O/CHCl3) containing R4N+OH− afforded α-bromo lactones in good yields. This method can be applied

• facilitate the industrial use of α-bromolactones as important intermediates. Keywords: α-bromolactone; metal-free; one-pot operation; tetraalkylammonium hydroxide; two-phase system; Introduction Lactones are important heterocycles in the organic chemistry, materials science, and medicinal chemistry fields

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• -lactones [146]. In 2020, Cai and co-workers reported a three-component intermolecular trifluoromethyl-esterification of activated alkenes 115 with NaOTf and aryl carboxylic acids 178 (Scheme 39) [147]. Notably, the use of NaOTf as a CF3 source, compared to pre-prepared trifluoromethylating agents like

Synthesis of highly substituted fluorenones via metal-free TBHP-promoted oxidative cyclization of 2-(aminomethyl)biphenyls. Application to the total synthesis of nobilone

• Ilya A. P. Jourjine,
• Lukas Zeisel,
• Jürgen Krauß and
• Franz Bracher

Beilstein J. Org. Chem. 2021, 17, 2668–2679, doi:10.3762/bjoc.17.181

• cyclic lactones [69]. The intramolecular cyclization of the acyl radical A gives the tricyclic radical species C, which then forms fluorenone (3) after abstraction of a hydrogen radical by an additional equivalent of the tert-butoxy radical. Conclusion In summary, we have demonstrated that the metal-free

Advances in mercury(II)-salt-mediated cyclization reactions of unsaturated bonds

• Sumana Mandal,
• Raju D. Chaudhari and
• Goutam Biswas

Beilstein J. Org. Chem. 2021, 17, 2348–2376, doi:10.3762/bjoc.17.153

• lactones had been synthesized from alkynoic acids via Hg(II)-salt-catalyzed cyclization reaction. For example, simple 4-pentynoic acid derivatives 137 afforded γ-methylene butyrolactones 139 in good yields via the formation of organomercural compounds 138 using catalytic mercuric oxide, mercuric acetate

Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

• Thiago S. Silva and
• Fernando Coelho

Beilstein J. Org. Chem. 2021, 17, 1565–1590, doi:10.3762/bjoc.17.112

• nucleophiles beyond the usually employed dicarbonyl compounds to cyanoacetates, nitroacetates, fluoroacetates, lactones, lactams, and aromatic and heteroaromatic carbonyl compounds. The reactions were carried out at higher temperatures (120 °C) than used in the previous protocols involving more reactive

• additions [92]. Using MBH acetates 63 as substrates, olefin hydroallylation products 64 were obtained via E1cB elimination of the acetate leaving group driven by the enolate intermediate (Scheme 25B). Six-membered lactones (Scheme 25A, 65a–c) were obtained in a cascade reaction when alkenyl alcohols were

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

Recent advances in palladium-catalysed asymmetric 1,4–additions of arylboronic acids to conjugated enones and chromones

• Jan Bartáček,
• Jan Svoboda,
• Martin Kocúrik,
• Jaroslav Pochobradský,
• Alexander Čegan,
• Miloš Sedlák and
• Jiří Váňa

Beilstein J. Org. Chem. 2021, 17, 1048–1085, doi:10.3762/bjoc.17.84

• acids to 3-methyl-2-cyclohexanone catalysed by L9/Pd(TFA)2 [49]. Addition reaction of phenylboronic acid to various enones, lactones, and chromones catalysed by L9/Pd(TFA)2 [48][51]. Addition reactions of arylboronic acids to substituted chromones and N-Cbz-4-quinolones catalysed by L9/Pd(TFA)2 [51

Identification of volatiles from six marine Celeribacter strains

• Anuj Kumar Chhalodia,
• Jan Rinkel,
• Dorota Konvalinkova,
• Jörn Petersen and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2021, 17, 420–430, doi:10.3762/bjoc.17.38

• experiments also led to a suggestion for the mechanism for sulfur incorporation, but further research is required for a deep understanding of TDA biosynthesis. Besides its function as an antibiotic, TDA acts as a signaling molecule, similar to N-acylhomoserine lactones, at concentrations 100 times lower than

• some of the investigated strains. A series of aldehydes ranging from hexanal (7) to tetradecanal (13) was found in strain specific patterns, with all identified compounds present in the bouquet from C. manganoxidans. A similar series of γ-lactones spanning from pentan-4-olide (14) to dodecan-4-olide

• (20), in addition to 3-methylbutan-4-olide (21) and 4-methylhex-5-en-4-olide (22), was detected in strain-specific patterns, with almost all of these compounds present in C. marinus; only C. halophilus did not emit lactones. Furans included furan-2-ylmethanol (23), furfural (24), and 2-acetylfuran (25

3-Acetoxy-fatty acid isoprenyl esters from androconia of the ithomiine butterfly Ithomia salapia

• Florian Mann,
• Daiane Szczerbowski,
• Lisa de Silva,
• Melanie McClure,
• Marianne Elias and
• Stefan Schulz

Beilstein J. Org. Chem. 2020, 16, 2776–2787, doi:10.3762/bjoc.16.228

• (Nymphalidae: Danainae) have hairpencils on the forewings (i.e., androconia) that disseminate semiochemicals during courtship. While most ithomiines are known to contain derivatives of pyrrolizidine alkaloids, dihydropyrrolizines, or γ-lactones in these androconia, here we report on a new class of fatty acid

• ][12]. While dihydropyrrolizines are also used by other Lepidoptera, e.g., danaines [13][14][15] or arctiines [16][17], γ-lactones derived from necic acids are specific to ithomiines of more derived taxa [11]. Past studies of the androconia of Ithomia have reported the presence of 3 in Ithomia

Bifurcated synthesis of methylene-lactone- and methylene-lactam-fused spirolactams via electrophilic amide allylation of γ-phenylthio-functionalized γ-lactams

• Tetsuya Sengoku,
• Koki Makino,
• Ayumi Iijima,
• Toshiyasu Inuzuka and
• Hidemi Yoda

Beilstein J. Org. Chem. 2020, 16, 2769–2775, doi:10.3762/bjoc.16.227

• -butyrolactone; spirolactams; Introduction α-Methylene-γ-butyrolactone is a pharmaceutically important motif which is found in a wide variety of bioactive molecules including natural products (Scheme 1a) [1][2][3]. For example, sesquiterpene lactones represented by parthenolide and helenalin have attracted

• interest because of their useful biological activities, and many synthetic efforts have been made so far [4][5][6]. On the other hand, syntheses and biological evaluation of nonnatural methylene-lactones also have been reported [4][6][7][8]. For instance, Heindel and his co-worker synthesized methylene

• key reaction (Scheme 1b) [10][11]. More recently, an amide-functionalized allyl boronate was developed as an alternative reagent for the allylstannane [12][13][14][15][16], which led to the syntheses of not only cytotoxic methylene-lactones spiro-fused to a lactam ring (B) but also their analogous

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

• photocycloaddition of coumarins 202 (Scheme 31) [89]. The proposed mechanism for this reaction is similar to that proposed by Bach and Krische, proceeding via a key hydrogen bonding complex 203. Interestingly, this catalyst allowed for reactivity with lactones, whereas Bach’s catalysts are limited to lactams. Yoon

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

• oxetane 16. The latter was subjected to the HBr/AcOH ring-opening reaction conditions (Scheme 6). Remarkably, the cyclic products β-hydroxymethyl and β-bromomethyl-γ-lactones 17 and 18 were obtained in an 8:92 ratio [32]. This complete reversal of selectivity in comparison with fluoroalkylidene-oxetane 12

• alkenes E-1d and E-9, was studied either on the bromomethyl (CH2Br) or on the hydroxymethyl (CH2OH) arm, when applicable. First, from a mixture of lactones 15 and 19 substitution on the bromomethyl arm was performed using sodium azide (Scheme 7). The reaction proceeded smoothly in DMF but it proved

• formation of derivative 10. Mechanism for the formation of dihydrofuran 10. Mechanism for the formation of unsaturated lactones 14 and 15. Opening reaction of ethyl 2-(oxetanyl-3-idene)acetate (16). Functionalization of bromomethyllactone 15 and its analogues. Functionalization by substitution reaction of

NHC-catalyzed enantioselective synthesis of β-trifluoromethyl-β-hydroxyamides

• Alyn T. Davies,
• Mark D. Greenhalgh,
• Alexandra M. Z. Slawin and
• Andrew D. Smith

Beilstein J. Org. Chem. 2020, 16, 1572–1578, doi:10.3762/bjoc.16.129

• with amine nucleophiles allowed access to β-trifluoromethyl-β-hydroxyamides in moderate to good yield as single diastereoisomers in excellent er following purification [61]. Organocatalytic enantioselective aldol approaches using trifluoroacetophenone derivatives. NHC-catalyzed approaches to β-lactones

The McKenna reaction – avoiding side reactions in phosphonate deprotection

• Katarzyna Justyna,
• Joanna Małolepsza,
• Damian Kusy,
• Waldemar Maniukiewicz and
• Katarzyna M. Błażewska

Beilstein J. Org. Chem. 2020, 16, 1436–1446, doi:10.3762/bjoc.16.119

• ester [9], which is cleaved in the second step, upon solvolysis, forming the final product (Scheme 1). Bromotrimethylsilane (BTMS) is the main reagent in this reaction and is also known for its ability to cleave lactones, epoxides, acetals, and ethers [10]. BTMS also acted as a brominating agent and

Oxime radicals: generation, properties and application in organic synthesis

• Igor B. Krylov,
• Stanislav A. Paveliev,
• Alexander S. Budnikov and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2020, 16, 1234–1276, doi:10.3762/bjoc.16.107

• (products 46a,b, 46m,n), 1,3-diketones (product 46r), as well as lactones (products 46o–q) were used in the oxidative C–O coupling reaction. The coupling of oximes with 1,3-diketones proceeded in lower yields than with 1,3-ketoesters (products 46a and 46r). Despite the presence of t-BuOOH in the system, a

Anthelmintic drug discovery: target identification, screening methods and the role of open science

• Frederick A. Partridge,
• Ruth Forman,
• Carole J. R. Bataille,
• Graham M. Wynne,
• Marina Nick,
• Angela J. Russell,
• Kathryn J. Else and
• David B. Sattelle

Beilstein J. Org. Chem. 2020, 16, 1203–1224, doi:10.3762/bjoc.16.105

• cattle treated annually is hundreds of millions [1]. Treatment of horses, other equids, and companion animals is also a major use of anthelmintics. Anthelmintic drug discovery has been a continued emphasis in the animal health industry, driven by the spread of resistance to the macrocyclic lactones [2

• action of anthelmintic compounds, since it has been recognised that we do not fully understand how many anthelmintics work – for example the concentrations of macrocyclic lactones that paralyse worms in vitro are much greater than the concentration achieved by effective doses in vivo [147]. Several

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

• 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

• gases were determined by mass spectrometry. In general, each type of surface group decomposes to a defined product such as CO2 from carboxylic acid or lactones and CO from carbonyl, hydroxide, phenol, ether or quinone groups and thus, information on the amounts of oxygen-containing surface groups are