Biosynthesis of α-pyrones

• Till F. Schäberle

Beilstein J. Org. Chem. 2016, 12, 571–588, doi:10.3762/bjoc.12.56

• formation yielding in the α-pyrone moiety can be accomplished in different ways. The different biosynthetic routes towards an α-pyrone ring will be presented. The biosynthetic mechanisms to yield saturated lactones, like the statin drug lovastatin, which is in application for lowering cholesterol, will not

• was inhibition of porcine Na+/K+-activated ATPase. Germicidin was the first known autoregulative inhibitor of spore germination in the genus Streptomyces [59]. Influence on plant germination was also shown for further lactones. An inhibiting effect was proven for 3,4-dimethylpentan-4-olid from the

New synthetic strategies for xanthene-dye-appended cyclodextrins

• Milo Malanga,
• Andras Darcsi,
• Mihaly Balint,
• Gabor Benkovics,
• Tamas Sohajda and
• Szabolcs Beni

Beilstein J. Org. Chem. 2016, 12, 537–548, doi:10.3762/bjoc.12.53

• University, Hlavova 8, 12843 Prague 2, Czech Republic 10.3762/bjoc.12.53 Abstract Xanthene dyes can be appended to cyclodextrins via an ester or amide bridge in order to switch the fluorescence on or off. This is made possible through the formation of nonfluorescent lactones or lactams as the fluorophore

Cross metathesis of unsaturated epoxides for the synthesis of polyfunctional building blocks

• Meriem K. Abderrezak,
• Kristýna Šichová,
• Nancy Dominguez-Boblett,
• Antoine Dupé,
• Zahia Kabouche,
• Christian Bruneau and
• Cédric Fischmeister

Beilstein J. Org. Chem. 2015, 11, 1876–1880, doi:10.3762/bjoc.11.201

• that was further efficiently transformed into a 1,2-diol, a 1,2-alkoxy alcohol and a 1,2-amino alcohol. This strategy opens the way for numerous potential transformations involving the epoxide but also the functional group of the electron-deficient olefin. In particular, lactones should be accessible

Recent applications of ring-rearrangement metathesis in organic synthesis

• Sambasivarao Kotha,
• Milind Meshram,
• Priti Khedkar,
• Shaibal Banerjee and
• Deepak Deodhar

Beilstein J. Org. Chem. 2015, 11, 1833–1864, doi:10.3762/bjoc.11.199

• 28a,b) in excellent yields (82–92%). Involvement of acrylates 29a,b delivered lactones 30a,b in moderate yields (30a 41%, 30b 50%) upon treatment with catalyst 2 in dichloromethane at reflux conditions. However, 29a generated lactone 30a in 65% yield when the metathesis was performed using Grela’s

• it was monoallylated to deliver an inseparable mixture of products 156 and 157 in 85% combined yield. Later, the mixture (156 and 157) was subjected to a RRM protocol under the influence of the catalyst 1 in the presence of ethylene (24) to yield a mixture (4:1) of tricyclic lactones 158 and 159 (70

Nitro-Grela-type complexes containing iodides – robust and selective catalysts for olefin metathesis under challenging conditions

• Andrzej Tracz,
• Mateusz Matczak,
• Katarzyna Urbaniak and
• Krzysztof Skowerski

Beilstein J. Org. Chem. 2015, 11, 1823–1832, doi:10.3762/bjoc.11.198

• small molecule of ethylene is coordinated to the ruthenium generating highly active methylidene species. Macrocyclization reactions As model substrates for macrocyclization we choose esters 17 and 18 which are metathesized to the 16- and 14- membered lactones. The RCM was run in toluene, at 70 °C and at

Surprisingly facile CO₂ insertion into cobalt alkoxide bonds: A theoretical investigation

• Willem K. Offermans,
• Claudia Bizzarri,
• Walter Leitner and
• Thomas E. Müller

Beilstein J. Org. Chem. 2015, 11, 1340–1351, doi:10.3762/bjoc.11.144

• such as ammonia, hydrogen, epoxides or lactones [8]. Nevertheless, the reactions frequently involve a substantial kinetic barrier or are accompanied by side reactions that, so far, have resulted in insufficient yields and/or selectivities. Even though there are numerous compounds that might react with

Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

Gold-catalyzed formation of pyrrolo- and indolo-oxazin-1-one derivatives: The key structure of some marine natural products

• Sultan Taskaya,
• Nurettin Menges and
• Metin Balci

Beilstein J. Org. Chem. 2015, 11, 897–905, doi:10.3762/bjoc.11.101

• acids has been reported in the literature to give the corresponding lactones [33][34][35][36][37][38][39][40]. For example, gold(I)-catalyzed reaction of 2-(phenylethynyl)benzoic acid (8) yielded the exo- and endo-dig cyclization products, lactones 9 and 10 in 62% yield in a ratio of 6:1 (Scheme 1) [41

• internal alkynes, two isomeric E- and Z-oxazinones during the cyclization reaction can be formed. However, we observed exclusive formation of a single isomer. Recently, Michelet et al. [70] and others [41][71][72] demonstrated selectively the formation of Z-lactones. The anti intramolecular addition of the

Diastereoselective and enantioselective conjugate addition reactions utilizing α,β-unsaturated amides and lactams

• Katherine M. Byrd

Beilstein J. Org. Chem. 2015, 11, 530–562, doi:10.3762/bjoc.11.60

• expanded to include α,β-unsaturated ketones, aldehydes, lactones, esters, nitroolefins, and to a lesser extent α,β-unsaturated amides and lactams. Review The lack of development in the CA of α,β-unsaturated amides and lactams is not surprising because these substrates are significantly less reactive than

• (78) ligand for the 1,4-addition of α,β-unsaturated lactones and lactams [148]. With these ligands the desired products were obtained in moderate to excellent yields and good to excellent enantioselectivities. This section illustrates that much work has been done in the development of asymmetric 1,4

Copper-catalyzed cascade reactions of α,β-unsaturated esters with keto esters

• Zhengning Li,
• Chongnian Wang and
• Zengchang Li

Beilstein J. Org. Chem. 2015, 11, 213–218, doi:10.3762/bjoc.11.23

• aldolization followed by a lactonization. This method provides a facile approach to prepare γ-carboxymethyl-γ-lactones and δ-carboxymethyl-δ-lactones under mild reaction conditions. Keywords: aldol addition; cascade reaction; catalysis; conjugate reduction; copper; lactonization; Introduction Paraconic acid

• –lactonization cascade reaction using diethylzinc as a reductant [9]. Floch et al. have reported a catalytic synthesis of the γ-lactones from aryl bromides, zinc, dimethyl itaconate and aldehydes/ketones [10][11], which is characteristic in its simplicity, conciseness and high yielding, however with low

• diastereoselectivity. As expected, a cyclic β-halo-α,β unsaturated aldehyde substrate led to the respective tricyclic lactone, the core structure of strigolactone [12]. Bertrand synthesized β-carboxylic acid-γ-lactones in high yields but with low diastereoselectivity via a dialkylzinc-mediated radical addition to the

Recent advances in the electrochemical construction of heterocycles

• Robert Francke

Beilstein J. Org. Chem. 2014, 10, 2858–2873, doi:10.3762/bjoc.10.303

• formation of a C,O-bond and generation of the five-membered heterocycle. Hydroxy, carboxy and oxime moieties were tested as nucleophiles for this reaction, leading to the corresponding tetrahydrofurans, γ-lactones and isoxazolines, respectively. The chemistry depicted in Scheme 13 was also used for the

Synthesis and biological evaluation of novel N-α-haloacylated homoserine lactones as quorum sensing modulators

• Michail Syrpas,
• Ewout Ruysbergh,
• Christian V. Stevens,
• Norbert De Kimpe and
• Sven Mangelinckx

Beilstein J. Org. Chem. 2014, 10, 2539–2549, doi:10.3762/bjoc.10.265

• Michail Syrpas Ewout Ruysbergh Christian V. Stevens Norbert De Kimpe Sven Mangelinckx Department of Sustainable Organic Chemistry and Technology, Ghent University, Coupure Links 653, B-9000 Ghent, Belgium 10.3762/bjoc.10.265 Abstract Novel N-α-haloacylated homoserine lactones, in which a halogen

• atom was introduced at the α-position of the carbonyl function of the N-acyl chain, have been studied as quorum sensing (QS) modulators and compared with a library of natural N-acylated homoserine lactones (AHLs). The series of novel analogues consists of α-chloro, α-bromo and α-iodo AHL analogues

• . Furthermore, the biological QS activity of the synthetic AHL analogues compared to the natural AHLs was evaluated. Halogenated analogues demonstrated a reduced activity in the Escherichia coli JB523 bioassay, with the α-iodo lactones being the less active ones and the α-chloro AHLs the most potent QS agonists

Total synthesis of the proposed structure of astakolactin

• Takayuki Tonoi,
• Keisuke Mameda,
• Moe Fujishiro,
• Yutaka Yoshinaga and
• Isamu Shiina

Beilstein J. Org. Chem. 2014, 10, 2421–2427, doi:10.3762/bjoc.10.252

• -sized lactones (8–11 membered rings) are significant structural motifs because they are found in many natural products possessing useful biological activities [14][15][16][17][18][19]. Among them, the 8-membered (and 9-membered) lactone framework is rather unusual in nature [20][21][22][23][24]. We have

• already developed the synthetic method of lactones with various ring sizes using 2-methyl-6-nitrobenzoic anhydride (MNBA) under mild reaction conditions in the presence of a nucleophilic catalyst such as 4-(dimethylamino)pyridine (DMAP) [25][26]. By using this method, we have demonstrated that unusual

• saturated medium-sized lactones, which are generally difficult to construct because of the ring strain and transannular interactions [27][28], can be effectively prepared [29][30]. Therefore, in order to determine the chemical structure and the expected biological activity of compound 1, we executed the

De novo macrolide–glycolipid macrolactone hybrids: Synthesis, structure and antibiotic activity of carbohydrate-fused macrocycles

• Richard T. Desmond,
• Anniefer N. Magpusao,
• Chris Lorenc,
• Jeremy B. Alverson,
• Nigel Priestley and
• Mark W. Peczuh

Beilstein J. Org. Chem. 2014, 10, 2215–2221, doi:10.3762/bjoc.10.229

• lactone 2 [5], on the other hand, represents one example of glycolipid macrolactone natural products. These novel compounds have many potential applications (e.g., food, cosmetics) based on their physical properties; some glycolipid lactones have also been shown to be cytotoxins [6] and 2 also has

• ], have investigated compounds that blend features of macrolides and glycolipid lactones. These natural product-like compounds fuse the carbohydrate ring to the macrocycle rather than connecting them through a glycosidic linkage. Compounds 3 and 4 in Figure 1 illustrate one approach that has been reported

Chiral phosphines in nucleophilic organocatalysis

• Yumei Xiao,
• Zhanhu Sun,
• Hongchao Guo and
• Ohyun Kwon

Beilstein J. Org. Chem. 2014, 10, 2089–2121, doi:10.3762/bjoc.10.218

• of ketoketenes Using the chiral catalysts (S,Rp)-Josiphos F5 and F6, the Kerrigan group developed the asymmetric homodimerization of ketenes (Scheme 49) [92]. This self-condensation of ketoketenes proceeded in dichloromethane at –25 °C to give chiral β-lactones in high yields (up to 99%) with good to

Application of cyclic phosphonamide reagents in the total synthesis of natural products and biologically active molecules

• Thilo Focken and
• Stephen Hanessian

Beilstein J. Org. Chem. 2014, 10, 1848–1877, doi:10.3762/bjoc.10.195

• high level of stereocontrol (Scheme 4) [37][38][39][40]. Thus, vicinal and quartenary carbon centers can be obtained in high diasteromeric purity by conjugate additions of allyl, crotyl, and cinnamyl-derived anions to Michael acceptors such as enones, lactones, lactams, and α,β-unsaturated esters

• used for limited exploratory studies. Cyclopropanation and aziridination The cyclopropanation of α,β-unsaturated esters and lactones using chiral phosphonamide reagents is a special case of the conjugate addition–enolate alkylation sequence. The application of chloroallyl phosphonamides such as (trans

• cyclopropane 50a. Starting with (cis,R,R)-47b, the isomeric exo,endo product 50b is obtained as major isomer. The cyclopropanation reaction tolerates a wide range of Michael acceptor subtrates such as enones, lactones, lactams, and acyclic α,β-unsaturated esters. The obtained products can easily be cleaved to

Selective allylic hydroxylation of acyclic terpenoids by CYP154E1 from Thermobifida fusca YX

• Anna M. Bogazkaya,
• Clemens J. von Bühler,
• Sebastian Kriening,
• Alexandrine Busch,
• Alexander Seifert,
• Jürgen Pleiss,
• Sabine Laschat and
• Vlada B. Urlacher

Beilstein J. Org. Chem. 2014, 10, 1347–1353, doi:10.3762/bjoc.10.137

• smenochromene D [21], pseudopteranes, furanocembranes [22], indole alkaloids [23], and antitumor cembrane lactones crassin and isolobophytolide [24][25]. Obviously, there is a need for P450s with changed chemoselectivity. Previously a systematic analysis of 31 P450 crystal structures and more than 6300 P450

Homogeneous and heterogeneous photoredox-catalyzed hydroxymethylation of ketones and keto esters: catalyst screening, chemoselectivity and dilution effects

• Axel G. Griesbeck and
• Melissa Reckenthäler

Beilstein J. Org. Chem. 2014, 10, 1143–1150, doi:10.3762/bjoc.10.114

• for aromatic ketones. Aliphatic ketones did not show conversion under TiO2 photolyses. These conditions were applied to keto ester substrates that feature an additional trapping site for the primary hydroxy group. We envisaged the formation of lactones from the corresponding hydroxymethylation

• products (Scheme 4). Methyl benzoylformate (21) gave a mixture of pinacol and the 1,2-diol without lactone formation. The higher homologs (Table 3, entries 2–4) resulted in the corresponding lactones with ring sizes of 5 and 6, respectively, with the δ-keto ester (Table 3, entry 4) leading to the δ

Synthesis of zearalenone-16-β,D-glucoside and zearalenone-16-sulfate: A tale of protecting resorcylic acid lactones for regiocontrolled conjugation

• Hannes Mikula,
• Julia Weber,
• Dennis Svatunek,
• Philipp Skrinjar,
• Gerhard Adam,
• Rudolf Krska,
• Christian Hametner and
• Johannes Fröhlich

Beilstein J. Org. Chem. 2014, 10, 1129–1134, doi:10.3762/bjoc.10.112

• natural product conjugates. Keywords: glycosylation; masked mycotoxins; resorcylic acid esters; sulfation; zearalenone; Introduction Resorcylic acid lactones (RALs, Figure 1), a compound class of benzannulated macrolides, are pharmacologically active secondary metabolites produced by a variety of

• course of ongoing research in the emerging field of masked mycotoxins, we were able to prepare ZEN-16-β,D-glucoside (7) and ZEN-16-sulfate (8, Figure 2B) in reasonable amounts after the development of reliable procedures that should be generally applicable to resorcylic acid lactones. Additionally the

• first chemical synthesis of the ZEN-derivative 14-O-acetylzearalenone (14-AcZEN, produced by some Fusarium strains) [28] is reported. Results and Discussion The general strategy for regiocontrolled conjugation at position 2’ of resorcylic acid esters and lactones is shown in Scheme 1. Regioselective

Visible-light-induced, Ir-catalyzed reactions of N-methyl-N-((trimethylsilyl)methyl)aniline with cyclic α,β-unsaturated carbonyl compounds

• Dominik Lenhart and
• Thorsten Bach

Beilstein J. Org. Chem. 2014, 10, 890–896, doi:10.3762/bjoc.10.86

• lactone and lactam substrates, the latter products were the only products isolated. For the six-membered lactones and lactams and for cyclopentenone the simple addition products prevailed. Keywords: cyclization; electron transfer; iridium; photochemistry; photoredox catalysis; radical reactions

• reactions to other cyclic α,β-unsaturated carbonyl compounds. In particular, we were interested to see whether cyclization reactions as for product 4 would be observed when using α,β-unsaturated lactones and lactams in combination with a silylated amine and an iridium catalyst. In this article, we provide

• full details of our studies in this field. Seven different substrates were tested as limiting reagents in the addition reactions and the structure of the respective products was elucidated. Results and Dicussion Addition to cyclic α,β-unsaturated lactones Our work commenced with attempted addition

Silver and gold-catalyzed multicomponent reactions

• Giorgio Abbiati and
• Elisabetta Rossi

Beilstein J. Org. Chem. 2014, 10, 481–513, doi:10.3762/bjoc.10.46

• expensive ligands and often harsh bases, whereas the silver-mediated process depends on a simple but efficient catalyst such as AgI and Cs2CO3 as base. This feature has been clearly highlighted by Anastas who realized the multicomponent synthesis of regioisomeric arylnaphthalene lactones 89 and 90 from

The regioselective synthesis of spirooxindolo pyrrolidines and pyrrolizidines via three-component reactions of acrylamides and aroylacrylic acids with isatins and α-amino acids

• Tatyana L. Pavlovskaya,
• Fedor G. Yaremenko,
• Victoria V. Lipson,
• Svetlana V. Shishkina,
• Oleg V. Shishkin,
• Vladimir I. Musatov and
• Alexander S. Karpenko

Beilstein J. Org. Chem. 2014, 10, 117–126, doi:10.3762/bjoc.10.8

• ], arylidenerhodanines [25][26], α,β-unsaturated lactones [27], nitrostyrenes [28], acrylic and propiolic esters [29], acrylonitriles [30] and arylidene-1,3-dimethylpyrimidine-2,4,6-triones [31] have been reported. However, the molecular diversity of suitable building blocks for construction of spirooxindoles is by far

SF002-96-1, a new drimane sesquiterpene lactone from an Aspergillus species, inhibits survivin expression

• Silke Felix,
• Louis P. Sandjo,
• Till Opatz and
• Gerhard Erkel

Beilstein J. Org. Chem. 2013, 9, 2866–2876, doi:10.3762/bjoc.9.323

• . It gave a pseudo-molecular ion of m/z 403.2090 (calcd for [C21H32O6 + Na]+, 403.2097) in its HR-ESI mass spectrum. The composition accounted for six double bond equivalents and a characteristic absorption band for α,β-unsaturated γ-lactones was revealed in the UV spectrum at 207 nm. This was

Bidirectional cross metathesis and ring-closing metathesis/ring opening of a C₂-symmetric building block: a strategy for the synthesis of decanolide natural products

• Bernd Schmidt and
• Oliver Kunz

Beilstein J. Org. Chem. 2013, 9, 2544–2555, doi:10.3762/bjoc.9.289

• -membered ring lactones stagonolide E and curvulide A were synthesized using a bidirectional olefin-metathesis functionalization of the terminal double bonds. Key steps are (i) a site-selective cross metathesis, (ii) a highly diastereoselective extended tethered RCM to furnish a (Z,E)-configured dienyl

• carboxylic acid and (iii) a Ru–lipase-catalyzed dynamic kinetic resolution to establish the desired configuration at C9. Ring closure was accomplished by macrolactonization. Curvulide A was synthesized from stagonolide E through Sharpless epoxidation. Keywords: dienes; enzyme catalysis; lactones; metathesis

• ° in the case of the diastereomeric epoxide 39b, and this value fits well to the observed 3J(H5–H6) value (Figure 2) [65]. Conclusion In summary, we synthesized the naturally occurring ten-membered lactones stagonolide E and curvulide A, starting from the ex-chiral pool building block (R,R)-hexa-1,5

Silica sulfuric acid: a reusable solid catalyst for one pot synthesis of densely substituted pyrrole-fused isocoumarins under solvent-free conditions

• Sudipta Pathak,
• Kamalesh Debnath and
• Animesh Pramanik

Beilstein J. Org. Chem. 2013, 9, 2344–2353, doi:10.3762/bjoc.9.269

• starting materials, and the excellent yields of products. Keywords: green chemistry; pyrrole-fused isocoumarin; reusable solid support; silica sulfuric acid; solvent-free condition; Introduction Isocoumarins are an important class of naturally occurring lactones [1][2][3], which has attracted the