Three new trixane glycosides obtained from the leaves of Jungia sellowii Less. using centrifugal partition chromatography

• Luíse Azevedo,
• Larissa Faqueti,
• Marina Kritsanida,
• Antonia Efstathiou,
• Despina Smirlis,
• Gilberto C. Franchi Jr,
• Grégory Genta-Jouve,
• Sylvie Michel,
• Louis P. Sandjo,
• Raphaël Grougnet and
• Maique W. Biavatti

Beilstein J. Org. Chem. 2016, 12, 674–683, doi:10.3762/bjoc.12.68

• supported by the theoretical calculation using time-dependent density functional theory. Thus, two Cotton Effects (CE) from the n→π* transition of the α,β-unsaturated lactone were revealed at 225 and 275 nm with alternative signs (Figure 5). The aforementioned data in conjunction to the absolute

• similar interactions with H-1 (δ 1.72) and H-9 (δ 1.56, 1.67). The absolute configuration of 2 was determined to be 2R, 3S, 6S, 7R, and 10S by ECD analysis. As compound 1, two Cotton Effects (CE) from the n→π* transition of the α,β-unsaturated lactone were revealed at 225 and 275 nm with alternative signs

• leukemic cell lines HL60, JURKAT and REH at 15 μM. Conclusion The chemical study of the leaves of J. sellowii led to the isolation and characterization of three new sesquiterpene glycosides, including the first report of trixane lactone glycosides. Liquid–liquid partition and CPC proved to be a very useful

Supported bifunctional thioureas as recoverable and reusable catalysts for enantioselective nitro-Michael reactions

• José M. Andrés,
• Miriam Ceballos,
• Alicia Maestro,
• Isabel Sanz and
• Rafael Pedrosa

Beilstein J. Org. Chem. 2016, 12, 628–635, doi:10.3762/bjoc.12.61

• -lactone (3e) with nitrostyrene derivatives 1a–d (Scheme 3 and Table 3). The electronic nature of the nitroolefins only affects the yield and the reaction time, being longer as the donating effect of the substituent increases, but maintaining good diastereoselectivity and excellent enantioselectivity for

• much more slowly than cyclopentanone derivative 3a (Table 3, entries 5, 6, and 8), although the reaction time could be reduced from 96 h to 10 h in the reaction of 1a with 3b by increasing the catalyst loading from 2 mol % to 5 mol % (Table 3, entry 7). It is also noteworthy that 2-acetyl-γ-lactone (3e

Biosynthesis of α-pyrones

• Till F. Schäberle

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

• cyclic unsaturated ester is present in a large number of natural products, and molecules containing α-pyrones can be found in all three kingdoms of life. Additionally α-pyrones, especially the structurally simple ones, i.e., triacetic acid lactone (2) and tetraacetic acid lactone (3) (Figure 1

• applied to A. thaliana, and the growth and defense reactions were verified. A. thaliana pre-exposed to 29 showed significantly reduced symptoms when challenged with B. cinerea and Alternaria brassicicola [36]. Beside the examples of simple substituted α-pyrone derivatives, such as triacetic acid lactone

• (2), tetraacetic acid lactone (3), and 6-pentyl-2-pyrone (29) also more complex systems, e.g., bufalin (31) [38], fusapyrones (32,33) [39], or the α-pyrone antibiotics corallopyronins (34,35) [40] and myxopyronins (36,37) [41], exist in the group of monocyclic α-pyrones (Figure 7). The bufadienolides

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

• careful analysis of the spectrum in Figure 4 concerns the asymmetry of the molecule. The proton spectrum of the rhodamine B both in lactone (Supporting Information File 1, Figure S5) and HCl form (Supporting Information File 1, Figure S6) shows only one kind of signal for the alkyl groups (CH3 and CH2 in

• of the preferred conformation assumed by Rho-β-CD in solution. These data, together with the results presented by Wang et al. [25] about the crystal structure of rhodamine B in lactone form, allowed us to propose the model shown in Figure 6 for the intermolecular inclusion mode of Rho-β-CD. This

• Information File 1, Figure S15 the IR spectra of Rho-β-CD, rhodamine B in acidic form (Rho∙HCl) and rhodamine B in lactone form (Rho-B lactone) are shown. The analysis of the spectra unambiguously proved that the fluorophore in Rho-β-CD is in lactam form. The frequency at 1755.9 cm−1 in the IR spectrum of Rho

Regiodefined synthesis of brominated hydroxyanthraquinones related to proisocrinins

• Joyeeta Roy,
• Tanushree Mal,
• Supriti Jana and
• Dipakranjan Mal

Beilstein J. Org. Chem. 2016, 12, 531–536, doi:10.3762/bjoc.12.52

• anthraquinone moiety in 31. Second synthetic route Keeping in view the problems of functionalization of the aldehyde group in 31, we contemplated the use of already homologated cyclohexenone 36 as the acceptor. Bicyclic lactone 33 [45] was treated with DIBAL-H to afford lactol 34 in 85% yield [46]. Treatment of

Synthesis and reactivity of aliphatic sulfur pentafluorides from substituted (pentafluorosulfanyl)benzenes

• Norbert Vida,
• Jiří Václavík and
• Petr Beier

Beilstein J. Org. Chem. 2016, 12, 110–116, doi:10.3762/bjoc.12.12

• good stability at ambient temperature in a strongly acidic and oxidizing environment. However, lactone 3 was found to be unstable in water or in aqueous base. Monitoring a solution of 3 in D2O by 1H and 19F NMR spectroscopy showed a gradual disappearance of the SF5 signal. After 55 h at ambient

• lactone 3 remained unaffected. At 80 °C the formation of levulinic acid derivative 18 was observed together with unidentified byproducts. Under elevated temperature (100 °C and above) the product of HF and SF4 elimination, (E)-4-oxopent-2-enoic acid (19) [28] formed (Scheme 7). In a preparative experiment

• . 19F NMR yields are given. Synthesis of para-benzoquinone 12 and oxidation to maleic acid 4. 19F NMR yields are shown, in parentheses isolated yields. Catalytic hydrogenation and Diels–Alder reaction of benzoquinone 12. Decomposition of 3 in water. Formation of acids 5, 18 and 19 from lactone 3

Synthesis of Xenia diterpenoids and related metabolites isolated from marine organisms

• Tatjana Huber,
• Lara Weisheit and
• Thomas Magauer

Beilstein J. Org. Chem. 2015, 11, 2521–2539, doi:10.3762/bjoc.11.273

• subfamilies: the xenicins (containing an 11-oxabicyclo[7.4.0]tridecane ring system with an acetal functionality) [2], the xeniolides (containing an 11-oxabicyclo[7.4.0]tridecane ring system with a lactone functionality) [3] and the xeniaphyllanes (with a bicyclo[7.2.0]undecane ring system) [4]. Later, an

• . Addition of lithium acetylide 41 to the keto group led to acetal 42. Hydrogenation of the triple bond under basic conditions resulted in cleavage of the acetal and ring closure to the corresponding lactol which was oxidized with chromic acid to furnish γ-lactone 43. An ensuing Dieckmann condensation [32

• afforded lactone 64. For the introduction of the side chain, the enolate derived from lactone 64 was treated with 1-bromo-4-methylpent-2-ene, giving a 1:6 mixture of coraxeniolide A (10) and its epimer 65. By equilibration with triazabicyclodecene (TBD), the ratio of 10:65 could be inverted to 3:1. In

Recent highlights in biosynthesis research using stable isotopes

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2015, 11, 2493–2508, doi:10.3762/bjoc.11.271

• malonyl moiety to the α,β-unsaturated thioester bound to the keto-synthase domain (KS). After this reaction, the polyketide chain is bound to the KS and the acyl carrier protein (ACP). The following lactonization to generate the δ-lactone structure in 4 can either proceed via nucleophilic attack of the δ

• branching module. NMR experiments on the ACP-bound product unambiguously showed the labeled 13C signals in the linear polyketide chain and not in the lactone ring, thus supporting mechanism A. Therefore, this labeling experiment took an important role on the road to a better understanding of this unusual

Convenient preparation of high molecular weight poly(dimethylsiloxane) using thermally latent NHC-catalysis: a structure-activity correlation

• Stefan Naumann,
• Johannes Klein,
• Dongren Wang and
• Michael R. Buchmeiser

Beilstein J. Org. Chem. 2015, 11, 2261–2266, doi:10.3762/bjoc.11.246

• (Scheme 2), often preferred by the six-membered NHCs [7][8][9][17], seems clearly disfavoured. In the absence of BnOH, it is therefore reasonable to assume zwitterionic propagation, in analogy to recent findings for NHC-mediated lactone polymerization [33]. The insoluble material received by the action of

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

• catalyst 1 delivered lactone 51 as a mixture of isomers (3:1) in 37% yield. When the substrate was modified as in 52, the RCM product was not formed; however, compound 52 gave the ring-opened product with ethylene (24) in low yield. Further, the ROM homodimer was obtained in 17% yield in the presence of

• 90% yield (Scheme 31). Ghosh and Maity [35][36] reported a stereoselective route to functionalized tricyclic system present in umbellactal (153) via a RRM protocol starting with intricate norbornene derivatives. The tricyclic anhydride 154 was reduced to lactone 155 using sodium borohydride and then

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

• 5 mM concentration; the catalysts were added in 10 portions with 7 minutes intervals. The 16-membered lactone 19 was synthesized with the catalyst loading of 0.3 mol % (Table 3, entries 1–4). The highest yield (91%) along with good selectivity (93%) was obtained with nG-I2 while only a 54% yield and

Preparation of conjugated dienoates with Bestmann ylide: Towards the synthesis of zampanolide and dactylolide using a facile linchpin approach

• Jingjing Wang,
• Samuel Z. Y. Ting and
• Joanne E. Harvey

Beilstein J. Org. Chem. 2015, 11, 1815–1822, doi:10.3762/bjoc.11.197

• couplings with a Bestmann ylide linchpin have enabled direct lactone and lactam synthesis [12][13][14][15], including the preparation of macrolactones [16][17][18]. An extension of this methodology to γ-hydroxyenone substrates allows the preparation of α-alkylidene-γ-butyrolactones through tandem acylation

Dicarboxylic esters: Useful tools for the biocatalyzed synthesis of hybrid compounds and polymers

• Ivan Bassanini,
• Karl Hult and
• Sergio Riva

Beilstein J. Org. Chem. 2015, 11, 1583–1595, doi:10.3762/bjoc.11.174

• ´-dithiodipropionic acid dimethyl ester in combination with pentadecalactone and 1,4-butandiol (Figure 8) [57]. When MeO-PEG-OH was used as chain terminator amphiphilic copolymers were formed. The hydrophobicity of the polymer could easily be changed by the content of the lactone. The copolymers had low toxicity and

Tandem cross enyne metathesis (CEYM)–intramolecular Diels–Alder reaction (IMDAR). An easy entry to linear bicyclic scaffolds

• Javier Miró,
• María Sánchez-Roselló,
• Álvaro Sanz,
• Fernando Rabasa,
• Carlos del Pozo and
• Santos Fustero

Beilstein J. Org. Chem. 2015, 11, 1486–1493, doi:10.3762/bjoc.11.161

• performed by heating 1.0 equiv of phenylacetylene (1a) and 3.0 equiv of diolefinic ester 2a in toluene in the presence of second generation Hoveyda–Grubbs catalyst [Ru-II]. After 6 hours at 90 °C, bicyclic lactone 3a was obtained in 25% yield (Table 1, entry 1), together with lactone 4a (15%, arising from

• Ru-II catalyst) were applied to other aromatic alkynes 1 and dienes 2, affording a new family of linear carbocycles and heterocycles 3 in moderate yields (Table 2). Bicyclic lactone 3a, ketone 3b and lactam 3c were obtained in moderate yields following the tandem CEYM-IMDAR protocol (Table 2, entries

Structure and conformational analysis of spiroketals from 6-O-methyl-9(E)-hydroxyiminoerythronolide A

• Ana Čikoš,
• Irena Ćaleta,
• Dinko Žiher,
• Mark B. Vine,
• Ivaylo J. Elenkov,
• Marko Dukši,
• Dubravka Gembarovski,
• Marina Ilijaš,
• Snježana Dragojević,
• Ivica Malnar and
• Sulejman Alihodžić

Beilstein J. Org. Chem. 2015, 11, 1447–1457, doi:10.3762/bjoc.11.157

• Park, Harlow, CM19 5AW, United Kingdom 10.3762/bjoc.11.157 Abstract Three novel spiroketals were prepared by a one-pot transformation of 6-O-methyl-9(E)-hydroxyiminoerythronolide A. We present the formation of a [4.5]spiroketal moiety within the macrolide lactone ring, but also the unexpected

• ; spiroketal; Introduction Macrolide antibiotics are natural or semi-synthetic products of polyketide origin, containing one or more desoxy sugars attached to a macrocyclic lactone aglycon. This large and structurally diverse category of compounds has traditionally been divided into classes based on the

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

The synthesis of active pharmaceutical ingredients (APIs) using continuous flow chemistry

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2015, 11, 1194–1219, doi:10.3762/bjoc.11.134

Chemoselective O-acylation of hydroxyamino acids and amino alcohols under acidic reaction conditions: History, scope and applications

• Tor E. Kristensen

Beilstein J. Org. Chem. 2015, 11, 446–468, doi:10.3762/bjoc.11.51

• anhydride under heating, followed by hydrolysis in dilute hydrochloric acid, gives cis-4-hydroxy-D-proline·HCl via an N-acetylated lactone [73], a product that can be acylated directly in the same manner as the natural hydroxyproline (Scheme 14) [48][74]. In addition to acrylic proline monomers [48], the O

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

• and its analogues, sharing the similar structure of a γ-lactone with an attached β-carboxylic acid, are widely found in natural products. Related syntheses have been actively explored due to the potential antitumor and antibiotic activities of these compounds [1][2][3][4]. The synthesis methods were

• not suitable for some acid-sensitive or base-sensitive intermediates. Alternatively, the lactone is also formed through the reaction of a carbonyl with an enolate that can be generated from a metal-catalyzed conjugate addition of an α,β-unsaturated diester. As shown in Figure 1, it involves a

• conjugate reduction of the α,β-unsaturated diester with newly generated copper hydride, followed by aldol reaction to yield the key intermediate alkoxide A, which is subjected to further lactonization to form the lactone. Lam’s group has furnished a cobalt-catalyzed conjugate reductive aldolization

Formulation development, stability and anticancer efficacy of core-shell cyclodextrin nanocapsules for oral chemotherapy with camptothecin

• Hale Ünal,
• Naile Öztürk and
• Erem Bilensoy

Beilstein J. Org. Chem. 2015, 11, 204–212, doi:10.3762/bjoc.11.22

• colon, breast, ovarian, lung cancers in in vitro cell culture studies [17][18]. However its poor aqueous solubility and the pH-dependent stability problem results in the diminishing of clinical efficacy for the drug [19]. CPT is in active lactone form under pH 5 but is rapidly hydrolysed into the

• probably attributed to the lactone–carboxylate equilibrium of CPT. It is known that the active lactone form of CPT rapidly hydrolyses into the inactive carboxylate form at physiological pH. As it was indicated in Supporting Information File 1, all the formulations were diluted with HBSS solution at pH 7.4

• for the permeability studies. At this pH, the active lactone form which is essential for the diffusion of the drug through membranes, was rapidly turned into the inactive carboxylate form which shows a poorer diffusibility than the lactone form [46][47]. Nanocapsules have the ability to maintain the

Cathodic reductive coupling of methyl cinnamate on boron-doped diamond electrodes and synthesis of new neolignan-type products

• Taiki Kojima,
• Rika Obata,
• Tsuyoshi Saito,
• Yasuaki Einaga and
• Shigeru Nishiyama

Beilstein J. Org. Chem. 2015, 11, 200–203, doi:10.3762/bjoc.11.21

• mixture, (±)-2 was submitted to the chemical conversion into the new neolignan-type derivatives E-5 and E-8. Thus, reduction of (±)-2 with LiAlH4 gave the alcohol (±)-4 [15] in quantitative yield, which on oxidation with PCC [16] gave the lactone E-5 in 32% yield. Selective DIBAL reduction of E-5 gave an

Formation of nanoparticles by cooperative inclusion between (S)-camptothecin-modified dextrans and β-cyclodextrin polymers

• Thorbjørn Terndrup Nielsen,
• Catherine Amiel,
• Laurent Duroux,
• Kim Lambertsen Larsen,
• Lars Wagner Städe,
• Reinhard Wimmer and
• Véronique Wintgens

Beilstein J. Org. Chem. 2015, 11, 147–154, doi:10.3762/bjoc.11.14

• potent anticancer activity by inhibition of topoisomerase II. Its major drawback is its extremely low aqueous solubility of 2.5 µg/mL leading to a low bioavailability and it is thus a considerable formulation challenge [4]. Furthermore, at physiological conditions its active lactone form is hydrolysed to

• significantly increase the stability of the CTP lactone, due to the protection from the aqueous environment. Conclusion Novel (S)-camptothecin-dextran polymers were obtained by “click” grafting of azide-modified (S)-camptothecin and alkyne-modified dextrans. Two series based on 10 kDa and 70 kDa dextrans were

Recent advances in the electrochemical construction of heterocycles

• Robert Francke

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

• , a tethered carboxy group can be used as the nucleophilic component, leading to the formation of lactone rings [39]. A further option is the hydrolysis of alkoxysulfonium species 7 with aqueous NaOH under formation of the corresponding secondary alcohol [40]. The idea of integrating a chemical

Aspergiloid I, an unprecedented spirolactone norditerpenoid from the plant-derived endophytic fungus Aspergillus sp. YXf3

• Zhi Kai Guo,
• Rong Wang,
• Wei Huang,
• Xiao Nian Li,
• Rong Jiang,
• Ren Xiang Tan and
• Hui Ming Ge

Beilstein J. Org. Chem. 2014, 10, 2677–2682, doi:10.3762/bjoc.10.282

• three methyl groups (δC 23.4, 24.5, 29.2), five aliphatic methylenes (δC 18.1, 23.7, 28.4, 28.5, 31.8), one olefinic methylene (δC 113.2), two oxygenated methines (δC 76.9, 64.7), one olefinic methine (δC 142.9), and six non-protonated carbon atoms (one of which was identified as lactone group) (δC 35.1

• . Here the hypothetical pimarane compound 2, the hemiketal lactone ring-opening product of aspergiloid E, was proposed as the most probable biosynthetic intermediate. As shown in Scheme 1, we suggest the biosynthesis of 1 starts from the classical diterpene precursor geranylgeranyl diphosphate [14], and

• intermediate 2 undergoes decarboxylation to form 3 through Baeyer–Villiger oxidation to form the 7-membered lactone 4, then hydrolyzation, decarboxylation and lactonization to finally give aspergiloid I (1). Aspergiloid I (1) was evaluated for its cytotoxicity against eleven human cancer cell lines, K562

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

• reports supporting this theory, it has to be noted that this view point has been challenged and is still under debate among scientists [6][7]. Most Gram-negative bacteria use N-acylated homoserine lactones (AHLs) as signal molecules [8]. The general structure of these compounds consist of a lactone ring

• lactone carbonyl group, could increase the affinity of AHLs to their cognate receptors [18]. It was shown that introduction of halogens as electron-withdrawing groups in the N-acyl chain reduced the nucleophilicity of the donor oxygen and led to attenuation of the n→π* interaction (Figure 1). Moreover

• atoms, that could be involved in such interactions seem an interesting strategy to be explored. Surprisingly, most of the studies focus on altering the fatty acid tail or the lactone ring of the AHL molecules [14][19], while modifications at the α-carbon position with respect to the carbonyl function of