A practical synthesis of long-chain iso-fatty acids (iso-C₁₂–C₁₉) and related natural products

• Mark B. Richardson and
• Spencer J. Williams

Beilstein J. Org. Chem. 2013, 9, 1807–1812, doi:10.3762/bjoc.9.210

• commencing with methyl undec-10-enoate (methyl undecylenate) (for iso-C12–C14) or the C15 and C16 lactones pentadecanolide (for iso-C15–C17) and hexadecanolide (for iso-C18–C19). Central to the approaches outlined is the two-step construction of the terminal isopropyl group through addition of

• methylmagnesium bromide to the ester/lactones and selective reduction of the resulting tertiary alcohols. Thus, the C12, C17 and C18 iso-fatty acids were obtained in three steps from commercially-available starting materials, and the remaining C13–C16 and C19 iso-fatty acids were prepared by homologation or

New tridecapeptides of the theonellapeptolide family from the Indonesian sponge Theonella swinhoei

• Annamaria Sinisi,
• Barbara Calcinai,
• Carlo Cerrano,
• Henny A. Dien,
• Angela Zampella,
• Claudio D’Amore,
• Barbara Renga,
• Stefano Fiorucci and
• Orazio Taglialatela-Scafati

Beilstein J. Org. Chem. 2013, 9, 1643–1651, doi:10.3762/bjoc.9.188

• the comparison of its spectroscopic data with those published in the literature [17]. Theonellapeptolides are tridecapeptide lactones characterized by the presence of aliphatic and non-polar amino acids including high ratio of D-amino acids, N-methyl amino acids, and β-amino acids. In particular, the

Anodic coupling of carboxylic acids to electron-rich double bonds: A surprising non-Kolbe pathway to lactones

• Robert J. Perkins,
• Hai-Chao Xu,
• John M. Campbell and
• Kevin D. Moeller

Beilstein J. Org. Chem. 2013, 9, 1630–1636, doi:10.3762/bjoc.9.186

• Robert J. Perkins Hai-Chao Xu John M. Campbell Kevin D. Moeller Washington University in Saint Louis, Saint Louis, Missouri 63130, United States 10.3762/bjoc.9.186 Abstract Carboxylic acids have been electro-oxidatively coupled to electron-rich olefins to form lactones. Kolbe decarboxylation does

• spirocyclic carbocyclic systems [3], cyclic amino acid derivatives [4], cyclic ethers [5][6], and lactones [7][8]. In most of these examples, the reactions can be viewed as arising from an oxidation that forms an olefinic radical cation that is then rapidly trapped by a nucleophile. This triggers a cascade of

Study on the total synthesis of velbanamine: Chemoselective dioxygenation of alkenes with PIFA via a stop-and-flow strategy

• Huili Liu,
• Kuan Zheng,
• Xiang Lu,
• Xiaoxia Wang and
• Ran Hong

Beilstein J. Org. Chem. 2013, 9, 983–990, doi:10.3762/bjoc.9.113

• 321004, China 10.3762/bjoc.9.113 Abstract A “stop-and-flow” strategy was developed for the chemoselective dioxygenation of alkenes with a PIFA-initiated cyclization. This method is conceived for the desymmetrization of seco-diene, and a series of substituted 5-hydroxymethyl-γ-lactones were constructed

• and the protecting groups. However, the direct dioxygenation can easily construct γ-lactones by a simple acidic work-up as shown in Scheme 8. For example, when 24a (R = Bn) was subjected to the PIFA-mediated cyclization, the desired γ-lactone 25a was isolated after hydrolysis in 94% yield with a ratio

• preferentially underwent cyclization to deliver a variety of 3-susbtituted-γ-lactones (25b–d). For comparison, the mCPBA-epoxidation approach in literature always demonstrated that electron-rich alkenes are more reactive leading to the reversal of chemoselectivity [70][71]. A cyclopropane group was also

Synthesis and ring openings of cinnamate-derived N-unfunctionalised aziridines

• Alan Armstrong and
• Alexandra Ferguson

Beilstein J. Org. Chem. 2012, 8, 1747–1752, doi:10.3762/bjoc.8.199

• found to be specific for tert-butyl esters, with γ- and δ-benzylidene lactones, methyl, ethyl, phenyl, and benzyl cinnamates all suffering from degradation, presumably via hydrolysis pathways. β-Alkyl-substituted enoates were not explored, and will be the subject of future investigation. A preliminary

The Amadori rearrangement as glycoconjugation method: Synthesis of non-natural C-glycosyl type glycoconjugates

• Katharina Gallas,
• Gerit Pototschnig,
• Florian Adanitsch,
• Arnold E. Stütz and
• Tanja M. Wrodnigg

Beilstein J. Org. Chem. 2012, 8, 1619–1629, doi:10.3762/bjoc.8.185

• heptonolactones 4 are expected to be formed as a mixture of diastereomers at position C-2. Consequently, the respective aldoheptoses 5, obtained by reduction of the lactones employing sodium borohydride, will be present as C-2 diastereomers as well. However, during the Amadori rearrangement this centre will be

• resulting cyanohydrin to aldonolactone 9 was accomplished by treatment with strong acidic ion-exchange resin IR-120 H+. In contrast to the described reduction employing sodium amalgam, we preferred sodium borohydride, which has been reported as a suitable agent for the reduction of lactones to the

On the proposed structures and stereocontrolled synthesis of the cephalosporolides

• Sami F. Tlais and
• Gregory B. Dudley

Beilstein J. Org. Chem. 2012, 8, 1287–1292, doi:10.3762/bjoc.8.146

• report focuses on 5,5-spiroketal lactones of the cephalosporolide and related families (Figure 2) [26][27]. Cephalosporolides E and F are co-isolated as a mixture, and previous syntheses likewise produce these compounds as a mixture in the absence of methods to control the spiro-center [28][29][30

• subjected to TEMPO oxidation to afford spiroketal lactones 1b and 1c. Spectroscopic data of 1b and 1c were similar to 1a and 1, respectively. Attempts to secure an authentic sample and/or copies of original NMR spectra for the natural material were unsuccessful, but two candidates emerged as good fits to

Stereoselective synthesis of trans-fused iridoid lactones and their identification in the parasitoid wasp Alloxysta victrix, Part II: Iridomyrmecins

• Robert Hilgraf,
• Nicole Zimmermann,
• Lutz Lehmann,
• Armin Tröger and
• Wittko Francke

Beilstein J. Org. Chem. 2012, 8, 1256–1264, doi:10.3762/bjoc.8.141

• chiral centers complicates a stereoselective synthesis despite the small size of the molecule. Several methods have been published for the preparation of optically active cis-fused bicyclic iridoid lactones [7][8][9][10], whereas only a few syntheses of trans-fused ring systems have been reported [11

• iridomyrmecins with corresponding data of the volatile substances Y and Z – which are present in pentane extracts of heads of Alloxysta victrix – allowed their unambiguous identification as trans-fused iridomyrmecins. Coupled GC/MS analysis using FFAP as the stationary phase revealed the natural iridoid lactones

• iridoid lactones which are present in the cephalic secretions of Alloxysta victrix show an unusual trans-fusion. Among the compounds showing this structure, only the lactone X [1] (Figure 1) and a compound with the same relative configuration [21] have been described from insects so far. In contrast to

Stereoselective synthesis of trans-fused iridoid lactones and their identification in the parasitoid wasp Alloxysta victrix, Part I: Dihydronepetalactones

• Nicole Zimmermann,
• Robert Hilgraf,
• Lutz Lehmann,
• Daniel Ibarra and
• Wittko Francke

Beilstein J. Org. Chem. 2012, 8, 1246–1255, doi:10.3762/bjoc.8.140

• few approaches specifically aiming at the synthesis of trans-fused iridoid lactones have been published. Starting from (S)-pulegone (9) or its enantiomer, Wolinsky [20][21] described a route to this group of iridoids that can be applied to synthesize pure stereoisomers of dihydronepetalactones as well

• dihydronepetalactones, starting from pure enantiomers of limonene. Our approach is also superior to that starting from optically active carvone that yields the starting material for the synthesis of trans-fused iridoid lactones only as a byproduct [15]. Identification of a trans-fused dihydronepetalactone in the

• few others, the stereogenic center carrying the methyl group in the five-membered ring of iridoid lactones including insect semiochemicals [13][14][15] generally shows (S)-configuration. Only recently, two isomeric iridoid lactones showing (7R)-configuration have been identified from the Drosophila

Algicidal lactones from the marine Roseobacter clade bacterium Ruegeria pomeroyi

• Ramona Riclea,
• Julia Gleitzmann,
• Hilke Bruns,
• Corina Junker,
• Barbara Schulz and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2012, 8, 941–950, doi:10.3762/bjoc.8.106

• Braunschweig, Germany 10.3762/bjoc.8.106 Abstract Volatiles released by the marine Roseobacter clade bacterium Rugeria pomeroyi were collected by use of a closed-loop stripping headspace apparatus (CLSA) and analysed by GC–MS. Several lactones were found for which structural proposals were derived from their

• mass spectra and unambiguously verified by the synthesis of reference compounds. An enantioselective synthesis of two exemplary lactones was performed to establish the enantiomeric compositions of the natural products by enantioselective GC–MS analyses. The lactones were subjected to biotests to

• investigate their activity against several bacteria, fungi, and algae. A specific algicidal activity was observed that may be important in the interaction between the bacteria and their algal hosts in fading algal blooms. Keywords: bacteria-algae symbiosis; lactones; Roseobacter; synthesis; volatiles

N-Heterocyclic carbene/Brønsted acid cooperative catalysis as a powerful tool in organic synthesis

• Rob De Vreese and
• Matthias D’hooghe

Beilstein J. Org. Chem. 2012, 8, 398–402, doi:10.3762/bjoc.8.43

• formed homoenolate 10 with the activated iminium salt 12 to provide a new entry into the class of pyrrolidin-2-ones 13 (Scheme 4), which is potentially complementary to other methods in terms of stereochemistry. However, the formation of lactones instead of lactams through the intervention of aldehydes

Synthesis and photooxidation of styrene copolymer bearing camphorquinone pendant groups

• Branislav Husár,
• Norbert Moszner and
• Ivan Lukáč

Beilstein J. Org. Chem. 2012, 8, 337–343, doi:10.3762/bjoc.8.37

• the formation of 11 can oxidize another molecule of CQ to 11. It is likely that common biradical intermediates are responsible for the formation of lactones 12 and 13 in solution [10] and acids 14a and 14b formed in the PS matrix [21]. The intramolecular recombination of biradical intermediates is

Conserved and species-specific oxylipin pathways in the wound-activated chemical defense of the noninvasive red alga Gracilaria chilensis and the invasive Gracilaria vermiculophylla

• Martin Rempt,
• Florian Weinberger,
• Katharina Grosser and
• Georg Pohnert

Beilstein J. Org. Chem. 2012, 8, 283–289, doi:10.3762/bjoc.8.30

• pronounced. It can be estimated that these metabolites can account for more than 50% of the total oxylipins, if integrals of the corresponding signals from the oxylipins are evaluated while neglecting possibly differences in the response factors in ESIMS. The novel lactones 5 and 6 were also detected in this

• . vermiculophylla. The isolated prostaglandins and the new lactones (5 and 6) did not exhibit any activity at natural concentrations (Figure 1) or 10-fold higher amounts (data not shown). Interestingly, 7,8-di-HETE (3), a compound that also proved to be the most-active metabolite in the chemical defense of G

Efficient oxidation of oleanolic acid derivatives using magnesium bis(monoperoxyphthalate) hexahydrate (MMPP): A convenient 2-step procedure towards 12-oxo-28-carboxylic acid derivatives

• Jorge A. R. Salvador,
• Vânia M. Moreira,
• Rui M. A. Pinto,
• Ana S. Leal and
• José A. Paixão

Beilstein J. Org. Chem. 2012, 8, 164–169, doi:10.3762/bjoc.8.17

• /bjoc.8.17 Abstract A new, straightforward and high yielding procedure to convert oleanolic acid derivatives into the corresponding δ-hydroxy-γ-lactones, by using the convenient oxidizing agent magnesium bis(monoperoxyphthalate) hexahydrate (MMPP) in refluxing acetonitrile, is reported. In addition, a

• : bismuth(III) triflate; δ-hydroxy-γ-lactones; MMPP; oleanolic acid; triterpenoid; Findings The molecular diversity that arises from research into natural products represents a valuable tool for driving drug discovery and development [1][2]. In this context, pentacyclic triterpenoids are currently regarded

• , anti-inflammatory, hepatoprotective, gastroprotective, antimicrobial, antidiabetic, and hemolytic properties, as well as many others [3][4][5]. Functionalized γ-lactones are important building blocks of bioactive natural products [6][7]. The δ-hydroxy-γ-lactone motif is part of such bioactive natural

Novel fatty acid methyl esters from the actinomycete Micromonospora aurantiaca

• Jeroen S. Dickschat,
• Hilke Bruns and
• Ramona Riclea

Beilstein J. Org. Chem. 2011, 7, 1697–1712, doi:10.3762/bjoc.7.200

•  2, the chromatogram of a representative sample is presented in Figure 3A, and the full results from two extracts are summarised in Table S1 of Supporting Information File 1. M. aurantiaca released more than 90 compounds from different compound classes including carboxylic acids, FAMEs, lactones

Gold(I)-catalyzed synthesis of γ-vinylbutyrolactones by intramolecular oxaallylic alkylation with alcohols

• Michel Chiarucci,
• Mirko Locritani,
• Gianpiero Cera and
• Marco Bandini

Beilstein J. Org. Chem. 2011, 7, 1198–1204, doi:10.3762/bjoc.7.139

• vinylbutyrolactones [18][19][20][21][22] as minor products in the Friedel–Crafts-type allylic alkylation of arenes [23]. The wide impact of functionalized γ-lactones on the synthesis of naturally occurring compounds [24][25][26] prompted us to optimize a direct synthesis of vinylbutyrolactones by direct gold

• alkylation procedure to obtain valuable precursors (i.e., lactams and lactones) of podophyllotoxin analogs [39][40]. However, to the best of our knowledge, no examples of metal-catalyzed lactonization through direct activation of allylic alcohols have been described so far. Results and Discussion At the

• alcohols 3a,b were subjected to cyclization in the presence of the gold catalytic system A. In both cases lactones 4a,b were isolated in good to excellent yields (93 and 75%, respectively, Scheme 1). Finally, the 1,3-ketoester 3c was also subjected to the optimized conditions, but a complex reaction

Molecular rearrangements of superelectrophiles

• Douglas A. Klumpp

Beilstein J. Org. Chem. 2011, 7, 346–363, doi:10.3762/bjoc.7.45

• center of 76. The loss of hydrogen peroxide affords the oxygen-centered cation 78 and subsequent migration of the adjacent group gives dication 75. Whittaker and Carr have described a series of superacid-promoted reactions to prepare bicyclic lactones [28]. Several of the conversions involve

Formation of macrocyclic lactones in the Paternò–Büchi dimerization reaction

• Junya Arimura,
• Tsutomu Mizuta,
• Yoshikazu Hiraga and
• Manabu Abe

Beilstein J. Org. Chem. 2011, 7, 265–269, doi:10.3762/bjoc.7.35

• lactones 2a,b with Ci symmetry including two oxetane-rings, which are the Paternò–Büchi dimerization products, were isolated in ca. 20% yield. The intramolecular cyclization products, such as 3-alkoxyoxetane and 2,7-dioxabicyclo[2.2.1]hept-5-ene derivatives, were not detected in the photolysate. Keywords

• of macrocyclic lactones. To investigate the effects of concentration, solvent, and temperature on the formation of 2a, the photochemical reaction of 1a was conducted under the variety of conditions (Table 1). The yield of intermolecular product 2a was expected to be improved when the concentration of

• on the yield of 2a (entries 7–9). In summary, the intramolecular products such as A and B were not observed in the photochemical reaction of furan derivatives 1a,b, but interestingly the Paternò–Büchi dimers 2a,b with the Ci symmetry, i.e., macrocyclic lactones, were isolated in ca. 20% yield. The

Ene–yne cross-metathesis with ruthenium carbene catalysts

• Cédric Fischmeister and
• Christian Bruneau

Beilstein J. Org. Chem. 2011, 7, 156–166, doi:10.3762/bjoc.7.22

• performed to reach 24,25-ethanovitamine D3 lactones (Scheme 7) [54]. Recently, conjugated dienes resulting from EYCM of terminal and symmetrical propargylic carbonates with ethylene have been prepared in the presence of Grubbs second generation catalyst II. They have been used in sequential catalytic

Application of the diastereoselective photodeconjugation of α,β-unsaturated esters to the synthesis of gymnastatin H

• Ludovic Raffier and
• Olivier Piva

Beilstein J. Org. Chem. 2011, 7, 151–155, doi:10.3762/bjoc.7.21

• application to the asymmetric synthesis of different natural products including (R)-lavandulol (8), (R)-arundic acid (9) and 2-fluoroacids or lactones [7][8][9] (Figure 1). Filamentous fungi are the source of a wide range of secondary metabolites which possess very promising biological activities. Among them

The cross-metathesis of methyl oleate with cis-2-butene-1,4-diyl diacetate and the influence of protecting groups

• Arno Behr and
• Jessica Pérez Gomes

Beilstein J. Org. Chem. 2011, 7, 1–8, doi:10.3762/bjoc.7.1

• -enoate (3) and undec-2-enyl acetate (4). The resulting protected α-hydroxy-ω-carboxylic acid derivatives have potential applications in the preparation of a variety of polymers [22] or lactones [14]. Moreover, undec-2-enyl acetate (4) could be processed into polyallylic alcohols under appropriate

Highly substituted benzannulated cyclooctanol derivatives by samarium diiodide-induced cyclizations

• Jakub Saadi,
• Irene Brüdgam and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2010, 6, 1229–1245, doi:10.3762/bjoc.6.141

• to the position of the methoxycarbonyl group and the hydroxyl group. In general, cis-configured products directly undergo a subsequent cyclization to the corresponding γ-lactones. It is noteworthy that the additionally introduced stereogenic centre bearing the methyl group is also generated

The catalytic performance of Ru–NHC alkylidene complexes: PCy₃ versus pyridine as the dissociating ligand

• Stefan Krehl,
• Diana Geißler,
• Sylvia Hauke,
• Oliver Kunz,
• Lucia Staude and
• Bernd Schmidt

Beilstein J. Org. Chem. 2010, 6, 1188–1198, doi:10.3762/bjoc.6.136

• ). Toluene was preferred over dichloromethane, because reactions are more conveniently conducted at elevated temperatures in this solvent. The acrylates 3 investigated in ring closing metathesis reactions with catalysts D, E and H are listed in Figure 5, together with the resulting unsaturated lactones 4

• . Results for the ring closing metathesis of acrylates 3a–g are summarized in Table 2. Lactones 4b–f [50] are accessible in preparatively useful yields with catalyst loadings of 2.5 mol % to 5.0 mol % if catalysts D and E are used. Conversions observed with catalyst H under otherwise identical conditions

• chromatography on silica to give the corresponding lactones 4. The ratio of lactone 4 to acrylate 3 was determined by integration of characteristic, baseline separated signals in the 1H NMR-spectrum of the crude reaction mixture. Representative example: 5-phenylfuran-2(5H)-one (4f). This compound was obtained as

Tandem catalysis of ring-closing metathesis/atom transfer radical reactions with homobimetallic ruthenium–arene complexes

• Yannick Borguet,
• Xavier Sauvage,
• Guillermo Zaragoza,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2010, 6, 1167–1173, doi:10.3762/bjoc.6.133

• generate active species in situ. The two catalytic processes were first carried out independently in a case study before the whole sequence was optimized and applied to the synthesis of several polyhalogenated bicyclic γ-lactams and lactones from α,ω-diene substrates bearing trihaloacetamide or

• reactions with homobimetallic ruthenium–indenylidene complex 1 to generate active species in situ. The two catalytic processes were first carried out independently in a case study before the whole sequence was optimized and applied to the synthesis of several polyhalogenated bicyclic γ-lactams and lactones

Systematic investigations on the reduction of 4-aryl-4-oxoesters to 1-aryl-1,4-butanediols with methanolic sodium borohydride

• Subrata Kumar Chaudhuri,
• Manabendra Saha,
• Amit Saha and
• Sanjay Bhar

Beilstein J. Org. Chem. 2010, 6, 748–755, doi:10.3762/bjoc.6.94

• the keto moiety. Results of a detailed and systematic investigation of the reaction are described. Keywords: diols; esters; lactones; reduction; Introduction Chemoselective reductions of aldehydes, ketones and imines are generally accomplished using NaBH4 in methanol where other reducible functional

• observed that the reduction of the keto group in the γ-oxoesters 1a and 3 (entries 1 and 2 in Table 3) with the formation of the lactones 9 and 4 as one of the products was much faster than the reduction of aryl alkyl ketones (entries 3 and 4 in Table 3). Therefore, formation of lactone as the intermediate

• corresponding saturated 1,4-butanediols has been firmly established. However, the reason for more facile reduction of the γ-aryl-lactones to diols and the relative reluctance of the γ-alkyl analogues is not yet clear. Conclusion From the above study, a novel method utilizing NaBH4 in methanol that can provide