Volatiles from the hypoxylaceous fungi Hypoxylon griseobrunneum and Hypoxylon macrocarpum

• Jan Rinkel,
• Alexander Babczyk,
• Tao Wang,
• Marc Stadler and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2018, 14, 2974–2990, doi:10.3762/bjoc.14.277

• volatiles seem to be involved in the plant pathogenicity of fungi, as recently observed for 3,4-dimethylpentan-4-olide (4), a volatile from the ash pathogen Hymenoscyphus fraxineus that currently threatens the European ash population [10]. Both enantiomers of this lactone were found to inhibit ash seed

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

• into the analytical window of the method. A wide variety of AHLs, e.g., widespread (Z)-N-(tetradec-7-enoyl)homoserine lactone (1, Z7-C-14:1-AHL, Figure 1), have been identified in roseobacters by these methods [19][20][21][22]. A related group of compounds occurring in Roseovarius only, are N

An overview on recent advances in the synthesis of sulfonated organic materials, sulfonated silica materials, and sulfonated carbon materials and their catalytic applications in chemical processes

• Hashem Sharghi,
• Pezhman Shiri and
• Mahdi Aberi

Beilstein J. Org. Chem. 2018, 14, 2745–2770, doi:10.3762/bjoc.14.253

• and 37 from active carbonyl compounds (e.g., isatins 32, acenaphthoquinone (33), and aldehydes 38), a variety of C–H activated acids (cyclohexane-1,3-dione (20a), 5,5-dimethylcyclohexane-1,3-dione (20b), 2-naphthol (23), ethyl acetoacetate (34a), 4-hydroxycoumarin (34b), triacetic acid lactone (34c

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

• . Starting from various cyclodienes, the corresponding derived bicyclic lactone, lactam, and isoxazoline derivatives were submitted to ROM under ethenolysis. These functionalized, strained bicyclic systems afforded novel highly-functionalized diolefinated heterocyclic scaffolds in ROM reactions with

• 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

• -membered ring system thus possessing ring strain, did not afford any ROM products. Interestingly, lactone (±)-3 in the presence of second generation catalysts (G-2 and HG-2) provided the corresponding ring-opened compound (±)-5 albeit with modest yields (Scheme 3, Table 1). In the presence of G-2 and HG-2

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

• , host colonization, and biofilm formation at high population densities. This cell–cell signaling process is regulated by N-acyl L-homoserine lactone (AHL) signals, or autoinducers, and LuxR-type receptors in Gram-negative bacteria. SdiA is an orphan LuxR-type receptor found in Escherichia, Salmonella

• and antagonism. Keywords: N-acyl L-homoserine lactone; LuxR-type receptor; Quorum sensing; Salmonella enterica serovar Typhimurium; SdiA; Introduction In the fight against bacterial infections, microbes have a decisive advantage over the medical community: evolution [1]. Using bacteriocidal or

• to coordinate group beneficial behaviors such as virulence factor production, host colonization, and biofilm formation at high population densities [12]. Gram-negative bacteria typically use N-acyl L-homoserine lactone (AHL) signals for QS, which are produced by LuxI-type synthases and sensed by

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

• . Abbreviations: OdDHL, N-(3-oxododecanoyl) homoserine lactone; IQS, integrating quorum sensing signal; BHL, N-butyryl-L-homoserine lactone; PQS, Pseudomonas quinolone signal. Positive control is represented by arrows, negative control by blunted arrow. Schematic overview of the PQS biosynthesis and involvement

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

• cells were stimulated with 20 µM of main P. aeruginosa QSSMs (OdDHL = N-(3-oxododecanoyl)-L-homoserine lactone, C4HSL = N-butyryl-L-homoserine lactone, PQS = 2-heptyl-3-hydroxy-4(1H)-quinolone and HHQ = 2-heptyl-4-quinolone). Adherence to endothelial cells, inert substratum and biofilm formation was

• ) molecules are N-(3-oxododecanoyl)homoserine lactone (OdDHL, 3-oxo-C12-HSL), and N-butyryl-L-homoserine lactone (C4-HSL), respectively. AHL systems are interconnected by a third mechanism that uses signaling molecules such as 2-alkyl-4-quinolone (AQ), the most relevant one being 3-hydroxy-4-quinolone (PQS

• ) and purifyed QSSMs (20µM) (OdDHL = N-(3-oxododecanoyl)-L-homoserine lactone; C4HSL = N-butyryl-L-homoserine lactone; PQS = 2-heptyl-3-hydroxy-4(1H)-quinolone; and HHQ = 2-heptyl-4-quinolone). For the adherence assay, Cravioto’s adapted method was used [29]. Briefly, the endothelial cells monolayers

Microfluidic light-driven synthesis of tetracyclic molecular architectures

• Javier Mateos,
• Nicholas Meneghini,
• Marcella Bonchio,
• Nadia Marino,
• Tommaso Carofiglio,
• Xavier Companyó and
• Luca Dell’Amico

Beilstein J. Org. Chem. 2018, 14, 2418–2424, doi:10.3762/bjoc.14.219

• product 4a. Its treatment with a solution of sodium hydroxide in water promoted a quantitative lactone-opening/decarboxylation cascade sequence, yielding 2,4-dihydronaphthalene 6a in quantitative yield without the need of chromatographic purification. Interestingly, scaffold 6a is a valuable intermediate

• manipulation involved the treatment of 4a with PhMgBr, converting the lactone moiety into the corresponding aromatic ketone. Product 8a formed in 71% yield without diastereoisomeric loss. Finally, LiAlH4 reduction of 4a furnished the bicyclic 1,3-diol 9a in quantitative yield, again without the need of

Studies towards the synthesis of hyperireflexolide A

• G. Hari Mangeswara Rao

Beilstein J. Org. Chem. 2018, 14, 2106–2111, doi:10.3762/bjoc.14.185

• G. Hari Mangeswara Rao Department of Chemistry, Indian Institute of Technology Kanpur, Kanpur-208016, India Department of Chemistry, Texila American University, Georgetown, Guyana 10.3762/bjoc.14.185 Abstract The first approach to hyperireflexolide A, based on the synthesis of γ-lactone-fused

• antifungal [2] and cytotoxic activities [3]. γ-Lactone-fused cyclopentanes are of vital importance in organic synthesis and are the most abundant substructures found in various naturally occurring molecules [4][5]. A cis-cyclopentane ring-fused γ-lactone is the key structural unit of many complex and

• challenging biologically active natural products [6][7][8][9][10][11][12][13][14][15][16][17][18][19]. The γ-lactone-fused cyclopentane ring system is also an important component for the synthesis of a variety of cyclopentanoid natural and unnatural products [20][21][22][23][24]. In the literature, numerous

Synthesis of spirocyclic scaffolds using hypervalent iodine reagents

• Fateh V. Singh,
• Priyanka B. Kole,
• Saeesh R. Mangaonkar and
• Samata E. Shetgaonkar

Beilstein J. Org. Chem. 2018, 14, 1778–1805, doi:10.3762/bjoc.14.152

• 35 as precatalyst in the presence of mCPBA. Iodine(III)-mediated asymmetric oxidative spirocyclization of naphthyl acids 37 to naphthyl spirolactones 39 using chiral iodoarene 38 as precatalyst. Oxidative cyclization of L-tyrosine 14 to spirocyclic lactone 16 using PIDA (15). Oxidative cyclization of

Glycosylation reactions mediated by hypervalent iodine: application to the synthesis of nucleosides and carbohydrates

• Yuichi Yoshimura,
• Hideaki Wakamatsu,
• Yoshihiro Natori,
• Yukako Saito and
• Noriaki Minakawa

Beilstein J. Org. Chem. 2018, 14, 1595–1618, doi:10.3762/bjoc.14.137

• described in Scheme 3, Jeong et al. chose a 2,3-di-O-isopropylidene-protected intermediate as a donor of glycosylation, which was synthesized based on their method developed for 4’-thionucleosides. Starting from compound 64, which was obtained from D-gulonic γ-lactone, dimesylate 66 was prepared. The

Lanyamycin, a macrolide antibiotic from Sorangium cellulosum, strain Soce 481 (Myxobacteria)

• Lucky S. Mulwa,
• Rolf Jansen,
• Dimas F. Praditya,
• Kathrin I. Mohr,
• Patrick W. Okanya,
• Joachim Wink,
• Eike Steinmann and
• Marc Stadler

Beilstein J. Org. Chem. 2018, 14, 1554–1562, doi:10.3762/bjoc.14.132

• ). The closure of the 16-membered lactone was apparent from the HMBC correlation between H-15 and C-1 (δC 166 ppm) and from the downfield shift of H-15 (δH 4.81 ppm). Together with four exchanged protons, the oxymethines (C-7, C-21, C-25, C-26) between δC 72 and 77 ppm were assigned as alcohol positions

• . Since the X-ray structure of bafilomycin A1 is available from CCDC it was used to calculate the 3D model of the lactone ring in 1/2 using HyperChem Prof. (version 8.0.10, Figure 4). Initially the X-ray structure was optimized with the mm+ method, which showed a good congruency of X-ray structure and mm

• + model especially of the macrolactone part. After deletion of the methyl group at C-10 and inversion of the C-7 configuration a simplified side chain of 1/2 was attached. In the resulting mm+ model of the lactone ring of 1/2 the calculated torsion angle between H-7 and H-8 was about 108°, explaining the

Acyl-group specificity of AHL synthases involved in quorum-sensing in Roseobacter group bacteria

• Lisa Ziesche,
• Jan Rinkel,
• Jeroen S. Dickschat and
• Stefan Schulz

Beilstein J. Org. Chem. 2018, 14, 1309–1316, doi:10.3762/bjoc.14.112

• synthesized, varying in chain length from C4 to C20, the degree of unsaturation and also including unusual acid esters, e.g., 2E,11Z-C18:2-PCE. The latter served as a precursor of the major AHL of D. shibae DFL-12 LuxI1, 2E,11Z-C18:2-homoserine lactone (HSL). Incubation experiments revealed that PgaI2 accepts

• characterized by saturated, unsaturated and sometimes oxygenated acyl chains ranging in length between C8 and C18 [8] with the exception of the aromatic p-coumaroylhomoserine lactone produced by Rugeria pomeroyi DSS-3 [17]. In a recent analysis we showed the AHL presence in 19 out of 24 Roseobacter group

• bacterial strains isolated from macroalgal surfaces [8]. The most widespread AHL was 7-tetradecenoylhomoserine lactone (7-C14:1-HSL), present in seven strains. No clear correlation between phylogeny and AHL occurrence was observed. In some strains only one AHL was detected, while others such as P

Recent advances in synthetic approaches for medicinal chemistry of C-nucleosides

• Kartik Temburnikar and
• Katherine L. Seley-Radtke

Beilstein J. Org. Chem. 2018, 14, 772–785, doi:10.3762/bjoc.14.65

• -Me analogues of pyrrolo- and imidazo[2,1-f][1,2,4]triazine C-nucleosides using a 2'-β-Me lactone that mimic adenosine and guanosine (12–19, Figure 8) [71][72]. The adenine analogues of pyrrolo- and imidazo[2,1-f][1,2,4]triazine were active as nucleosides in HCV1b RNA replication assays, and as

Nanoreactors for green catalysis

• M. Teresa De Martino,
• Loai K. E. A. Abdelmohsen,
• Floris P. J. T. Rutjes and
• Jan C. M. van Hest

Beilstein J. Org. Chem. 2018, 14, 716–733, doi:10.3762/bjoc.14.61

• of glucose oxidase (GOx) to convert glucose into D-glucono-δ-lactone and hydrogen peroxide was the first step of the reaction (Scheme 3A); subsequently, myoglobin (Myo) employed the hydrogen peroxide produced to oxidize guaiacol to quinone and water (Scheme 3B). When the pH was below 7, the

High-yielding continuous-flow synthesis of antimalarial drug hydroxychloroquine

• Eric Yu,
• Hari P. R. Mangunuru,
• Nakul S. Telang,
• Caleb J. Kong,
• Jenson Verghese,
• Stanley E. Gilliland III,
• Saeed Ahmad,
• Raymond N. Dominey and
• B. Frank Gupton

Beilstein J. Org. Chem. 2018, 14, 583–592, doi:10.3762/bjoc.14.45

• catalyst in a continuous stirring tank reactor (CSTR) for the synthesis of compound 12, and have incorporated it into a fully continuous telescoped process for the synthesis of 12 from lactone 8 and aminoethanol 7. Feeding the output stream containing 12 from the above CSTR into a second CSTR in which 12

Investigations towards the stereoselective organocatalyzed Michael addition of dimethyl malonate to a racemic nitroalkene: possible route to the 4-methylpregabalin core structure

• Denisa Vargová,
• Rastislav Baran and
• Radovan Šebesta

Beilstein J. Org. Chem. 2018, 14, 553–559, doi:10.3762/bjoc.14.42

• -methylpregabalin (1) in an analogy to literature procedures (Scheme 4) [47]. Adduct 7 was transformed to lactone 13 via nitro group reduction with NaBH4/NiCl2 followed by spontaneous lactamization. In the last step, lactam 13 was hydrolyzed and decarboxylated to give 4-methylpregabalin hydrochloride (1·HCl). We

Electrochemical Corey–Winter reaction. Reduction of thiocarbonates in aqueous methanol media and application to the synthesis of a naturally occurring α-pyrone

• Ernesto Emmanuel López-López,
• José Alvano Pérez-Bautista,
• Fernando Sartillo-Piscil and
• Bernardo A. Frontana-Uribe

Beilstein J. Org. Chem. 2018, 14, 547–552, doi:10.3762/bjoc.14.41

• (Scheme 1) [4]. Despite this advantage, the low availability and high cost of this reagent [5] makes this reaction difficult to be used in industry. Previously, starting from the versatile chiron 7,3-lactone-xylofuranose (7,3-LXF) [6], the first non-biological synthesis of chiral 6-pentyl-2H-pyran-2-ones

Stimuli-responsive oligonucleotides in prodrug-based approaches for gene silencing

• Françoise Debart,
• Christelle Dupouy and
• Jean-Jacques Vasseur

Beilstein J. Org. Chem. 2018, 14, 436–469, doi:10.3762/bjoc.14.32

The selective electrochemical fluorination of S-alkyl benzothioate and its derivatives

• Shunsuke Kuribayashi,
• Tomoyuki Kurioka,
• Shinsuke Inagi,
• Ho-Jung Lu,
• Biing-Jiun Uang and
• Toshio Fuchigami

Beilstein J. Org. Chem. 2018, 14, 389–396, doi:10.3762/bjoc.14.27

• place to give the corresponding lactone derivatives in reasonable yields as shown in Scheme 4. Reaction mechanism In the cases of open-chain benzothioate derivatives, the anodic fluorination is initiated by an electron transfer occurring mainly from the sulfur atom of the benzothioates following two

Recent developments in the asymmetric Reformatsky-type reaction

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 325–344, doi:10.3762/bjoc.14.21

• linear epothilone precursor 37 [32]. As shown in Scheme 15, the macrocyclization of the latter into the corresponding enantiopure 16-membered highly functionalized chiral lactone 38 (>99% de) was achieved in moderate yield (36%) through a Reformatsky reaction mediated by CrCl2 in THF at room temperature

• (II)- or Yb(II)-mediated Reformatsky reaction of the corresponding aldehyde 40 [33]. Starting from a diastereomerically enriched aldehyde 40 (82% de), the reaction performed in THF at −40 °C in the presence of 3 equivalents of SmI2 or YbI2 provided the corresponding chiral lactone 39 as major

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

• Ranjana Aggarwal and
• Suresh Kumar

Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15

Nucleophilic fluoroalkylation/cyclization route to fluorinated phthalides

• Masanori Inaba,
• Tatsuya Sakai,
• Shun Shinada,
• Tsuyuka Sugiishi,
• Yuta Nishina,
• Norio Shibata and
• Hideki Amii

Beilstein J. Org. Chem. 2018, 14, 182–186, doi:10.3762/bjoc.14.12

• good yields. Keywords: cyclization; fluorine; lactone; phthalide; trifluoromethylation; Introduction Phthalides (1(3H)-isobenzofuranones) are frequently found in natural products and exhibit a range of bioactivity (Scheme 1) [1][2]. Substituted phthalides have been used as building blocks for the

Gram-scale preparation of negative-type liquid crystals with a CF₂CF₂-carbocycle unit via an improved short-step synthetic protocol

• Tatsuya Kumon,
• Shohei Hashishita,
• Takumi Kida,
• Shigeyuki Yamada,
• Takashi Ishihara and
• Tsutomu Konno

Beilstein J. Org. Chem. 2018, 14, 148–154, doi:10.3762/bjoc.14.10

• , generating the lactone Int-H. Accordingly, Int-H could undergo a second Grignard reaction with vinylmagnesium chloride present in the reaction mixture, resulting in the formation of Int-I. The latter intermediate, Int-I which is also in equilibrium with Int-J at reflux temperature, can react with the vinylic

Volatiles from the tropical ascomycete Daldinia clavata (Hypoxylaceae, Xylariales)

• Tao Wang,
• Kathrin I. Mohr,
• Marc Stadler and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2018, 14, 135–147, doi:10.3762/bjoc.14.9

• -pyrone 17 exhibited a moderate antifungal and weak antibacterial effect, while the lactone 9 was moderately cytotoxic, but devoid of significant antimicrobial activity. The chlorinated aromatic compound 14 only weakly inhibited the sensitive test organisms Chromobacterium violaceum and Mucor hiemalis