Pathoblockers or antivirulence drugs as a new option for the treatment of bacterial infections

• Matthew B. Calvert,
• Varsha R. Jumde and
• Alexander Titz

Beilstein J. Org. Chem. 2018, 14, 2607–2617, doi:10.3762/bjoc.14.239

• signal molecules and mimic their structures. The PQS system of P. aeruginosa is particularly attractive and can be considered as a pathogen specific target. The biosynthesis of the PQS signal 23 involves a set of biosynthetic enzymes PqsABCDEH and its autocatalytic receptor PqsR (MvfR). Biaryl methanols

Synthesis of eunicellane-type bicycles embedding a 1,3-cyclohexadiene moiety

• Alex Frichert,
• Peter G. Jones and
• Thomas Lindel

Beilstein J. Org. Chem. 2018, 14, 2461–2467, doi:10.3762/bjoc.14.222

• if there are examples, where this was not the case [21][22]. Access to partially unsaturated eunicellane systems could also be of interest for studies on biosynthesis and chemical interconversion [7][10]. Results and Discussion Dihydrocarvone 9 was converted to the enolate and quenched with ethyl

The enzymes of microbial nicotine metabolism

• Paul F. Fitzpatrick

Beilstein J. Org. Chem. 2018, 14, 2295–2307, doi:10.3762/bjoc.14.204

• involved in uptake of molybdenum and biosynthesis of the molybdopterin cofactor [11]. The mechanism of Scheme 2 can be written for nicotine dehydrogenase by analogy to the mechanism of xanthine oxidoreductase [8]. Here, the oxygen that is incorporated into the product initially comes from water, and the

Synthesis of 1,4-imino-L-lyxitols modified at C-5 and their evaluation as inhibitors of GH38 α-mannosidases

• Maroš Bella,
• Sergej Šesták,
• Ján Moncoľ,
• Miroslav Koóš and
• Monika Poláková

Beilstein J. Org. Chem. 2018, 14, 2156–2162, doi:10.3762/bjoc.14.189

• swainsonine, interferes with the glycosylation pathway where it specifically inhibits GH38 glycoside hydrolases [23][24]. Up to date, swainsonine is the most potent Golgi mannosidase II (GMII) inhibitor. It is known that inhibition of the biosynthesis of complex N-glycans in the Golgi apparatus influences

β-Hydroxy sulfides and their syntheses

• Mokgethwa B. Marakalala,
• Edwin M. Mmutlane and
• Henok H. Kinfe

Beilstein J. Org. Chem. 2018, 14, 1668–1692, doi:10.3762/bjoc.14.143

• fascinating biosynthesis of sulfur-containing secondary metabolites can be found in a recent review by Hertweck and co-workers [9]. 2. β-Hydroxy sulfides β-Hydroxy sulfides, often in disguised form, comprise a significant segment of sulfur-containing natural products, with a few examples shown in Figure 2

• notable synthesis of leukotriene C-1 (119), Corey and co-workers synthesized (−)-methyl trans-5(S),6(S)-oxido-7,9-trans-11,14-cis-eicosatetraenoate leukotriene A methyl ester (120), the key intermediate in its synthesis and biosynthesis, starting from the 2,3,5-tribenzoyl derivative of D-(−)-ribose [82

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

• cell viability, their biological synthesis, including the synthesis of their monomer units, e.g., nucleotides, is highly regulated. Damage to these vital molecules often results in congenital disease with ultimately fatal consequences [2][3]. Accordingly, the study of polymers and their biosynthesis is

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

• on its biosynthesis and comparison of the homology of the respective gene clusters appear interesting in order to address the hypothesis that a horizontal gene transfer of the biosynthesis gene cluster between an actinobacterium and a myxobacterium may have occurred. Experimental General experimental

Design and biological characterization of novel cell-penetrating peptides preferentially targeting cell nuclei and subnuclear regions

• Anja Gronewold,
• Mareike Horn and
• Ines Neundorf

Beilstein J. Org. Chem. 2018, 14, 1378–1388, doi:10.3762/bjoc.14.116

• . Therefore, HeLa and MCF-7 cells were exposed to the chemotherapeutic drug doxorubicin (DOX) that is already clinically applied in cancer therapy [37]. Doxorubicin interacts with DNA by intercalation and thereby inhibits the macromolecular biosynthesis [38]. Instead of covalent conjugation of the drug, we

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

• Phaeobacter inhibens strains, revealing strain-specific mixtures. Although large differences were present between the species, the fatty acid profiles, the pool for the acyl precursors for AHL biosynthesis, were very similar. To test the acyl-chain selectivity, the three enzymes LuxI1 and LuxI2 from D. shibae

• . gallaeciensis BS107 produced eight different AHLs [8]. The biosynthesis of AHLs is mediated by the enzyme LuxI or its homologs, and often accompanied by a regulator protein, LuxR [18][19]. An ACP-bound fatty acid acyl group 1 is transferred onto the amino group of S-adenosylmethionine (SAM, 2) that is followed

• [28], probably involved in the biosynthesis of the long chain AHLs. Here we report on the characterization of PgaI2 from P. inhibens and of LuxI1 and LuxI2 from D. shibae by in vitro incubation experiments. Results and Discussion The AHL production of four Roseobacter group strains was analyzed by a

Oligonucleotide analogues with cationic backbone linkages

• Melissa Meng and
• Christian Ducho

Beilstein J. Org. Chem. 2018, 14, 1293–1308, doi:10.3762/bjoc.14.111

• and binds to double-stranded DNA to form a triple helix. The triple helix is not a substrate for the transcription machinery, and hence, RNA biosynthesis (and therefore protein formation) is blocked. In the antisense pathway [3], the ON binds to single-stranded mRNA in the cytoplasm, thus furnishing a

• duplex structure (usually a DNA–RNA heteroduplex) which cannot undergo ribosomal protein biosynthesis. Alternatively, the DNA–RNA heteroduplex can be a substrate for RNAse H-mediated degradation of the mRNA strand. This way, catalytic amounts of the ON can mediate the efficient cleavage of mRNA encoding

The first Pd-catalyzed Buchwald–Hartwig aminations at C-2 or C-4 in the estrone series

• Ildikó Bacsa,
• Dávid Szemerédi,
• János Wölfling,
• Gyula Schneider,
• Lilla Fekete and
• Erzsébet Mernyák

Beilstein J. Org. Chem. 2018, 14, 998–1003, doi:10.3762/bjoc.14.85

• -aminated estrone derivatives are described as inhibitors of estrogen biosynthesis. They are often synthesized via a three-step method including nitration, reduction, and functionalization of the amino group [1][2]. This three-step protocol may be simplified to involve only one or two steps by the

On the design principles of peptide–drug conjugates for targeted drug delivery to the malignant tumor site

• Eirinaios I. Vrettos,
• Gábor Mező and
• Andreas G. Tzakos

Beilstein J. Org. Chem. 2018, 14, 930–954, doi:10.3762/bjoc.14.80

• sugar moiety. The difference between Dau and Dox is a hydroxy group substituted at the C-14 carbon atom on Dox providing an extra conjugation site for ester linkage (Figure 6). The mechanism of action of anthracyclines is based on their intercalation to DNA inhibiting the macromolecular biosynthesis

Volatiles from three genome sequenced fungi from the genus Aspergillus

• Jeroen S. Dickschat,
• Ersin Celik and
• Nelson L. Brock

Beilstein J. Org. Chem. 2018, 14, 900–910, doi:10.3762/bjoc.14.77

• terpenes, including traces of the widespread monoterpenes limonene (3) and linalool (4). The C12 compounds (8S*,9R*,10S*)-8,10-dimethyl-1-octalin (5) and (8S*,10R*)-8,10-dimethyl-1(9)-octalin (6) are intermediates of the biosynthesis of the earthy odorant geosmin that is itself a degraded sesquiterpene [29

• ][30], but geosmin could not be observed as a volatile of A. fischeri. The bacterial geosmin synthase is a class I terpene synthase (TS) with two domains [31] that occurs in many actinomycetes, cyanobacteria and myxobacteria, but fungal geosmin biosynthesis must require a different enzyme, because no

• homolog of the geosmin synthase is encoded in the genome of A. fischeri or of any other fungus. Furthermore, the diterpene pimara-8(14),15-diene (7) was one of the main compounds in the bouquet of A. fischeri. The biosynthesis of this compound is a two-step process that requires cyclisation of

Crystal structure of the inclusion complex of cholesterol in β-cyclodextrin and molecular dynamics studies

• Elias Christoforides,
• Andreas Papaioannou and
• Kostas Bethanis

Beilstein J. Org. Chem. 2018, 14, 838–848, doi:10.3762/bjoc.14.69

• significant role in biology as an essential structural component of the cell walls and as precursor for the biosynthesis of several substances such as vitamin D, bile acids and steroid hormones. However, the consumption of food rich in cholesterol like meat, eggs and dairy products has been associated with

Volatiles from the xylarialean fungus Hypoxylon invadens

• Jeroen S. Dickschat,
• Tao Wang and
• Marc Stadler

Beilstein J. Org. Chem. 2018, 14, 734–746, doi:10.3762/bjoc.14.62

• index and best matching mass spectrum (Table 5). Notably, a common biosynthesis for all the identified aromatic compounds can be assumed that further strengthens their structure elucidations (Scheme 1). Starting from 11, an oxidation step at the 2-methyl group (red) could lead via the benzyl alcohol

• reported from the fungi Nodulisporium sp. [18][28], Sporothrix sp. [31], and Leptographium wageneri [32]. The compound comprises the bis-methylation product of 1,8-dihydroxynaphthalene, an important precursor of melanin-type pigments in fungi [33], while 20 has been reported to inhibit melanin biosynthesis

Latest development in the synthesis of ursodeoxycholic acid (UDCA): a critical review

• Fabio Tonin and
• Isabel W. C. E. Arends

Beilstein J. Org. Chem. 2018, 14, 470–483, doi:10.3762/bjoc.14.33

• biosynthesis takes place in the liver starting from cholesterol: 17 enzymes are involved in the production of these molecules. The final products are the so-called primary bile acids: CDCA and CA [23]. Subsequently, these bile acids can be modified by intestinal bacteria to form the secondary bile acids as

Recent developments in the asymmetric Reformatsky-type reaction

• Hélène Pellissier

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

• undergo a Si attack through transition state A. A related methodology was also applied by Jiménez and Rodriguez to develop the first total synthesis of prepiscibactin, which is an intermediate in the biosynthesis of piscibactin [22]. Indeed, the sequence was based on the diastereoselective SmI2-mediated

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

• Nodulisporium spp. (shown in the box in Scheme 7) [28][39] that may be formed by a similar PKS. Further investigations are required to identify the PKSs for this family of metabolites and to confirm the hypothetical biosynthesis as shown in Scheme 7. The volatile 9, a compound emitted in small amounts by D

• 47436. Synthesis of manicone (10). Synthesis of a racemic mixture of all four diastereomers of 11. Enantioselective synthesis of (4R,5S,6S)-11c and (4S,5R,6S)-11d. Epimerisations of (4R,5S,6S)-11c and (4S,5R,6S)-11d under basic conditions. Proposed biosynthesis for (4R,5R,6S)-11a. Synthesis of 6-methyl

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

Beilstein J. Org. Chem. 2018, 14, 25–53, doi:10.3762/bjoc.14.3

• micro-heterogeneous structure distinguished by three regions: the lipid A [5], the core oligosaccharide [6] and the O-antigen [7] (Figure 1B). The TLR4·MD-2 receptor complex senses picomolar amounts of LPS and initiates the biosynthesis of diverse mediators of inflammation (such as tumor necrosis factor

• esterified with a peculiar long chain fatty acid, 27-hydroxyoctacosanoate, which is not found in enteric Gram-negative bacteria [112]. The biosynthesis of lipid A in R. leguminosarum proceeds under the action of the same enzymes as in E. coli to generate the conserved phosphate containing precursor, Kdo2

Herpetopanone, a diterpene from Herpetosiphon aurantiacus discovered by isotope labeling

• Xinli Pan,
• Nicole Domin,
• Sebastian Schieferdecker,
• Hirokazu Kage,
• Martin Roth and
• Markus Nett

Beilstein J. Org. Chem. 2017, 13, 2458–2465, doi:10.3762/bjoc.13.242

• Biology, Hans Knöll Institute, Beutenbergstr. 11a, 07745 Jena, Germany 10.3762/bjoc.13.242 Abstract The genome of the predatory bacterium Herpetosiphon aurantiacus 114-95T harbors a number of biosynthesis genes, including four terpene cyclase genes. To identify the terpenes biosynthesized from H

• labeling pattern in IPP and DMAPP (Figure 1) [8]. This feature has proven extremely useful to unravel complex cyclization cascades and carbon–carbon rearrangements in the biosynthesis of some terpenoids [9][10][11][12]. We anticipated that the resulting mass shifts could also be valuable in the field of

• increased production of carotenoids and it was hence speculated that VNY medium might also support the biosynthesis of other terpenoids. The cultivation was conducted for 7 days in the presence of [1-13C]-labeled D-glucose. Cultures supplemented with non-labeled D-glucose served as a control. Extracts from

Hydrolysis, polarity, and conformational impact of C-terminal partially fluorinated ethyl esters in peptide models

• Vladimir Kubyshkin and
• Nediljko Budisa

Beilstein J. Org. Chem. 2017, 13, 2442–2457, doi:10.3762/bjoc.13.241

• experiments are remarkably sensitive [4]. Fluorine-containing groups can be incorporated into biopolymers by various approaches, including those that utilize biosynthesis [5][6][7], enzymatic conversion [8], chemical synthesis [9][10], and ligation reactions [11]. Depending on the research target, 19F NMR

Sulfation and amidinohydrolysis in the biosynthesis of giant linear polyenes

• Hui Hong,
• Markiyan Samborskyy,
• Katsiaryna Usachova,
• Katharina Schnatz and
• Peter F. Leadlay

Beilstein J. Org. Chem. 2017, 13, 2408–2415, doi:10.3762/bjoc.13.238

• as donor, efficiently converted mediomycin B to mediomycin A in vitro. Thus, in the final steps of mediomycin A biosynthesis deamidination and sulfotransfer can take place in either order. Keywords: amidinohydrolase; clethramycin; mediomycin; polyketide synthase; sulfotransferase; Introduction

• Streptomyces neyagawaensis (Scheme 1), is a potent inhibitor of the fibrinogen receptor, which suggests an even wider potential utility for such compounds [8][9]. We have previously shown that in the biosynthesis of giant macrocyclic antifungal polyketides (so-called marginolactones) compounds bearing a

• terminal amino moiety are formed by specific final-stage deamidination of a precursor bearing a guanidino substituent at this position [10]. The aim of the present study was to test whether the same "protective group" strategy is operating in the biosynthesis of the giant linear mediomycins. If true, then

Synthesis of ergostane-type brassinosteroids with modifications in ring A

• Vladimir N. Zhabinskii,
• Darya A. Osiyuk,
• Yuri V. Ermolovich,
• Natalia M. Chaschina,
• Tatsiana S. Dalidovich,
• Miroslav Strnad and
• Vladimir A. Khripach

Beilstein J. Org. Chem. 2017, 13, 2326–2331, doi:10.3762/bjoc.13.229

• naturally occurring BS (e.g., epibrassinolide [8]) have found practical application in agriculture and thus are commercially available and a cheap source for further chemical modifications. As a part of our programme aimed at the study of BS biosynthesis, we focussed in the present investigation on the

Phosphonic acid: preparation and applications

• Charlotte M. Sevrain,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2017, 13, 2186–2213, doi:10.3762/bjoc.13.219

• simultaneously to the formation of phosphonic acid (section 6) or the oxidation of phosphinic acid (section 7). The last section (section 8) includes additional miscellaneous methods to prepare phosphonic acids. Of note, the biosynthesis of phosphonic acid, which is a dynamic field of research aiming to discover

• biosynthesis involves, as one of the key steps, the isomerization of phosphoenolpyruvate to phosphonopyruvate which is catalyzed by phosphopyruvate mutase [34]. Recent studies indicate that up to 25% of the phosphorus available in the ocean would consist of phosphorus species featuring one P–C bond [35

• applications in biology and medicine to mimic the phosphate group leading to antiretroviral drugs (e.g., tenofovir (1)) [39], isoprenoid biosynthesis inhibitors [40][41], antibiotics (e.g., fosfomycin (2)) [42], tyrosine phosphatase inhibitors 3 [43], antimalarial 4 [44], antihypertensive drugs (e.g., K4 5 and

Enzymatic synthesis of glycosides: from natural O- and N-glycosides to rare C- and S-glycosides

• Jihen Ati,
• Pierre Lafite and
• Richard Daniellou

Beilstein J. Org. Chem. 2017, 13, 1857–1865, doi:10.3762/bjoc.13.180

• acceptor. UGT74B1, involved in glucosinolate biosynthesis (see supra), was one of these 17 enzymes. Other studies have identified S-GT activities when assaying the catalytic promiscuity of O-GT with a wide range of aglycone acceptors (Figure 3). OleD from Streptomyces antibioticus has been the first

• Salmonella enterica and Escherichia coli [44][45][46] that are involved in the biosynthesis of siderophores, that were shown to be C-glycosylated enterobactins. In addition to these naturally occurring C-GTs, engineering of O-GT to C-GT were successfully performed in several studies [37][47][48], and

• -catalysed glycosylation. Desulfoglucosinolate biosynthesis by UGT74B1. Examples of thiol-containing acceptors used in the chemo-enzymatic biosynthesis of S-glycosides catalysed by S-GT. Examples of C-glycosylated products biosynthesized by natural C-GT. Compounds showed are formed by the action of C-GT