Rearrangements of organic peroxides and related processes

• Ivan A. Yaremenko,
• Vera A. Vil’,
• Dmitry V. Demchuk and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2016, 12, 1647–1748, doi:10.3762/bjoc.12.162

• both fragments of the polypropionate metabolite dolabriferol from a common precursor. The endoperoxide 304 was converted into ketone 305 with the help of the pseudo-enantiomeric quinine-derived catalyst (deMeQ-Ac) in toluene with moderate 47% yield. The peroxide 306 was transformed into ketone 307 with

Total synthesis of leopolic acid A, a natural 2,3-pyrrolidinedione with antimicrobial activity

• Atul A. Dhavan,
• Rahul D. Kaduskar,
• Loana Musso,
• Leonardo Scaglioni,
• Piera Anna Martino and
• Sabrina Dallavalle

Beilstein J. Org. Chem. 2016, 12, 1624–1628, doi:10.3762/bjoc.12.159

• Veterinary Medicine - Microbiology and Immunology, Università degli Studi di Milano, via Celoria 10, I-20133 Milano, Italy 10.3762/bjoc.12.159 Abstract The first total synthesis of leopolic acid A, a fungal metabolite with a rare 2,3-pyrrolidinedione nucleus linked to an ureido dipeptide, was designed and

• ]. Chemical analysis of a terrestrial-derived Streptomyces sp. isolated from the rhizosphere of the plant Juniperus excelsa yielded a new metabolite, leopolic acid A (1, Figure 1) [2]. Leopolic acid has unprecedented structural features consisting of an aliphatic side chain attached to a 2,3-pyrrolidinedione

Selective bromochlorination of a homoallylic alcohol for the total synthesis of (−)-anverene

• Frederick J. Seidl and
• Noah Z. Burns

Beilstein J. Org. Chem. 2016, 12, 1361–1365, doi:10.3762/bjoc.12.129

• regio- and enantioselectivity. Disclosed herein, this discovery has enabled the first total synthesis of (−)-anverene (1) (Scheme 1, bottom), a secondary metabolite from the algae Plocamium cartilagineum with selective antibiotic activity against vancomycin-resistant Enterococcus faecium (VREF) [10

Cyclisation mechanisms in the biosynthesis of ribosomally synthesised and post-translationally modified peptides

• Andrew W. Truman

Beilstein J. Org. Chem. 2016, 12, 1250–1268, doi:10.3762/bjoc.12.120

• for a number of characterised secondary metabolite pathways. For example, the bottromycin gene cluster encodes two stand-alone YcaO domain proteins that have been postulated to participate in heterocyclisation reactions [10][11][12][13]. Lanthionine bond formation in lanthipeptides Lanthipeptides

• that have been characterised for both RiPPs and for other secondary metabolite pathways, but it is interesting to note that there are a significant number of biochemical modifications that, thus far, appear to be unique to RiPP biosynthesis. For example, lanthionine formation, YcaO protein-catalysed

Marine-derived myxobacteria of the suborder Nannocystineae: An underexplored source of structurally intriguing and biologically active metabolites

• Antonio Dávila-Céspedes,
• Peter Hufendiek,
• Max Crüsemann,
• Till F. Schäberle and
• Gabriele M. König

Beilstein J. Org. Chem. 2016, 12, 969–984, doi:10.3762/bjoc.12.96

• that large genomes often correlate with the potential for prolific secondary metabolite production by revealing almost 8.6% of the genome to be possibly involved in the biosynthesis of secondary metabolites [36]. Mining this genome for the presence of PKS and NRPS genes exposed 18 biosynthetic clusters

• of compounds that have recently been shown to have antiproliferative effects on leukemic K-562 cells [27]. Halotolerant and halophilic marine myxobacteria are poorly investigated regarding secondary metabolite production. Therefore, the pool of secondary metabolites isolated from organisms of this

• osmolytes like betaine and ectoine were detected in the halotolerant bacterium. Taxonomy, cultivation and secondary metabolite chemistry of marine-derived myxobacteria (Nannocystineae) The following sections summarize features of three halotolerant and three marine-derived bacterial taxa clustered in the

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

• aglycone to be a sesquiterpene [33]. Based on previous reports, the signals of a CH group at δ 2.12/65.2 (C-10) and a quaternary carbon at δ 53.8 (C-6) observed in the NMR spectra of compound 1 suggested a trixane scaffold for this secondary metabolite [34]. C-10 and C-6 are respectively shared by two and

Antibiotics from predatory bacteria

• Juliane Korp,
• María S. Vela Gurovic and
• Markus Nett

Beilstein J. Org. Chem. 2016, 12, 594–607, doi:10.3762/bjoc.12.58

• presence of putative secondary metabolite gene clusters using the publicly available online tool antiSMASH 3.0 [51]. This analysis revealed that all strains possess extraordinary capacities for natural product assembly. Interestingly, however, the number of biosynthetic loci is not linearly correlated with

• the genome size. The largest number of secondary metabolite gene clusters was found in Corallococcus coralloides DSM 2259 and not in the two Sorangium cellulosum strains, although the latter feature significantly larger genomes (Table 1). When the number of detected loci is related to the genome size

• of biosynthesis gene clusters provide no information about the identity or biological role of the associated natural products, we note that predatory myxobacteria possess a higher density of secondary metabolite gene clusters in their genomes than their non-predatory relatives. But are these clusters

Biosynthesis of α-pyrones

• Till F. Schäberle

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

• temperature. Alternaria spp. had also been linked to a poultry disease outbreak called poultry hemorrhagic syndrome. However, the main toxic effects seem to be linked to other toxins produced, e.g., the non pyrone metabolite tenuazonic acid [20]. Nevertheless, alternariol (17) and altenuene (18) were studied

Studies on the synthesis of peptides containing dehydrovaline and dehydroisoleucine based on copper-mediated enamide formation

• Franziska Gille and
• Andreas Kirschning

Beilstein J. Org. Chem. 2016, 12, 564–570, doi:10.3762/bjoc.12.55

• of myxovalargin (1), a secondary metabolite from Myxococcus fulvus with antibacterial activity [14][15], we report on copper-mediated cross-coupling chemistry to create peptide fragments bearing dehydrovaline and dehydroisoleucine. We faced difficulties to use the reported conditions for the C–N

Natural products from microbes associated with insects

• Christine Beemelmanns,
• Huijuan Guo,
• Maja Rischer and
• Michael Poulsen

Beilstein J. Org. Chem. 2016, 12, 314–327, doi:10.3762/bjoc.12.34

• molecular analysis of the biosynthetic gene cluster of pederin (3) [49][50][51][52]. Beetle larvae hatching from pederin-containing eggs were less prone to predation by wolf spiders than pederin-free larvae, indicating the ecological significance of this secondary metabolite [53]. The biosynthetic gene

• moiety with a pyran ring. A follow-up study via genomic analysis and metabolomic profiles revealed that piperazic acid-containing cyclic depsipeptides are very common in this ecological niche of ant-associated bacteria. Fermentation and purification of metabolite extracts of three ant-associated

• typical for all other attine ant fungi. The fungus was found to produce several antifungal diketopiperazines (e.g., 33) [114]. In another study, also reported by Clardy and co-workers, the secondary metabolite profile of the symbiotic fungus Bionectria sp. associated with the fungus-growing ant

Synthesis of cyclic N¹-pentylinosine phosphate, a new structurally reduced cADPR analogue with calcium-mobilizing activity on PC12 cells

• Ahmed Mahal,
• Stefano D’Errico,
• Nicola Borbone,
• Brunella Pinto,
• Agnese Secondo,
• Valeria Costantino,
• Valentina Tedeschi,
• Giorgia Oliviero,
• Vincenzo Piccialli and
• Gennaro Piccialli

Beilstein J. Org. Chem. 2015, 11, 2689–2695, doi:10.3762/bjoc.11.289

• ]. Among these NNs there is the cyclic ADP-ribose (cADPR 1, Figure 1), a metabolite strictly involved in the homeostasis of cellular calcium ions. cADPR is a second messenger that activates the ryanodine receptors of the sarcoplasmic reticulum and mobilizes Ca2+ ions in many cell types of protozoa, plants

• [17]. Using the Aplysia ADP-ribosyl cyclase many metabolite analogues of cADPR have been produced starting from NAD+ and NADP+ [18][19][20][21]. However, the specificity of the enzymatic cyclization mechanism drastically limits its applicability for enzymatic or chemo-enzymatic procedures. For this

Inclusion complexes of 2-methoxyestradiol with dimethylated and permethylated β-cyclodextrins: models for cyclodextrin–steroid interaction

• Mino R. Caira,
• Susan A. Bourne,
• Halima Samsodien and
• Vincent J. Smith

Beilstein J. Org. Chem. 2015, 11, 2616–2630, doi:10.3762/bjoc.11.281

• endogenous metabolite of the most common estrogen hormone, 17β-estradiol, has been intensively studied owing to its proven potent antiangiogenic, antiproliferative and antitumoral activities [2][3]. However, its poor bioavailability has retarded its development as a drug [4][5]. Although recent reports of

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

• . Although the key 2,3-Wittig–Still rearrangement proceeded in low yield and further improvements are necessary, a promising route towards the synthesis of umbellacetal (114) and xenibellol (15) was thus established. Yao and co-workers have investigated a synthetic approach towards the soft coral metabolite

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

• of the metabolite did not prove to be suitable for broader applications, and therefore, after the discovery of the isotopes by Frederick Soddy, for which he was awarded the Nobel prize in 1921, the first labeling experiments using isotopes quickly changed the way of investigating metabolic pathways

Two strategies for the synthesis of the biologically important ATP analogue ApppI, at a multi-milligram scale

• Janne Weisell,
• Jouko Vepsäläinen and
• Petri A. Turhanen

Beilstein J. Org. Chem. 2015, 11, 2189–2193, doi:10.3762/bjoc.11.237

• -methylbut-3-enyl)triphosphoric acid diester] (1) are described. ApppI is an active metabolite of the mevalonate pathway and thus is of major biological significance. Chemically synthezised ApppI was purified by using triethylammonium bicarbonate as the counter ion in ion-pair chromatography and

• synthesize the very important metabolite ApppI (1) have been described and for the first time, the methods are described in detail. ApppI is a rather interesting compound which is known to exert several unique biological effects and it is possible that novel properties await discovery. Now we can produce

• ApppI at a multi-milligram scale which will be important in advancing research into this interesting metabolite. Experimental 1H, 31P and 13C NMR spectra were recorded on a 500 MHz spectrometer operating at 500.1, 202.5 and 125.8 MHz, respectively. Dimethyl phosphorochloridate (3) is commercially

The marine sponge Agelas citrina as a source of the new pyrrole–imidazole alkaloids citrinamines A–D and N-methylagelongine

• Christine Cychon,
• Ellen Lichte and
• Matthias Köck

Beilstein J. Org. Chem. 2015, 11, 2029–2037, doi:10.3762/bjoc.11.220

• alkaloids (PIAs), the citrinamines A–D (1–4) and the bromopyrrole alkaloid N-methylagelongine (5). All citrinamines are dimers of hymenidin (6) which was also isolated from this sponge as the major metabolite. Citrinamines A (1) and B (2) are derivatives of the PIA dimer mauritiamine (7), whereas

Synthesis, antimicrobial and cytotoxicity evaluation of new cholesterol congeners

• Mohamed Ramadan El Sayed Aly,
• Hosam Ali Saad and
• Shams Hashim Abdel-Hafez

Beilstein J. Org. Chem. 2015, 11, 1922–1932, doi:10.3762/bjoc.11.208

• II, were triggered to release bioactive coumarines by photolysis at 350 nm [14]. Dendrogenin A (DDA, III) is a natural metabolite in healthy mammals. It arises from conjugation of 5,6α-epoxycholesterol (5,6α-EC) with histamine. In vitro studies showed that DDA induced tumor cell re-differentiation

• ]. Chitinases are special enzymes involved in processing this valuable metabolite. Therefore, triazolocholesterol–glucopyranosylamine conjugates 16, 17 and 20 (Scheme 4) were prepared to compare the pharmacological effects of the modification of the D-glucopyranose moiety in VI (Figure 1) as glucosamine in

Pyridinoacridine alkaloids of marine origin: NMR and MS spectral data, synthesis, biosynthesis and biological activity

• Louis P. Sandjo,
• Victor Kuete and
• Maique W. Biavatti

Beilstein J. Org. Chem. 2015, 11, 1667–1699, doi:10.3762/bjoc.11.183

• to a substructure that could be considered complete with the aforementioned observation. Furthermore, the assignment of the 13C shifts of a new, isolated metabolite could be made by comparing with those compiled in Table 6, where the mass spectrometry data provides information on the elemental

• ]. Synthesis of ascididemin (42) The first synthesis of ascididemin was performed in 1992 by Moody et al. [64] and included four steps with an overall yield of 21%. Recently, the same secondary metabolite was prepared by six efficient steps which afforded a yield two-fold (45%) of that of the previous

• using phosphoryl bromide. Another organozinc substrate was coupled to the obtained intermediate by a Negishi cross-coupling and cyclisation occurred to give the expected secondary metabolite (Scheme 8) [68]. The yield of the last step in the preparation of 9 could be improved by using the synthetic

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

• , R1 = cyclopropyl, R2 = piperazinyl) [44]. An important early industry-based example was disclosed by scientists at Bristol-Myers Squibb in 2008 detailing a flow approach towards converting the psychotropic agent buspirone (7) into its major active metabolite, 6-hydroxybuspirone (9) [45]. This work

(2R,1'S,2'R)- and (2S,1'S,2'R)-3-[2-Mono(di,tri)fluoromethylcyclopropyl]alanines and their incorporation into hormaomycin analogues

• Armin de Meijere,
• Sergei I. Kozhushkov,
• Dmitrii S. Yufit,
• Christian Grosse,
• Marcel Kaiser and
• Vitaly A. Raev

Beilstein J. Org. Chem. 2014, 10, 2844–2857, doi:10.3762/bjoc.10.302

• (fluoromethylcyclopropyl)alanine moieties have been synthesized and subjected to preliminary tests of their antibiotic activity. Keywords: amino acids; biosynthesis; building blocks; cyclopropanes; natural products; synthetic methods; Introduction The intermolecular signal metabolite hormaomycin (1, Figure 1) was first

• provided close to 20 hormaomycin analogues that have contributed to an understanding of the biosynthetic pathways, the conformational behavior in solution and the structure–activity relationship. After the initial observation that hormaomycin (1) has a marked influence on the secondary metabolite

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

• liquid fermentation broth of Aspergillus sp. YXf3 and isolated a novel norditerpenoid, namely, aspergiloid I (1) (Figure 1). Herein, we report the production, isolation, structure characterization, and biological activity of 1, a rare spirolactone metabolite with a novel carbon skeleton. Results and

A small azide-modified thiazole-based reporter molecule for fluorescence and mass spectrometric detection

• Stefanie Wolfram,
• Hendryk Würfel,
• Stefanie H. Habenicht,
• Christine Lembke,
• Phillipp Richter,
• Eckhard Birckner,
• Rainer Beckert and
• Georg Pohnert

Beilstein J. Org. Chem. 2014, 10, 2470–2479, doi:10.3762/bjoc.10.258

• ,4E)-deca-2,4-dien-9-ynal (DDY, 10) served as reactive group. DDY (10) mimics the natural product 2,4-decadienal that is produced by some diatoms as potential chemical defense metabolite against their grazers [34]. Structure-activity tests have revealed that 2,4-decadienal can be modified in the alkyl

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

• sesterterpene metabolite isolated from the marine sponge Cacospongia scalaris, has been achieved, mainly featuring Johnson–Claisen rearrangement, asymmetric Mukaiyama aldol reaction and MNBA-mediated lactonization. Keywords: aldol reaction; astakolactin; lactonization; MNBA; terpenoids; Introduction

• Astakolactin (1) is a novel sesterterpene metabolite [1][2][3][4][5] first reported in 2003 by Roussis et al [6]. It was isolated from the marine sponge Cacospongia scalaris, which was collected from the gulf of Astakos in the Ionian Sea near Greece. The structure proposed for compound 1 is a bicyclic linear

A new approach for the synthesis of bisindoles through AgOTf as catalyst

• Jorge Beltrá,
• M. Concepción Gimeno and
• Raquel P. Herrera

Beilstein J. Org. Chem. 2014, 10, 2206–2214, doi:10.3762/bjoc.10.228

• the synthesis of the interesting compound vibrindole A (Scheme 2), an isolated metabolite of the marine bacteria Vibrio parahaemolyticus, which is active against Bacillus subtilis, Staphylococcus aureus and Staphylococcus albus as has been previously demonstrated [43]. In order to prevent the loss of

Sacrolide A, a new antimicrobial and cytotoxic oxylipin macrolide from the edible cyanobacterium Aphanothece sacrum

• Naoya Oku,
• Miyako Matsumoto,
• Kohsuke Yonejima,
• Keijiroh Tansei and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2014, 10, 1808–1816, doi:10.3762/bjoc.10.190

• alga was achieved in a fast, simple, and inexpensive manner, which offers a useful option when consumers wish to enjoy the crispy texture of fresh alga, but feel uneasy about the possibility of food intoxication. Conclusion We explored a bioactive secondary metabolite from the very rare but edible