Sustainable synthesis of 3-substituted phthalides via a catalytic one-pot cascade strategy from 2-formylbenzoic acid with β-keto acids in glycerol

• Lina Jia and
• Fuzhong Han

Beilstein J. Org. Chem. 2017, 13, 1425–1429, doi:10.3762/bjoc.13.139

• [3][4][5], exhibit a broad spectrum of pharmacological activity, such as antibacterial, anti-HIV, antifungal, antibiotic, antitumor and immunosuppressive effects [6][7][8][9][10]. In addition, the one-pot cascade transformation has proven to be the key step in organic syntheses because of its broad

Synthesis of the heterocyclic core of the D-series GE2270

• Christophe Berini,
• Thibaut Martin,
• Pierrik Lassalas,
• Francis Marsais,
• Christine Baudequin and
• Christophe Hoarau

Beilstein J. Org. Chem. 2017, 13, 1407–1412, doi:10.3762/bjoc.13.137

• as readily available starting material. Keywords: antibiotic; bromination; BSC; C–H arylation; cross-coupling; Hantzsch synthesis; thiopeptide; Introduction Thiopeptide antibiotics are a class of peptide-derived macrocycles which contain many thiazole and thiazoline units, with almost 90 structures

• heterocyclic core of the D-series thiopeptide antibiotic GE2270 was prepared. The synthetic strategy that combines direct C–H arylation, Borylation Suzuki–Miyaura cross-coupling (BSC) and Hantzsch thiazole synthesis methods proved to be highly effective regarding the fair 22% yield over 7 synthetic steps from

Total synthesis of elansolids B1 and B2

• Liang-Liang Wang and
• Andreas Kirschning

Beilstein J. Org. Chem. 2017, 13, 1280–1287, doi:10.3762/bjoc.13.124

• bacterium Chitinophaga sancti. They show antibacterial activity against Gram-positive bacteria. A second generation total synthesis of the antibiotic elansolid B1 (2) and the first synthesis of elansolid B2 (3) are reported. In contrast to previous work, the (Z,E,Z)-triene at C10–C15 was assembled by using

• Flexibacter spec.) (Figure 1) [1][2]. Elansolid A2 (1*), an atropisomer of elansolid A1 (1), showed antibiotic activity against Gram-positive bacteria in the range of 0.2 to 64 µg/mL and cytotoxicity against L929 mouse fibroblast cells with an IC50 value of 12 µg/mL. Besides these two macrocylic members also

• data determined for both synthetic products were identical with those of authentic samples of elansolid B1 (2) and elansolid B2 (3) (copies of spectra, see Supporting Information File 1). Conclusion In conclusion, we describe an improved second generation synthesis of the highly active antibiotic

Glyco-gold nanoparticles: synthesis and applications

• Federica Compostella,
• Olimpia Pitirollo,
• Alessandro Silvestri and
• Laura Polito

Beilstein J. Org. Chem. 2017, 13, 1008–1021, doi:10.3762/bjoc.13.100

• -antibiotic conjugates, were prepared and resulted able to overcome antibiotic resistance of microbial biofilms, since CA NPs render streptomycin more accessible to biofilms, thereby more available to interact with biofilm bacteria [89]. Similarly, a novel recyclable E.coli-specific killing GAuNP

First total synthesis of kipukasin A

• Chuang Li,
• Haixin Ding,
• Zhizhong Ruan,
• Yirong Zhou and
• Qiang Xiao

Beilstein J. Org. Chem. 2017, 13, 855–862, doi:10.3762/bjoc.13.86

• ) and AZT, etc. [5][6]. Nucleosides and their analogues will continue to play an important role in future drug discovery [7]. In the past decades, exploration of novel naturally occurring marine nucleosides has made expeditious achievements [8][9][10]. Some of them showed promising antibiotic, antiviral

Opportunities and challenges for the sustainable production of structurally complex diterpenoids in recombinant microbial systems

• Katarina Kemper,
• Max Hirte,
• Markus Reinbold,
• Monika Fuchs and
• Thomas Brück

Beilstein J. Org. Chem. 2017, 13, 845–854, doi:10.3762/bjoc.13.85

• ), artemisinin [2] (antimalarial agent) and α-pinene [3] (antibiotic, anti-inflammatory). Apart from bioactive compounds with applications as drugs/pharmaceuticals [4] or in the nutrition or agricultural sector, isoprenoids of minor structural complexity are used as bulk chemicals or fuel additives [5][6]. To

N-Propargylamines: versatile building blocks in the construction of thiazole cores

• S. Arshadi,
• E. Vessally,
• L. Edjlali,
• R. Hosseinzadeh-Khanmiri and
• E. Ghorbani-Kalhor

Beilstein J. Org. Chem. 2017, 13, 625–638, doi:10.3762/bjoc.13.61

• ], antimicrobial [57][58][59], and specially antibiotic [60][61][62][63][64] agents. Despite their great relevance in drug design, only very few synthetic methods towards these compounds have been reported to date [44]. N-Propargylamines are one of the most specific class of alkynes having diverse reaction

Posttranslational isoprenylation of tryptophan in bacteria

• Masahiro Okada,
• Tomotoshi Sugita and
• Ikuro Abe

Beilstein J. Org. Chem. 2017, 13, 338–346, doi:10.3762/bjoc.13.37

• at a high population cell density in B. subtilis [19][20]. In addition, the ComX pheromone promotes the production of surfactin A, a cyclic lipopeptide with antibiotic and biological surfactant activities (Figure 2A) [21][22]. Furthermore, the ComXnatto pheromone from B. subtilis subsp. natto

Synthesis of acylhydrazino-peptomers, a new class of peptidomimetics, by consecutive Ugi and hydrazino-Ugi reactions

• Angélica de Fátima S. Barreto,
• Veronica Alves dos Santos and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2016, 12, 2865–2872, doi:10.3762/bjoc.12.285

• -hydrazino acid moiety, e.g., the vitamin B6 antagonist linatine and the antibiotic negamycin (Figure 3). In the early 1970s, the first attempts to peptide modifications by hydrazino acids generated bioactive pseudopeptides [39]. Analogously to azapeptides, these compounds possess a conformational constraint

Biochemical and structural characterisation of the second oxidative crosslinking step during the biosynthesis of the glycopeptide antibiotic A47934

• Veronika Ulrich,
• Clara Brieke and
• Max J. Cryle

Beilstein J. Org. Chem. 2016, 12, 2849–2864, doi:10.3762/bjoc.12.284

• homologues can display significantly different catalytic propensities despite their overall similarities. Keywords: crystal structure; cytochrome P450; glycopeptide antibiotic; peptide; phenolic coupling; Introduction The glycopeptide antibiotics (GPAs) are a series of highly modified heptapeptide natural

Enduracididine, a rare amino acid component of peptide antibiotics: Natural products and synthesis

• Darcy J. Atkinson,
• Briar J. Naysmith,
• Daniel P. Furkert and
• Margaret A. Brimble

Beilstein J. Org. Chem. 2016, 12, 2325–2342, doi:10.3762/bjoc.12.226

• 10.3762/bjoc.12.226 Abstract Rising resistance to current clinical antibacterial agents is an imminent threat to global public health and highlights the demand for new lead compounds for drug discovery. One such potential lead compound, the peptide antibiotic teixobactin, was recently isolated from an

• promising antibiotic activity. This review highlights the presence of enduracididine in natural products, its biosynthesis together with a review of analogues of enduracididine. Reported synthetic approaches to the cyclic guanidine structure of enduracididine are discussed, illustrating the challenges

• fungicidicus [18]. Enduracidin A (7) and B (8) are depsipeptides with the same composition of seventeen amino acids, sixteen of which make up the cyclic core [11][13][19] and are structurally related to the non-enduracididine containing antibiotic, ramoplanin [19]. The enduracidins are active against Gram

The direct oxidative diene cyclization and related reactions in natural product synthesis

• Juliane Adrian,
• Leona J. Gross and
• Christian B. W. Stark

Beilstein J. Org. Chem. 2016, 12, 2104–2123, doi:10.3762/bjoc.12.200

• coupling [53][54]. The oxidative cyclization diastereoselectively led to the THF diol 13 in 88% yield from which neodysiherbaine A (14) was obtained in a further three steps. Ionomycin Ionomycin (19), an ionophore antibiotic isolated from Streptomyces conglobatus in 1978 [55][56][57], has a high affinity

• monensin A, another well-known ionophore antibiotic, applying an oxidative cyclization approach using potassium permanganate [64]. Amphidinolide F Amphidinolide F (24) is a marine natural product isolated from the dinoflagellate Amphidinium sp. in 1991 [65]. The macrocyclic core of these highly cytotoxic

Synthesis of the C8’-epimeric thymine pyranosyl amino acid core of amipurimycin

• Pramod R. Markad,
• Navanath Kumbhar and
• Dilip D. Dhavale

Beilstein J. Org. Chem. 2016, 12, 1765–1771, doi:10.3762/bjoc.12.165

• this regard are in progress. Antifungal antibiotic amipurimycin (1). Conformational analysis of 13 and 14. Geometrically optimized conformation of 12 and 13 respectively by DFT study. Retrosynthesis of 2. Synthesis of 1,3-anhydrosugar 12 and 13. Formation of 2,7-dioxabicyclo[3.2.1]octane 12/13

TMSBr-mediated solvent- and work-up-free synthesis of α-2-deoxyglycosides from glycals

• Mei-Yuan Hsu,
• Yi-Pei Liu,
• Sarah Lam,
• Su-Ching Lin and
• Cheng-Chung Wang

Beilstein J. Org. Chem. 2016, 12, 1758–1764, doi:10.3762/bjoc.12.164

• ); Introduction Deoxyglycosides are essential moieties of numerous bioactive natural products, and are prevalent subunits in antitumor and antibiotic agents [1][2][3]. Furthermore, 2-deoxy- and 2,6-dideoxyglycosides are crucial components for the pharmacology and bioactivity of many biologically active compounds

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

• rearrangement plays an important role not only in fine organic synthesis but also in biological processes. Scheme 63 shows the proposed mechanism for the biosynthetic conversion of 217 to 218, which is an important component of the structural skeleton of the antitumor–antibiotic CC-1065 [333]. The synthetic

Organic chemistry meets polymers, nanoscience, therapeutics and diagnostics

• Vincent M. Rotello

Beilstein J. Org. Chem. 2016, 12, 1638–1646, doi:10.3762/bjoc.12.161

• above ramble that predicting where I am going next is an incredibly challenging question for me. We have a number of areas we are currently exploring, including the creation of nanoparticle-based antimicrobials [88][89] building on our studies showing that nanoparticles are effective against antibiotic

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

• suggests that they could be considered as promising candidates for future developments. Keywords: antimicrobial; heterocyclic compounds; natural products; pyrrolidinedione; total synthesis; Introduction Great concern has recently been expressed about the diminishing efficacy of current antibiotic

• derivative [16][17][22][23]. The oxazolidinone ring is rare among natural products, but there are successful examples in medicinal chemistry of drugs containing this skeleton, such as the antibiotic linezolid [24]. As the core structure of compound 14 represents a new scaffold, never isolated or synthesized

Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides

• Franziska Hemmerling and
• Frank Hahn

Beilstein J. Org. Chem. 2016, 12, 1512–1550, doi:10.3762/bjoc.12.148

• clinically important antibiotic against Gram-positive bacteria, which consists of a mixture of pseudomonic acids from Pseudomonas fluorescens NCIMB 10586 with pseudomonic acid A (61) being the main compound (Scheme 9) [37][38][39][40][41][42][43][44]. It belongs to the group of trans-AT-PKS products and the

• strains. Pamamycins. Recently, the gene cluster of the macrodiolide antibiotic group of the pamamycins 73 was sequenced and the function of some of the genes studied (Figure 2) [60]. This cluster contains a NonS homolog, PamS, that was proposed to catalyse all three oxa-Michael additions that lead to

Discovery of an inhibitor of the production of the Pseudomonas aeruginosa virulence factor pyocyanin in wild-type cells

• Bernardas Morkunas,
• Balint Gal,
• Warren R. J. D. Galloway,
• James T. Hodgkinson,
• Brett M. Ibbeson,
• Yaw Sing Tan,
• Martin Welch and
• David R. Spring

Beilstein J. Org. Chem. 2016, 12, 1428–1433, doi:10.3762/bjoc.12.137

• antibiotic-resistant biofilms [7][8][9]. The incidence of multidrug-resistant P. aeruginosa infections is on the rise on a global scale [8][9][10] and this bacterium is now considered to have joined the ranks of the ‘superbugs’ [1]. Thus, there is an urgent need to discover new therapeutic strategies to

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

• only been described bioinformatically [123]. Subtilosin is a Bacillus RiPP antibiotic that belongs to the sactipeptide family of natural products that are defined by the presence of one or more sulphur to α-carbon bonds [125]. Three thioethers in subtilosin are formed by a single SPASM protein, AlbA

• understood, such as enterocin AS-48 [137][138] (also known as bacteriocin 21 [139]). AS-48 is a 70-residue cyclic antibiotic produced by Enterococcus faecalis and was recently shown to enhance the ability of the strain to colonise the mammalian gastrointestinal tract by outcompeting bacteria that are

Antibacterial structure–activity relationship studies of several tricyclic sulfur-containing flavonoids

• Lucian G. Bahrin,
• Henning Hopf,
• Peter G. Jones,
• Laura G. Sarbu,
• Cornelia Babii,
• Alina C. Mihai,
• Marius Stefan and
• Lucian M. Birsa

Beilstein J. Org. Chem. 2016, 12, 1065–1071, doi:10.3762/bjoc.12.100

• of one of the greatest problems faced by modern medicine: multidrug-resistant bacteria. Resistance may arise via various mechanisms including changes in cell-wall permeability, target site mutation, antibiotic inactivation and the development of efflux pumps that transport the drugs out of the cell

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

• metabolites and for the biosynthesis of antimicrobials [59]. In these studies, PKS genes could be amplified, sequenced and compared with known sequences in the BLAST database. The potential of producing active molecules was established by using disc diffusion antibiotic activity testing of the bacterial

• cultivation in NaBr-containing medium was selected for antibiotic production. The diminished strength of salinity in the medium implies an optimal salt range concentration for growth of 0.5–1% (w/v), at pH 7.2 and a temperature of 27 °C. Fermentation and the production of antibiotic compounds were performed

A cross-metathesis approach to novel pantothenamide derivatives

• Jinming Guan,
• Matthew Hachey,
• Lekha Puri,
• Vanessa Howieson,
• Kevin J. Saliba and
• Karine Auclair

Beilstein J. Org. Chem. 2016, 12, 963–968, doi:10.3762/bjoc.12.95

• larger groups via cross-metathesis. The method was applied in the synthesis of a new pantothenamide with improved stability in human blood. Keywords: antibiotic; antiplasmodial; coenzyme A; metathesis; pantothenate; Introduction Bacteria, fungi, and parasites are all rapidly acquiring resistance to

• currently applied antimicrobials and as a result, our ability to treat infections effectively is diminishing. Efforts to control infections in this resistance era have taken a variety of paths from a renewed push for novel antimicrobial agents to a fresh understanding of antibiotic resistance mechanisms [1

Muraymycin nucleoside-peptide antibiotics: uridine-derived natural products as lead structures for the development of novel antibacterial agents

• Daniel Wiegmann,
• Stefan Koppermann,
• Marius Wirth,
• Giuliana Niro,
• Kristin Leyerer and
• Christian Ducho

Beilstein J. Org. Chem. 2016, 12, 769–795, doi:10.3762/bjoc.12.77

• which have a uridine-derived core structure in common. Their antibiotic potency is based on the inhibition of MraY, thereby blocking a membrane-associated intracellular step of bacterial cell-wall biosynthesis. The structure elucidation was carried out using one- and two-dimensional NMR experiments as

• group B. Capuramycin, a nucleoside antibiotic isolated in 1986 from Streptomyces griseus, shares the uracil-derived nucleoside moiety with the muraymycins [33][34]. The antibiotic FR-900493, which is structurally closely related to muraymycins, was isolated from Bacillus cereus and characterised in 1990

• activity against Gram-positive bacteria, Pseudomonas and M. tuberculosis [48]. The related liposidomycins display good activity against M. phlei, while they are not active against a range of other bacteria [45]. Mode of action To develop an effective antibiotic one needs to choose a target that is