Chemoenzymatic synthesis of macrocyclic peptides and polyketides via thioesterase-catalyzed macrocyclization

• Senze Qiao,
• Zhongyu Cheng and
• Fuzhuo Li

Beilstein J. Org. Chem. 2024, 20, 721–733, doi:10.3762/bjoc.20.66

• produce over 67% of naturally occurring antibiotics [47]. Notably, daptomycin, branded as Cubicin, was approved by the FDA as a last-resort antibiotic in 2003 for the treatment of infections caused by numerous Gram-positive bacterial strains [48], including methicillin-resistant S. aureus (MRSA) and

Green and sustainable approaches for the Friedel–Crafts reaction between aldehydes and indoles

• Periklis X. Kolagkis,
• Eirini M. Galathri and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2024, 20, 379–426, doi:10.3762/bjoc.20.36

• are responsible for bacterial cell division, such as FtsZ, which reduces the rate of bacterial growth in a reversible manner. BIMs have also been implemented against methicillin-resistant Staphylococcus aureus (MRSA), which is a drug-resistant bacterium that is usually encountered in health-care

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

• Peyssonnelia sp. This diterpene showed promising biological activity against methicillin-resistant Staphylococcus aureus (MRSA) and liver-stage Plasmodium berghei. Structurally, peyssonnoside A belongs to a new class of diterpene glycosides with a distinctive tetracyclic carbon skeleton. From the point of view

Isolation and characterization of new phenolic siderophores with antimicrobial properties from Pseudomonas sp. UIAU-6B

• Emmanuel T. Oluwabusola,
• Olusoji O. Adebisi,
• Fernando Reyes,
• Kojo S. Acquah,
• Mercedes De La Cruz,
• Larry L. Mweetwa,
• Joy E. Rajakulendran,
• Digby F. Warner,
• Deng Hai,
• Rainer Ebel and
• Marcel Jaspars

Beilstein J. Org. Chem. 2021, 17, 2390–2398, doi:10.3762/bjoc.17.156

• unit [40]. Biological evaluation Compounds 1–7 were evaluated for their antimicrobial activities against methicillin-resistant Staphylococcus aureus (MRSA), methicillin-sensitive Staphylococcus aureus (MSSA), Escherichia coli, Acinetobacter Bahmani, vancomycin-resistant E. faecium VanA15167, vancomycin

• , respectively. Additionally, compounds 2 and 3 exhibited moderate antitubercular activity with MICs of 7.8 and 15.6 µg/mL, respectively. Besides, compound 5 showed low activity (MIC of 125 µg/mL) against the latter pathogen. None of the compounds inhibited the growth of E. coli, A. baumannii, MRSA, MSSA, or E

Nocarimidazoles C and D, antimicrobial alkanoylimidazoles from a coral-derived actinomycete Kocuria sp.: application of ¹J_C,H coupling constants for the unequivocal determination of substituted imidazoles and stereochemical diversity of anteisoalkyl chains in microbial metabolites

• Md. Rokon Ul Karim,
• Enjuro Harunari,
• Amit Raj Sharma,
• Naoya Oku,
• Kazuaki Akasaka,
• Daisuke Urabe,
• Mada Triandala Sibero and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 2719–2727, doi:10.3762/bjoc.16.222

• metabolite of marine Verrucosispora, effective against methicillin-resistant Staphylococcus aureus (MRSA) and Mycobacterium tuberculosis [11][12]. The genus Kocuria, formerly categorized in the genus Micrococcus, is a Gram-positive unicellular coccus belonging to the family Micrococcaceae [13]. Members of

Muyocopronones A and B: azaphilones from the endophytic fungus Muyocopron laterale

• Ken-ichi Nakashima,
• Junko Tomida,
• Tomoe Tsuboi,
• Yoshiaki Kawamura and
• Makoto Inoue

Beilstein J. Org. Chem. 2020, 16, 2100–2107, doi:10.3762/bjoc.16.177

• ), methicillin-resistant S. aureus (PAGU 841, MRSA), S. epidermidis (PAGU 283T), Enterococcus faecalis (PAGU 102T), and vancomycin-resistant E. faecalis (PAGU 100). Although muyocopronone B (2) exhibited an antibacterial activity against both antibiotic-resistant and antibiotic-susceptible strains, with minimum

• Staphylococcus aureus (PAGU 273T), methicillin-resistant S. aureus (PAGU 841, MRSA), Staphylococcus epidermidis (PAGU 283T), Enterococcus faecalis (PAGU 102T), and vancomycin-resistant E. faecalis (PAGU 100, VRE). Piperacillin, vancomycin, and amikacin were used as positive controls. The isolated substances and

Skeletocutins M–Q: biologically active compounds from the fruiting bodies of the basidiomycete Skeletocutis sp. collected in Africa

• Tian Cheng,
• Clara Chepkirui,
• Cony Decock,
• Josphat C. Matasyoh and
• Marc Stadler

Beilstein J. Org. Chem. 2019, 15, 2782–2789, doi:10.3762/bjoc.15.270

• (B. subtilis), S. aureus, methicillin-resistant S. aureus (MRSA), and Micrococcus luteus (M. luteus). In the antimicrobial assay, compounds 3 and 5 were observed to interfere with the formation of biofilms commonly associated with S. aureus. When compounds 3 and 5 were evaluated for biofilm

• determined in serial dilution assays using several microorganisms, as described previously [8][9]. Herein, Gram-positive bacteria used were B. subtilis DSM10, MRSA DSM11822, S. aureus DSM346, M. luteus DSM20030, and Mycobacterium smegmatis (M. smegmatis) ATCC700084, Gram-negative bacteria were Escherichia

Synthesis of novel sulfide-based cyclic peptidomimetic analogues to solonamides

• José Brango-Vanegas,
• Luan A. Martinho,
• Lucinda J. Bessa,
• Andreanne G. Vasconcelos,
• Alexandra Plácido,
• Alex L. Pereira,
• José R. S. A. Leite and
• Angelo H. L. Machado

Beilstein J. Org. Chem. 2019, 15, 2544–2551, doi:10.3762/bjoc.15.247

• , methicillin-resistant S. aureus (MRSA) is considered an endemic cause of nosocomial infections and has spread into the community and livestock animals as well [8]. Expression of many S. aureus virulence factors is controlled by a sophisticated intercellular chemical signalling pathway named quorum-sensing (QS

Current understanding and biotechnological application of the bacterial diterpene synthase CotB2

• Ronja Driller,
• Daniel Garbe,
• Norbert Mehlmer,
• Monika Fuchs,
• Keren Raz,
• Dan Thomas Major,
• Thomas Brück and
• Bernhard Loll

Beilstein J. Org. Chem. 2019, 15, 2355–2368, doi:10.3762/bjoc.15.228

• -dolabellatriene (12) possesses a mainly weak antibiotic activity against different types of Staphylococcus aureus strains (two epidemic MRSA strains, a macrolide-resistant variant and two multidrug-resistant efluxing strains) [72]. By contrast, 3,7,18-dolabellatriene (12, Scheme 3), only altered at C14 with a

• hydroxy group, showed a significant increase in potency (compound 14). Here the MIC values were as low as 4 µg mL−1 for a macrolide-resistant and one multidrug-resistant effluxing variant, as well as 2 µg mL−1 for two epidemic MRSA and another multidrug-resistant effluxing strain. The first bioactive

Synthesis and biological evaluation of truncated derivatives of abyssomicin C as antibacterial agents

• Leticia Monjas,
• Peter Fodran,
• Johanna Kollback,
• Carlo Cassani,
• Thomas Olsson,
• Maja Genheden,
• D. G. Joakim Larsson and
• Carl-Johan Wallentin

Beilstein J. Org. Chem. 2019, 15, 1468–1474, doi:10.3762/bjoc.15.147

• structure–activity relationship studies towards novel antibiotics targeting 4-amino-4-deoxychorismate (ADC) synthase. Specifically, it is demonstrated that the synthetically challenging bicyclic motif is essential for activity towards methicillin-resistant Staphylococcus aureus (MRSA). Keywords

• : abyssomicin C; antibiotic; antibiotic resistance; MRSA; truncated natural products; Introduction Antibiotic resistance is a major threat to global health, and numerous actions are presently taken in both academia and industry to combat this major societal challenge. There are many different approaches to

• methicillin- and vancomycin-resistant Staphylococcus aureus (MRSA and VRSA) with minimum inhibitory concentration (MIC) values of 4 and 13 µg/mL, respectively [4]. AbC belongs to a small family of NPs and two congeners of this family lacking the enone functionality, abyssomicins B and D, were discovered at

Synthesis and SAR of the antistaphylococcal natural product nematophin from Xenorhabdus nematophila

• Frank Wesche,
• Hélène Adihou,
• Thomas A. Wichelhaus and
• Helge B. Bode

Beilstein J. Org. Chem. 2019, 15, 535–541, doi:10.3762/bjoc.15.47

• relationship of the simple and antistaphylococcal amide nematophin from Xenorhabdus nematophila and synthetic derivatives are described. Moreover, the synthesis of intrinsic fluorescent derivatives, incorporating azaindole moieties was achieved for the first time. Keywords: azaindole; fluorescent dye; MRSA

• -oxopentanoic acid and tryptamine and showed good activities against different Gram-positive pathogens like Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA) comparable with activities of vancomycin. Recently, the biosynthesis of 1 was elucidated by our group as well as the 2

• , the above mentioned compounds were tested against different pathogenic strains, i.e., methicillin-susceptible S. aureus (MSSA), methicillin-resistant S. aureus (MRSA), Enterococcus faecalis, and Micrococcus luteus. The yields and bioactivities are summarized in Table 1 (and Table S1, Supporting

Protein–protein interactions in bacteria: a promising and challenging avenue towards the discovery of new antibiotics

• Laura Carro

Beilstein J. Org. Chem. 2018, 14, 2881–2896, doi:10.3762/bjoc.14.267

• an issue. Nonetheless, this study represents a step forward towards the potential development of next-generation anti-transcription antibiotics and validates the correlation between the NusB/NusE PPI and the in vitro antibiotic effect. The first specific inhibitor against S. aureus, including MRSA

• Staphylococcus aureus. However, in spite of the fact that NusB and NusE are highly conserved in bacteria, the compound exhibited preferred antibacterial activity against S. aureus strains (including MRSA) with minimum inhibitory values as low as 8 μg/mL. Pleasingly, unlike the aminoguanidine 42, compound 43 did

Synthesis of pyrrolidine-based hamamelitannin analogues as quorum sensing inhibitors in Staphylococcus aureus

• Jakob Bouton,
• Kristof Van Hecke,
• Reuven Rasooly and
• Serge Van Calenbergh

Beilstein J. Org. Chem. 2018, 14, 2822–2828, doi:10.3762/bjoc.14.260

• system and antibiotics. The Centers for Disease Control and Prevention (CDC) have listed a number of bacteria that present serious, urgent and concerning threats [8]. One of these problematic bacteria is methicillin-resistant Staphylococcus aureus (MRSA), a human pathogen that causes a wide range of

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

• shown to bind A·T-rich regions preferentially. The compounds containing branched N-alkylpyrrole, hydrophobic N-terminal amide, and especially C-isopropylthiazole (thiazotropsin A as shown in the Figure 4) showed significant antimicrobial activity against MRSA and Candida albicans strains. Thiazotropsin

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

• revised from S to R, upon total synthesis [33]. The mannopeptimycins contain a unique sugar substituted hydroxyenduracididine residue (blue, Figure 5). The mannopeptimycins displayed moderate activity against Gram-positive bacteria, including MRSA, but only exhibited weak activity against Gram-negative

• . Teixobactin (17) was isolated from the β-protobacterium, Eleftheria terrae that belongs to a new genus. Teixobactin (17) demonstrated potent activity against the resistant Gram-positive bacteria, MRSA and vancomycin-resistant Enterococci (VRE), as well as other bacterial species including, Mycobacterium

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

• -resistant bacteria such as MRSA [90] and nanocapsule systems work against the biofilms [91] made by these nasties [92]. We have also made a foray into bioorthogonal chemistry, using nanoparticles to encapsulate transition metal catalysts, generating “nanozymes” that can catalyze processes in cells that even

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

• extracts, whereby an inhibitory effect of the extracts of E. salina SWB005 on various test organisms, including the clinically relevant MRSA (methicillin resistant Staphylococcus aureus) strains LT1334, LT1338 and MRSE methicillin resistant Staphylococcus epidermidis strain LT1324 was observed [59]. To

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

• proven quite successful [11][18]. One of the promising derivatives reported is a methyl allyl (2, Figure 1) with a MIC of 3.2 μM against S. aureus and MRSA, compared to MICs of 7 μM for 1 against the same strains [18]. This result encouraged us to synthesize more derivatives with different substituents

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

• methicillin-resistant Staphylococcus aureus (MRSA) [18][19] and vancomycin-resistant Enterococcus (VRE) [20]. This development raises the demand for antibiotics exploiting yet unused modes of action. Potential targets within bacteria include peptidoglycan biosynthesis, protein biosynthesis, DNA and RNA

• , 92c) in order to investigate the role of the cyclic guanidine functionality (Figure 10) [77]. These compounds were all active against MRSA and VRE with varying MIC values (Table 2). The most active analogues of this series were 92a and 92b (Figure 10, highlighted in orange) with MIC values between 1

Effective in silico prediction of new oxazolidinone antibiotics: force field simulations of the antibiotic–ribosome complex supervised by experiment and electronic structure methods

• Jörg Grunenberg and
• Giuseppe Licari

Beilstein J. Org. Chem. 2016, 12, 415–428, doi:10.3762/bjoc.12.45

• portion displayed in blue [15]. While only the S-enantiomer seems to be potent, linezolid shows activity against a wide range of Gram-positive bacteria such as vancomycin-resistant Enterococcus (VRE), methicillin-resistant Staphylococcus aureus (MRSA) and penicillin-resistant Streptococcus pneumoniae

• 2 and 3, the morpholine ring was replaced by a 3-methyl-1,2,4-oxadiazole ring [44]. Whereas 2 maintains the linezolid C5 side chain, compound 3 is substituted by a imidazole-1-yl. With its MIC value of 2 mg/L compound 2 seems to be comparable (or even more effective against the MRSA 433 strain, see

• potency both in vitro and in vivo antibacterial activities [46]. Candidate 7 represents the active form of the prodrug torezolid, the phosphate disodium salt, which was synthetized in order to improve the solubility of its parent drug. Highly active against MRSA, MSSA (methicillin-sensitive Staphylococcus

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

• Pseudoalteromonas sp. SANK 73390 [54], which exhibits antibiotic activity against methicillin-resistant Staphylococcus aureus (MRSA) [55]. Particularly interesting results of feeding experiments with [1,2-13C2]-, [2-13C]- and [1-13C,18O2]acetate were the unexpectedly low incorporation into C-5’ to C-8’ of the

Bromotyrosine-derived alkaloids from the Caribbean sponge Aplysina lacunosa

• Qun Göthel,
• Thanchanok Sirirak and
• Matthias Köck

Beilstein J. Org. Chem. 2015, 11, 2334–2342, doi:10.3762/bjoc.11.254

• -phase HPLC [70:30 H2O (0.1% TFA)/MeCN (0.1% TFA), v/v] to get a mixture of 3 and 15 (3.5 mg) as well as 4 (3.0 mg). Biological activity test The antimicrobial activities of isolated compounds were evaluated against five microorganisms [Gram-positive: Straptococcus aureus (MRSA and MSSA) and Micrococcus

Atherton–Todd reaction: mechanism, scope and applications

• Stéphanie S. Le Corre,
• Mathieu Berchel,
• Hélène Couthon-Gourvès,
• Jean-Pierre Haelters and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2014, 10, 1166–1196, doi:10.3762/bjoc.10.117

The chemistry of isoindole natural products

• Klaus Speck and
• Thomas Magauer

Beilstein J. Org. Chem. 2013, 9, 2048–2078, doi:10.3762/bjoc.9.243

• natural product and synthetic precursor of 193 shows strong antibiotic activity against methicillin-resistant Staphylococcus aureus (MRSA, MIC = 84 nM) and vancomycin-resistant Enterococcus (VRE, MIC = 178 nM) [148]. The structural similarity between pestalachloride A (193) and pestalone (192), which both

• : Lactonamycin (215) and lactonamycin Z (217) were isolated from Streptomyces rishiriensis and Streptomyces anglieri in 1996 and 2003 [157][158]. Both compounds are potent antibacterial agents against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant

Synthesis and antibacterial activity of monocyclic 3-carboxamide tetramic acids

• Yong-Chul Jeong and
• Mark G. Moloney

Beilstein J. Org. Chem. 2013, 9, 1899–1906, doi:10.3762/bjoc.9.224

• ). Antibacterial activity The antibiotic activities of tetramates 2a–h and 3a–f along with analogues 1c and 1d (reported by Novartis [8]) were determined against 4 species of Gram-positive bacteria, consisting of 4 strains of Staphylococcus aureus, including a methicillin-resistant strain (MRSA, S2), vancomycin

• bacteria, although the activity depends on the substituent identities. Importantly, the variation of antibacterial activity for analogues 2 and 3 was less pronounced in the resistant strains MRSA, VRE and MDRSP (normally less than 8 times variation, with the exception of analogues 2e and 3b), while the

• activities of Novartis analogue 1c against MRSA [8], amoxicillin against MDRSP and ciprofloxacin against MRSA and VRE were significantly lower (more than 250 times compared with the activity against the most sensitive strain). Among the various substituent groups, N-alkyl phenyl derivatives 2a,b,h were