One-pot Ugi-azide and Heck reactions for the synthesis of heterocyclic systems containing tetrazole and 1,2,3,4-tetrahydroisoquinoline

• Jiawei Niu,
• Yuhui Wang,
• Shenghu Yan,
• Yue Zhang,
• Xiaoming Ma,
• Qiang Zhang and
• Wei Zhang

Beilstein J. Org. Chem. 2024, 20, 912–920, doi:10.3762/bjoc.20.81

• can be found in natural products and synthetic compounds with antitumor, anti-HIV, antibiotic, antifungal, antivirus, and anti-inflammatory activities [18][19][20][21]. The antischistosomal drug praziquantel (PZQ), a tetrahydroisoquinoline derivative, is a commercialized drug for the treatment of

Activity assays of NnlA homologs suggest the natural product N-nitroglycine is degraded by diverse bacteria

• Kara A. Strickland,
• Brenda Martinez Rodriguez,
• Ashley A. Holland,
• Shelby Wagner,
• Michelle Luna-Alva,
• David E. Graham and
• Jonathan D. Caranto

Beilstein J. Org. Chem. 2024, 20, 830–840, doi:10.3762/bjoc.20.75

• antibiotic activity towards Gram-negative bacteria. An NNG degrading heme enzyme, called NnlA, has recently been discovered in the genome of Variovorax sp. strain JS1663 (Vs NnlA). Evidence is presented that NnlA and therefore, NNG degradation activity is widespread. To achieve this objective, we

• often exhibit antibiotic activity and it has been shown that NNG exhibits antibiotic activity towards Gram-negative bacteria (0.18 to 25 μg/mL) [24]. Moreover, the nitramine functional group has potential to serve as a potent warhead in an antibiotic. For example, a cytochrome P450 homolog, XplA

• portion of NNG would be expected to exist as the inhibitory nitronate form at physiological pH, suggesting another potential role for nitramine groups as potent warheads in antibiotics. This antibiotic activity may also require further modification of NNG or its incorporation into a larger natural product

Synthesis of new representatives of A₃B-type carboranylporphyrins based on meso-tetra(pentafluorophenyl)porphyrin transformations

• Victoria M. Alpatova,
• Evgeny G. Rys,
• Elena G. Kononova and
• Valentina A. Ol'shevskaya

Beilstein J. Org. Chem. 2024, 20, 767–776, doi:10.3762/bjoc.20.70

• biosensors, bioimaging probes, and especially as photosensitizers (PSs) in photodynamic therapy (PDT) [2]. PDT is a treatment modality that uses the combination of a non-toxic PS, oxygen, and light to treat diseases ranging from cancer to age-related macular degeneration and antibiotic-resistant infections

Methodology for awakening the potential secondary metabolic capacity in actinomycetes

• Shun Saito and
• Midori A. Arai

Beilstein J. Org. Chem. 2024, 20, 753–766, doi:10.3762/bjoc.20.69

• production of secondary metabolites. For example, overexpression of Streptomyces antibiotic regulatory protein (SARP) family transcriptional activators led to the discovery of many new secondary metabolites [42]. Du et al. searched for SARP family transcriptional activators from the draft genome of

• inducing resistance, and this approach has contributed to the isolation of many new compounds [47]. The ribosome engineering method is based on the principle that a mutation in the ribosomal S12 protein, which is associated with the acquisition of antibiotic resistance, activates secondary metabolism. The

• production of antibiotics such as actinorhodin (ACT, 8), undecylprodigiosin (RED, 21), and calcium-dependent antibiotic (CDA, 22) in Streptomyces coelicolor M145 (Figure 3b). Chen et al. and Shu et al. reported that under stress associated with high concentrations of glutamate, AfsQ1/Q2 is important not only

Substrate specificity of a ketosynthase domain involved in bacillaene biosynthesis

• Zhiyong Yin and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2024, 20, 734–740, doi:10.3762/bjoc.20.67

• understanding of polyketide biosynthesis has been reached, including a detailed knowledge of the extender unit selection and the stereochemical implications that are predictable from amino acid sequences [5][6]. The polyene antibiotic bacillaene was first isolated from Bacillus subtilis [7]. This soil-dwelling

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

• -product biosynthesis and combinatorial solid-phase chemistry, this strategy has expanded the sequence space of macrocyclic peptides significantly (Scheme 2c). The daptomycins The calcium-dependent antibiotic (CDA, 11), daptomycin (12), and A54145 are acidic lipopeptides isolated from Streptomycetes, which

• 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

• biosynthesis of these acidic lipopeptides, Marahiel and co-workers accomplished a chemoenzymatic synthesis of the calcium-dependent antibiotic (CDA,11) utilizing CDA3 TE, a cyclase derived from CDA synthetase [53]. To simulate the native peptide-S-PCP substrate, they evaluated four leaving groups: SNAC

Genome mining of labdane-related diterpenoids: Discovery of the two-enzyme pathway leading to (−)-sandaracopimaradiene in the fungus Arthrinium sacchari

• Fumito Sato,
• Terutaka Sonohara,
• Shunta Fujiki,
• Akihiro Sugawara,
• Yohei Morishita,
• Taro Ozaki and
• Teigo Asai

Beilstein J. Org. Chem. 2024, 20, 714–720, doi:10.3762/bjoc.20.65

• inhibitor aphidicolin [28] and a ribosome-targeting antibiotic pleuromutilin [29] (Figure 1), they remained as underexplored targets in genome-mining approaches. In this study, we examined the biosynthetic genes for LRDs and identified two TCs consisting of αβ and αβγ domains. Heterologous expression in

Chemical and biosynthetic potential of Penicillium shentong XL-F41

• Ran Zou,
• Xin Li,
• Xiaochen Chen,
• Yue-Wei Guo and
• Baofu Xu

Beilstein J. Org. Chem. 2024, 20, 597–606, doi:10.3762/bjoc.20.52

• antibiotic mycophenolic acid originally isolated by Gosio in the 1890s [2], the important antibiotic penicillin was characterized more than one decade after Fleming discovered the antibacterial activity of a Penicillium extract, and since then, Penicillium has been an important target in drug development

A myo-inositol dehydrogenase involved in aminocyclitol biosynthesis of hygromycin A

• Michael O. Akintubosun and
• Melanie A. Higgins

Beilstein J. Org. Chem. 2024, 20, 589–596, doi:10.3762/bjoc.20.51

• Michael O. Akintubosun Melanie A. Higgins Department of Biological Sciences, The University of Alabama, 3314 Science and Engineering Complex, Tuscaloosa, AL 35487, USA 10.3762/bjoc.20.51 Abstract Hygromycin A is a broad-spectrum antibiotic that contains a furanose, cinnamic acid, and

• was discovered in the 1950s and is produced by the soil bacterium Streptomyces hygroscopicus [1]. It has broad spectrum antibiotic activity, antitreponemal activity against the pathogen that causes swine dysentery, and selective activity against the spirochete that causes Lyme disease [1][2][3]. It

• /bleomycin resistance protein/dioxygenase superfamily (PF00903) sequences, 81 associated with CrcB-like protein, camphor resistance (PF02537) sequences, 22 associated with aminoglycoside antibiotic resistance kinase (PF04655) sequences, and 2 associated with putative multidrug resistance efflux protein

Entry to new spiroheterocycles via tandem Rh(II)-catalyzed O–H insertion/base-promoted cyclization involving diazoarylidene succinimides

• Alexander Yanovich,
• Anastasia Vepreva,
• Ksenia Malkova,
• Grigory Kantin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2024, 20, 561–569, doi:10.3762/bjoc.20.48

• products. For example, spirocyclic Δα,β-butenolides (furan-2(5H)-ones) represent a valuable class of molecular frameworks for drug design and are abundant in nature [15]. Bioactive naturally occurring spiro Δα,β-butenolides include spirofragilide (with anti-inflammatory, antibiotic, antitumor, anti-HIV

A new analog of dihydroxybenzoic acid from Saccharopolyspora sp. KR21-0001

• Rattiya Janthanom,
• Yuta Kikuchi,
• Hiroki Kanto,
• Tomoyasu Hirose,
• Arisu Tahara,
• Takahiro Ishii,
• Arinthip Thamchaipenet and
• Yuki Inahashi

Beilstein J. Org. Chem. 2024, 20, 497–503, doi:10.3762/bjoc.20.44

• but showed potent antioxidant activity. Keywords: antioxidant activity; dihydroxybenzoic acid analog; rare actinomycetes; Introduction Actinomycetes are Gram-positive bacteria with high GC content in their genome. They are well-known as the main producers of bioactive compounds such as antibiotic

Development of a chemical scaffold for inhibiting nonribosomal peptide synthetases in live bacterial cells

• Fumihiro Ishikawa,
• Sho Konno,
• Hideaki Kakeya and
• Genzoh Tanabe

Beilstein J. Org. Chem. 2024, 20, 445–451, doi:10.3762/bjoc.20.39

• ) domain, consequently resulting in the formation of the final products. Inhibitors that target each domain of NRPSs are valuable for elucidating the biosynthetic pathways associated with bioactive NRPs and for developing antibiotic molecules. Burkart et al. reported a systematic strategy for inhibiting

Synthesis of π-conjugated polycyclic compounds by late-stage extrusion of chalcogen fragments

• Aissam Okba,
• Pablo Simón Marqués,
• Kyohei Matsuo,
• Naoki Aratani,
• Hiroko Yamada,
• Gwénaël Rapenne and
• Claire Kammerer

Beilstein J. Org. Chem. 2024, 20, 287–305, doi:10.3762/bjoc.20.30

• , which have been shown to be particularly sensitive to light [70]. Upon exposure to UV or visible light, thiarubrine A (36) undergoes a desulfurization process to give rise to the corresponding thiophene 37, exhibiting enhanced antibiotic activity (Scheme 10, bottom). This naturally-occurring S-extrusion

Substitution reactions in the acenaphthene analog of quino[7,8-h]quinoline and an unusual synthesis of the corresponding acenaphthylenes by tele-elimination

• Ekaterina V. Kolupaeva,
• Narek A. Dzhangiryan,
• Alexander F. Pozharskii,
• Oleg P. Demidov and
• Valery A. Ozeryanskii

Beilstein J. Org. Chem. 2024, 20, 243–253, doi:10.3762/bjoc.20.24

• and used in medicine, food industry, catalysts, dyes, functional materials, oil refining, and electronics [1][2]. Quinoline and its derivatives have antibiotic, antimalarial, antitumor, anti-inflammatory, antihypertensive, and antiretroviral properties [3][4]. Therefore, at present, there is a need

Optimizations of lipid II synthesis: an essential glycolipid precursor in bacterial cell wall synthesis and a validated antibiotic target

• Milandip Karak,
• Cian R. Cloonan,
• Brad R. Baker,
• Rachel V. K. Cochrane and
• Stephen A. Cochrane

Beilstein J. Org. Chem. 2024, 20, 220–227, doi:10.3762/bjoc.20.22

• is synthesized on the inner leaflet of the cytoplasmic membrane, before translocation to the outer leaflet, where it is then used as the monomeric building block of peptidoglycan biosynthesis. Lipid II is a validated antibiotic target for clinically prescribed antibiotics including vancomycin and

Two new lanostanoid glycosides isolated from a Kenyan polypore Fomitopsis carnea

• Winnie Chemutai Sum,
• Sherif S. Ebada,
• Didsanutda Gonkhom,
• Cony Decock,
• Rémy Bertrand Teponno,
• Josphat Clement Matasyoh and
• Marc Stadler

Beilstein J. Org. Chem. 2023, 19, 1161–1169, doi:10.3762/bjoc.19.84

• against Staphylococcus aureus and Bacillus subtilis at MIC values comparable to gentamycin and oxytetracycline (positive controls), respectively. Keywords: antimicrobial activity; Fomitopsis carnea; lanostane glycosides; Polyporales; Introduction Great success was realized on antibiotic discovery

• between 1930 and 1960 during the ‘golden era’ of antibiotics. Unfortunately, the pace of antibiotic research and development in the face of emerging resistant pathogens has not been kept up, thus raising a big concern for a return to the pre-antibiotic era [1][2]. Recently, the danger posed by previously

• ]. Chemical investigations of F. pinicola or F. betulina revealed their cytotoxic [21][23] and antidiabetic propensities [19]. In addition, the recent review on F. officinalis, elaborated the potential use of its compounds as antibiotic leads [19]. In this study we report the isolation and structure

Clauson–Kaas pyrrole synthesis using diverse catalysts: a transition from conventional to greener approach

• Dileep Kumar Singh and
• Rajesh Kumar

Beilstein J. Org. Chem. 2023, 19, 928–955, doi:10.3762/bjoc.19.71

• ], antiviral [11][12], antibacterial [13][14][15], antimalarial [16][17], anti-inflammatory [18][19], anti-oxidant [20][21][22], antifungal [23][24] and antibiotic [25][26] and as enzyme inhibitors [27][28]. Several pharmaceuticals, polymers and naturally occurring compounds, including heme, chlorophyll

Palladium-catalyzed enantioselective three-component synthesis of α-arylglycine derivatives from glyoxylic acid, sulfonamides and aryltrifluoroborates

• Bastian Jakob,
• Nico Schneider,
• Luca Gengenbach and
• Georg Manolikakes

Beilstein J. Org. Chem. 2023, 19, 719–726, doi:10.3762/bjoc.19.52

• , e.g., the antiplatelet drug clopidogrel [7] or the β-lactam antibiotic amoxicillin [8] (Figure 1). Therefore, the chemical synthesis of α-aryglycines has received considerable attention. Among the different methods introduced over time, multicomponent reactions utilizing an in situ generated reactive

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

• bacterial species. The C14 analogs, tiamulin, and valnemulin have been used by veterinarians since the 1980s. The topical antibiotic retapamulin was approved by FDA in 2007 for the treatment of the skin infection impetigo. In 2019–2020, lefamulin was introduced both in the USA and the EU to treat community

Phenanthridine–pyrene conjugates as fluorescent probes for DNA/RNA and an inactive mutant of dipeptidyl peptidase enzyme

• Josipa Matić,
• Tana Tandarić,
• Marijana Radić Stojković,
• Filip Šupljika,
• Zrinka Karačić,
• Ana Tomašić Paić,
• Lucija Horvat,
• Robert Vianello and
• Lidija-Marija Tumir

Beilstein J. Org. Chem. 2023, 19, 550–565, doi:10.3762/bjoc.19.40

• (4.5 g/L) Dulbecco's Modified Eagle's Medium (DMEM, Sigma Aldrich) with the addition of 10% fetal bovine serum (FBS), 1% non-essential amino acids and 1% antibiotic/antimycotic solution (all chemicals were purchased by Capricorn Scientific GmbH). The cells were kept at 37 °C and 5% CO2 in a Heracell

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

• arnottianum Maxim which possesses some antibiotic properties [34]. Mechanistically, the authors proposed the reaction begins with the in situ reduction of Ni(II) to Ni(0) by zinc to generate Ni(0) which undergoes oxidative addition with the organo iodide to yield Ni(II) intermediate 11. Coordination of 11 to

Nostochopcerol, a new antibacterial monoacylglycerol from the edible cyanobacterium Nostochopsis lobatus

• Naoya Oku,
• Saki Hayashi,
• Yuji Yamaguchi,
• Hiroyuki Takenaka and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2023, 19, 133–138, doi:10.3762/bjoc.19.13

• testing To each well of a sterile 96-well microtiter plate was dispensed 100 μL of tryptic soy broth. Additionally, 98 μL of the same medium and 2 μL of the solutions of test compounds in MeOH or a reference antibiotic, kanamycin monosulfate, in H2O, were added to the wells at the top row. To make two

Digyalipopeptide A, an antiparasitic cyclic peptide from the Ghanaian Bacillus sp. strain DE2B

• Adwoa P. Nartey,
• Aboagye K. Dofuor,
• Kofi B. A. Owusu,
• Anil S. Camas,
• Hai Deng,
• Marcel Jaspars and
• Kwaku Kyeremeh

Beilstein J. Org. Chem. 2022, 18, 1763–1771, doi:10.3762/bjoc.18.185

• it is important not to overlook Bacillus and their natural products especially in this current era of spreading antibiotic resistance and demands for ecologically friendly pest control strategies. Primary structure of digyalipopeptide A (1). Key COSY and HMBC correlations for compound 1. Key TOCSY

Navigating and expanding the roadmap of natural product genome mining tools

• Friederike Biermann,
• Sebastian L. Wenski and
• Eric J. N. Helfrich

Beilstein J. Org. Chem. 2022, 18, 1656–1671, doi:10.3762/bjoc.18.178

• initiated the field of microbial NP research. In the "golden age" of antibiotic discovery from the 1940s to 1970s, microbes and especially bacteria have been identified as an almost untapped treasure trove for the discovery of bioactive NPs. For the longest time, researchers focused on a few talented NP

Efficient synthesis of aziridinecyclooctanediol and 3-aminocyclooctanetriol

• Emine Salamci and
• Ayse Kilic Lafzi

Beilstein J. Org. Chem. 2022, 18, 1539–1543, doi:10.3762/bjoc.18.163

• antibiotic activities. Therefore, synthetic methodologies for the preparation of the aziridinyl system have attracted attention in recent decades. Opening of the aziridine ring by using different nucleophiles gives the corresponding amino alcohols, amino esters, azido amines, amines, and other derivatives [9