Synthesis of 3,4,5-trisubstituted isoxazoles in water via a [3 + 2]-cycloaddition of nitrile oxides and 1,3-diketones, β-ketoesters, or β-ketoamides

• Md Imran Hossain,
• Md Imdadul H. Khan,
• Seong Jong Kim and
• Hoang V. Le

Beilstein J. Org. Chem. 2022, 18, 446–458, doi:10.3762/bjoc.18.47

• and γ-amino alcohols [1]. Isoxazoles, appearing in 33 patents from the year 2016 to 2018 [3], are an important drug class due to their wide range of biological activities, such as anticancer [5], antibiotic [6][7], antimicrobial [8], antifungal [9], and anti-inflammatory [10]. Therefore, new methods

Synthesis of novel [1,2,4]triazolo[1,5-b][1,2,4,5]tetrazines and investigation of their fungistatic activity

• Anna V. Korotina,
• Svetlana G. Tolshchina,
• Rashida I. Ishmetova,
• Natalya P. Evstigneeva,
• Natalya A. Gerasimova,
• Natalya V. Zilberberg,
• Nikolay V. Kungurov,
• Gennady L. Rusinov,
• Oleg N. Chupakhin and
• Valery N. Charushin

Beilstein J. Org. Chem. 2022, 18, 243–250, doi:10.3762/bjoc.18.29

• , thus leading to a disturbance of their functions. Up to date, there is a considerable data set, providing an evidence that azolo-annulated 1,2,4,5-tetrazines have a pronounced biological activity. It is worth, for instance, to mention antimicrobial activity of 1,4-dihydroimidazo[1,2-b][1,2,4,5

Glycosylated coumarins, flavonoids, lignans and phenylpropanoids from Wikstroemia nutans and their biological activities

• Meifang Wu,
• Xiangdong Su,
• Yichuang Wu,
• Yuanjing Luo,
• Ying Guo and
• Yongbo Xue

Beilstein J. Org. Chem. 2022, 18, 200–207, doi:10.3762/bjoc.18.23

• antimicrobial activities [27], the antimicrobial activity of compounds 1–4 was also evaluated against the bacteria Escherichia coli, Staphylococcus aureus subsp. aureus, Salmonella enterica subsp. enterica, and Pseudomonas aeruginosa. However, all of them were found to be devoid of inhibitory activity (MIC >250

• antimicrobial activities. This is the first report of the isolation of coumarins, flavonoids, lignans and phenylpropanoid glycosides from W. nutans, while compounds 1–3, 8, and 11 was encountered from the genus Wikstroemia for the first time. Our work will enrich the chemistry and structure diversity of natural

• concentration in the supernatants with Griess reagent as described previously [28]. Antimicrobial assay Compounds 1–4 were evaluated for their antimicrobial activities against Escherichia coli, Staphylococcus aureus subsp. aureus, Salmonella enterica subsp. enterica, and Pseudomonas aeruginosa. Antimicrobial

Tenacibactins K–M, cytotoxic siderophores from a coral-associated gliding bacterium of the genus Tenacibaculum

• Yasuhiro Igarashi,
• Yiwei Ge,
• Tao Zhou,
• Amit Raj Sharma,
• Enjuro Harunari,
• Naoya Oku and
• Agus Trianto

Beilstein J. Org. Chem. 2022, 18, 110–119, doi:10.3762/bjoc.18.12

• related compounds such as nocardichelins [31] and MBJ-0003 [32], compounds 1–3 did not show appreciable antimicrobial activity against bacteria or a yeast (see Experimental) at 50 μg/mL but exhibited cytotoxicity against 3Y1 rat embryonic fibroblasts and P388 murine leukemia cells (Table 3). Among the

• Antimicrobial activity was examined as previously reported [41]. Kocuria rhizophila ATCC9341, Staphylococcus aureus FDA209P JC-1, Ralstonia solanacearum SUPP1541, Escherichia coli NIHJ JC-2, Rhizobium radiobacter NBRC14554, and Candida albicans NBRC0197 were used as indication strains. Cytotoxicity against 3Y1

Unsaturated fatty acids and a prenylated tryptophan derivative from a rare actinomycete of the genus Couchioplanes

• Shun Saito,
• Kanji Indo,
• Naoya Oku,
• Hisayuki Komaki,
• Masashi Kawasaki and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2021, 17, 2939–2949, doi:10.3762/bjoc.17.203

• H-13 (Figure 6). Thus, an S-configuration, corresponding to an ʟ-chirality for tryptophan, was assigned. Compounds 1–6 were not cytotoxic against P388 murine leukemia cells (IC50 > 100 μM), nor antimicrobial against five bacteria, Bacillus subtilis, Staphylococcus aureus, Ralstonia solanacearum

• doxorubicin hydrochloride was 0.13 μM. Antimicrobial assay Antimicrobial assays were carried out against five bacteria, K. rhizophila ATCC 9341, S. aureus FDA209P JC-1, E. coli NIHJ JC-2, R. solanacearum SUPP1541, and R. radiobacter NBRC 14554, and a yeast C. albicans NBRC 0197 in the same manner as reported

Selective sulfonylation and isonitrilation of para-quinone methides employing TosMIC as a source of sulfonyl group or isonitrile group

• Chuanhua Qu,
• Run Huang,
• Yong Li,
• Tong Liu,
• Yuan Chen and
• Guiting Song

Beilstein J. Org. Chem. 2021, 17, 2822–2831, doi:10.3762/bjoc.17.193

• , antimicrobial, antimalarial, and anticancer activities [1][2]. Diarylmethane motifs are widely present in natural products and pharmaceuticals that exhibit extraordinary biological activity [3][4] (Figure 1). Among them, their anticancer activity is particularly attractive, demonstrated by drugs such as

Photophysical, photostability, and ROS generation properties of new trifluoromethylated quinoline-phenol Schiff bases

• Inaiá O. Rocha,
• Yuri G. Kappenberg,
• Wilian C. Rosa,
• Clarissa P. Frizzo,
• Nilo Zanatta,
• Marcos A. P. Martins,
• Isadora Tisoco,
• Bernardo A. Iglesias and
• Helio G. Bonacorso

Beilstein J. Org. Chem. 2021, 17, 2799–2811, doi:10.3762/bjoc.17.191

• imines, Schiff bases have the general organic function -C=N- [2], and are known to have a wide range of biological activities, including antioxidant [3], antitubercular [4], antibacterial [5], antimicrobial [6], and antifungal properties [7], in addition to their role as chemosensors [8] (Figure 1

The ethoxycarbonyl group as both activating and protective group in N-acyl-Pictet–Spengler reactions using methoxystyrenes. A short approach to racemic 1-benzyltetrahydroisoquinoline alkaloids

• Marco Keller,
• Karl Sauvageot-Witzku,
• Franz Geisslinger,
• Nicole Urban,
• Michael Schaefer,
• Karin Bartel and
• Franz Bracher

Beilstein J. Org. Chem. 2021, 17, 2716–2725, doi:10.3762/bjoc.17.183

• °C for 1 h (Table 2). Spectroscopic data of the racemic products were in full agreement with published data from former total syntheses [24][25][36][38][42][43][44][45]. Screening Bisbenzylisoquinoline alkaloids like tetrandrine and cepharanthine exhibit a broad spectrum of antimicrobial activities

Cryogels: recent applications in 3D-bioprinting, injectable cryogels, drug delivery, and wound healing

• Luke O. Jones,
• Leah Williams,
• Tasmin Boam,
• Martin Kalmet,
• Chidubem Oguike and
• Fiona L. Hatton

Beilstein J. Org. Chem. 2021, 17, 2553–2569, doi:10.3762/bjoc.17.171

• such as antimicrobial properties. A work reported by Koshy et al. in 2018 was testing the use of injectable nanocomposite cryogels for versatile protein-drug delivery [37]. Injectable and porous cryogels were prepared using a bio-orthogonal click chemistry crosslinking approach with alginate employing

• method for the preparation of super-macroporous polymer hydrogels. They have large pore sizes which can easily contain samples and additives whilst also retaining biocompatible structures [86]. Some reports focus on the use of model drug compounds [87][88][89], or newly synthesised antimicrobial

• promotion of cell proliferation [117]. The tannic acid and ferric ions provide photothermal properties whereby under near infrared (NIR) radiation the temperature increased to enhance the antimicrobial properties, while also showing good hemostasis properties such as blood absorption and clotting, and cell

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

• analyses. The absolute configuration of the threonine residue in compounds 1–5 was determined by Marfey analysis. The antimicrobial evaluation of compound 4 exhibited the most potent activity against vancomycin-sensitive Enterococcus faecium VS144754, followed by 3 and 5, with MIC values ranging from 8 to

• ; pseudomonine; Pseudomonas sp.; vancomycin-sensitive Enterococcus faecium; Introduction The introduction of antimicrobial drugs in the mid-20th century has had an unprecedented positive impact on human health, but the current threat of multiple drug resistance may well roll back all these past achievements [1

• transporting system as a cellular entry gateway [31][32]. Thus far, a few Pseudomonas-derived siderophores including ferrocins [33], thioquinolobactin [34], and (+)-(S)-dihydroaeruginioc acid [35] have been reported as active antimicrobial agents. Our continued exploration of new bioactive compounds from

Synthesis and antimicrobial activity of 1H-1,2,3-triazole and carboxylate analogues of metronidazole

• Satya Kumar Avula,
• Syed Raza Shah,
• Khdija Al-Hosni,
• Muhammad U. Anwar,
• Rene Csuk,
• Biswanath Das and
• Ahmed Al-Harrasi

Beilstein J. Org. Chem. 2021, 17, 2377–2384, doi:10.3762/bjoc.17.154

• -Wittenberg, Kurt-Mothes-Str. 2, d-06120, Halle (Saale), Germany 10.3762/bjoc.17.154 Abstract Herein, a series of novel 1H-1,2,3-triazole and carboxylate derivatives of metronidazole (5a–i and 7a–e) were synthesized and evaluated for their antimicrobial activity in vitro. All the newly synthesized compounds

• metronidazole derivatives. The antimicrobial (antifungal and antibacterial) activity of the prepared compounds was studied. All compounds (except 2 and 3) showed a potent inhibition rate of fungal growth as compared to control and metronidazole. The synthetic compounds also showed higher bacterial growth

• inhibiting effects compared to the activity of the parent compound. Amongst the tested compounds 5b, 5c, 5e, 7b and 7e displayed excellent potent antimicrobial activity. The current study has demonstrated the usefulness of the 1H-1,2,3-triazole moiety in the metronidazole skeleton. Keywords: antimicrobial

Nomimicins B–D, new tetronate-class polyketides from a marine-derived actinomycete of the genus Actinomadura

• Zhiwei Zhang,
• Tao Zhou,
• Taehui Yang,
• Keisuke Fukaya,
• Enjuro Harunari,
• Shun Saito,
• Katsuhisa Yamada,
• Chiaki Imada,
• Daisuke Urabe and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2021, 17, 2194–2202, doi:10.3762/bjoc.17.141

• absolute configuration was determined by combination of NOESY/ROESY and ECD analyses. Nomimicins B, C, and D showed antimicrobial activity against Gram-positive bacteria, Kocuria rhizophila and Bacillus subtilis, with MIC values in the range of 6.5 to 12.5 μg/mL. Nomimicins B and C also displayed

• antimicrobial activity against Kocuria rhizopila with a MIC value of 6.5 μg/mL and 1 and 2 were also active against Bacillus subtilis with a MIC value of 12.5 μg/mL. Compounds 1–3 were inactive against Staphylococcus aureus, Ralstonia solanacearum, Rhizobium radiobacter, and Candida albicans. In addition, 1 and

• tautomer are included in Supporting Information File 1. Biological assays Antimicrobial activity and cytotoxicity were evaluated according to the procedures previously described [29]. Structures of nomimicins A–D (4 and 1–3). COSY and key HMBC correlations for 1. Relative configuration of 1 determined by

Recent advances in the syntheses of anthracene derivatives

• Giovanni S. Baviera and
• Paulo M. Donate

Beilstein J. Org. Chem. 2021, 17, 2028–2050, doi:10.3762/bjoc.17.131

• , anthracene derivatives display useful biological activities; for instance, the anthraquinone derivatives 5 and 6 exert antimicrobial and anti-inflammatory activity, respectively (Figure 1) [15][16]. Despite some difficulties and limitations, a number of synthetic methods for preparing anthracene derivatives

Progress and challenges in the synthesis of sequence controlled polysaccharides

• Giulio Fittolani,
• Theodore Tyrikos-Ergas,
• Denisa Vargová,
• Manishkumar A. Chaube and
• Martina Delbianco

Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129

• tuning of the DP and fraction of acetylation (FA). Chitooligosaccharides (COS: β(1–4)-linked oligomers of GlcNAc and/or GlcN) have gained popularity due to their exceptional antimicrobial, antitumor, and immune modulatory activities [29][213][214][215][216][217]. Methods to obtain well-defined COS with

Volatile emission and biosynthesis in endophytic fungi colonizing black poplar leaves

• Christin Walther,
• Pamela Baumann,
• Katrin Luck,
• Beate Rothe,
• Peter H. W. Biedermann,
• Jonathan Gershenzon,
• Tobias G. Köllner and
• Sybille B. Unsicker

Beilstein J. Org. Chem. 2021, 17, 1698–1711, doi:10.3762/bjoc.17.118

• exhibit antimicrobial activity; however, they are also known to induce the growth and vigor of the host plant and to shape plant community structure [27][28][29][30][31]. Furthermore, volatiles released from endophytic fungi can also affect insect behavior. Daisy et al. isolated the endophytic fungus

• produced by endophytic fungi and are known to act as antimicrobial agents (Table 2) [63]. Sesquiterpenes make up the largest proportion of fungus-produced terpenoids [64] and in our study we also detected several sesquiterpenes, e.g., (E)-β-caryophyllene (1), β-chamigrene (4), aristolene (15), sativene (16

Iodine-catalyzed electrophilic substitution of indoles: Synthesis of (un)symmetrical diindolylmethanes with a quaternary carbon center

• Thanigaimalai Pillaiyar,
• Masoud Sedaghati,
• Andhika B. Mahardhika,
• Lukas L. Wendt and
• Christa E. Müller

Beilstein J. Org. Chem. 2021, 17, 1464–1475, doi:10.3762/bjoc.17.102

• biological activities (Figure 1) [10]. Unsubstituted DIM (I), for example, exhibits antimicrobial [5], anticancer [11][12][13], and anti-inflammatory effects (Figure 1) [14]. There is preclinical evidence for activity against several types of cancer [15], and DIM has been clinically evaluated for the

Double-headed nucleosides: Synthesis and applications

• Vineet Verma,
• Jyotirmoy Maity,
• Vipin K. Maikhuri,
• Ritika Sharma,
• Himal K. Ganguly and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2021, 17, 1392–1439, doi:10.3762/bjoc.17.98

• , Bose Institute, P1/12 CIT Scheme VIIM, Kolkata-700 054, India 10.3762/bjoc.17.98 Abstract Double-headed nucleoside monomers have immense applications for studying secondary nucleic acid structures. They are also well-known as antimicrobial agents. This review article accounts for the synthetic

Analogs of the carotane antibiotic fulvoferruginin from submerged cultures of a Thai Marasmius sp.

• Birthe Sandargo,
• Leon Kaysan,
• Rémy B. Teponno,
• Christian Richter,
• Benjarong Thongbai,
• Frank Surup and
• Marc Stadler

Beilstein J. Org. Chem. 2021, 17, 1385–1391, doi:10.3762/bjoc.17.97

• fulvoferruginins A–F (1–6), aside from the known antifungal activity of fulvoferruginin (1), no other antimicrobial activities were observed (Table S2 in Supporting Information File 1). All metabolites were also tested against the murine fibroblast cell line L929 and the cervix carcinoma cell line KB3.1. While all

• in CD3OD are collected in Table 1 and copies of spectra are collected in Supporting Information File 1; HRMS–ESI (m/z): [M + H]+ calcd for C15H21O3+, 249.1490; found, 249.1480. Antimicrobial activity The minimum inhibitory concentrations (MIC) of metabolites 1–6 were assessed using a serial dilution

• assay in 96-well microtiter plates with YM6.3 media (10 g/L malt extract, 4 g/L glucose, 4 g/L yeast extract, pH 6.3) for filamentous fungi and yeasts, and with BD DifcoTM Mueller Hinton Broth for bacteria. The antimicrobial assays were performed as previously described [13]. Cytotoxicity assay The

Synthesis of functionalized imidazo[4,5-e]thiazolo[3,2-b]triazines by condensation of imidazo[4,5-e]triazinethiones with DMAD or DEAD and rearrangement to imidazo[4,5-e]thiazolo[2,3-c]triazines

• Alexei N. Izmest’ev,
• Dmitry B. Vinogradov,
• Natalya G. Kolotyrkina,
• Angelina N. Kravchenko and
• Galina A. Gazieva

Beilstein J. Org. Chem. 2021, 17, 1141–1148, doi:10.3762/bjoc.17.87

• rearrangement; cyclocondensation; heterocycles; thiazolidine-4-one; 1,2,4-triazine; Introduction The thiazolidin-4-one heterocyclic system is a well-known, accessible and, as a consequence, a widely used pharmacophore in the chemistry of biologically active compounds possessing antimicrobial [1

• well as related thiazolo[3,2-b]-1,2,4-triazines and thiazolo[2,3-c]-1,2,4-triazines possessing antimicrobial, antidepressant, anti-HIV, and anticancer activities [10][11][12][13][14][15]. Modifications of the position 5 of the thiazolidine cycle often lead to an enhancement of the pharmacological

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

• transformed into β-lactam 60 in 90% yield by treatment with LDA in THF at −78 °C [90]. Compound 60 was converted after 9 steps in target batzelladines D 61 and 62 (Scheme 19). The authors explored also the antimicrobial activity of these compounds against a series of pathogens with starting promising results

• , and regulation of the immune response. Starting from α-alkoxy aldimines ent-126, the utility of this methodology was also demonstrated in the synthesis of alkaloid (+)-cassine (130), isolated from the leaves and twigs of Cassia excelsa, displaying antimicrobial activity. Methylmagnesium bromide was

Synthesis of 10-O-aryl-substituted berberine derivatives by Chan–Evans–Lam coupling and investigation of their DNA-binding properties

• Peter Jonas Wickhorst,
• Mathilda Blachnik,
• Denisa Lagumdzija and
• Heiko Ihmels

Beilstein J. Org. Chem. 2021, 17, 991–1000, doi:10.3762/bjoc.17.81

• also been employed in modern medicine because of its antimicrobial [3], antiprotozoal [4], antiviral [5], and anti-inflammatory [6] activity, and it is used in the treatment of tuberculosis [7], diarrhea [8], diabetes [9], cardiovascular diseases [10] or high cholesterol levels [11]. Most interestingly

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

• . Observations revealed that the conventional refluxing method produced only 10% of the desired product and brought microwave assistance to light. The synthesized molecules showed good antimicrobial activity against Escherichia coli, Candida tropicalis, Staphylococcus aureus and Pseudomonas aeruginosa (Scheme 12

• (47) for prevention of influenza A and B. β-Lapachone (48) shows diverse biological activities like anticancer, antibacterial and anti-inflammatory activities [53]. Benzopyrans and naphthopyrans represent a class of fused pyrans that has been studied for antimicrobial effects (49 and 50, Figure 4) [54

• cancer cell lines along with good antimicrobial activity (Scheme 24). The proposed mechanism (Scheme 25) involved a Knoevenagel condensation between aldehyde 5 and malononitrile (51) to form arylidene intermediate A. Then A reacts with isocyanide 21 to produce intermediate B which coordinates with 1,10

Synthesis of β-triazolylenones via metal-free desulfonylative alkylation of N-tosyl-1,2,3-triazoles

• Soumyaranjan Pati,
• Renata G. Almeida,
• Eufrânio N. da Silva Júnior and
• Irishi N. N. Namboothiri

Beilstein J. Org. Chem. 2021, 17, 762–770, doi:10.3762/bjoc.17.66

• class of heterocycles presents important biological properties, such as antiviral, anti-inflammatory, antimicrobial etc. and are considered as key building blocks in pharmaceutical industry [6][7][8][9]. Thus, they marked their presence as prominent scaffolds in many drug molecules such as tazobactam

β-Lactamase inhibition profile of new amidine-substituted diazabicyclooctanes

• Zafar Iqbal,
• Lijuan Zhai,
• Yuanyu Gao,
• Dong Tang,
• Xueqin Ma,
• Jinbo Ji,
• Jian Sun,
• Jingwen Ji,
• Yuanbai Liu,
• Rui Jiang,
• Yangxiu Mu,
• Lili He,
• Haikang Yang and
• Zhixiang Yang

Beilstein J. Org. Chem. 2021, 17, 711–718, doi:10.3762/bjoc.17.60

• MIC from <0.125 mg/L to 2 mg/L, and is comparable to avibactam against both E. coli strains with a MIC value of <0.125 mg/L. Keywords: amidine; antibacterial activity; β-lactamase inhibitors; diazabicyclooctane; synthesis; Introduction Survival stress posed by antimicrobial agents triggers multiple

Amino- and polyaminophthalazin-1(2H)-ones: synthesis, coordination properties, and biological activity

• Zbigniew Malinowski,
• Emilia Fornal,
• Agata Sumara,
• Renata Kontek,
• Karol Bukowski,
• Beata Pasternak,
• Dariusz Sroczyński,
• Joachim Kusz,
• Magdalena Małecka and
• Monika Nowak

Beilstein J. Org. Chem. 2021, 17, 558–568, doi:10.3762/bjoc.17.50

• analogs are an interesting group of pharmacologically active heterocycles [1][2], many of which possess, e.g., antimicrobial [3][4], antifungal [5], antidepressant [6][7], and antihistaminic [8][9][10] properties. Amino- and amidophthalazine derivatives have been examined, e.g., as inhibitors of PGE2