Synthesis of imidazo[1,2-a]pyridine-containing peptidomimetics by tandem of Groebke–Blackburn–Bienaymé and Ugi reactions

• Oleksandr V. Kolomiiets,
• Alexander V. Tsygankov,
• Maryna N. Kornet,
• Aleksander A. Brazhko,
• Vladimir I. Musatov and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2023, 19, 727–735, doi:10.3762/bjoc.19.53

• microorganisms (see Table 3 for details). Both Gram-positive and Gram-negative bacteria (specifically, strains of E. coli and B. subtilis) were equally inhibited in their growth. Compound 7o, in particular, was able to inhibit the growth of B. subtilis at a concentration of 125 mg/L. Bacteriostatic activity

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

• war against resistant bacteria strains. The tricyclic diterpene fungal metabolite (+)-pleuromutilin was isolated in 1951 [104]. Since then it has served as a starting point for developing new antibiotics, including semisynthetic derivatives effective against Gram-positive or even both types of

Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities

• Jorge de Lima Neto and
• Paulo Henrique Menezes

Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31

• ) against the bacteria Staphylococcus aureus, Bacillus subtilis, Micrococcus luteus, Escherichia coli, Klebsiella pneumoniae, and the fungi Aspergillus niger, Aspergillus terreus, and Aspergillus flavus. Unfortunately, all compounds were found to be inactive [14]. The use of compounds capable to delay

Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

• -positive and Gram-negative bacteria (Scheme 31B). 4.4 Photocatalyzed oxidative ring expansion: alternative radical chemistry for pleuromutilin scaffold construction Following the advent of photoredox catalysis in ring-opening and ring-expansion chemistry [75], a new route was proposed by Foy and Pronin 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

• ethanolic extract of this alga and found that a mid-polar fraction inhibited the growth of two Gram-positive bacteria, Bacillus subtilis and Staphylococcus aureus. Activity-guided fractionation led to the discovery of a new monoacylglycerol, nostochopcerol (1, Figure 1). Part of this study have been

• -hexane. The resulting three layers were tested against four Gram-positive bacteria, five Gram-negative bacteria, six fungi, and two yeasts, which detected antibacterial activity against two Gram-positive bacteria, Bacillus subtilis and Staphylococcus aureus, from the 90% aqueous MeOH layer. The

Preparation of β-cyclodextrin/polysaccharide foams using saponin

• Max Petitjean and
• José Ramón Isasi

Beilstein J. Org. Chem. 2023, 19, 78–88, doi:10.3762/bjoc.19.7

• , their aglycone forms but also the number of sugar molecules involved [11]. They can be found in beverage emulsions [12], and as food surfactants [13], because they are useful also to prevent the development of virus or bacteria in food or beverages [14][15]. As for medical purposes, it has been reported

Combining the best of both worlds: radical-based divergent total synthesis

• Kyriaki Gennaiou,
• Antonios Kelesidis,
• Maria Kourgiantaki and
• Alexandros L. Zografos

Beilstein J. Org. Chem. 2023, 19, 1–26, doi:10.3762/bjoc.19.1

• maydis in 2014 and were reported to possess antibacterial activity against a small panel of both gram-positive and -negative bacteria [89][90]. Interestingly, their chemical structure bears no resemblance to recognize antibiotics and their mechanism of action remains unknown. Based on the knowledge

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

• of different bacteria from highly diverse, low human activity environments in Ghana and the subsequent characterization and biological activity studies of their secondary metabolites, we found both Gram-positive and Gram-negative Bacillus strains to be ubiquitous and widespread. One of such strains

• -negative and Gram-positive standard laboratory bacteria including Escherichia coli, Staphylococcus aureus, Bacillus cereus, Shigella flexneri, Shigella sonnei, Salmonella paratyphi B, Salmonella enteritidis, Salmonella typhimurium, and Shigella dysenteriae (Table 3). Compound 1 was found to possess

• promising antimicrobial properties in comparison to the laboratory standards ampicillin and amphotericin B. Compound 1 produced interesting biological activity against the Gram-negative bacteria Shigella sonnei, Shigella flexneri and the multidrug resistant Gram-positive Staphylococcus aureus with IC50 of

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

Using UHPLC–MS profiling for the discovery of new sponge-derived metabolites and anthelmintic screening of the NatureBank bromotyrosine library

• Sasha Hayes,
• Aya C. Taki,
• Kah Yean Lum,
• Joseph J. Byrne,
• Merrick G. Ekins,
• Robin B. Gasser and
• Rohan A. Davis

Beilstein J. Org. Chem. 2022, 18, 1544–1552, doi:10.3762/bjoc.18.164

• natural product chemists have shifted their attention to marine-derived microorganisms such as bacteria and fungi over the past 10 years [2], sponges continue to be a source of novel and biologically active metabolites and remain an important taxonomic phylum for the discovery of new and bioactive natural

• the purealidin bromotyrosine structure class, however, quorum sensing inhibition and antifouling activities against several strains of bacteria and microalgae appears in the literature [33][34], while HIV-1 replication inhibition and anti-Leishmania and Plasmodium activity has also been recorded [35

Cyclometalated iridium complexes-catalyzed acceptorless dehydrogenative coupling reaction: construction of quinoline derivatives and evaluation of their antimicrobial activities

• Hongling Shui,
• Yuhong Zhong,
• Renshi Luo,
• Zhanyi Zhang,
• Jiuzhong Huang,
• Ping Yang and
• Nianhua Luo

Beilstein J. Org. Chem. 2022, 18, 1507–1517, doi:10.3762/bjoc.18.159

• against Gram-positive bacteria and compound 3ck against C. albicans were better than the reference drug norfloxacin. Keywords: acceptorless dehydrogenative coupling reaction; antibacterial; cyclometalated iridium complexes; quinolines; Introduction As an important class of heterocyclic compounds

• -triazoquinoline derivatives, and the biological activity evaluation showed that most of the compounds had a higher antibacterial activity (the optimal MIC value was 6.25 mg/mL) against Gram-positive bacteria, Gram-negative bacteria and all tested fungi than the standard ciprofloxacin (Figure 1a). Bodke's group

• Gram-positive bacteria. In particular, the antibacterial activity of compound 3ad against Staphylococcus aureus (MIC = 2 μg/mL) was much higher than that of the positive control norfloxacin. Meanwhile, the antifungal activity of compound 3ck (MIC = 64 μg/mL) was stronger than norfloxacin. However, 3an

Characterization of a new fusicoccane-type diterpene synthase and an associated P450 enzyme

• Jia-Hua Huang,
• Jian-Ming Lv,
• Liang-Yan Xiao,
• Qian Xu,
• Fu-Long Lin,
• Gao-Qian Wang,
• Guo-Dong Chen,
• Sheng-Ying Qin,
• Dan Hu and
• Hao Gao

Beilstein J. Org. Chem. 2022, 18, 1396–1402, doi:10.3762/bjoc.18.144

• their abundant structural architectures [1]. Fusicoccane (FC)-type terpenoids are a subgroup of diterpenoids possessing a unique 5-8-5 tricyclic skeleton, which can be produced by plants, fungi and bacteria [2]. This type of diterpenoids, represented by fusicoccin A and cotylenin A, can serve as

• nature. To date, only five distinct FC-type DTSs, including fungi-derived PaFS/SdnA/MgMS and bacteria-derived CotB2/CpCS, have been reported (Figure 1) [20][21][22][23][24], implying that there still exists a large enzymatic space remaining to be explored. Herein, we characterize a two-gene cluster from

On drug discovery against infectious diseases and academic medicinal chemistry contributions

• Yves L. Janin

Beilstein J. Org. Chem. 2022, 18, 1355–1378, doi:10.3762/bjoc.18.141

• ] was a SmithKline Beecham/GSK patent which disclosed in 1999 the effect on the growth of Gram-negative and Gram-positive bacteria of compounds such as E-105 (9) [116]. Extensive hit to lead programs were undertaken in quite a few pharmaceutical companies and in 2008 Novexel, a spinoff of Aventis/Sanofi

Synthesis of tryptophan-dehydrobutyrine diketopiperazine and biological activity of hangtaimycin and its co-metabolites

• Houchao Xu,
• Anne Wochele,
• Minghe Luo,
• Gregor Schnakenburg,
• Yuhui Sun,
• Heike Brötz-Oesterhelt and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2022, 18, 1159–1165, doi:10.3762/bjoc.18.120

• inactivity of 4 against bacteria was confirmed in this study, and also 2 is an inactive metabolite of S. spectabilis, while for 1 moderate growth retardation against A. baumannii and B. subtilis, and growth inhibition against PMBN-treated E. coli was observed. However, the low activity of 1 in these assays

• , growth control (no inhibitor), SC, sterile control (no bacteria), DMSO, culture medium supplemented with 1% DMSO, reflecting the DMSO concentrations in the hangtaimycin-containing samples. Structures of hangtaimycin (1) and its co-metabolites. First synthetic route towards TDD (4). Second synthetic route

Experimental and theoretical studies on the synthesis of 1,4,5-trisubstituted pyrrolidine-2,3-diones

• Nguyen Tran Nguyen,
• Vo Viet Dai,
• Nguyen Ngoc Tri,
• Luc Van Meervelt,
• Nguyen Tien Trung and
• Wim Dehaen

Beilstein J. Org. Chem. 2022, 18, 1140–1153, doi:10.3762/bjoc.18.118

• the fungal endophyte Acremonium zeae and its chemical structure was elucidated in 2002 (Figure 2). This natural 3-pyrrolin-2-one derivative exhibits potent antivity against Gram-positive bacteria [12]. Moreover, 1,5-dihydro-2H-pyrrol-2-ones and especially, 3-hydroxy-1,5-dihydro-2H-pyrrol-2-ones are

• also important substructures in a variety of non-natural compounds and their pharmacological effects against bacteria [13][14][15][16], inflammation [17][18], viruses [19], radical [20], and cancer [21][22][23][24][25][26] have been proven. It is undoubtedly true that heterocyclic compounds containing

A Streptomyces P450 enzyme dimerizes isoflavones from plants

• Run-Zhou Liu,
• Shanchong Chen and
• Lihan Zhang

Beilstein J. Org. Chem. 2022, 18, 1107–1115, doi:10.3762/bjoc.18.113

• , which extends the insights into P450-mediated biaryl coupling reactions in biosynthesis. Keywords: biaryl coupling; cytochrome P450; dimerization; isoflavone; natural product; Introduction Dimerization is a ubiquitous biotransformation in nature. Almost all forms of life, including bacteria, fungi

• [1][10][11][12][13][14]. In plants and fungi, laccases and cytochrome P450 monooxygenases play pivotal roles in the biaryl bond formation of various polyketide dimers [10][15][16]. In contrast, in bacteria, P450 enzymes are the dominant catalysts, but no laccases have been reported for dimerization

• of polyphenols in plants is mostly catalyzed by laccases, the dimerization of (iso)flavones by a P450 in Streptomyces may represent a convergent evolution in enzyme chemistry between plants and bacteria. Conclusion In conclusion, we have characterized three novel isoflavone dimers from S. cattleya

New azodyrecins identified by a genome mining-directed reactivity-based screening

• Atina Rizkiya Choirunnisa,
• Kuga Arima,
• Yo Abe,
• Noritaka Kagaya,
• Kei Kudo,
• Hikaru Suenaga,
• Junko Hashimoto,
• Manabu Fujie,
• Noriyuki Satoh,
• Kazuo Shin-ya,
• Kenichi Matsuda and
• Toshiyuki Wakimoto

Beilstein J. Org. Chem. 2022, 18, 1017–1025, doi:10.3762/bjoc.18.102

• , antifungal, nematicidal, and cytotoxic activities (Figure 1) [1][2][3]. Since the discovery of the natural azoxy compound macrozamin in 1951 as the first example of a nitrogen–nitrogen bond-containing natural product [4], azoxy compounds have been isolated from various natural sources including bacteria

Efficient production of clerodane and ent-kaurane diterpenes through truncated artificial pathways in Escherichia coli

• Fang-Ru Li,
• Xiaoxu Lin,
• Qian Yang,
• Ning-Hua Tan and
• Liao-Bin Dong

Beilstein J. Org. Chem. 2022, 18, 881–888, doi:10.3762/bjoc.18.89

• diterpenoids are two categories of diterpenoids that are widely distributed in terrestrial plants, fungi, and a few bacteria and possess broad pharmacological bioactivities [1][2][3]. Representative natural products containing these skeletons are terpentecin (cytotoxic and antibiotic), salvinorin A (kappa

The stereochemical course of 2-methylisoborneol biosynthesis

• Binbin Gu,
• Anwei Hou and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2022, 18, 818–824, doi:10.3762/bjoc.18.82

• recognized that many soil bacteria including various genera from the actinobacteria [3][4][5][6][7] and myxobacteria [8] produce the volatile musty odour compound 2-methylisoborneol (1). The compound is also found in marine Streptomyces strains [9] and aquatic cyanobacteria that can cause drinking water

• from Micromonospora humi can convert DMAPP into (R)-2-Me-IPP with a methyltransferase [27], naturally providing the C6 building block for this hypothetical alternative pathway towards 1 (Scheme 1B). Today the genomes of many bacteria from the genus Streptomyces have been made available, showing that

• the genes for the biosynthesis of 1 are present in about half of the species [28], which is reflected by the frequent detection of 1 among the volatiles emitted by a large number of streptomycetes and closely related bacteria [3][4][5][6][7]. A series of side products of the 2MIBS has been identified

Identification of the new prenyltransferase Ubi-297 from marine bacteria and elucidation of its substrate specificity

• Jamshid Amiri Moghaddam,
• Huijuan Guo,
• Karsten Willing,
• Thomas Wichard and
• Christine Beemelmanns

Beilstein J. Org. Chem. 2022, 18, 722–731, doi:10.3762/bjoc.18.72

• prenyltransferase; Introduction Marine bacteria harbor an enormous potential to produce structurally diverse natural products, including prenylated aromatic metabolites [1][2]. Prenylation of metabolites most often confers increased biological activities due to enhanced lipophilicity, solubility, and improved

• biosynthetic repertoire of marine bacteria [14][15], the diversity of the encoded and yet often unexplored bacterial Ptases of Flavobacteria and Saccharomonospora strains sparked our interest. In this study we investigated three yet poorly described homologous Ptases within the UbiA superfamily and evaluated

• their substrate scope by heterologous production and enzymatic bioassays. Results of our study showcase that marine bacteria harbor still a broad unexplored enzymatic repertoire. Results and Discussion In silico analysis of Ptases in marine Flavobacteria and the genus Saccharomonospora In a first step

Structural basis for endoperoxide-forming oxygenases

• Takahiro Mori and
• Ikuro Abe

Beilstein J. Org. Chem. 2022, 18, 707–721, doi:10.3762/bjoc.18.71

• endoperoxide containing alkaloids, terpenoids, and polyketides have been isolated from plants, animals, bacteria, fungi, and other organisms (Figure 1) [6][7]. Because of the high reactivity of the cyclic peroxide O–O bond, these compounds exhibit various biological activities [1][2][3][4][5]. For example

Cholyl 1,3,4-oxadiazole hybrid compounds: design, synthesis and antimicrobial assessment

• Anas J. Rasras,
• Mohamed El-Naggar,
• Nesreen A. Safwat and
• Raed A. Al-Qawasmeh

Beilstein J. Org. Chem. 2022, 18, 631–638, doi:10.3762/bjoc.18.63

• acid with the heterocyclic moiety 1,3,4-oxadizole was synthesized, and tested for antimicrobial activity against Gram-positive, Gram-negative bacteria, and fungi. Among the synthesized compounds, the most potent derivatives against S. aureus were 4t, 4i, 4p, and 4c with MIC values between 31 and 70 µg

• /mL, while compound 4p was the most active one against Bacillus subtilis with a MIC value of 70 µg/mL. Interestingly, compounds 4a and 4u exerted selective activity against Gram-positive bacteria. The synthesized compounds showed good activity against A. fumigatus and C. albicans and compound 4v

• exhibited selective activity against fungi only. Keywords: antibacterial; cholic acid; heterocyclic; Mannich reaction; oxadiazole; Introduction Microbial infections caused by Gram-negative and Gram-positive bacteria embarrass the health care system worldwide [1]. Pathogens such as Escherichia coli

The asymmetric Henry reaction as synthetic tool for the preparation of the drugs linezolid and rivaroxaban

• Martin Vrbický,
• Karel Macek,
• Jaroslav Pochobradský,
• Jan Svoboda,
• Miloš Sedlák and
• Pavel Drabina

Beilstein J. Org. Chem. 2022, 18, 438–445, doi:10.3762/bjoc.18.46

• -2-one antibiotics only the S-enantiomers are able to block bacterial ribosomes, which leads to the prevention of translation processes in bacteria [9][10]. With regards to these facts, a high enantiomeric purity is one of the fundamental requirements in the production of such pharmaceutical

Amamistatins isolated from Nocardia altamirensis

• Till Steinmetz,
• Wolf Hiller and
• Markus Nett

Beilstein J. Org. Chem. 2022, 18, 360–367, doi:10.3762/bjoc.18.40

• must be able to control the uptake of this important nutrient from the environment. In bacteria and fungi this is usually accomplished with the help of siderophores [2]. Siderophores are small molecules which, upon secretion, solubilize and coordinate ferric iron with high affinity. The ability to bind

• filamentous Actinobacteria, which live as saprophytes and were reported from a variety of environments. Although the soil is likely the primary reservoir of these bacteria, a considerable number of Nocardia strains was isolated from human tissue and can be associated with infectious diseases [5]. The genus

Anomeric 1,2,3-triazole-linked sialic acid derivatives show selective inhibition towards a bacterial neuraminidase over a trypanosome trans-sialidase

• Peterson de Andrade,
• Sanaz Ahmadipour and
• Robert A. Field

Beilstein J. Org. Chem. 2022, 18, 208–216, doi:10.3762/bjoc.18.24

• (GH) families and play fundamental roles in the biology of humans, viruses, bacteria and parasitic protozoa by cleaving glycosidic linkages and releasing (or transferring) sialic acid from sialylated substrates [2]. In fact, sialidases have been associated with the pathogenesis of various diseases and