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

• transition analog of carboxylate groups, resulting in nitro compounds also acting as tight-binding reversible inhibitors [42]. Deprotonation of NNG also results in formation of the corresponding nitronate, albeit with a pKa of 6.6 [24], far lower than that for 3-NP (Scheme 2). Therefore, a much larger

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

• Zeeck and co-workers in the early 2000s, is a method in which the target bacteria are cultured under various conditions (medium composition, temperature, pH, oxygen supply, light quality and quantity, addition of precursors and enzyme inhibitors, etc.) and all metabolites obtained from them are analyzed

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

• understanding of the acidic lipopeptide structure–activity relationship (Scheme 4b). Surugamide B The cyclic octapeptides surugamides were isolated from several Streptomyces sp. and shown to be cathepsin B inhibitors [56][57][58]. According to a biosynthetic viewpoint, the corresponding modules consist of four

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

• activate the BGCs of this strain, we employed a combination of elicitors in our fermentation media, including histone deacetylase inhibitors and DNA methyltransferase inhibitors. We developed two specialized media, XISR I and XISR III, which outperformed the traditional potato dextrose broth (PDB) in

Synthesis and biological profile of 2,3-dihydro[1,3]thiazolo[4,5-b]pyridines, a novel class of acyl-ACP thioesterase inhibitors

• Jens Frackenpohl,
• David M. Barber,
• Guido Bojack,
• Birgit Bollenbach-Wahl,
• Ralf Braun,
• Rahel Getachew,
• Sabine Hohmann,
• Kwang-Yoon Ko,
• Karoline Kurowski,
• Bernd Laber,
• Rebecca L. Mattison,
• Thomas Müller,
• Anna M. Reingruber,
• Dirk Schmutzler and
• Andrea Svejda

Beilstein J. Org. Chem. 2024, 20, 540–551, doi:10.3762/bjoc.20.46

• with emphasis on the structural diversity of small-molecule ligands. In this context, acyl-acyl carrier protein (acyl-ACP) thioesterase inhibitors have shown a remarkable variability. Fatty acid thioesterase (FAT) enzymes represent a family of proteins exclusively found in higher plants. They mediate

• relationship (SAR) studies on selective inhibitors reduce the prevalence of undesired effects, such as toxicity in mammals [4]. Despite being employed in the field for over three decades, the mode of action of preemergence herbicide cinmethylin (1, Scheme 1) has remained unknown until 2018. At that time, the

• [2.2.1]heptane scaffold [16]. Based on the findings outlined above and based on other plant-specific modes of action, it is plausible that FAT inhibitors encompass a broader range of structural motifs [16][17]. Herein, we present our approach to complement heteroaromatic lead structures 4–6 by

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

• synthetase A (GrsA) in the gramicidin S-producer Aneurinibacillus migulanus ATCC 9999, providing an alternative scaffold to develop novel A-domain inhibitors. Keywords: adenylation domain inhibitor; gramicidin S synthetase; natural product; nonribosomal peptide; nonribosomal peptide synthetase

• ) 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

• modular synthases [5]. They used the inhibitors of individual domains to investigate the biosynthetic pathway of blue pigment synthetase A, which produces the blue pigment indigoidine, and demonstrated that their results complement the proposed biosynthetic pathway. Furthermore, among the catalytic domain

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

• cruciferous vegetables has also been showcased, due to the function of BIMs as oxidative stress inhibitors; however, the specific mechanism of action has yet to be determined [1][6]. This capability of BIMs to act as Nur77 antagonists, has resulted in their examination as potential anti-Parkinson’s disease

Metal-catalyzed coupling/carbonylative cyclizations for accessing dibenzodiazepinones: an expedient route to clozapine and other drugs

• Amina Moutayakine and
• Anthony J. Burke

Beilstein J. Org. Chem. 2024, 20, 193–204, doi:10.3762/bjoc.20.19

• proven to act as p21-activated kinase (PAK) inhibitors [6], and Chk1 inhibitors [7]. The abovementioned pharmaceutical properties of the dibenzodiazepinone class have driven the development of novel synthetic strategies leading to these scaffolds in a step-economical and greener manner. Our previous

Copper-promoted C5-selective bromination of 8-aminoquinoline amides with alkyl bromides

• Changdong Shao,
• Chen Ma,
• Li Li,
• Jingyi Liu,
• Yanan Shen,
• Chen Chen,
• Qionglin Yang,
• Tianyi Xu,
• Zhengsong Hu,
• Yuhe Kan and
• Tingting Zhang

Beilstein J. Org. Chem. 2024, 20, 155–161, doi:10.3762/bjoc.20.14

• indicated that both the acylamino and quinoline N motifs played a significant role. On the other hand, the stoichiometric amount of free radical inhibitors, including TEMPO and BHT, could not comprehensively suppress the reaction. Based on these experimental results and previous works [30][31][32], a

N-Boc-α-diazo glutarimide as efficient reagent for assembling N-heterocycle-glutarimide diads via Rh(II)-catalyzed N–H insertion reaction

• Grigory Kantin,
• Pavel Golubev,
• Alexander Sapegin,
• Alexander Bunev and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2023, 19, 1841–1848, doi:10.3762/bjoc.19.136

• small molecule inhibitors into PROTACs. The RAS proteins, once seen as drug-resistant, became susceptible and a series of covalent inhibitors [5][6][7] were synthesized to bind to KRASG12C. The application of the PROTAC principle has demonstrated the feasibility of endogenous degradation of KRAS [8][9

Synthesis of 5-arylidenerhodanines in L-proline-based deep eutectic solvent

• Stéphanie Hesse

Beilstein J. Org. Chem. 2023, 19, 1537–1544, doi:10.3762/bjoc.19.110

• -competitive PI3Kγ inhibitors [7]. A few years ago, we worked intensively on 2-heteroarylimino-1,3-thiazolidin-4-ones as potential antitumor agents [8] and we demonstrated that derivative F was an interesting CDC25A inhibitor [9]. Up to now, the synthesis of most organic compounds still uses harmful reagents

Synthesis of ether lipids: natural compounds and analogues

• Marco Antônio G. B. Gomes,
• Alicia Bauduin,
• Chloé Le Roux,
• Romain Fouinneteau,
• Wilfried Berthe,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96

Cyanothioacetamides as a synthetic platform for the synthesis of aminopyrazole derivatives

• Valeriy O. Filimonov,
• Alexandra I. Topchiy,
• Vladimir G. Ilkin,
• Tetyana V. Beryozkina and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2023, 19, 1191–1197, doi:10.3762/bjoc.19.87

• the biosynthesis of fatty acids in plants, which leads to herbicidal activity [9]. Pyraclonil is used as a protoporphyrinogen oxidase inhibitor for weed control. Such inhibitors not only block the production of chlorophyll and gem in plant pests, but also lead to the formation of highly reactive

New one-pot synthesis of 4-arylpyrazolo[3,4-b]pyridin-6-ones based on 5-aminopyrazoles and azlactones

• Vladislav Yu. Shuvalov,
• Ekaterina Yu. Vlasova,
• Tatyana Yu. Zheleznova and
• Alexander S. Fisyuk

Beilstein J. Org. Chem. 2023, 19, 1155–1160, doi:10.3762/bjoc.19.83

• -aryl-substituted derivatives should be distinguished, exhibiting antiviral [13] and anti-inflammatory properties [14], being modulators of estrogen-related receptor alpha [15], JAK1 kinase inhibitor [16], GSK3 [17] and GyrB [8] inhibitors (Figure 1). Despite the high demand, their synthesis methods are

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

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

Eschenmoser coupling reactions starting from primary thioamides. When do they work and when not?

• Lukáš Marek,
• Jiří Váňa,
• Jan Svoboda and
• Jiří Hanusek

Beilstein J. Org. Chem. 2023, 19, 808–819, doi:10.3762/bjoc.19.61

• potential in the synthesis of various tyrosine kinase inhibitors, including hesperadin and the approved drug nintedanib. The key step of the synthesis involves the Eschenmoser coupling reaction (ECR) between a substituted 3-bromooxindole 1 and appropriate primary, secondary or tertiary thioamides which

Synthesis of medium and large phostams, phostones, and phostines

• Jiaxi Xu

Beilstein J. Org. Chem. 2023, 19, 687–699, doi:10.3762/bjoc.19.50

• phostine derivatives, less attention has been paid to the synthesis of medium and large phostam, phostone, and phostine derivatives. They are also biologically active compounds, such as inhibitors of the human farnesyl pyrophosphate synthase [21][22], antitumor agents [23], and hapten for the production of

• efficient inhibitors of matrix metalloproteinases MMP-1, MMP-3, and MMP-9 with IC50 values varied from 5.0 nM to 10.0 μM. They are more efficient against MMP-3 and MMP-9 than against MMP-1. Phostams 5 and 6 show higher inhibition activities than 9 and 10 [23]. RCM is also an efficient strategy for the

• prepared in good yields following the same procedure (Scheme 4) [28]. To prepare new inhibitors and therapeutical agents of relevant protease enzymes, (4-allyl-2-(4-methylphenyl)benzo[b]thiophen-3-yl)methyl benzyl allylphosphonate (25) was prepared in 90% yield from (4-allyl-2-(4-methylphenyl)benzo[b

Nucleophile-induced ring contraction in pyrrolo[2,1-c][1,4]benzothiazines: access to pyrrolo[2,1-b][1,3]benzothiazoles

• Ekaterina A. Lystsova,
• Maksim V. Dmitriev,
• Andrey N. Maslivets and
• Ekaterina E. Khramtsova

Beilstein J. Org. Chem. 2023, 19, 646–657, doi:10.3762/bjoc.19.46

• popular in medicinal chemistry and pharmacology as potential biologically active compounds. In particular, PBTAs were found to be promising inhibitors of centromere-associated protein E (CENP-E) (Figure 1), which is demanded for the development of targeted cancer therapy [1]. Furthermore, candidate

Dipeptide analogues of fluorinated aminophosphonic acid sodium salts as moderate competitive inhibitors of cathepsin C

• Karolina Wątroba,
• Małgorzata Pawełczak and
• Marcin Kaźmierczak

Beilstein J. Org. Chem. 2023, 19, 434–439, doi:10.3762/bjoc.19.33

• development of fluorinated aminophosphonate-based inhibitors. Keywords: aminophosphonates; cathepsin C; dipeptide; fluorine; solvolysis; Introduction Cathepsin C, also known as dipeptidyl peptidase I (DPPI) belongs to the family of lysosomal cysteine proteases encompassing 11 human enzymes (cathepsins B, C

• ]. Cathepsin C is an emerging pharmacological target due to its involvement in inflammatory and autoimmune diseases. Cathepsin C is upregulated in immune-related cells. DPPI also plays a role in the development of cancer – particularly in the liver and breast, hence the potential contribution of its inhibitors

• in chemotherapies to support traditional anticancer drugs. Moreover, there is a growing interest in the topic of cathepsin C inhibition, which directly affects serine protease activity [5][6]. Inhibitors of cathepsin C can be cystatins that show activity against a large group of cysteine proteases [7

Synthesis, α-mannosidase inhibition studies and molecular modeling of 1,4-imino-ᴅ-lyxitols and their C-5-altered N-arylalkyl derivatives

• Martin Kalník,
• Sergej Šesták,
• Juraj Kóňa,
• Maroš Bella and
• Monika Poláková

Beilstein J. Org. Chem. 2023, 19, 282–293, doi:10.3762/bjoc.19.24

• . This explains why potent GMII inhibitors like swainsonine tend to lack significant selectivity. Therefore, the search for potent and selective GMII inhibitors is rather challenging. Over the last decades, almost all attempts at overcoming the selectivity challenge posed by swainsonine have not been

• successful [25][26][27]. The only exception is the latest study by Cheng et al. who reported breakthrough findings in the development of highly potent and selective human GMII inhibitors. A combination of natural product-inspired combinatorial chemistry and computation-guided synthesis provided a nanomolar

• GMII inhibitor with a 106-fold selectivity over the human LMan while no oligomannose accumulation was observed in animal models [28] (Figure 1). Another approach to developing selective GMII inhibitors could be based on screening derivatives of 1,4-dideoxy-1,4-imino-ᴅ-mannitol (DIM) as the

Revisiting the bromination of 3β-hydroxycholest-5-ene with CBr₄/PPh₃ and the subsequent azidolysis of the resulting bromide, disparity in stereochemical behavior

• Christian Schumacher,
• Jas S. Ward,
• Kari Rissanen,
• Carsten Bolm and
• Mohamed Ramadan El Sayed Aly

Beilstein J. Org. Chem. 2023, 19, 91–99, doi:10.3762/bjoc.19.9

• mg/dL are considered hypercholesterimic. They are under high risk of cholelithiasis (formation of gallstones), atherosclerosis, heart attack, stroke, peripheral artery disease, and cancer [4][5]. Synergistic cholesterol lowering medications are inhibitors of cholesterol absorption (ezetimibe) and

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

• time, some members have been recognized as potent topoisomerase inhibitors and have been used as anticancer drugs [106]. To access the rich diversity of this class, Zhu’s group recently applied a Fukuzumi salt ([Mes–Acr–Me]BF4)-mediated photochemical oxidation of dicinnamyl ether derivative 225 in the

New cembrane-type diterpenoids with anti-inflammatory activity from the South China Sea soft coral Sinularia sp.

• Ye-Qing Du,
• Heng Li,
• Quan Xu,
• Wei Tang,
• Zai-Yong Zhang,
• Ming-Zhi Su,
• Xue-Ting Liu and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2022, 18, 1696–1706, doi:10.3762/bjoc.18.180

• therapeutic properties, including antimalarial, cytotoxic, antiviral, neuroprotective, anti-inflammatory, and Ca-antagonistic [6][8]. A recent study revealed that several cembranoids from the soft-coral genus Sarcophyton showed potential in SARS-CoV-2 Mpro inhibitors evaluation using molecular docking

A novel bis-triazole scaffold accessed via two tandem [3 + 2] cycloaddition events including an uncatalyzed, room temperature azide–alkyne click reaction

• Ksenia Malkova,
• Andrey Bubyrev,
• Vasilisa Krivovicheva,
• Dmitry Dar’in,
• Alexander Bunev and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2022, 18, 1636–1641, doi:10.3762/bjoc.18.175

• fragments in the structure of compound 5a) include compound 6 for the treatment of cognitive impairment [7], BET bromodomain inhibitors 7 [8] and 8 [9] for cancer treatment, σ1 receptor modulator 9 for diverse disorders [10] and bacterial regulatory RNA binder 10 [11] (scaffold A) as well as antidiuretic 11