pKalculator: A pK_a predictor for C–H bonds

• Rasmus M. Borup,
• Nicolai Ree and
• Jan H. Jensen

Beilstein J. Org. Chem. 2024, 20, 1614–1622, doi:10.3762/bjoc.20.144

• complex molecules by exchanging a C–H bond with different functional groups to modify the biological activity of drugs [2]. However, pinpointing which C–H bond is reacting can be challenging. Grzybowski and co-workers recently addressed this gap by predicting pKa values for C–H bonds in dimethyl sulfoxide

The Ugi4CR as effective tool to access promising anticancer isatin-based α-acetamide carboxamide oxindole hybrids

• Carolina S. Marques,
• Aday González-Bakker and
• José M. Padrón

Beilstein J. Org. Chem. 2024, 20, 1213–1220, doi:10.3762/bjoc.20.104

• . Overall, the results of the biological activity allow speculating that the compounds from the series 8a–n might exhibit diverse mode of actions. Taking all these considerations as a whole, further studies of the biological activity of compounds 8d, 8h and 8k might provide insights into the mode of action

Stability trends in carbocation intermediates stemming from germacrene A and hedycaryol

• Naziha Tarannam,
• Prashant Kumar Gupta,
• Shani Zev and
• Dan Thomas Major

Beilstein J. Org. Chem. 2024, 20, 1189–1197, doi:10.3762/bjoc.20.101

• microbes, in the form of alcohols, ketones, lactones, and glycosides, and of these various forms, the oxo derivatives in particular have strong aroma and biological activity. Interestingly, in addition to being used routinely as flavorings and aromatic agents, sesquiterpene oxo derivatives also have

Mild and efficient synthesis and base-promoted rearrangement of novel isoxazolo[4,5-b]pyridines

• Vladislav V. Nikol’skiy,
• Mikhail E. Minyaev,
• Maxim A. Bastrakov and
• Alexey M. Starosotnikov

Beilstein J. Org. Chem. 2024, 20, 1069–1075, doi:10.3762/bjoc.20.94

• fields of chemistry and materials science. These compounds are widespread in medicinal chemistry [1][2][3], production of high-energy-density compounds [4][5][6][7], and many others. In particular, isoxazolo[4,5-b]pyridines are of considerable interest due to their remarkable variety of biological

• activity, such as antibacterial [8], anticancer [9] or antiproliferative [10]. In addition, isoxazolo[4,5-b]pyridines were found to inhibit cytochrome P450 CYP17 responsible for the biosynthesis of androgens and estrogen precursors [11]. Some biologically active isoxazolo[4,5-b]pyridines are shown on

Novel analogues of a nonnucleoside SARS-CoV-2 RdRp inhibitor as potential antivirotics

• Luca Julianna Tóth,
• Kateřina Krejčová,
• Milan Dejmek,
• Eva Žilecká,
• Blanka Klepetářová,
• Lenka Poštová Slavětínská,
• Evžen Bouřa and
• Radim Nencka

Beilstein J. Org. Chem. 2024, 20, 1029–1036, doi:10.3762/bjoc.20.91

• modifications of HeE1-2Tyr: conversion of the core from a benzothiazole to a benzoxazole moiety and two different scaffold simplifications, respectively. We provide a novel synthetic approach and, in addition, evaluate the final molecules in an in vitro polymerase assay for biological activity. Keywords

Innovative synthesis of drug-like molecules using tetrazole as core building blocks

• Jingyao Li,
• Ajay L. Chandgude,
• Qiang Zheng and
• Alexander Dömling

Beilstein J. Org. Chem. 2024, 20, 950–958, doi:10.3762/bjoc.20.85

• the Passerini reaction involving atypical substrates, we aimed to investigate the unprecedented use of the tetrazole building block as an oxo component in the Passerini reaction to build a library that would possess drug-like molecules and could be easily screened for biological activity and

(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

• early drug discovery process. In many cases, the primary aim is the enhancement of biological activity, but in others, modulation of other critical properties such as aqueous solubility, metabolic stability, polarity, or lipophilicity is the target. In the latter cases, there is often a desire to retain

• otherwise potent biological activity and here the application of bioisosteric fragments can play a leading role. Bioisosteres are structurally distinct from the groups they replace, leading to changes in the physiochemical properties of the overall compound, but allow for retention of the biological

• biological activity are similar to the parent compound. For simplicity, geometric isosteres will be simply referred to as isosteres. More densely substituted scaffolds will be briefly discussed at the end of the review. Geometrical equivalence between disubstituted benzenes and scaffolds will be quantified

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

• properties and to modify the profile of biological activity due to optimum fluorine lipophylic properties, and enhanced interaction with lipid membranes [12][13][14]. Pentafluorophenyl-substituted porphyrin systems are especially useful for the connection of various functionalities capable for coupling with

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

• actinomycetes based on original ideas. For example, in searching for compounds based on biological activity, a proper screening system is critical [15]. Screening systems are broadly classified as either forward screening (searching for compounds that induce phenotypic changes) or reverse screening (searching

• . At a concentration of 182 μM, murecholamide exhibits biological activity in inhibiting the migration of HT29 cancer cells. The second HSM is noaoxazole (39), which was discovered in Streptomyces sp. HR41 [79]. This substance has a chemical structure with a methylated oxazole ring at the end of a

• ]. Nocarjamide exhibited biological activity by activating Wnt signaling at an effective concentration of 20–40 μM. Wnt signaling plays an important role in a number of vital processes, such as the formation of various tissues and the differentiation/proliferation of eukaryotic cells [122]. It is interesting

Research progress on the pharmacological activity, biosynthetic pathways, and biosynthesis of crocins

• Zhongwei Hua,
• Nan Liu and
• Xiaohui Yan

Beilstein J. Org. Chem. 2024, 20, 741–752, doi:10.3762/bjoc.20.68

• ) ameliorates myocardial ischemia or myocardial infarction induced by coronary ligation. Although crocin and crocetin derivatives exhibit a diverse scope of biological activity, they are characterized by poor stability and low bioavailability, which has significantly impeded clinical developments. Recently

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

• review summarizes recent advances in combining thioesterase-catalyzed macrocyclization and typical chemical approaches in the rapid generation of these complex cyclic natural products and their analogs with exquisite biological activity. Moreover, multistep enzyme cascades simplify synthesis by reducing

New variochelins from soil-isolated Variovorax sp. H002

• Jabal Rahmat Haedar,
• Aya Yoshimura and
• Toshiyuki Wakimoto

Beilstein J. Org. Chem. 2024, 20, 692–700, doi:10.3762/bjoc.20.63

• variochelins [20]. Biological activity The antimicrobial activities of 1–5 were evaluated against several Gram-negative and Gram-positive bacteria (Table 1). As a result, 1–5 inhibited the growth of the Gram-negative bacteria Escherichia coli and Burkholderia multivorans, but lacked activity against Bacillus

Production of non-natural 5-methylorsellinate-derived meroterpenoids in Aspergillus oryzae

• Jia Tang,
• Yixiang Zhang and
• Yudai Matsuda

Beilstein J. Org. Chem. 2024, 20, 638–644, doi:10.3762/bjoc.20.56

• -derived counterpart of 3, displayed weaker activity against the two bacterial strains and was not active at the concentration of 500 µg/mL. Thus, the lack of the C-5′ methyl group somehow contributes to the biological activity of 3. Conclusion We employed a pathway engineering approach to create a series

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

• commercially important grass weed LOLRI, paired with insufficient control of ECHCG by methiozolin (2) in our greenhouse tests. Furthermore, we used thiazolo[4,5-b]pyridine 5 as a strong internal standard to assess how modification of the thiazole moiety would affected the biological activity. It is worth

Switchable molecular tweezers: design and applications

• Pablo Msellem,
• Maksym Dekthiarenko,
• Nihal Hadj Seyd and
• Guillaume Vives

Beilstein J. Org. Chem. 2024, 20, 504–539, doi:10.3762/bjoc.20.45

• molecular tweezers has been in molecular recognition with reversible guest binding, we believe that the scope of applications can be significantly broader. Recent examples have demonstrated their potential to regulate biological activity, facilitate transmembrane transport, enable switchable catalysis

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

• spectrum, did not match any compound in the Dictionary of Natural Products database (version 32.1). Fermentation, isolation, structural elucidation, and biological activity of 1 are described in the following. Results and Discussion Saccharopolyspora sp. KR21-0001 was isolated from soil in Ōha island

• to red). Next, the mixtures were incubated at 37 °C for 1 h. After incubation, 25 µL of 1 M HCl was added to each sample for neutralization. The mixtures were concentrated to dryness in vacuo, dissolved in acetonitrile, and analyzed by LC–MS. Biological activity Antioxidant activity The antioxidant

Synthesis of spiropyridazine-benzosultams by the [4 + 2] annulation reaction of 3-substituted benzoisothiazole 1,1-dioxides with 1,2-diaza-1,3-dienes

• Wenqing Hao,
• Long Wang,
• Jinlei Zhang,
• Dawei Teng and
• Guorui Cao

Beilstein J. Org. Chem. 2024, 20, 280–286, doi:10.3762/bjoc.20.29

• . Inspired by the potential biological activity of pyridazines and in continuation of our work on the synthesis of spirobenzosultams [31][32][33], we herein report a highly diastereoselective route for the synthesis of spiropyridazine-benzosultams through [4 + 2] annulation reactions of 3-substituted

Photochromic derivatives of indigo: historical overview of development, challenges and applications

• Gökhan Kaplan,
• Zeynel Seferoğlu and
• Daria V. Berdnikova

Beilstein J. Org. Chem. 2024, 20, 228–242, doi:10.3762/bjoc.20.23

• assemblies as well as precise switching of the biological activity of the photoswitchable derivative. Along these lines, in 2023, Leung and co-workers prepared amphiphilic indigo-based photoswitches and incorporated them into vesicles [88]. Irradiation of the vesicles with red light resulted in the E–Z

Visible-light-induced radical cascade cyclization: a catalyst-free synthetic approach to trifluoromethylated heterocycles

• Chuan Yang,
• Wei Shi,
• Jian Tian,
• Lin Guo,
• Yating Zhao and
• Wujiong Xia

Beilstein J. Org. Chem. 2024, 20, 118–124, doi:10.3762/bjoc.20.12

• their biological activity and potential applications, continuous efforts have been dedicated to the synthesis of DHPI derivatives. Various synthetic strategies have been explored (Scheme 1), including transition-metal-catalyzed cross-coupling reactions [8][9][10], annulation reaction of carbenoids [11

Photoinduced in situ generation of DNA-targeting ligands: DNA-binding and DNA-photodamaging properties of benzo[c]quinolizinium ions

• Julika Schlosser,
• Olga Fedorova,
• Yuri Fedorov and
• Heiko Ihmels

Beilstein J. Org. Chem. 2024, 20, 101–117, doi:10.3762/bjoc.20.11

• biological activity. Furthermore, we have discovered that this class of compounds has a large potential to operate as photosensitizer that induces DNA damage already at relatively low irradiation times and low concentrations. Most notably, the photoinduced DNA damage does not necessarily require oxygen

Synthesis and biological evaluation of Argemone mexicana-inspired antimicrobials

• Jessica Villegas,
• Bryce C. Ball,
• Katelyn M. Shouse,
• Caleb W. VanArragon,
• Ashley N. Wasserman,
• Hannah E. Bhakta,
• Allen G. Oliver,
• Danielle A. Orozco-Nunnelly and
• Jeffrey M. Pruet

Beilstein J. Org. Chem. 2023, 19, 1511–1524, doi:10.3762/bjoc.19.108

• explored screening methanol and hexane extracts of various parts of the A. mexicana plant (seeds, leaves, inner vs outer roots) for biological activity with the outer root methanol extract showing the highest activity against Gram-positive bacteria as well as inhibitory effects against human colon cancer

One-pot nucleophilic substitution–double click reactions of biazides leading to functionalized bis(1,2,3-triazole) derivatives

• Hans-Ulrich Reissig and
• Fei Yu

Beilstein J. Org. Chem. 2023, 19, 1399–1407, doi:10.3762/bjoc.19.101

• abstained from the conversion of compounds 24, 25 or 26 into their sulfated form due to the presence of the impurities in these samples. However, only the sulfated forms of this type of multivalent carbohydrate mimetics had earlier shown respectable biological activity as ligands of P- and L-selectins [44

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

• to prepare alkyl ether lipids. The synthesis methods specifically designed for the preparation of alkenyl ether lipids (plasmalogen) are not reviewed herein. For each compound, their synthesis is reported jointly, when appropriate, with some elements relative to their biological activity. The next

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

• exhibit a variety of biological activity. Their application is known in pharmacy [1][2][3][4] and agro-industry [5][6][7][8]. Especially such compounds are used to protect plants from insects and weeds (Figure 1). Thus, pinoxaden is a commercially available inhibitor of acetyl-CoA carboxylase and affects

• biologically active substances containing amide groups [14]. The presence of a pyrazole core and a thioamide group within the hybrid molecules that we are planning to obtain, allows us to expect both an increase in their activity and the emergence of other types of biological activity, and also high synthetic

Five new sesquiterpenoids from agarwood of Aquilaria sinensis

• Hong Zhou,
• Xu-Yang Li,
• Hong-Bin Fang,
• He-Zhong Jiang and
• Yong-Xian Cheng

Beilstein J. Org. Chem. 2023, 19, 998–1007, doi:10.3762/bjoc.19.75

• from agarwood. Unfortunately, none of the new compounds exhibits biological activity against LPS-induced inflammation in Raw264.7 cells and human breast cancer cells. However, we have drawn good conclusions for SAR studies based on the current study and our previous study. These compounds will be

• isolated by other researchers in the future, who could consider our conclusions and choose other aspects of biological activity to study. Experimental General procedures NMR spectra were recorded on a Bruker AV-500 or AV-600 spectrometer with TMS as an internal standard. Silica gel (200–300 mesh; Qingdao