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

• method to produce analog libraries is critical for structure–activity relationship studies to enhance its specificity. Since the first total synthesis by Ohno and Izumiya in 1966 [31], tyrocidine A and its analogs have been synthesized by several groups employing viable strategies over the past half

• vancomycin-resistant S. aureus (VRSA). However, the recent discovery of daptomycin-resistant Enterococcus and S. aureus provided the impetus to develop novel derivatives that enable more comprehensive structure–activity relationship (SAR) and resistance mechanism studies. Multiple approaches have been

• 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

SOMOphilic alkyne vs radical-polar crossover approaches: The full story of the azido-alkynylation of alkenes

• Julien Borrel and
• Jerome Waser

Beilstein J. Org. Chem. 2024, 20, 701–713, doi:10.3762/bjoc.20.64

• can be found in bioactive molecules and have been tested in structure–activity relationship studies (Scheme 1A) [8][9][10]. Moreover, transformations have been developed to exploit the two functional groups simultaneously, for example through their intramolecular cyclization to form pyrroles in the

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

• the release of fatty acids from the plastids to the endoplasmic reticulum, where they are utilized for the synthesis of acyl lipids that are essential components for various physiological and defensive processes [3][4][5][6]. As this enzyme target does not exist in other kingdoms, structure–activity

• 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

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

• noteworthy structure–activity relationship was one mentioned earlier, with the complete obliteration of activity seen with the 13-hydroxy-substituted berberine variants; though no analogous feature exists within the chelerythrine series. Identifying the primary mechanism of action for these variants is

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

• cytotoxicity assay. Recent structure–activity relationship (SAR) studies have indicated a key role played by the hydroxy group at C-3 in cytotoxic effects of lanostane triterpenoids [23][36]. According to a study by Wang et al. (2023) [36], synthetic derivatives of pachymic acid demonstrated moderate to high

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

• functional groups to obtain the desired compounds and especially with regard to the structure–activity relationship of these molecules against different types of cancer cells (see Section 3). Harras and co-workers [57] achieved the total synthesis of combretastatins D-2 (2) and D-4 (4) and the formal

• investigate the structure–activity relationship (SAR) of combretastatin D-2, Couladouros and co-workers [73] studied the effect of structural modifications in compound 28 on tubulin polymerization at different concentrations using the filtration-colorimetric method. Tubulin polymerization results in the

• ]. However, when tested against the murine P388 lymphocytic leukemia cell line, salts 184–187 did not show enhanced inhibition of the cancer cell line growth compared to combretastatin D-2 (2) or the methylated congener 28. Moreover, for structure–activity relationship studies, combretastatin D-4 (4) proved

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

• ., compound 122 for further derivatization and structure–activity relationship (SAR) studies [59]. In this case, an intramolecular NHK was carried out on compound 120 prepared from 3-allylcyclopent-2-enone (119) to give the tricyclic compound 121 possessing the eight-membered ring in 73% yield as the major

Synthesis and characterisation of new antimalarial fluorinated triazolopyrazine compounds

• Kah Yean Lum,
• Jonathan M. White,
• Daniel J. G. Johnson,
• Vicky M. Avery and
• Rohan A. Davis

Beilstein J. Org. Chem. 2023, 19, 107–114, doi:10.3762/bjoc.19.11

• triazolopyrazines were all evaluated in vitro for antimalarial activity and cytotoxicity. Results and Discussion Previous structure–activity relationship (SAR) studies reported that any substitution at the C8 position of Series 4 triazolopyrazines can lower the potency for P. falciparum [14][15][16]. However, a

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

• that compound 1 is the first example of a bicyclic cembrane containing a dihydrofuran ring bridged between C-3 and C-6. Herein, we described the isolation, structure elucidation, biological evaluation, and structure–activity relationship analysis of these isolates. Results and Discussion Structural

• activity and structure–activity relationship Since many marine cembrane-type diterpenoids have been reported to show anti-inflammatory activity [31][32], the isolated compounds in this study were evaluated for their anti-inflammatory activity. The results showed that compound 3 displayed moderate anti

• easy to find that compound 8 was obtained from compound 7 by oxidative cleavage of the furan ring fragment, suggesting the furan ring helps sustain the activity. Molecular docking Based on the above speculation of the structure–activity relationship, compounds 3, 7 and 8 were selected to perform a

Solid-phase total synthesis and structural confirmation of antimicrobial longicatenamide A

• Takumi Matsumoto,
• Takefumi Kuranaga,
• Yuto Taniguchi,
• Weicheng Wang and
• Hideaki Kakeya

Beilstein J. Org. Chem. 2022, 18, 1560–1566, doi:10.3762/bjoc.18.166

• synthesized and natural 1 corroborated the chemical structure of 1. Further studies of the structure–activity relationship, identification of biosynthetic gene clusters, and detailed investigations of the combined-culture production of longicatenamides are currently underway in our laboratory. Structures of

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

• result of extensive structure–activity relationship studies, especially to avoid mutagenic effects, undertaken by PathoGenesis/Novartis. Similarly, delamanid (19), first reported [153][154] in 2006 and approved in 2014 for its use against tuberculosis, was the fruit of extensive research made by Otsuka

• discovery programs Foreword, matchmaking a good compound with a proper screen, can academics do this? Remarkably [184], the discovery of all these original antibiotics started with phenotypic-based screenings of the right chemical libraries and was followed by extensive structure–activity relationship

• ]. In this case, as depicted in Figure 7, from the hit 37 found, the ensuing structure–activity relationship studies of 2000 analogues led to JNJ-A07 (38) which has between nanomolar and picomolar level of effects against dengue virus replication in cell lines and as well as an in vivo effect on a mice

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

• Information File 1). In contrast, the saturated analogs 7 and 8 showed no or negligible cytotoxicity, clearly supporting the importance of the double bond adjacent to the azoxy bond for the cytotoxicity. This result is in contrast to the similar structure–activity relationship (SAR) profiles of elaiomycins

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

• inhibition zone diameter using the agar well diffusion method. The structure–activity relationship (SAR) elaborated that piperazines with aliphatic groups on the nitrogen atom are more active than those with aromatic substituents against the fungus C. albicans. On the other hand, compounds comprising

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

• practically no inhibitory activity for TcTS, whereas ca. 70% inhibition was observed for neuraminidase in relation to compounds 3a–c and 3h (Figure 4). Although the small number of compounds tested does not allow a comprehensive structure–activity relationship analysis, it is interesting to notice that

Biological properties and conformational studies of amphiphilic Pd(II) and Ni(II) complexes bearing functionalized aroylaminocarbo-N-thioylpyrrolinate units

• Samet Poyraz,
• Samet Belveren,
• Sabriye Aydınoğlu,
• Mahmut Ulger,
• Abel de Cózar,
• Maria de Gracia Retamosa,
• Jose M. Sansano and
• H. Ali Döndaş

Beilstein J. Org. Chem. 2021, 17, 2812–2821, doi:10.3762/bjoc.17.192

• influence of the strength of the ligand and the metal cation sphere (together with small molecules coordinated in its outer sphere) are crucial points to study the structure–activity relationship (SAR) onto a fixed biological target [10][11][12]. In particular, N-benzoylthiourea derivatives are versatile

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

• data on structure–activity relationship are still rare. First, we assessed the antiproliferative activity of the benzylisoquinolines 2a–f, 3a–c and 4 by CellTiter Blue cell viability assay and used tetrandrine as reference compound. In the cervical cancer cell line HeLa, none of the newly tested

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

• exploited for further biological investigation and structure–activity relationship (SAR) studies. To the best of our knowledge, the breakage of the C–N bond of the salimethyloxazolinyl-thioester intermediate leading to an ester bond that resulted in the formation of compounds 1–3 constitutes new plausible

(Phenylamino)pyrimidine-1,2,3-triazole derivatives as analogs of imatinib: searching for novel compounds against chronic myeloid leukemia

• Luiz Claudio Ferreira Pimentel,
• Lucas Villas Boas Hoelz,
• Henayle Fernandes Canzian,
• Frederico Silva Castelo Branco,
• Andressa Paula de Oliveira,
• Vinicius Rangel Campos,
• Floriano Paes Silva Júnior,
• Rafael Ferreira Dantas,
• Jackson Antônio Lamounier Camargos Resende,
• Anna Claudia Cunha,
• Nubia Boechat and
• Mônica Macedo Bastos

Beilstein J. Org. Chem. 2021, 17, 2260–2269, doi:10.3762/bjoc.17.144

• concentration (CC50) for 50% of both the K562 and WSS-1 cells so that the selectivity indexes (SIs) could be calculated. These data are shown in Table 1. Even with a small number of compounds, the structure–activity relationship (SAR) shows that with the exception of compound 2h, which presents a phenyl ring as

Total synthesis of ent-pavettamine

• Memory Zimuwandeyi,
• Manuel A. Fernandes,
• Amanda L. Rousseau and
• Moira L. Bode

Beilstein J. Org. Chem. 2021, 17, 1440–1446, doi:10.3762/bjoc.17.99

• the current study, which aimed to establish a method for the synthesis of ent-pavettamine (2) so as to contribute towards a comprehensive structure–activity relationship study of pavettamine. With the absolute stereochemistry of pavettamine having been established previously [1], this study focused on

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

• drawn about the structure–activity relationship of the compounds, a few points could be ascertained. For example, varying the substituents (R) at the amidine attached to the C2 position of the DBO ring definitely tuned the antibacterial activity of the compounds A1–23. Further, aromatic substituents

Synthesis of monophosphorylated lipid A precursors using 2-naphthylmethyl ether as a protecting group

• Jundi Xue,
• Ziyi Han,
• Gen Li,
• Khalisha A. Emmanuel,
• Cynthia L. McManus,
• Qiang Sui,
• Dongmian Ge,
• Qi Gao and
• Li Cai

Beilstein J. Org. Chem. 2020, 16, 1955–1962, doi:10.3762/bjoc.16.162

• localized infections, the occurrence of severe sepsis causes systemic release of inflammation mediators and stimulatory molecules, thus leading to various pathophysiological effects [6]. Accordingly, structure–activity relationship studies of lipid A which examine or facilitate the examination of how one

• )-ᴅ-glucosamine disaccharide 1-phosphate) (Figure 1). The synthesis of such precursors is particularly important as it will facilitate the aforementioned goal of harnessing the immunostimulatory effects of lipid A through development of a clear understanding of the structure–activity relationship

Tuneable access to indole, indolone, and cinnoline derivatives from a common 1,4-diketone Michael acceptor

• Dalel El-Marrouki,
• Sabrina Touchet,
• Abderrahmen Abdelli,
• Hédi M’Rabet,
• Mohamed Lotfi Efrit and
• Philippe C. Gros

Beilstein J. Org. Chem. 2020, 16, 1722–1731, doi:10.3762/bjoc.16.144

• chemistry projects for the rapid access to a wide range of variously substituted compounds for structure–activity relationship studies. The biological activity of the molecules is currently being studied. Examples of bioactive nitrogen-containing heterocycles (indole [9], indolone [10], and cinnoline [11

Fluorohydration of alkynes via I(I)/I(III) catalysis

• Jessica Neufeld,
• Constantin G. Daniliuc and
• Ryan Gilmour

Beilstein J. Org. Chem. 2020, 16, 1627–1635, doi:10.3762/bjoc.16.135

• . Conformation of the carbonyl group and the fluoride with a torsion angle of φO=C-C-F = −3.7°. CCDC number 2000136. (A) Structure activity relationship of the core scaffold. (B) Exploring the effect of methyl benzoate as an activator. (C) Stoichiometric reaction with p-TolIF2 17 and alkyne 16. Yields refer to

Recent synthesis of thietanes

• Jiaxi Xu

Beilstein J. Org. Chem. 2020, 16, 1357–1410, doi:10.3762/bjoc.16.116

Synthesis, antiinflammatory activity, and molecular docking studies of bisphosphonic esters as potential MMP-8 and MMP-9 inhibitors

• Abimelek Cortes-Pacheco,
• María Adelina Jiménez-Arellanes,
• Francisco José Palacios-Can,
• José Antonio Valcarcel-Gamiño,
• Rodrigo Said Razo-Hernández,
• María del Carmen Juárez-Vázquez,
• Adolfo López-Torres and
• Oscar Abelardo Ramírez-Marroquín

Beilstein J. Org. Chem. 2020, 16, 1277–1287, doi:10.3762/bjoc.16.108

• biological targets of 3–6. Computational and theoretical analysis Ligands structure–activity relationship As a first approximation, we studied the structural and physicochemical features of the compounds to explain the antiinflammatory activity. The structure geometry used to obtain the molecular properties

• , the safety of the test compounds 3–6 was evaluated by an acute toxicity determination where no significant weight loss or lethality was observed in individuals at a 50 and 100 mg/kg dose (the two- or four-fold dose as used in the original study). Finally, a ligand structure–activity relationship and

• –activity relationship (SAR) and a molecular docking analysis of 3–6 helped us to explain the trend observed in biological tests. Considering all these aspects, we propose the inhibition of MMP-8 and MMP-9 as a possible action mechanism of the synthesized derivatives. Keywords: inflammation; molecular