Enhancing structural diversity of terpenoids by multisubstrate terpene synthases

• Min Li and
• Hui Tao

Beilstein J. Org. Chem. 2024, 20, 959–972, doi:10.3762/bjoc.20.86

• selectivity with the noncanonical prenyl substrates. To enable the biotechnological synthesis of irregular terpenes, the product selectivity of 2-methylenebornane synthase from Pseudomonas fluorescenes was altered using a semi-rational engineering approach [56]. In contrast to GPP methylation, modification of

• selective sesqui-TSs failed to transform 104–112. After further modification with cytochrome P450 CYP720B1 in the yeast host, 28 noncanonical terpenoids were generated, 10 of them are shown in Figure 8c (113–122) [58]. Notably, the widespread biosynthesis of C16 terpenoids was reported in a recent study in

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

• moiety is introduced in a late-stage-modification approach, mostly from nitriles or isocyanides (Figure 1b) [13]. On the other hand, accessing diverse tetrazole scaffolds from MCRs, typically involves first de novo construction of the tetrazole scaffold and subsequent post-modifications (Figure 1c) [14

• synthetic utility of this tetrazole scaffold continues, particularly in other MCRs and post-modification processes, we anticipate more applications in the near future. Investigation of these drug-like molecules for the targets PD-1/PDL-1, caspase-1, and IL-17A are currently in progress in our laboratory

Enantioselective synthesis of β-aryl-γ-lactam derivatives via Heck–Matsuda desymmetrization of N-protected 2,5-dihydro-1H-pyrroles

• Arnaldo G. de Oliveira Jr.,
• Martí F. Wang,
• Rafaela C. Carmona,
• Danilo M. Lustosa,
• Sergei A. Gorbatov and
• Carlos R. D. Correia

Beilstein J. Org. Chem. 2024, 20, 940–949, doi:10.3762/bjoc.20.84

• commercial drug baclofen as hydrochloride. Keywords: desymmetrization; enantioselective Heck–Matsuda reaction; lactam synthesis; N,N-ligands; palladium; Introduction Desymmetrization reactions consist in the modification of a molecule with the loss of one or more symmetry elements, such as those which

Monitoring carbohydrate 3D structure quality with the Privateer database

• Jordan S. Dialpuri,
• Haroldas Bagdonas,
• Lucy C. Schofield,
• Phuong Thao Pham,
• Lou Holland and
• Jon Agirre

Beilstein J. Org. Chem. 2024, 20, 931–939, doi:10.3762/bjoc.20.83

• filtering by linkage type is also possible, allowing niche glycosylation targets to be obtained. For example, filtering for C-glycans with a ‘BMA-1,1-TRP’ (the correct pair would be ‘MAN-1,1-TRP’, as the linkage in the modification is an alpha linkage) returns nine instances of incorrect sugar conformations

Synthesis and properties of 6-alkynyl-5-aryluracils

• Ruben Manuel Figueira de Abreu,
• Till Brockmann,
• Alexander Villinger,
• Peter Ehlers and
• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 898–911, doi:10.3762/bjoc.20.80

• targets, making uracil very interesting for medical applications. The first modification of uracil was already synthesized in 1906 [6]. However, the medical potential of uracil was not discovered until 40 years later. One of the first antibacterial studies was carried out in 1945. The first

(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

• well as the impact they have on the physiochemical and biological properties of pharmaceuticals and agrochemicals. Keywords: bioisosteres; drug discovery; meta-benzene; ortho-benzene; Introduction The logical and iterative modification of the structure of a drug candidate is a critical part of the

• -workers also reported the modification of these 1,2-BCHs to increase the number of derivatives accessible using this approach (Scheme 3B) [38]. Transformation of the naphthyl ketone moiety of BCH (±)-25d by Baeyer–Villiger oxidation followed by hydrolysis gave carboxylic acid (±)-26. Through Curtius

• -substituted endo-1,5-BCHs (±)-57a–e. Substrate modification was also possible, with oxidative transformation of a bridgehead furan leading to 1,5-BCH acid (±)-60 and pyridine reduction to secondary amine (±)-61 (Scheme 5B) [42]. Furthermore, 1,5-BCH (±)-64 was synthesised as a bioisostere of the fungicide

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

• portion of NNG would be expected to exist as the inhibitory nitronate form at physiological pH, suggesting another potential role for nitramine groups as potent warheads in antibiotics. This antibiotic activity may also require further modification of NNG or its incorporation into a larger natural product

• pET-28a(+)-TEV by GenScript. For protein expression, plasmids were electroporated into E. coli BL21(DE3) cells and protein was expressed and purified by immobilized metal affinity chromatography (IMAC) as previously described for Vs NnlA [21]. The only modification was that plasmids using pET-28a

Discovery and biosynthesis of bacterial drimane-type sesquiterpenoids from Streptomyces clavuligerus

• Dongxu Zhang,
• Wenyu Du,
• Xingming Pan,
• Xiaoxu Lin,
• Fang-Ru Li,
• Qingling Wang,
• Qian Yang,
• Hui-Min Xu and
• Liao-Bin Dong

Beilstein J. Org. Chem. 2024, 20, 815–822, doi:10.3762/bjoc.20.73

• derivatives 7–9. This study marks the first discovery of natural DMTs from bacteria and unveils the role of CavA in a novel late-stage modification pathway, expanding DMT biosynthesis beyond fungi and plants. Results and Discussion Discovery of three DMTs in S. clavuligerus S. clavuligerus is notably

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

Beilstein J. Org. Chem. 2024, 20, 787–814, doi:10.3762/bjoc.20.72

• oxidation, whereas in Nicewicz's report, the alkene is oxidized. This modification allows for a significantly larger reaction scope (Scheme 29). Terminal alkenes and several functional groups such as ethers (163), esters (165), ketones (166), nitriles (167), and enones (170) are tolerated. The

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

• porphyrins to other biological substrates and thus facilitate the conjugation with biomacromolecules [10][11]. The modification of the porphyrin periphery with amino-, azido-, epoxy-, hydroxy-, and maleimido-functionalities is usually used for the covalent linkage of the porphyrin to the targeted

• next studied the modification of the pentafluorophenyl substituents with carborane clusters via the SNAr substitution reaction with carborane nucleophiles [17][24][25][26][27]. These reactions are well studied for porphyrin 1 [17][24][25][26][27] to afford the corresponding carborane derivatives

• has become one of the most popular route for the site-selective modification of cysteine residues in bioconjugation technology. We suppose that the maleimide group in porphyrin 11 is a useful target for thiol conjugation via Michael addition reactions [44]. This also concerns biotin-conjugated organic

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

• with potential for further modification by cross-coupling. The full scope of the transformation can be found in Supporting Information File 1, Schemes S2 and S3 [45]. Concerning scope limitations, the azido-alkynylation of vinyl-pyridine 1b was unsuccessful and thiazole 1c only afforded 18% of the

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

• , we also identified a var gene cluster containing NRPS and PKS genes: the domain organizations of NRPS and PKS, and the adjacently encoded modification enzymes, were comparable to those of the gene cluster reported by Nett et al. with 92–99% identity at the protein level [5] (Figure 3a and Figure S42

Evaluation of the enantioselectivity of new chiral ligands based on imidazolidin-4-one derivatives

• Jan Bartáček,
• Karel Chlumský,
• Jan Mrkvička,
• Lucie Paloušová,
• Miloš Sedlák and
• Pavel Drabina

Beilstein J. Org. Chem. 2024, 20, 684–691, doi:10.3762/bjoc.20.62

• to synthesise ligands featuring two chiral imidazolidin-4-one units linked to the pyridine ring at the 2- and 6- positions (Figure 1 – ligands I and II). These newly designed ligands represent tridentate entities. Such structure modification provides the ligands structurally conformable to well-known

Regioselective quinazoline C2 modifications through the azide–tetrazole tautomeric equilibrium

• Dāgs Dāvis Līpiņš,
• Andris Jeminejs,
• Una Ušacka,
• Anatoly Mishnev,
• Māris Turks and
• Irina Novosjolova

Beilstein J. Org. Chem. 2024, 20, 675–683, doi:10.3762/bjoc.20.61

• [9][10] are commonly employed for quinazoline modification (Scheme 1). Existing literature underscores the reactivity of the C4 position in aromatic nucleophilic substitutions of quinazolines I while achieving regioselective replacement at the C2 position poses challenges [11]. Modification of the C2

• position of quinazolines requires longer time, higher temperatures, and sometimes the use of expensive transition-metal catalysts [12]. A selective C2 modification can be achieved by using 2-chloroquinazolines IV, where the C4 position is blocked by an unreactive C–C or C–H bond (Scheme 1). Cyclization

• terazosin and prazosin [20]. Herein, we report the use of the sulfonyl group dance to synthesize novel 4-azido-2-sulfonylquinazolines and their C2-selective modification in SNAr reactions. In addition, we offer an approach for the synthesis of terazosin and prazosin, known medications against hypertension

Palladium-catalyzed three-component radical-polar crossover carboamination of 1,3-dienes or allenes with diazo esters and amines

• Geng-Xin Liu,
• Xiao-Ting Jie,
• Ge-Jun Niu,
• Li-Sheng Yang,
• Xing-Lin Li,
• Jian Luo and
• Wen-Hao Hu

Beilstein J. Org. Chem. 2024, 20, 661–671, doi:10.3762/bjoc.20.59

• , amoxapine, an ibrutinib derivative, N-desmethyl sildenafil, silodosin, and lapatinib (4d–k, 35–67%). The late-stage modification of these drug agents and their derivatives in this MCR underlined the synthetic value and high functional group tolerance (e.g., aromatic amine, amide, alcohol, heterocycle). We

• modification of pharmaceutical scaffolds. Naturally, we were eager to acquire detailed mechanistic insights into this protocol. To validate the radical nature of this transformation, both model reactions of 1,3-diene 2a and allene 5a were terminated completely with 2.5 equiv 2,2,6,6-tetramethylpiperidinyloxyl

Enhanced reactivity of Li⁺@C₆₀ toward thermal [2 + 2] cycloaddition by encapsulated Li⁺ Lewis acid

• Hiroshi Ueno,
• Yu Yamazaki,
• Hiroshi Okada,
• Fuminori Misaizu,
• Ken Kokubo and
• Hidehiro Sakurai

Beilstein J. Org. Chem. 2024, 20, 653–660, doi:10.3762/bjoc.20.58

• the burgeoning family of ion-endohedral fullerenes, holds substantial promise for diverse applications owing to its distinctive ionic properties. Despite the high demand for precise property tuning through chemical modification, there have been only a few reports detailing synthetic protocols for the

• through chemical modification has been in high demand for its further applications, which is similar to what has been developed during the recent empty fullerene sciences. As a continuation of our studies on the synthesis of Li+@C60 derivatives, we herein focus on the modification of Li+@C60 through

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

• unusual methyl modification at the oxygen atom of the typical succinimide ring, a feature not seen in the structurally similar brocaeloid D. Additionally, shentonin A (1) exhibits a cis relationship between H-3 and H-4, as opposed to the trans configuration in brocaeloid D, suggesting a divergent

• transformation of the five-membered pyrrole ring in compound 2 to the six-membered ring in compound 1 is particularly intriguing. For this transformation, three hypotheses are considered. One suggests that the methyl modification at the oxygen atom of the succinimide ring occurs first, which is then followed by

• a ring-opening rearrangement. Alternatively, it is proposed that the ring-opening rearrangement precedes the methyl modification at the oxygen atom of the succinimide ring. We aim to confirm the initial step of this pathway, where tryptophan and DMAPP are catalyzed by the enzyme ShnA to form a

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

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

• investigated the influence of a modification of 2′-OH in the AMS scaffold with different functional groups on binding to target enzymes and bacterial cell penetration. The inhibitor 7 with a cyanomethyl group at 2′-OH showed desirable inhibitory activity against both recombinant and intracellular gramicidin S

• of the GrsA A-domain with ʟ-Phe and AMP revealed that the 2′-OH of the adenosine skeleton is oriented toward the outside of the active site of the GrsA A-domain, suggesting that chemical modification at the 2′-OH group of the adenosine skeleton would be tolerated [16] (Figure 2b). Moreover, these

• modification at the 2′-OH group of the adenosine in AA-AMS might affect the cell permeability of the compounds. Given the high hydrophilicity of the bisubstrate AMS scaffold, it is reasonable to conclude that the BPyne component increases hydrophobicity and facilitates accumulation in live E. coli. In the

Elucidating the glycan-binding specificity and structure of Cucumis melo agglutinin, a new R-type lectin

• Jon Lundstrøm,
• Emilie Gillon,
• Valérie Chazalet,
• Nicole Kerekes,
• Antonio Di Maio,
• Ten Feizi,
• Yan Liu,
• Annabelle Varrot and
• Daniel Bojar

Beilstein J. Org. Chem. 2024, 20, 306–320, doi:10.3762/bjoc.20.31

• binding in solution and a further confirmation of the binding specificity obtained by the array experiments. We note that the functional activity of bacterially produced CMA1 indicates that potential modification by glycosylation is not required for ligand binding. Next, we set out to quantify the binding

Nucleophilic functionalization of thianthrenium salts under basic conditions

• Xinting Fan,
• Duo Zhang,
• Xiangchuan Xiu,
• Bin Xu,
• Yu Yuan,
• Feng Chen and
• Pan Gao

Beilstein J. Org. Chem. 2024, 20, 257–263, doi:10.3762/bjoc.20.26

• generation of alkyl radicals [39]. After that, a series of methods for the modification of alkylthianthrenium salts have been developed, including the transition-metal-catalyzed cross-coupling with terminal alkynes [40], sulfonylation with DABCO·(SO2)2 [41][42][43], or alkylation of active alkenes [44][45

Substitution reactions in the acenaphthene analog of quino[7,8-h]quinoline and an unusual synthesis of the corresponding acenaphthylenes by tele-elimination

• Ekaterina V. Kolupaeva,
• Narek A. Dzhangiryan,
• Alexander F. Pozharskii,
• Oleg P. Demidov and
• Valery A. Ozeryanskii

Beilstein J. Org. Chem. 2024, 20, 243–253, doi:10.3762/bjoc.20.24

• , protonation, and luminescence, have recently been studied by us in sufficient detail [15], nothing is known so far about the possibility of chemical modification of this molecule. It should be emphasized that the presence of a dimethylene moiety in the peri-positions of the naphthalene system will not only

Optimizations of lipid II synthesis: an essential glycolipid precursor in bacterial cell wall synthesis and a validated antibiotic target

• Milandip Karak,
• Cian R. Cloonan,
• Brad R. Baker,
• Rachel V. K. Cochrane and
• Stephen A. Cochrane

Beilstein J. Org. Chem. 2024, 20, 220–227, doi:10.3762/bjoc.20.22

• -(phenylsulfonyl)ethyl ester, as previously reported by Saha and co-workers [44]. This modification prevents a deleterious side reaction occurring, wherein during glycosylation, muramic acid esters undergo a 6-exo-trig cyclization with the 4-OH group. Comprehensive experimental protocols detailing the preparation

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

• desired product was clean without competitive byproducts. Finally, 3-indoleacetonitrile, a plant growth hormone, furnished the desired product in good yield (3v, 68%). Combined with melatonin, these examples demonstrate the suitability of our approach to be used in drug modification and development. In