Young investigators in natural products chemistry, biosynthesis, and enzymology

• Jeffrey D. Rudolf,
• Lena Barra and
• Takayoshi Awakawa

Beilstein J. Org. Chem. 2024, 20, 2720–2721, doi:10.3762/bjoc.20.229

• , Japan 10.3762/bjoc.20.229 There is just something about natural products. When staring at these structurally complex molecules produced by diverse organisms on our planet, one may wonder why a particular natural product is made, how it is made, how I can make it, or how I can use it. The isolation and

Synthesis of benzo[f]quinazoline-1,3(2H,4H)-diones

• Ruben Manuel Figueira de Abreu,
• Peter Ehlers and
• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 2708–2719, doi:10.3762/bjoc.20.228

• investigation or modulation of desired properties. Conclusion In summary, we have developed the synthesis of novel polycyclic uracil-based compounds. Careful optimisation of the reaction conditions led to the isolation of the desired products in excellent to moderate yields. The developed methodology tolerates

Transition-metal-free decarbonylation–oxidation of 3-arylbenzofuran-2(3H)-ones: access to 2-hydroxybenzophenones

• Bhaskar B. Dhotare,
• Seema V. Kanojia,
• Chahna K. Sakhiya,
• Amey Wadawale and
• Dibakar Goswami

Beilstein J. Org. Chem. 2024, 20, 2655–2667, doi:10.3762/bjoc.20.223

• . However, it must be noted that the yields recorded in Table 1 are isolated yields. For the sake of eliminating errors in isolation, we have carried out every reaction in triplicate, and have considered the average yield as the isolated yield. Earlier, Qui et al. reported [2] that a transition-metal

The scent gland composition of the Mangshan pit viper, Protobothrops mangshanensis

• Jonas Holste,
• Paul Weldon,
• Donald Boyer and
• Stefan Schulz

Beilstein J. Org. Chem. 2024, 20, 2644–2654, doi:10.3762/bjoc.20.222

• ) were observed with similar mass spectra. The amount of secretion available and the complex mixture did not allow for the isolation of enough material for NMR analysis. Therefore, for the structure elucidation of these unknown compounds, we used different analytical methods, including GC–MS, GC–IR, and

Applications of microscopy and small angle scattering techniques for the characterisation of supramolecular gels

• Connor R. M. MacDonald and
• Emily R. Draper

Beilstein J. Org. Chem. 2024, 20, 2608–2634, doi:10.3762/bjoc.20.220

• materials, it is important that the data obtained from such techniques cannot be used in isolation. For example, a wide variety of models are available to characterise scattering data, however, solving the equations leads to multiple solutions. With scattering, the ‘best’ model is often chosen from the fit

Base-promoted cascade recyclization of allomaltol derivatives containing an amide fragment into substituted 3-(1-hydroxyethylidene)tetronic acids

• Andrey N. Komogortsev,
• Constantine V. Milyutin and
• Boris V. Lichitsky

Beilstein J. Org. Chem. 2024, 20, 2585–2591, doi:10.3762/bjoc.20.217

• method for the synthesis of a wide range of (3E,5E)-3-(1-hydroxyethylidene)-5-(5-oxopyrrolidin-2-ylidene)furan-2,4(3H,5H)-diones was elaborated. The advantages of the presented protocol are easily available starting compounds and simple isolation of the target products without chromatographic

Transition-metal-free synthesis of arylboronates via thermal generation of aryl radicals from triarylbismuthines in air

• Yuki Yamamoto,
• Yuki Konakazawa,
• Kohsuke Fujiwara and
• Akiya Ogawa

Beilstein J. Org. Chem. 2024, 20, 2577–2584, doi:10.3762/bjoc.20.216

• also tolerable, and the corresponding products 3i and 3j were selectively obtained in moderate yields. Notably, the bulky 2,4,6-trimethylphenyl group of bisumuthine 1l did not inhibit the transformation, and the boronate 3l was obtained in 78% yield. The isolation of arylboronates 3c, 3i, and 3j was

• somewhat difficult due to strong adsorption or decomposition on silica gel. Since some arylboronates are somewhat unstable, it is desirable to synthesize such compounds and then use them in a one-pot manner for the following reactions without isolation. To gain insight into the reaction pathways, several

HFIP as a versatile solvent in resorcin[n]arene synthesis

• Hormoz Khosravi,
• Valeria Stevens and
• Raúl Hernández Sánchez

Beilstein J. Org. Chem. 2024, 20, 2469–2475, doi:10.3762/bjoc.20.211

• ) use of 2-substituted electron-poor resorcinols with aldehydes larger than acetaldehyde produce intractable mixtures leading to no product isolation [9], in turn access to halogenated or deactivated electron-poor resorcin[n]arenes typically require an extra step as shown in Scheme 1b [8][56][57][58][59

Photoredox-catalyzed intramolecular nucleophilic amidation of alkenes with β-lactams

• Valentina Giraldi,
• Giandomenico Magagnano,
• Daria Giacomini,
• Pier Giorgio Cozzi and
• Andrea Gualandi

Beilstein J. Org. Chem. 2024, 20, 2461–2468, doi:10.3762/bjoc.20.210

• well known as a potent β-lactamase inhibitor [33][34]. It is produced by the filamentous bacterium Streptomyces clavuligerus, but in low yield. Various clavams 2–5 have been identified (Figure 2B), either through isolation as natural metabolites or obtained by synthetic methods [35][36][37][38][39][40

• 8d exhibited an enhancement in reaction diastereoselectivity, resulting in the isolation of product 11d with a dr of 6.7:1 in favor of the trans-diastereoisomer. Remarkably, the formation of a fully substituted quaternary center was possible, as observed for the product 11g, where the trans

• starting from succinimide (Scheme 3). Through a simple reaction in toluene at 80 °C in the presence of Zn(OAc)2, the hemiaminal derivative 13 underwent substitution with cinnamyl alcohol, resulting in the isolation of 14 with a satisfactory yield. Under optimized reaction conditions, the photocatalytic

Improved deconvolution of natural products’ protein targets using diagnostic ions from chemical proteomics linkers

• Andreas Wiest and
• Pavel Kielkowski

Beilstein J. Org. Chem. 2024, 20, 2323–2341, doi:10.3762/bjoc.20.199

• . Acquisition techniques benefit from possible multistage ion separation and isolation, and diverse fragmentation techniques. All of that is nowadays combined in one instrument to provide greater flexibility of the spectra acquisition setup [7][8][9][10][11][12][13][14][15][16]. Given the sheer amount of data

gem-Difluorination of carbon–carbon triple bonds using Brønsted acid/Bu₄NBF₄ or electrogenerated acid

• Mizuki Yamaguchi,
• Hiroki Shimao,
• Kengo Hamasaki,
• Keiji Nishiwaki,
• Shigenori Kashimura and
• Kouichi Matsumoto

Beilstein J. Org. Chem. 2024, 20, 2261–2269, doi:10.3762/bjoc.20.194

• the case of an aliphatic terminal alkyne, such as dec-1-yne (1d), the 19F NMR study indicated 46% yield with method A (Table 2, entry 5), but it was difficult to purify and isolate product 2d because of the low molecular weight. Scale up conditions of method A, for the purpose of the isolation, led to

• the formation of the corresponding product 2d in 40% yield as the 19F NMR analysis (Table 2, entry 6), but the isolation of 2d was difficult [54]. Method B gave 2d in 35% yield, as shown by the 19F NMR analysis (Table 2, entry 7). Another alkyne, namely, octadec-1-yne (1e), was found to be a nice

Heterocycle-guided synthesis of m-hetarylanilines via three-component benzannulation

• Andrey R. Galeev,
• Maksim V. Dmitriev,
• Alexander S. Novikov and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2024, 20, 2208–2216, doi:10.3762/bjoc.20.188

• reaction in the presence of molecular sieves and 1.5-fold excess of aniline (conditions B) dramatically reduced the reaction time to 1 d, allowing isolation of diarylamine 3ac in 75% yield (Scheme 2). Next, we started to screen various heterocyclic 1,3-diketones with the model amine series. The reaction of

Natural resorcylic lactones derived from alternariol

• Joachim Podlech

Beilstein J. Org. Chem. 2024, 20, 2171–2207, doi:10.3762/bjoc.20.187

• fungi, are discussed with view on their isolation, structure, biological activities, biosynthesis, and total syntheses. This class of compounds consists until now of 127 naturally occurring compounds, with very divers structural motifs. Although only a handful of these toxins (i.e., alternariol and its

• members), and cyclopenta-fused derivatives (26 members). These compounds will be strictly organized due to their structures and not due a possible concurrent isolation or even to common names (e.g., graphislactones A, C, E, and G will be treated in different sub-chapters, although graphislactones A and C

• [131][132][133], it is quite likely that alternariol and its derivatives are partly present in the organisms as O-glucosides, acetates, or sulfates [134][135], where these substituents are most generally cleaved during the isolation and work-up processes. These derivatives (glucosides and sulfates) are

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

• chlorides furnishes alkynones 104 under mild reaction conditions [124][125]. Without isolation alkynones 104, hydrazines react directly by Michael addition–cyclocondensation, affording 1,3,5-trisubstituted pyrazoles 102 and 103 with remarkable regioselectivity (Scheme 37) [126][127]. The nucleophilicity of

• -component reaction, with a concluding cyclocondensation employing Boc hydrazine, 1,5-diacyl-5-hydroxypyrazoline 127 is formed, as later confirmed by isolation [149]. Upon alkaline workup, this gives 3-acylpyrazole 128 in good yield (Scheme 45) [147]. Ynediones are also accessible from α-ketocarboxylic acids

Allostreptopyrroles A–E, β-alkylpyrrole derivatives from an actinomycete Allostreptomyces sp. RD068384

• Marwa Elsbaey,
• Naoya Oku,
• Mohamed S. A. Abdel-Mottaleb and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2024, 20, 1981–1987, doi:10.3762/bjoc.20.174

• Allostreptomyces sp. RD068384, including a new congener, allostreptamide [24]. Further investigation of this strain led to the isolation of five new β-alkylpyrroles, designated allostreptopyrroles A–E (1–5) (Figure 1). Results and Discussion The fermentation extract of strain RD068384, cultured in A-3M medium, was

• , and isolation Details on the supplier of Allostreptomyces sp. RD068384, fermentation, extraction, and fractionation are described in Supporting Information File 1. While a CHCl3/MeOH 2:1-eluting fraction by silica gel open column chromatography eventually yielded allostreptamide [24], a less polar

• min), 2 (0.9 mg, tR 12.1 min), 3 (0.8 mg, tR 13.7 min), and 4 (2.3 mg, tR 17.3 min). At time 22 min, the MeCN concentration was raised to 35%, which eluted 5 (1.7 mg) at tR 28.9 min. To obtain higher amounts of compounds, fermentation with 4 L culture and isolation were repeated twice to afford in

A facile three-component route to powerful 5-aryldeazaalloxazine photocatalysts

• Ivana Weisheitelová,
• Radek Cibulka,
• Marek Sikorski and
• Tetiana Pavlovska

Beilstein J. Org. Chem. 2024, 20, 1831–1838, doi:10.3762/bjoc.20.161

• reactivity, thus giving higher yields than those bearing electron-withdrawing groups. The best reactivity was observed for 3,4-dimethylaniline (3a) and 3,4-dimethoxyaniline (3b) with the isolation of 5-aryldeazaalloxazines 2a–h, with yields of 43–79%. Additionally, 5-aryldeazaalloxazines bearing methoxy

• derivatives, 2i–l and 2m–p, respectively, was accompanied by several complications, and the isolation of the products required precipitation with 2-propanol in several cases. The heating time was prolonged to two days for 8-methoxy derivatives 2m–p, nevertheless giving moderate yields. For 7-methoxy

Discovery of antimicrobial peptides clostrisin and cellulosin from Clostridium: insights into their structures, co-localized biosynthetic gene clusters, and antibiotic activity

• Moisés Alejandro Alejo Hernandez,
• Katia Pamela Villavicencio Sánchez,
• Rosendo Sánchez Morales,
• Karla Georgina Hernández-Magro Gil,
• David Silverio Moreno-Gutiérrez,
• Eddie Guillermo Sanchez-Rueda,
• Yanet Teresa-Cruz,
• Brian Choi,
• Armando Hernández Garcia,
• Alba Romero-Rodríguez,
• Oscar Juárez,
• Siseth Martínez-Caballero,
• Mario Figueroa and
• Corina-Diana Ceapă

Beilstein J. Org. Chem. 2024, 20, 1800–1816, doi:10.3762/bjoc.20.159

• microbiota members. The habitat of C. cellulovurans, the strain of origin of the lanthipeptide clusters, appears to be plant-associated due to its metabolism and isolation environment (wood). Our results raise numerous questions regarding the ecological functions of the lantibiotics we discovered. Our

Oxidative fluorination with Selectfluor: A convenient procedure for preparing hypervalent iodine(V) fluorides

• Samuel M. G. Dearman,
• Xiang Li,
• Yang Li,
• Kuldip Singh and
• Alison M. Stuart

Beilstein J. Org. Chem. 2024, 20, 1785–1793, doi:10.3762/bjoc.20.157

• protocol using TCCA (4 equivalents) and KF (6 equivalents) was then applied to both bicyclic iodine(III) amides 11a and 11b, but these reactions also failed to form either difluoroiodane 7a or 7b. Following the successful preparation and isolation of difluoroiodane 6, we investigated its ability to

• increased by the stepwise incorporation of the trifluoromethyl groups into the sidearm, but trifluoroiodane 22 was less stable than bicyclic difluoro(aryl)-λ5-iodane 6. Conclusion In summary, we have developed a new strategy using Selectfluor for the convenient preparation and isolation of hypervalent

Ugi bisamides based on pyrrolyl-β-chlorovinylaldehyde and their unusual transformations

• Alexander V. Tsygankov,
• Vladyslav O. Vereshchak,
• Tetiana O. Savluk,
• Serhiy M. Desenko,
• Valeriia V. Ananieva,
• Oleksandr V. Buravov,
• Yana I. Sakhno,
• Svitlana V. Shishkina and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2024, 20, 1773–1784, doi:10.3762/bjoc.20.156

• for two days and then heating the reaction mixture in a closed vessel at 80 °C for 3 hours (Scheme 5). This procedure led to the formation and isolation of the products 10d and 12e with yields which are similar to the tandem reaction. Using the example of bisamide 8c, it was found that changing the

Synthesis of polycyclic aromatic quinones by continuous flow electrochemical oxidation: anodic methoxylation of polycyclic aromatic phenols (PAPs)

• Hiwot M. Tiruye,
• Solon Economopoulos and
• Kåre B. Jørgensen

Beilstein J. Org. Chem. 2024, 20, 1746–1757, doi:10.3762/bjoc.20.153

• multiple products were formed. The lability of the acetals prompted us to submit the crude intermediate directly to hydrolysis without prior isolation (Table 4). As mentioned above, having an aqueous reaction mixture in the electrochemical oxidation will give reduced yields. The overall yield of 9b from 6b

• of 1-chrysenol (3b) at different electron equivalents.a Anodic methoxylation of PAPs followed by hydrolysis in two separate steps.a Synthesis of o- and p-quinones without isolation of the acetal intermediate.a Electrochemical properties of PAPs. Supporting Information Supporting Information File 6

Chemo-enzymatic total synthesis: current approaches toward the integration of chemical and enzymatic transformations

• Ryo Tanifuji and
• Hiroki Oguri

Beilstein J. Org. Chem. 2024, 20, 1693–1712, doi:10.3762/bjoc.20.151

• reaction with biotin azide, which led to selective pull-down with streptavidin agarose and isolation of the probe–protein covalent complex. Proteomic analysis of the isolated proteins narrowed down the MaMO and MaDA candidates, including several berberine bridge enzyme (BBE)-like enzymes. This FAD-linked

• enzyme SfmCy2, lead to saframycin S (95) [100][101]. To convert the labile hemiaminal moiety at C21 to a more stable aminonitrile, the extracts of the microorganism containing 95 were treated with KCN, allowing the isolation as saframycin A (5) [89]. A notable feature of this biosynthetic machinery is

• 98 [104]. Without isolation of any intermediate from the simple synthetic substrates 88 and 96, rapid access to 98 was achieved in 13% yield over two pots based on peptidyl aldehyde 96. From chemo-enzymatically constructed scaffold 98, chemical manipulations of functional groups were investigated to

Polymer degrading marine Microbulbifer bacteria: an un(der)utilized source of chemical and biocatalytic novelty

• Weimao Zhong and
• Vinayak Agarwal

Beilstein J. Org. Chem. 2024, 20, 1635–1651, doi:10.3762/bjoc.20.146

• not only a wide variety of polysaccharides including cellulose, agar, chitin, alginate, and xylan [8][9][10][11], but also plastics [4][12]. Progressing from their isolation and cultivation, natural product discovery from Microbulbifer bacteria is starting to gather steam [6][13][14]. The major

• -695 showed antimicrobial activity against E. coli [14]. Bioassay-guided fractionation led to the isolation of two new acetamidobenzoate esters: bulbiferate A (13) and bulbiferate B (14, Figure 6). Their structures were established on the basis of comprehensive spectroscopic and spectrometric data

• algae [17]. Further investigation indicated that the bioactive substance was mainly located in the cell-free supernatant of Microbulbifer sp. RZ01. Fractionation and spectroscopic characterization led to the isolation and identification of the extracellularly secreted molecule, 3,3´,5,5´-tetrabromo-2,2

Mining raw plant transcriptomic data for new cyclopeptide alkaloids

• Draco Kriger,
• Michael A. Pasquale,
• Brigitte G. Ampolini and
• Jonathan R. Chekan

Beilstein J. Org. Chem. 2024, 20, 1548–1559, doi:10.3762/bjoc.20.138

• transcripts [37][38]. For our analysis, the previously distinct Chenopodioideae family was viewed as members of the Amaranthaceae family based on the most up to date Angiosperm Phylogeny Group classification (APG IV) [23]. Isolation of burpitides from C. americanus Three separate extractions were performed

Benzylic C(sp³)–H fluorination

• Alexander P. Atkins,
• Alice C. Dean and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 1527–1547, doi:10.3762/bjoc.20.137

• predominately considered to be stable to isolation conditions, secondary and tertiary suffer from the elimination of HF, especially in the presence of silica gel or glass vessels. Therefore, benzyl fluorides have been derivatised, for example in C–O, C–N and C–C bond-forming reactions [18][19][20], thereby also

• several secondary and tertiary benzyl fluorides were unstable to silica during isolation or storage in glass vessels, and therefore, demonstrated several downstream diversifications of the benzyl fluorides. Sevov, Zhang and co-workers reported in 2023 a stable copper(III) fluoride complex that was capable

Synthesis of substituted triazole–pyrazole hybrids using triazenylpyrazole precursors

• Simone Gräßle,
• Laura Holzhauer,
• Nicolai Wippert,
• Olaf Fuhr,
• Martin Nieger,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2024, 20, 1396–1404, doi:10.3762/bjoc.20.121

• the triazole unit via a copper-catalyzed azide–alkyne cycloaddition. The developed methodology was used to synthesize a library of over fifty new multi-substituted pyrazole–triazole hybrids. We also demonstrate a one-pot strategy that renders the isolation of potentially hazardous azides obsolete. In

• 50 °C. This optimization allowed for the isolation of the corresponding azides 19a–v in yields of 51% to quantitative (Scheme 2), usually with durations of 3–16 h. Longer reaction times were necessary for some CN-substituted triazene derivatives (19o, 19q, 19s, 19v), especially in combination with