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

Synthetic applications of the Cannizzaro reaction

• Bhaskar Chatterjee,
• Dhananjoy Mondal and
• Smritilekha Bera

Beilstein J. Org. Chem. 2024, 20, 1376–1395, doi:10.3762/bjoc.20.120

• also simplifies product isolation and purification and improves the overall sustainability of the process [23][24]. However; specific reaction requirements ensure efficient and selective utilization of solvents. Marvi and Talakoubi carried out the Cannizzaro reaction [25] using montmorillonite K-10 and

Computation-guided scaffold exploration of 2E,6E-1,10-trans/cis-eunicellanes

• Zining Li,
• Sana Jindani,
• Volga Kojasoy,
• Teresa Ortega,
• Erin M. Marshall,
• Khalil A. Abboud,
• Sandra Loesgen,
• Dean J. Tantillo and
• Jeffrey D. Rudolf

Beilstein J. Org. Chem. 2024, 20, 1320–1326, doi:10.3762/bjoc.20.115

• epoxide 9, but the similar reaction with 2 yields gersemienol 8. Isolation yields are provided. (B and C) Results of DFT calculations on the protonation-induced cyclizations of 1 and 2. The energies of the cationic intermediates (italicized values) are not on the same energy scale as for the substrates

• be 3.5 kcal mol−1 higher in energy than the one shown, an energy difference that is larger than expected based on experiment. Cope rearrangement in trans-eunicellanes. (A) The 2E-trans-eunicellane undergoes thermal Cope rearrangement, yielding atropisomers 10a/10b; an isolation yield of 96% was

Sustainable tandem acylation/Diels–Alder reaction toward versatile tricyclic epoxyisoindole-7-carboxylic acids in renewable green solvents

• Ayhan Yıldırım

Beilstein J. Org. Chem. 2024, 20, 1308–1319, doi:10.3762/bjoc.20.114

• bisepoxyisoindole-7-carboxylic acids were obtained in good yields after a practical isolation procedure. The results obtained in this study demonstrate the potential of vegetable oils and their renewable materials to provide a reaction medium that is more sustainable than conventional organic solvents in cascade

• as the reaction medium seven times under optimum conditions and the results for the cycloadduct 2k are shown in Figure 1. As shown in the figure, there is no significant decrease in product yield. The reaction conditions and isolation method used in the literature procedures for the previous

• transformations is the purification of the synthesized product, since these oils are non-volatile and non-polar. However, in this study, the choice of these materials as green solvents allows convenient isolation of the cycloadducts by precipitation followed by filtration with hexane or diethyl ether. Thus, IMDAF

Light on the sustainable preparation of aryl-cored dibromides

• Fabrizio Roncaglia,
• Alberto Ughetti,
• Nicola Porcelli,
• Biagio Anderlini,
• Andrea Severini and
• Luca Rigamonti

Beilstein J. Org. Chem. 2024, 20, 1076–1087, doi:10.3762/bjoc.20.95

• undetectable 1H NMR impurities. The application of the same protocol on o-xylene (1, Figure 3) cleanly gave dibromide 1a in almost quantitative yield. Some issues emerged during the isolation step, because of the high lacrimatory activity of 1a [53][54], while 3a lacks the same effect. Higher nucleophilic

A Diels–Alder probe for discovery of natural products containing furan moieties

• Alyssa S. Eggly,
• Namuunzul Otgontseren,
• Carson B. Roberts,
• Amir Y. Alwali,
• Haylie E. Hennigan and
• Elizabeth I. Parkinson

Beilstein J. Org. Chem. 2024, 20, 1001–1010, doi:10.3762/bjoc.20.88

• agar plates (1 mg/L titer or 5 µM). However, this initial isolation was enabled by heterologous expression of their biosynthetic genes from Streptomyces coelicolor to produce higher titers of the MMF molecules compared to the native producer [7]. Given the challenges of isolating furans generally and

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

• presence of a methoxy group after the Heck–Matsuda reaction indicates methanolysis after arylation. Given the importance of the lactam rings, we envisioned a sequential Jones oxidation protocol without isolation of the methyl N,O-acetal products to obtain the corresponding lactams 4. As observed in

Direct synthesis of acyl fluorides from carboxylic acids using benzothiazolium reagents

• Lilian M. Maas,
• Alex Haswell,
• Rory Hughes and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2024, 20, 921–930, doi:10.3762/bjoc.20.82

• unreliable isolation of acyl fluoride intermediates, we next considered whether BT-SCF3-mediated deoxyfluorination of carboxylic acids could be coupled with a subsequent acylation in an overall one-pot process. Selecting amines as nucleophilic coupling partners, a short optimisation study was carried out to

• the optimised one-pot conditions with benzylamine (4a) resulted in the formation of the desired amide product, however, significant by-products were also observed. Careful column chromatography of the crude reaction mixture allowed for the partial isolation and characterisation of the

• , complicating isolation (Scheme 3a). As Boc-deprotection is seemingly feasible under the reaction conditions, to avoid formation of by-product 6, the process was tested using the N-Cbz-valine (1s). Moreover, the BT-SCF3 reagent was substituted for the longer chain BT-reagent BT-SC5F11. The use of this

Three-component N-alkenylation of azoles with alkynes and iodine(III) electrophile: synthesis of multisubstituted N-vinylazoles

• Jun Kikuchi,
• Roi Nakajima and
• Naohiko Yoshikai

Beilstein J. Org. Chem. 2024, 20, 891–897, doi:10.3762/bjoc.20.79

• -membered aromatic azacycles, imidazole completely failed to undergo the present N-alkenylation, whereas the reaction of 1,2,4-triazole was too sluggish to allow for the isolation and unambiguous characterization of the expected product. Next, the reaction of pyrazole (2a) was explored using different

(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

• intramolecular crossed [2 + 2] cycloaddition strategy (Scheme 4C) [36]. They were able to avoid purification by column chromatography by transformation of BCH ester (±)-53 into BCH acid (±)-54, allowing isolation of pure 1,2-BCH (±)-54 by crystallisation. Through their synthesis they were able to access both

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

• they are found in bacteria found in widespread classes and environments. Herein, we report the characterization of five NnlA homologs. It is shown that all five homologs exhibited NNG degradation activity. Isolation and characterization of four of these homologs showed that all contain heme, the

Skeletal rearrangement of 6,8-dioxabicyclo[3.2.1]octan-4-ols promoted by thionyl chloride or Appel conditions

• Martyn Jevric,
• Julian Klepp,
• Johannes Puschnig,
• Oscar Lamb,
• Christopher J. Sumby and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2024, 20, 823–829, doi:10.3762/bjoc.20.74

• chiral auxiliary 10a, and following a survey of conditions and isolation protocols, a 90% yield was obtained when 10a was heated in the presence of 2 equivalents of SOCl2 and 5 equivalents of pyridine in DCE. Flash chromatography of the chloroalkyl ether 11a resulted in significant loss due to hydrolysis

• , although 11a was sufficiently stable for filtration through a pad of silica. Applying these conditions and isolation protocols to all 3,3-disubstituted alcohols 10c–f gave moderate to excellent yields of the rearrangement products 11c–f as single stereoisomers. The reactions of alcohols 10b,d,e also gave

• some sulfites 13b,d,e, attributed to the reduced steric hindrance in the chlorosulfite intermediate allowing for the second alcohol to approach prior to rearrangement. The isolation of these materials suggested that dialkyl sulfite formation could compete with the rearrangement if the neighbouring

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

• drug discovery. However, it is becoming difficult to obtain novel compounds because of repeated isolation around the world. Therefore, a new strategy for discovering novel secondary metabolites is needed. Many researchers believe that actinomycetes have as yet unanalyzed secondary metabolic activities

• inducing resistance, and this approach has contributed to the isolation of many new compounds [47]. The ribosome engineering method is based on the principle that a mutation in the ribosomal S12 protein, which is associated with the acquisition of antibiotic resistance, activates secondary metabolism. The