Green and sustainable approaches for the Friedel–Crafts reaction between aldehydes and indoles

• Periklis X. Kolagkis,
• Eirini M. Galathri and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2024, 20, 379–426, doi:10.3762/bjoc.20.36

Discovery of unguisin J, a new cyclic peptide from Aspergillus heteromorphus CBS 117.55, and phylogeny-based bioinformatic analysis of UngA NRPS domains

• Sharmila Neupane,
• Marcelo Rodrigues de Amorim and
• Elizabeth Skellam

Beilstein J. Org. Chem. 2024, 20, 321–330, doi:10.3762/bjoc.20.32

• facilitate release from the NRPS. Of the fungal NRPS studied to date, many appear to have some tolerance for the range of amino acids incorporated by the A domains and the C domain has been highlighted as a gatekeeper [13]. Here, we describe the isolation of unguisin B, and a new congener named unguisin J

• . heteromorphus CBS 117.55 on rice solid medium yielded an organic-soluble extract, which was subjected to fractionation using preparative HPLC-PDA-ELSD and purification by semipreparative HPLC-PDA; this led to the isolation of a new cyclic peptide 1, along with unguisin B (2, Figure 2). The structure of the new

• ). To the best of our knowledge these are the first metabolites reported from A. heteromorphus CBS 117.55. The co-isolation of unguisins B and J indicates that module 4 of the NRPS is able to accept two different amino substrates and so may possess subtle differences to UngA from A. violaceofuscus CBS

Catalytic multi-step domino and one-pot reactions

• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2024, 20, 254–256, doi:10.3762/bjoc.20.25

• because they are time-saving, waste-reducing, and atom efficient [1][2][3][4][5][6]. These efficient and straightforward synthetic methods make the isolation and purification of intermediate products after each reaction step superfluous, thereby drastically reducing the number of workup and purification

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

• several minutes with a good yield (Scheme 4). The spectral data fully confirmed the purity and asymmetric structure of product 11. It should be emphasized that the isolation and purification of nitro compounds 10 and 11 is complicated by their low solubility in traditional organic solvents, sensitivity to

• difficult to purify compound 8. At the same time, isolation of the new product 8 turned out to be more convenient on using the simple KOH/EtOH system. These conditions did not affect the yield of acenaphthylene 8 (Scheme 9). Compound 8 possesses fluorescence in solutions and the solid state both as the base

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

• forward and backward isomerization of N,N'-diacetylindigo (9a) in toluene without isolation of the Z-form [49]. The Fischer method remains relevant up to date and is frequently used for the characterization of the photoinduced forms of various indigoid photoswitches [50][51][52][53][54]. To assess an

Synthesis of the 3’-O-sulfated TF antigen with a TEG-N₃ linker for glycodendrimersomes preparation to study lectin binding

• Mark Reihill,
• Hanyue Ma,
• Dennis Bengtsson and
• Stefan Oscarson

Beilstein J. Org. Chem. 2024, 20, 173–180, doi:10.3762/bjoc.20.17

• , led to isolation of a mixture of 2 and a tin-related impurity (n-butyl chain evident by NMR). Acetylation of this material followed by flash chromatography proved ineffective in removing the unwanted entity. To overcome this problem, flash chromatography was performed before stirring with the ion

Tandem Hock and Friedel–Crafts reactions allowing an expedient synthesis of a cyclolignan-type scaffold

• Viktoria A. Ikonnikova,
• Cristina Cheibas,
• Oscar Gayraud,
• Alexandra E. Bosnidou,
• Nicolas Casaretto,
• Gilles Frison and
• Bastien Nay

Beilstein J. Org. Chem. 2024, 20, 162–169, doi:10.3762/bjoc.20.15

• leading to the isolation of dihydronaphthalenic product 4 in 82% yield (Table 1, entry 4, these conditions will later be taken as the reference). Trying to reduce this reagent stoichiometry only resulted in a poor yield of 4 and in the isolation of aldehyde 3 in 42% yield (Table 1, entry 5). By contrast

Identification of the p-coumaric acid biosynthetic gene cluster in Kutzneria albida: insights into the diazotization-dependent deamination pathway

• Seiji Kawai,
• Akito Yamada,
• Yohei Katsuyama and
• Yasuo Ohnishi

Beilstein J. Org. Chem. 2024, 20, 1–11, doi:10.3762/bjoc.20.1

• product produced by K. albida [30]. Although rare actinomycetes have been expected to be a source of novel natural products, reports of natural product isolation from rare actinomycetes are limited because of the difficulty in cultivation and genetic manipulation. This study demonstrates that heterologous

• 2.6C18 Packed column (2.1 mm ID × 100 mm, Nacalai Tesque) coupled with a model LCMS-8040 liquid chromatography–mass spectrometer (LC–MS) (Shimazu Corp.). The compounds were eluted with a linear gradient of water/acetonitrile containing 0.1% formic acid. Isolation and structural determination of compound

Long oligodeoxynucleotides: chemical synthesis, isolation via catching-by-polymerization, verification via sequencing, and gene expression demonstration

• Yipeng Yin,
• Reed Arneson,
• Alexander Apostle,
• Adikari M. D. N. Eriyagama,
• Komal Chillar,
• Emma Burke,
• Martina Jahfetson,
• Yinan Yuan and
• Shiyue Fang

Beilstein J. Org. Chem. 2023, 19, 1957–1965, doi:10.3762/bjoc.19.146

• have difficulty to produce sequences containing stable secondary structures. Here, we report a direct de novo chemical synthesis of 400 nt ODNs, and their isolation from the complex reaction mixture using the catching-by-polymerization (CBP) method. To determine the authenticity of the ODNs, 399 and

• , the GFP gene was expressed in E. coli. The long ODN synthesis and isolation method presented here provides a pathway to the production of genes and genomes containing long repeats or stable secondary structures that cannot be produced or are highly challenging to produce using existing technologies

• to address all the aforementioned problems, such as generating sequences having highly stable secondary structures [18]. In this paper, we report a method to access long ODNs involving automated direct de novo chemical synthesis and isolation of full-length sequences using the catching-by

Aldiminium and 1,2,3-triazolium dithiocarboxylate zwitterions derived from cyclic (alkyl)(amino) and mesoionic carbenes

• Nedra Touj,
• François Mazars,
• Guillermo Zaragoza and
• Lionel Delaude

Beilstein J. Org. Chem. 2023, 19, 1947–1956, doi:10.3762/bjoc.19.145

• NHC·CS2 zwitterions relies on the deprotonation of an azolium salt with a strong base, typically potassium tert-butoxide or potassium bis(trimethylsilyl)amide (also known as potassium hexamethyldisilazide, KHMDS) followed by the addition of carbon disulfide either in one pot or after the isolation of the

Controlling the reactivity of La@C₈₂ by reduction: reaction of the La@C₈₂ anion with alkyl halide with high regioselectivity

• Yutaka Maeda,
• Saeka Akita,
• Mitsuaki Suzuki,
• Michio Yamada,
• Takeshi Akasaka,
• Kaoru Kobayashi and
• Shigeru Nagase

Beilstein J. Org. Chem. 2023, 19, 1858–1866, doi:10.3762/bjoc.19.138

• -electron reduction of Gd@C2v-C82 for the addition reaction to occur at room temperature [22]. Supporting Information File 1, Figure S1 depicts the three HPLC separation steps including recycling for the isolation. The matrix-assisted laser desorption/ionization time-of-flight (MALDI–TOF) mass spectra of 2a

N-Boc-α-diazo glutarimide as efficient reagent for assembling N-heterocycle-glutarimide diads via Rh(II)-catalyzed N–H insertion reaction

• Grigory Kantin,
• Pavel Golubev,
• Alexander Sapegin,
• Alexander Bunev and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2023, 19, 1841–1848, doi:10.3762/bjoc.19.136

• product 6b in high yield. The reaction with methyl pyrrole-2-carboxylate resulted in the isolation of only the C–H insertion product 9c in low yield. Similar reaction progress was observed in the case with imidazole, the product N–H insertion was observed only in trace amounts (according to NMR data of

Synthetic approach to 2-alkyl-4-quinolones and 2-alkyl-4-quinolone-3-carboxamides based on common β-keto amide precursors

• Yordanka Mollova-Sapundzhieva,
• Plamen Angelov,
• Danail Georgiev and
• Pavel Yanev

Beilstein J. Org. Chem. 2023, 19, 1804–1810, doi:10.3762/bjoc.19.132

• -substitution in R1 drove the yields of 3 below 50% and for this reason isolation and further elaboration of such products were considered impractical. Once prepared, the key intermediates 3 could be transformed either directly to 2-alkyl-4-quinolone-3-carboxamides 5 or to 2-alkyl-4-quinolones 8, after an

• preferential isolation of N-hydroxy derivatives 7. Further experiments for palladium-catalyzed hydrogenation with H2 at atmospheric pressure did not show any advantage over the transfer hydrogenation conditions. Overall, the described synthetic approach (Scheme 1 and Scheme 2) allowed us to prepare in an

Active-metal template clipping synthesis of novel [2]rotaxanes

• Cătălin C. Anghel,
• Teodor A. Cucuiet,
• Niculina D. Hădade and
• Ion Grosu

Beilstein J. Org. Chem. 2023, 19, 1776–1784, doi:10.3762/bjoc.19.130

• [2]rotaxanes was further confirmed by MS2 experiments, i.e., isolation of the peaks corresponding to the [2]rotaxanes followed by collision-induced dissociation (CID) yielded the protonated molecular ions of the axle 6 and macrocycles M1 and M2, respectively (Figures S18 and S28 in Supporting

Unprecedented synthesis of a 14-membered hexaazamacrocycle

• Anastasia A. Fesenko and
• Anatoly D. Shutalev

Beilstein J. Org. Chem. 2023, 19, 1728–1740, doi:10.3762/bjoc.19.126

• isolation allows to remove residual impurities that arose from long-time reflux of aminopyrazole 3 in triethyl orthoformate (see the Experimental section). According to the DFT B3LYP/6-311++G(d,p) calculations in DMSO solution, the polyunsaturated 14-membered ring in 5 is almost planar with a maximum atom

• -pyrazolo[3,4-d]pyrimidin-5-amine (8) was developed. Under the optimized conditions (1.5 equiv of N2H4·H2O, MeOH, reflux, 3 h), the macrocycle 5 was obtained in a 35% isolated yield after crystallization. We believe that, despite the moderate yield of the macrocycle, the ease of its isolation and

Decarboxylative 1,3-dipolar cycloaddition of amino acids for the synthesis of heterocyclic compounds

• Xiaofeng Zhang,
• Xiaoming Ma and
• Wei Zhang

Beilstein J. Org. Chem. 2023, 19, 1677–1693, doi:10.3762/bjoc.19.123

• for 6 h to afford the monocycloaddition compounds. Without isolation, the reaction mixtures were then used for the N-propargylation in the presence of K2CO3 under microwave heating at 110 °C for 1 h to give triazolobenzodiazepines 21a–f in 35–65% yields with 2:1 to 7:1 dr (Scheme 13). Other than 2

Sulfur-containing spiroketals from Breynia disticha and evaluations of their anti-inflammatory effect

• Ken-ichi Nakashima,
• Naohito Abe,
• Masayoshi Oyama,
• Hiroko Murata and
• Makoto Inoue

Beilstein J. Org. Chem. 2023, 19, 1604–1614, doi:10.3762/bjoc.19.117

• four known spiroketals – probreynin I (4) [13], phyllaemblic acid (5) [10], breynin B (6) [2], and epibreynin B (7) [2] – from the roots of B. disticha, a species that has not previously been chemically investigated (Figure 1). Herein, we describe the isolation and structural elucidation of new

• expert botanist, Ms. Hiroko Murata (Setsunan University, retired). A voucher specimen (GPU-0812) has been deposited at the Gifu Pharmaceutical University for future reference. Extraction and isolation The dried roots (767 g) of B. disticha were extracted with MeOH (5 L × 3 times) at room temperature, and

Secondary metabolites of Diaporthe cameroonensis, isolated from the Cameroonian medicinal plant Trema guineensis

• Bel Youssouf G. Mountessou,
• Élodie Gisèle M. Anoumedem,
• Blondelle M. Kemkuignou,
• Yasmina Marin-Felix,
• Frank Surup,
• Marc Stadler and
• Simeon F. Kouam

Beilstein J. Org. Chem. 2023, 19, 1555–1561, doi:10.3762/bjoc.19.112

• chemical constituents of another new species of Diaporthe. This genus contains many plant pathogenic, endophytic, and saprobic species [7]. So far, the investigations of chemical constituents of Diaporthe species, have led to the isolation and characterization of a myriad of potent natural products with

• takes preference over Phomopsis. Regarding the potent talents of Diaporthe, we are on the quest to the exploration of structure–activity relationships of cytochalasins to establish their trends for various medical applications [5]. Along the same lines, we herein report the isolation and structural

• acetic acid (data not shown), we can exclude that it is an isolation artefact. The fifteen known compounds isolated from Diaporthe cameroonensis extract, which included alternariol (3) [14], 2-hydroxyalternariol (4) [15], 4-hydroxyalternariol (5) [16][17], 2,5-dimethyl-7-hydroxychromone (6) [18

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

• tumor cytotoxicity effects for a number of the berberine derivatives. Keywords: benzylisoquinoline; berberine; chelerythrine; drug discovery; plant-derived antimicrobials; Introduction The isolation, or creation of novel antimicrobial agents is currently at the forefront of modern healthcare due to

• these optimized conditions still resulted in exclusive isolation of B2 with no evidence of the product lacking the oxygen at position-13. Subsequent variants B7 and B8 were synthesized as the expected berberine derivatives, without formation of the oxidation byproduct. Of this initial set of berberine

• cell lines. Conclusion Motivated by our prior isolation of three phytochemicals from the extracts of the Argemone mexicana plant, a library of structural variants of berberine and chelerythrine were prepared. Due to a greater synthetic ease, a larger number of berberine derivatives were explored. The

Cyclization of 1-aryl-4,4,4-trichlorobut-2-en-1-ones into 3-trichloromethylindan-1-ones in triflic acid

• Vladislav A. Sokolov,
• Andrei A. Golushko,
• Irina A. Boyarskaya and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2023, 19, 1460–1470, doi:10.3762/bjoc.19.105

• , which are subsequently cyclized into indanones 3. From a synthetic point of view, the use of hydroxy ketones 1 as starting compounds for the cyclization without additional preparation and isolation of the corresponding enones 2 is more economical as it reduces the number of steps in the synthesis. Other

Functions of enzyme domains in 2-methylisoborneol biosynthesis and enzymatic synthesis of non-natural analogs

• Binbin Gu,
• Lin-Fu Liang and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2023, 19, 1452–1459, doi:10.3762/bjoc.19.104

• allowed for the isolation of the 2-methylisoborneol homolog 3 (Scheme 2B, Supporting Information File 1, Table S3 and Figures S12–S19). Furthermore, two inseparable hydrocarbons were obtained as a mixture (8:3) whose structures were tentatively assigned based on the NMR spectra (Supporting Information

Application of N-heterocyclic carbene–Cu(I) complexes as catalysts in organic synthesis: a review

• Nosheen Beig,
• Varsha Goyal and
• Raj K. Bansal

Beilstein J. Org. Chem. 2023, 19, 1408–1442, doi:10.3762/bjoc.19.102

• amidating reagent leading to the isolation of copper–arylcarbamato species and the desired product. The developed amidation protocol works highly efficiently and selectively over a broad range of substrates including polyfluorobenzenes, azoles, and quinoline N-oxides (Scheme 74). 2.10 C(sp2)–H thiolation

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

• aminopyrans [54], should be converted into divalent compounds via coupling of the terminal propynyl group with benzylic biazides. Since biazides are potentially explosive [22] it was very desirable to avoid their isolation and to generate these reactive species in situ from the corresponding benzylic halides

Functional characterisation of twelve terpene synthases from actinobacteria

• Anuj K. Chhalodia,
• Houchao Xu,
• Georges B. Tabekoueng,
• Binbin Gu,
• Kizerbo A. Taizoumbe,
• Lukas Lauterbach and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2023, 19, 1386–1398, doi:10.3762/bjoc.19.100

• accepted. A preparative scale incubation of FPP (80 mg, 185 μmol) allowed for the isolation of 10 (5.5 mg, 25 μmol, 14%) for structure elucidation through NMR spectroscopy (Table S2, Figures S3–S10, Supporting Information File 1), confirming the structure of δ-cadinol. The optical rotation of [α]D25

Consecutive four-component synthesis of trisubstituted 3-iodoindoles by an alkynylation–cyclization–iodination–alkylation sequence

• Nadia Ledermann,
• Alae-Eddine Moubsit and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2023, 19, 1379–1385, doi:10.3762/bjoc.19.99

• isolation) accounts for an average yield of 55–90% per bond-forming step which can be considered to be relative efficient, also because only a single terminal purification step is required. However, noteworthy, the 3-iodoindoles are sensitive to light and prolonged storage at room temperature, even under