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

Unravelling a trichloroacetic acid-catalyzed cascade access to benzo[f]chromeno[2,3-h]quinoxalinoporphyrins

• Chandra Sekhar Tekuri,
• Pargat Singh and
• Mahendra Nath

Beilstein J. Org. Chem. 2023, 19, 1216–1224, doi:10.3762/bjoc.19.89

• afford copper(II) benzo[f]chromeno[2,3-h]quinoxalinoporphyrin 3 in 65% yield (Scheme 2). The successful isolation of intermediate 17 and its conversion to copper(II) benzo[f]chromeno[2,3-h]quinoxalinoporphyrin 3 as shown in Scheme 2 clearly support the proposed mechanism for the formation of the desired

Exploring the role of halogen bonding in iodonium ylides: insights into unexpected reactivity and reaction control

• Carlee A. Montgomery and
• Graham K. Murphy

Beilstein J. Org. Chem. 2023, 19, 1171–1190, doi:10.3762/bjoc.19.86

• ]. The authors discounted a free carbene-based C–H insertion because conducting the reaction in the presence of the radical trap phenyl N-tert-butyl nitrone (PBN) and the radical scavenger TEMPO resulted in decreased yields and isolation of their iodonium ylide adducts. Additional kinetic isotope effect

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

• ]. Chemical investigations of F. pinicola or F. betulina revealed their cytotoxic [21][23] and antidiabetic propensities [19]. In addition, the recent review on F. officinalis, elaborated the potential use of its compounds as antibiotic leads [19]. In this study we report the isolation and structure

• incubation following the aforementioned established procedures to afford 0.5 g (mycelial) and 1.5 g (supernatant) ethyl acetate extracts for Q6/2 cultures and 3.44 g ethyl acetate extract for rice cultures. Isolation of compounds 1–4 Purification of the rice and Q6/2 media cultures was achieved by using a

New one-pot synthesis of 4-arylpyrazolo[3,4-b]pyridin-6-ones based on 5-aminopyrazoles and azlactones

• Vladislav Yu. Shuvalov,
• Ekaterina Yu. Vlasova,
• Tatyana Yu. Zheleznova and
• Alexander S. Fisyuk

Beilstein J. Org. Chem. 2023, 19, 1155–1160, doi:10.3762/bjoc.19.83

• carried out as one-pot synthesis, without isolation of the intermediate dihydro derivative 3а. In this case, the solvent (DMSO) could be added at the stage of obtaining dihydro derivative 3a or introduced into the reaction together with t-BuOK. We have explored both variants. When intermediate 3a was

Synthesis of imidazo[4,5-e][1,3]thiazino[2,3-c][1,2,4]triazines via a base-induced rearrangement of functionalized imidazo[4,5-e]thiazolo[2,3-c][1,2,4]triazines

• Dmitry B. Vinogradov,
• Alexei N. Izmest’ev,
• Angelina N. Kravchenko,
• Yuri A. Strelenko and
• Galina A. Gazieva

Beilstein J. Org. Chem. 2023, 19, 1047–1054, doi:10.3762/bjoc.19.80

• ][1,3]thiazino[2,3-c][1,2,4]triazines 3a–i as a result of ester group hydrolysis and thiazolidine ring expansion to the corresponding thiazine (Scheme 3). The potassium salts 3a,b were isolated in 81 and 63% yield, respectively. Compounds 3c–i were used in further transformations without isolation. 1H

Linker, loading, and reaction scale influence automated glycan assembly

• Marlene C. S. Dal Colle,
• Manuel G. Ricardo,
• Nives Hribernik,
• José Danglad-Flores,
• Peter H. Seeberger and
• Martina Delbianco

Beilstein J. Org. Chem. 2023, 19, 1015–1020, doi:10.3762/bjoc.19.77

• light (λ = 360 nm), L1 releases the glycan equipped with an aminoalkyl spacer at the reducing end, whereas L2 affords the free reducing sugar (α/β mixture). Previous data suggested that UV cleavage of L1 and L2 was equally efficient, permitting the isolation of a tetramannoside in around 60% yield [3

Five new sesquiterpenoids from agarwood of Aquilaria sinensis

• Hong Zhou,
• Xu-Yang Li,
• Hong-Bin Fang,
• He-Zhong Jiang and
• Yong-Xian Cheng

Beilstein J. Org. Chem. 2023, 19, 998–1007, doi:10.3762/bjoc.19.75

• deep insight into novel molecules with effective bioactivities from agarwood. Therefore, the continued study of Aquilaria sinensis has led to the isolation of ten sesquiterpenoids, including five new eudesmane-type sesquiterpenoids (Figure 1). Herein, we describe the isolation, structural elucidation

• , Shenzhen University, P.R. China. Extraction and isolation The dried and powdered agarwood sample (15.0 kg) was extracted by percolating with 95% EtOH to afford a crude extract, which was suspended in water followed by partition with EtOAc to afford an EtOAc-soluble extract (1.7 kg). The EtOAc extract was

Synthesis of tetrahydrofuro[3,2-c]pyridines via Pictet–Spengler reaction

• Elena Y. Mendogralo and
• Maxim G. Uchuskin

Beilstein J. Org. Chem. 2023, 19, 991–997, doi:10.3762/bjoc.19.74

• . In most cases, we observed the abundant tarring of the reaction mixture and we could not achieve the full conversion of the starting tetrahydrofuro[3,2-c]pyridine 4a in any experiment. The best results were achieved when HCl in 1,4-dioxane was used (Scheme 3). However, upon isolation and purification

• , without isolation of the intermediate 3-(2-oxopropyl)piperidin-4-one 5a, the reaction mixture after acid hydrolysis was treated with aniline and the desired tetrahydro-1H-pyrrolo[3,2-с]pyridine 6а was isolated in 19% yield only (Scheme 4). Finally, we studied some reactions of the obtained tetrahydrofuro

Clauson–Kaas pyrrole synthesis using diverse catalysts: a transition from conventional to greener approach

• Dileep Kumar Singh and
• Rajesh Kumar

Beilstein J. Org. Chem. 2023, 19, 928–955, doi:10.3762/bjoc.19.71

• amines 50 were reacted with 2,5-DMTHF (2) in 5 mol % Bi(NO3)3·5H2O in solvent-free conditions under ultrasound irradiation at room temperature. The main advantages of this procedure are its simple isolation process, excellent product yield without using expensive or sensitive solvents and reagents

• °C (Scheme 35). This solvent-free protocol has many advantages, including better selectivity and excellent product yields, mild reaction conditions, and ease of product isolation. (iii) Microwave-assisted reactions under organic solvents: Silveira and co-workers [90] developed the Clauson–Kaas

Intermediates and shunt products of massiliachelin biosynthesis in Massilia sp. NR 4-1

• Till Steinmetz,
• Blaise Kimbadi Lombe and
• Markus Nett

Beilstein J. Org. Chem. 2023, 19, 909–917, doi:10.3762/bjoc.19.69

• -chelating molecules, which are structurally and likely also biosynthetically linked to massiliachelin. However, these compounds are not related to the predicted lipopeptide siderophore. Herein, we describe their isolation, characterization and antibacterial activities, and we discuss their biosynthetic

• (Supporting Information File 1, Figure S1). In the absence of sodium pyruvate, the identification and isolation of minor metabolites from Massilia sp. NR 4-1 is facilitated, as already observed in the discovery of massinidine [17]. In the present study, several batch fermentations with a total culture volume

• a second reversed-phase HPLC run. This led to the isolation of six compounds (1–6, Figure 2). The NMR spectroscopic data of compound 1 (brownish oil, 1.7 mg) were found to be very similar to those of the previously reported massiliachelin [18], suggesting a structural relatedness. The empirical

Synthesis of aliphatic nitriles from cyclobutanone oxime mediated by sulfuryl fluoride (SO₂F₂)

• Xian-Lin Chen and
• Hua-Li Qin

Beilstein J. Org. Chem. 2023, 19, 901–908, doi:10.3762/bjoc.19.68

• the [Cun] catalyst and intermediate V. The critical β-H elimination step occurs smoothly in the presence of excessive base to generate the final nitrile product. Due to the high reactivity of the intermediate fluorosulfonate I, the attempt of isolation or detecting the in situ generated intermediate I

Asymmetric tandem conjugate addition and reaction with carbocations on acylimidazole Michael acceptors

• Brigita Mudráková,
• Renata Marcia de Figueiredo,
• Jean-Marc Campagne and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 881–888, doi:10.3762/bjoc.19.65

• charges at C-2 of enolates cannot account for the differences in the yields of the trapping products as these are affected by their specific stabilities and issues during isolation and purification. As an additional question that we tried to answer with these calculations was the comparison of the Zn

Eschenmoser coupling reactions starting from primary thioamides. When do they work and when not?

• Lukáš Marek,
• Jiří Váňa,
• Jan Svoboda and
• Jiří Hanusek

Beilstein J. Org. Chem. 2023, 19, 808–819, doi:10.3762/bjoc.19.61

• , whose isolation in the pure state failed. Comparable results were obtained in DCM at 25 °C with KHCO3 (Table 1, entry 13) but with TEA (Table 1, entry 14) only moderate yields of 8a and 9a were obtained. To generalize the results obtained with thiobenzamide, the reaction of 2b with thioacetamide was

• -bromoisoquinoline-1,3(2H,4H)-dione (3) with a yield of 65%. Its reaction with thiobenzamide and thioacetamide in DMF was carried out without isolation of the intermediary thioiminium salts 10a and 10b and only gave the ECR products 11a,b (Scheme 5) in good yield (75 and 78%, respectively). No thiazole (cf

• . reactions of compound 2b) formation was observed. An even better yield of ECR (11c, 91%) was achieved with thiobenzanilide, again without isolation of the intermediary salt 10c. The presence of any base or thiophile had no positive effect on the course of the reaction. Simplification of a structure of

Non-peptide compounds from Kronopolites svenhedini (Verhoeff) and their antitumor and iNOS inhibitory activities

• Yuan-Nan Yuan,
• Jin-Qiang Li,
• Hong-Bin Fang,
• Shao-Jun Xing,
• Yong-Ming Yan and
• Yong-Xian Cheng

Beilstein J. Org. Chem. 2023, 19, 789–799, doi:10.3762/bjoc.19.59

• -peptide small molecules, leading to the isolation of six new and three known compounds (Figure 1) from its extract. These structures were determined by 1D and 2D NMR spectra and the experimental and calculated electronic circular dichroism (ECD) spectra. The six new compounds have been named kronopoone A

• Science Center, Shenzhen University, PR China. Extraction and isolation The dried and powdered bodies of Kronopolites svenhedini (Verhoeff) (49 kg) were extracted using 50% EtOH (4 × 120 L, 24 h each time) to yield a crude extract. This extract (5.2 kg) was partitioned into six fractions (Fr. A–Fr. F