One-pot Ugi-azide and Heck reactions for the synthesis of heterocyclic systems containing tetrazole and 1,2,3,4-tetrahydroisoquinoline

• Jiawei Niu,
• Yuhui Wang,
• Shenghu Yan,
• Yue Zhang,
• Xiaoming Ma,
• Qiang Zhang and
• Wei Zhang

Beilstein J. Org. Chem. 2024, 20, 912–920, doi:10.3762/bjoc.20.81

• the reported procedures [41], the Ugi-azide reaction of 2-bromobenzaldehyde (1a, 1 mmol), allylamine hydrochloride (2, 1 mmol), trimethylsilyl azide (3, 1 mmol) and tert-butyl isocyanide (4a, 1 mmol) in MeOH at 40 °C for 24 h afforded 1,5-DS-1H-T 5a in 92% yield after chromatography purification. Our

• purification. Thus, to the solution of crude 5a dissolved in MeCN (3 mL) were added 10 mol % of Pd(OAc)2, 20 mol % of PPh3, and 2 equiv of K2CO3 and the mixture stirred for 3 h at 105 °C under N2 atmosphere to give the desired product 6a in 60% isolated yield (entry 17 in Table 1). With the optimized one-pot

• . The initial Ugi-azide four-component reaction constructs the tetrazole motif while the subsequent intramolecular Heck reaction assembles the tetrahydroisoquinoline. The one-pot reaction avoids the intermediate purification which has favorable PASE in the synthesis of heterocyclic compounds

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

• performed on a Bruker Apex Kappa-II CCD diffractometer. The solvents used, dimethyl sulfoxide and 1,4-dioxane, were purchased as dry solvents and applied without further purification. Other reagents, catalysts, ligands, acids, and bases were used as purchased from commercial suppliers. Column chromatography

(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

• grade and contained 0.1% vol/vol formic acid. Protein expression and purification The vectors to express Vs NnlA and H73A Vs NnlA were previously reported [21]. Pd, Mr, Ms, Ps, and Pj nnla genes were synthesized as E. coli codon-optimized constructs and cloned into the NdeI and XhoI restriction sites of

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

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

• , yielding 4 with 90% yield and 99% conversion. A drawback of the Rolla protocol is the cost associated with the phase-transfer catalyst, and that the crude mixture requires purification through distillation or column chromatography. Another inconvenience is the high reaction temperature which limits 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

• temperature under argon. Under these reaction conditions, the tris(carboranyl)-substituted porphyrin 6 was obtained in 39% yield after purification by column chromatography on SiO2 using CHCl3/hexane 1:1 as eluent (Scheme 3). It should be noted that the reaction of porphyrin 6 with NaN3 in DMSO at 20 °C for

Substrate specificity of a ketosynthase domain involved in bacillaene biosynthesis

• Zhiyong Yin and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2024, 20, 734–740, doi:10.3762/bjoc.20.67

• gene coding for the glutamate decarboxylase from Escherichia coli K12 (accession no. AAA23833) was cloned through homologous recombination in yeast into the expression vector pYE-Express [26]. Heterologous expression and purification of the recombinant enzyme (Figure S1, Supporting Information File 1

• ) allowed for test incubations with unlabelled glutamic acid in the presence of the cofactor pyridoxal phosphate (PLP), showing the complete conversion of glutamic acid (3) into γ-aminobutyric acid (4) (Scheme 2). The crude product was used without purification for a Schotten–Baumann esterification with

• His-tagged enzyme was obtained through heterologous expression and purification by Ni2+-NTA affinity chromatography (Figure S1, Supporting Information File 1). After incubation of the purified enzyme with the 13C-labelled SNAC derivatives (S)-11 or (R)-11 for 30 minutes at 25 °C, the incubation buffer

Chemoenzymatic synthesis of macrocyclic peptides and polyketides via thioesterase-catalyzed macrocyclization

• Senze Qiao,
• Zhongyu Cheng and
• Fuzhuo Li

Beilstein J. Org. Chem. 2024, 20, 721–733, doi:10.3762/bjoc.20.66

• limitations, such as possible Cα epimerization [45] during SNAC coupling and essential HPLC purification, which was generally difficult and time-consuming. Developing other different methods, exceptionally more straightforward approaches to access activated substrates, would solve this inevitable bottleneck

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

• desired product, which proved to be unstable during purification (Scheme 4). Homopropargylic azides containing electron-rich nitrogen heterocycles could not be obtained. No product was observed by using vinylindole 1d probably due its high tendency to polymerize. Although a slight amount of

• % yield of the azido-arylated product, and using the more nucleophilic 13 only slightly improved the yield. Finally, a small amount of product resulting from the addition of allyl-BF3K 14 could be observed but decomposed during purification. Based on literature precedence [41][42][44] and experimental

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

• % conversion when 1 equivalent of sulfinate was used. Products 8 exhibited instability in the presence of water, leading to the formation of hydrolysis product 9 [25] in the reaction mixture. This instability caused issues during the reaction work-up, and attempts for purification using column chromatography

• 12a, diazide 13, and hydrolysis product 9 [25] which were inseparable using common purification methods (Table 1). The pivotal advancement occurred when attempting the reaction in DMSO (Table 1). In the case of 8a (R = 4-CH3C6H4), the product precipitated out when full conversion was reached

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

• Corp., TCI, Sigma-Aldrich) and used as received without further purification. Li+@C60TFSI− was purchased as PF6− salt from Idea International Corp., and then its counter anion was exchanged to TFSI− according to reported procedures [9]. NMR spectra were recorded on a JEOL JNM-ECZ400S (1H: 400 MHz, 7Li

HPW-Catalyzed environmentally benign approach to imidazo[1,2-a]pyridines

• Luan A. Martinho and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2024, 20, 628–637, doi:10.3762/bjoc.20.55

• ][21][22]. Multicomponent reactions (MCRs) provide one-pot reactions, simple synthetic procedures, less waste being produced, fewer purification steps, and a high atom economy [23]. The GBB three-component reaction is carried out in the presence of Lewis or Brønsted acid catalysis to increase the

• furnished good results for the HPW-catalyzed GBB-3CR with yields greater than 63% (5m–o). It is always important to point out the limitations of a given method and in our case, we did have some. Purification by column chromatography became necessary since product isolation by precipitation was not effective

• . The catalyst was impregnated in the isolated crude product, and its removal through a recrystallization step was not successful. The use of a liquid–liquid extraction work-up step proved less effective compared to column chromatography purification. Moreover, attempts to recover the catalyst were not

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

• yield an ethanol extract. This extract was further processed with ethyl acetate (EtOAc) three times. The combined EtOAc phase was then dried using a rotary evaporator to obtain the EtOAc extract, which was stored at −80 °C until further purification process. The above fermentation broth was adsorbed

• EtOAc extracts were dried using a rotary evaporator to obtain the final EtOAc extract, which was stored at −80 °C until further isolation process. Compounds purification The EtOAc extract (3.5 g) obtained from the fermentation broth of XISR I medium underwent column chromatography on silica using a

A myo-inositol dehydrogenase involved in aminocyclitol biosynthesis of hygromycin A

• Michael O. Akintubosun and
• Melanie A. Higgins

Beilstein J. Org. Chem. 2024, 20, 589–596, doi:10.3762/bjoc.20.51

• Cloning, expression, and purification Streptomyces leeuwenhoekii NRRL B-24963 [28] was used as a template to amplify the hyg17 (GenBank CQR59633) with the primers 5’-GTTAGCCATATGACGGTCGCCGTCGTGGGC-3’ and 5’-GTAATGCTCGAGCGGCGCCACCGGCACCGA-3’. hyg17 was cloned into pTip-QC1 [10] using NdeI and XhoI

• /off cycles for 5 min at a duty cycle of 50). Initial purification was performed with gravity filtration using nickel-nitrilotriacetic acid (Ni-NTA) resin (GE Healthcare). Cell lysate was loaded onto the Ni-NTA resin and washed with binding buffer. Protein was eluted using increasing concentrations of

• NaCl, 20 mM Tris pH 7.5) for another 10 min. Then MgSO4 (to ≈1 mM) and 0.2 mg DNase (Thermo Fisher Scientific) were added and stirred for 10 min. The lysate was centrifuged to remove debris for 45 min at 10,000 rpm and 4 °C, and the lysate was collected into a beaker. Purification was then performed

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

• (SORHA), Triticum aestivum (TRZAS), and Zea mays (ZEAMX). LpFAT A expression and purification: The fat a03 gene from Lemna paucicostata, in which the N-terminal amino acids representing the chloroplast transit peptide were replaced by an N-terminal 6xHis-tag, was cloned into a pET24 vector [3]. The LpFAT

A new analog of dihydroxybenzoic acid from Saccharopolyspora sp. KR21-0001

• Rattiya Janthanom,
• Yuta Kikuchi,
• Hiroki Kanto,
• Tomoyasu Hirose,
• Arisu Tahara,
• Takahiro Ishii,
• Arinthip Thamchaipenet and
• Yuki Inahashi

Beilstein J. Org. Chem. 2024, 20, 497–503, doi:10.3762/bjoc.20.44

• compound producers. Among the rare actinomycetes, Saccharopolyspora sp. KR21-0001 isolated from soil on Ōha Island, Okinawa, Japan was selected as a potential producer. The strain was cultured in 20 L of production medium in a jar fermenter and the culture broth was extracted. Further purification revealed

• minute) for 7 days. Purification and extraction The 7-day culture broth of Saccharopolyspora sp. KR21-0001 was centrifuged at 3000 rpm for 10 min. The supernatant fraction was eluted stepwise with 1.5 L of MeOH/H2O (0%, 50%, and 100%) through a HP20 column (55 i.d. × 500 mm), and all fractions were

Pseudallenes A and B, new sulfur-containing ovalicin sesquiterpenoid derivatives with antimicrobial activity from the deep-sea cold seep sediment-derived fungus Pseudallescheria boydii CS-793

• Zhen Ying,
• Xiao-Ming Li,
• Sui-Qun Yang,
• Hong-Lei Li,
• Xin Li,
• Bin-Gui Wang and
• Ling-Hong Meng

Beilstein J. Org. Chem. 2024, 20, 470–478, doi:10.3762/bjoc.20.42

• sesquiterpenoids (1, 2), together with three known related analogs (3–5) [10][11][12][13] have been isolated and identified from the bioactive fraction of P. boydii CS-793. Details of the isolation and purification, structure elucidation, and biological evaluation of compounds 1–5 are described herein. Results and

• Discussion For chemical investigation, the solvent EtOAc was used to extract the fermentation culture of the fungus P. boydii CS-793 to afford an organic extract. Isolation and purification of the crude extract with a combination of column chromatography (CC) by Lobar LiChroprep RP-18, silica gel, Sephadex

• chromatography (TLC) was performed with precoated Si gel GF254 plates (Merck, Darmstadt, Germany). Solvents used for extraction and purification were distilled prior to use. Peptone from yeast extract was purchased from Sigma-Aldrich. Rice, monosodium glutamate, and corn steep liquor were purchased from China

Synthesis of 2,2-difluoro-1,3-diketone and 2,2-difluoro-1,3-ketoester derivatives using fluorine gas

• Alexander S. Hampton,
• David R. W. Hodgson,
• Graham McDougald,
• Linhua Wang and
• Graham Sandford

Beilstein J. Org. Chem. 2024, 20, 460–469, doi:10.3762/bjoc.20.41

• Supporting Information File 1). To isolate the main difluorinated product 3a, the reaction vessel was purged with nitrogen and the product mixture was partitioned between water and DCM to remove HF and salt by-products. Purification of 3a by column chromatography gave 3a as a white crystalline solid in 65

• . Again, purification by column chromatography gave the products 3 as white crystalline solids and the structures of compounds 3f and 3i were confirmed by X-ray crystallography (Figure 2 and Supporting Information File 1). Molecules 3a, f, and i all exist in the solid state with the dicarbonyl moiety

• difluorinated product 5a in 85% isolated yield. Purification of 5a was achieved very readily by eluting the reaction mixture through a small quantity of silica gel with chloroform and evaporating the residual solvent to leave the crude product which could be further purified by recrystallization. Subsequently

Mono or double Pd-catalyzed C–H bond functionalization for the annulative π-extension of 1,8-dibromonaphthalene: a one pot access to fluoranthene derivatives

• Nahed Ketata,
• Linhao Liu,
• Ridha Ben Salem and
• Henri Doucet

Beilstein J. Org. Chem. 2024, 20, 427–435, doi:10.3762/bjoc.20.37

• of PdCl(C3H5)(dppb) (30.5 mg, 0.05 mmol) at 150 °C during 16 h in DMA (4 mL) under argon affords the coupling products 1–18 after evaporation of the solvent and purification on silica gel. Eluent EtOAc/heptane 1:9 for compounds 3–8, 10–18; heptane for compounds 1, 2, and 9. General procedure for the

• DMA (4 mL) under argon affords the coupling products 19–27 after evaporation of the solvent and purification on silica gel. Eluent EtOAc/heptane 1:9 for compounds 19–24; heptane for compounds 25 and 26; EtOAc/heptane 2:8 for compound 27. General procedure for the palladium-catalyzed synthesis of 9

• (4 mL) under argon affords the coupling products 28–30 after evaporation of the solvent and purification on silica gel. Eluent EtOAc/heptane 1:9 for all compounds. Structure of fluoranthene. Pd-catalyzed access to fluoranthenes. Scope of the Pd-catalyzed direct arylation reaction of arenes with 1,8

Facile approach to N,O,S-heteropentacycles via condensation of sterically crowded 3H-phenoxazin-3-one with ortho-substituted anilines

• Eugeny Ivakhnenko,
• Vasily Malay,
• Pavel Knyazev,
• Nikita Merezhko,
• Nadezhda Makarova,
• Oleg Demidov,
• Gennady Borodkin,
• Andrey Starikov and
• Vladimir Minkin

Beilstein J. Org. Chem. 2024, 20, 336–345, doi:10.3762/bjoc.20.34

• . Results and Discussion We found that a convenient way toward 6,8-di-tert-butyl-2-(arylamino)-3H-phenoxazin-3-ones 4 involves the short-term heating (30 min) of a molten mixture of 1 and an arylamine at 250 °C, followed by purification of the products by column chromatography. No preliminary grinding of

• potential for testing as potential donors for organic solar cells or as dye sensitizers for dye-sensitized solar cells [24][25]. Experimental All reagents and solvents were purchased from commercial sources (Aldrich) and used without additional purification. The compounds were characterized by 1H, 13C, and

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

• . 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

• performed on a Shimadzu LC-20AP preparative liquid chromatograph (SCL-40 System Controler Deliver and LH-40 Liquid Handler) coupled to a Shimadzu SPD-M40 Photo Diode Array Detector (PDA) system using a RP-18 column (Phenomenex, Kinetex 250 × 30 mm i.d., 5 µm, flow rate of 18.0 mL min−1). The purification of

• consisted of H2O + 0.05% formic acid (eluent A) and MeCN + 0.05% formic acid (eluent B), which was eluted of 20–100% of B with flow rate of 18 mL min−1, yielding 20 fractions. Fractions Fr13 and Fr15 were subjected to a purification by semipreparative HPLC-UV using a Premier RP18 column (250 mm × 10 mm i.d

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

• and subsequent reverse Ni-NTA affinity chromatography resulted in significant co-purification of E. coli contaminants, necessitating an extra purification step, where cation exchange chromatography allowed us to obtain pure fractions of CMA16–291. Of note, this additional purification step was not

• necessary for the purification of the CMA1 N-terminal domain (Figure 1d). Expression of the CMA1 C-terminal domain did not yield sufficiently pure and monodisperse protein for further biochemical and structural analyses. Cucumis melo agglutinin binds C2-substituted, beta-linked galactose We then set out to

• polymerase (Takara #TAKR045A); then the product was digested by DpnI and finally transformed in NEB5α strain (New England Biolabs, #C2992H). Both gene and vector were digested by NcoI and XhoI restriction enzymes (New England Biolabs) prior to purification on agarose gel using Monarch Gel extraction kit and

Synthesis of π-conjugated polycyclic compounds by late-stage extrusion of chalcogen fragments

• Aissam Okba,
• Pablo Simón Marqués,
• Kyohei Matsuo,
• Naoki Aratani,
• Hiroko Yamada,
• Gwénaël Rapenne and
• Claire Kammerer

Beilstein J. Org. Chem. 2024, 20, 287–305, doi:10.3762/bjoc.20.30

• devices [1][2][3][4][5][6][7][8]. In this regard, the planar character of most (non-substituted) π-CPCs represents a challenge, as it results in very low solubility in common organic solvents due to favorable intermolecular π–π stacking interactions. This inherently hampers the purification of the target

• endoperoxide formation. To overcome these issues, the “precursor approach” was developed and relies on the synthesis, purification and characterization of soluble and stable precursors of the target active π-CPCs, followed by their (solution) processing and their final deprotection once assembled in thin-films

• purification by column chromatography prior to their on-surface deposition. By way of example, the synthesis of decacene precursor 59 was achieved in three synthetic steps by iterative [4 + 2] cycloadditions with an overall yield of 4.7% (Scheme 17). The synthesis of epoxyacene 59 started with the mono-Diels

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

• by chromatographic purification in 88% yield (Table 1, entry 1). Reducing the amount of DIPEA gave diminished yield (Table 1, entry 2). Adding more base was unnecessary to get a higher yield (Table 1, entry 3). Subsequently, the use of other bases was not appropriate for promoting the generation of

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

• activator of NBS, as was previously shown by the example of a very successful bromination of 6-methylquinoline at position 5 with a preparative yield of 74% [27]. Indeed, under the new conditions, we obtained dibromo derivative 15 in high yield without heating and subsequent purification (Scheme 7). The