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 for 4 h. Under these reaction conditions, monoazide derivative 2 was obtained in 40% yield along with a mixture of porphyrin 1, di- and triazido-substituted derivatives. The reaction mixture was separated by column chromatography on SiO2 using CH2Cl2/hexane 2:8 as an eluent. The reduction of the

• 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

• 48 h resulted in a mixture of azidoporphyrin 7 and amino derivative 5 which were separated by column chromatography on SiO2 to give porphyrin 7 and porphyrin 5 in 66% and 33% yields, respectively. The reduction of porphyrin 7 with SnCl2·2H2O in MeOH afforded porphyrin 5 in 92% yield. We investigated

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

• 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

Genome mining of labdane-related diterpenoids: Discovery of the two-enzyme pathway leading to (−)-sandaracopimaradiene in the fungus Arthrinium sacchari

• Fumito Sato,
• Terutaka Sonohara,
• Shunta Fujiki,
• Akihiro Sugawara,
• Yohei Morishita,
• Taro Ozaki and
• Teigo Asai

Beilstein J. Org. Chem. 2024, 20, 714–720, doi:10.3762/bjoc.20.65

• determined to be (−)-sandaracopimaradiene (Figure 3B). We then turned our attention to the individual function of these enzymes. With this aim, AsPS and AsCPS were expressed in Escherichia coli as N-terminal hexa-histidine-tagged proteins and purified by Ni-affinity chromatography (see Supporting Information

New variochelins from soil-isolated Variovorax sp. H002

• Jabal Rahmat Haedar,
• Aya Yoshimura and
• Toshiyuki Wakimoto

Beilstein J. Org. Chem. 2024, 20, 692–700, doi:10.3762/bjoc.20.63

• remove salt and carbohydrate residues. After the retained siderophores were extracted with methanol, the obtained crude extract was further fractionated through several rounds of column chromatography, guided by a colorimetric-based chrome azurol sulfonate siderophore assay (CAS assay) [13], to yield

• , which was packed into a column for chromatography. The packed resin was washed with water several times and then eluted with an excess of methanol. The collected methanol fraction was concentrated in vacuo to obtain a crude extract. Subsequently, the crude extract was subjected to Sephadex LH-20 column

• chromatography, with methanol as the mobile phase. After monitoring the fractions by a CAS assay, the positive fractions were concentrated and purified by semi-preparative HPLC on a Cosmosil 5C18-MS-II column (10 mm ID × 250 mm, Nacalai Tesque), using a gradient system with MeCN/H2O (3:7 to 7:3) as the mobile

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

• anhydrous THF, MeCN, and dioxane, using such azide sources as NaN3, LiN3, and TMS-N3. Full conversion towards product 12a was observed by HPLC with NaN3 in anhydrous DMF. However, precipitation, direct, and reversed-phase column chromatography provided low yields (Scheme 5) due to the degradation of the

Isolation and structure determination of a new analog of polycavernosides from marine Okeania sp. cyanobacterium

• Kairi Umeda,
• Naoaki Kurisawa,
• Ghulam Jeelani,
• Tomoyoshi Nozaki,
• Kiyotake Suenaga and
• Arihiro Iwasaki

Beilstein J. Org. Chem. 2024, 20, 645–652, doi:10.3762/bjoc.20.57

• hexane. The aqueous MeOH portion was purified by reversed-phase column chromatography (ODS silica gel, MeOH/H2O), automated flash chromatography (hexane/EtOAc), and repeated reversed-phase HPLC to give polycavernoside E (1, 0.5 mg as a colorless oil). The isolation of compound 1 was directed by its

• based on HMBC and HMQC experiments. HRESIMS spectra were obtained on a Bruker timsTOF mass spectrometer. For reversed-phase column chromatography, ODS silica gel Cosmosil 75C18-OPN (Nacalai Tesque) was used. For medium pressure column chromatography, AFCS (Smart Flash AKROS, Yamazen) consisting of a

• ). The aqueous MeOH layer was concentrated, and the obtained residue (673 mg) was separated by column chromatography on ODS (7 g) eluted with 35 mL of 40%, 60%, 80%, and 90% aqueous MeOH, followed by 35 mL of MeOH and 70 mL of CHCl3/MeOH 1:1. The fraction (244.4 mg) eluted with 80% MeOH was subjected to

Production of non-natural 5-methylorsellinate-derived meroterpenoids in Aspergillus oryzae

• Jia Tang,
• Yixiang Zhang and
• Yudai Matsuda

Beilstein J. Org. Chem. 2024, 20, 638–644, doi:10.3762/bjoc.20.56

• earlier. We then analyzed the metabolites from the resulting transformants using high-performance liquid chromatography (HPLC), which revealed that all of the enzymes, except AdrI, accepted 1 and produced 5-MOA-derived meroterpenoids (Figure 2B, traces iii to vii). Since the transformation plasmid with

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

• 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

• use of glyoxals did not provide the desired products. Instead, the respective starting materials were almost quantitatively recovered from the column chromatography purification step. The use of very reactive aldehydes such as formaldehyde and crotonaldehyde also did not provide the GBB adduct

Introduction of a human- and keyboard-friendly N-glycan nomenclature

• Friedrich Altmann,
• Johannes Helm,
• Martin Pabst and
• Johannes Stadlmann

Beilstein J. Org. Chem. 2024, 20, 607–620, doi:10.3762/bjoc.20.53

• oligomannosidic-type glycans, but this only makes sense if the true structure of a glycan is known, e.g., if glycans are analyzed by porous graphitic carbon chromatography [50]. Only the mannoses that occur in addition to those on the common core have to be explicitly defined and this is realized by their linkage

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

• extract was partitioned between EtOAc and H2O. The EtOAc fraction was chromatographed repeatedly over silica gel and reversed-phase high-performance liquid chromatography (RP-HPLC), resulting in the isolation of pure compounds 1–12 (Figure 2). According to literature reports of known compounds, some of

• onto macroporous resin for 4 hours or left overnight. It was then eluted with deionized water and ethanol through a chromatography column. The ethanol eluate was concentrated to dryness using a rotary evaporator. Subsequently, the ethanol extract underwent a triple extraction with EtOAc. The combined

• 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

• Bacillus subtilis, BsIDH, has an optimal pH between 9.5–10 [12][13]. We also compared product formation between reactions with Hyg17 or BsIDH and myo-inositol using thin-layer chromatography (Supporting Information File 1, Figure S3). We found that both enzymes generated a ketone product with identical

• chromatography column (Cytiva) equilibrated in 50 mM NaCl, 20 mM Tris pH 8.0 and run on a Bio-Rad NGC chromatography system. Protein-containing fractions were identified by UV absorbance at 280 nm and were pooled and concentrated using a centrifugal device with a 10 kDa molecular weight cut-off (Pall Corporation

• using the same protocol as described above for Hyg17 except that a HiLoad 26/600 Superdex 200 pg size-exclusion chromatography column (Cytiva) equilibrated in 50 mM NaCl, 20 mM Tris pH 8.0 was used. Protein concentration was determined by UV absorbance at 280 nm using the calculated extinction

Entry to new spiroheterocycles via tandem Rh(II)-catalyzed O–H insertion/base-promoted cyclization involving diazoarylidene succinimides

• Alexander Yanovich,
• Anastasia Vepreva,
• Ksenia Malkova,
• Grigory Kantin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2024, 20, 561–569, doi:10.3762/bjoc.20.48

• previously tested using 3-bromopropanol. When the reaction was carried out in a one-pot format, with the replacement of DCM by acetone, the desired product 5a could only be isolated in moderate yield (52%). In the case of preliminary isolation of the OH-insertion product 16a (flash chromatography), the

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

• reduced pressure. The remaining residue was purified via column chromatography (gradient ethyl acetate/hexane) to afford 6-(2-fluorophenyl)pyridin-2-ylamine (9b, 9.98 g, 93%). 1H NMR (400 MHz, CDCl3, δ) 7.92–7.88 (m, 1H), 7.53–7.49 (m, 1H), 7.36–7.31 (m, 1H), 7.25–7.20 (m, 1H), 7.16–7.10 (m, 1H), 6.50

• was added, followed by thorough extraction. The combined organic layer was dried over magnesium sulfate, filtered, and dried under reduced pressure. The remaining residue was purified via column chromatography (gradient ethyl acetate/hexane) to afford 6-bromo-5-(2-fluorophenyl)[1,3]thiazolo[4,5-b

• acetonitrile, formic acid was added, and the reaction mixture was stirred at room temperature for 2 h. The phases were separated via phase separator, and the organic layer was concentrated under reduced pressure. The remaining crude product was purified via column chromatography (gradient ethyl acetate/hexane

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

• (Scheme 1). KR21-0001A (1) was purified from the culture broth guided by the ion peak (m/z 316) using LC–MS. The supernatant of the culture broth underwent HP20 column chromatography, but 1 was not retained in the resin and eluted in the flowthrough fraction. Since 1 was an acidic compound, the pH of the

• flowthrough fraction was adjusted to 3 with formic acid (FA) and chromatographed again on HP20 column. Now, 1 was retained in the resin and eluted by 50% MeOH with 0.05% FA. Then 1 was purified by silica gel and ODS column chromatography, and ethyl acetate extraction under acidic conditions. As the result of

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

• 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

• by Chromeleon software (version 6.80). LC–MS were obtained with a Bruker maXis plus Q-TOF. Column chromatography was carried out using commercially available silica gel (200–300 mesh, Qingdao Haiyang Chemical Co.), Lobar LiChroprep RP-18 (40–63 μm, Merck), and Sephadex LH-20 (Pharmacia). Thin-layer

• 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

• , a range of ethyl benzoylacetate derivatives was prepared (see Supporting Information File 1) [45][46] and successfully subjected to difluorination conditions (Table 3). Purification by column chromatography using the minimum amount of silica gel with chloroform as the eluent yielded 5c–g in high

(E,Z)-1,1,1,4,4,4-Hexafluorobut-2-enes: hydrofluoroolefins halogenation/dehydrohalogenation cascade to reach new fluorinated allene

• Nataliia V. Kirij,
• Andrey A. Filatov,
• Yurii L. Yagupolskii,
• Sheng Peng and
• Lee Sprague

Beilstein J. Org. Chem. 2024, 20, 452–459, doi:10.3762/bjoc.20.40

• 11 had an allene structure. It was also important to note that the reaction proceeded more selectively in ether, which significantly reduced the amount of byproducts. Pure final alcohol 10 was isolated by column chromatography on SiO2 in 46% yield and 1H, 19F and 13C NMR spectra were in full

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

• III 400 MHz and Bruker Avance neo 500 MHz spectrometers. High-resolution mass spectra were measured on a Bruker MaXis 4G spectrometer. Melting points were determined with a Kofler hot bench system. Chromatography purifications were performed using a CombiFlash NextGen 300 with Buchi FlashPure

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

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

• compounds was performed on a Shimadzu LC-20AD liquid chromatography (CBM-20A Communication Bus Module, CTO-20A column oven, DGU-20A Degassing Unit and SIL-20A AutoSampler) coupled to a Shimadzu SPD-20A UV–vis Detector system using a RP-18 column (Shimadzu, Premier 250 × 10 mm i.d., 5 µm, flow rate of 3.0 mL

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

• in bacteria as well as the oxidative environment of the secretory pathway, as CMA1 exhibits predicted disulfide bridges. A single step of His-tag affinity chromatography was sufficient to yield protein of adequate purity and good yield (≈15 mg of eluted protein from 800 mL of cell culture, Figure 1c

• hexa-His tag, cleavable by TEV (Tobacco etch virus) protease. Despite the presence of the DsbC signal peptide, we did not observe periplasmic localization, and all proteins were instead purified from the cytoplasm. Ni-NTA affinity chromatography followed by TEV protease cleavage of the fusion construct

• 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

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

• 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

Unveiling the regioselectivity of rhodium(I)-catalyzed [2 + 2 + 2] cycloaddition reactions for open-cage C₇₀ production

• Cristina Castanyer,
• Anna Pla-Quintana,
• Anna Roglans,
• Albert Artigas and
• Miquel Solà

Beilstein J. Org. Chem. 2024, 20, 272–279, doi:10.3762/bjoc.20.28

• heating at 90 °C for 4 hours. The crude reaction mass obtained with these conditions was then purified by column chromatography (toluene). After eluting unreacted pristine C70, a dark reddish fraction was isolated and analyzed by HPLC. A major peak was observed at a retention time of 17.5 minutes, which

• has Cs symmetry [50], we can conclude that the major product formed was the α-isomer, as previously anticipated. All attempts to separate the two isomers by column chromatography and preparative TLC were unsuccessful. Malonate-tethered compound 2b had the same spectroscopic behavior as 2a though in

• column chromatography, giving an inseparable mixture of different isomers. The oxygenation process was confirmed by HRMS, which gave a single peak at m/z = 1170.0756 corresponding to [3a + Na]+. On analyzing carefully the mixture by 1H NMR spectroscopy, we observed three different sets of three methyl

Additive-controlled chemoselective inter-/intramolecular hydroamination via electrochemical PCET process

• Kazuhiro Okamoto,
• Naoki Shida and
• Mahito Atobe

Beilstein J. Org. Chem. 2024, 20, 264–271, doi:10.3762/bjoc.20.27

• in vacuo and the resulting residue was subjected to 1H NMR spectroscopy or column chromatography. A divided-cell experiment was performed using an H-type cell (4G glass filter). Compound 1 (0.2 mmol), Bu4NPF6 (387 mg, 1 mmol), phosphate base (90 mg, 0.2 mmol), CH2Cl2 (10 mL), and methyl vinyl ketone

• was removed by filtration through a short silica gel pad under reduced pressure. The filtrate was concentrated in vacuo and the resulting residue was subjected to 1H NMR spectroscopy or column chromatography. Application of amidyl radical species generated by PCET. (A) Effect of phosphate base on the