Emerging trends in the optimization of organic synthesis through high-throughput tools and machine learning

• Pablo Quijano Velasco,
• Kedar Hippalgaonkar and
• Balamurugan Ramalingam

Beilstein J. Org. Chem. 2025, 21, 10–38, doi:10.3762/bjoc.21.3

• into actionable inputs for building ML models for optimization: (i) extraction and categorization of appropriate spectra; (ii) fitting of spectral peaks utilizing predefined functional models, alongside deconvolution of overlapping signals; (iii) consolidation of extracted peak information and

Intramolecular C–H arylation of pyridine derivatives with a palladium catalyst for the synthesis of multiply fused heteroaromatic compounds

• Yuki Nakanishi,
• Shoichi Sugita,
• Kentaro Okano and
• Atsunori Mori

Beilstein J. Org. Chem. 2024, 20, 3256–3262, doi:10.3762/bjoc.20.269

• efficient and selective extraction of lanthanides and actinides and, furthermore, a number of heterocycles involving pyridine rings have been reported to exhibit biological activities [14][15][16][17][18][19][20][21][22]. We have recently reported, as shown in Figure 1, that the introduction of a multiply

• fused structure toward a phenanthroline diamide (Phen-2,9-diamide) [23] can be achieved by employing a palladium-catalyzed intramolecular C–H arylation [24][25][26][27][28]. One of the thus obtained products exhibited a remarkable extraction performance for a lanthanide ion, in which a metal-specific

• extraction was found despite the similarities in the lanthanide series [23]. Chakravorty and co-workers reported that a similar arylation reaction gave access to the fused skeleton of the diamide of 2,6-pyridinedicarboxlic acid (Py-2,6-diamide) [29]. Our interest has thus turned to extend the substrate scope

Ceratinadin G, a new psammaplysin derivative possessing a cyano group from a sponge of the genus Pseudoceratina

• Shin-ichiro Kurimoto,
• Kouta Inoue,
• Taito Ohno and
• Takaaki Kubota

Beilstein J. Org. Chem. 2024, 20, 3215–3220, doi:10.3762/bjoc.20.267

• 49.8 ppm were used as internal references. Mass spectra were acquired on a JEOL JMS-T100LP spectrometer. Flash column chromatography was performed using a Biotage Isolera flash purification system. Extraction and isolation The EtOAc-soluble material (2.45 g) of the methanol extract (38.06 g) from the

Discovery of ianthelliformisamines D–G from the sponge Suberea ianthelliformis and the total synthesis of ianthelliformisamine D

• Sasha Hayes,
• Yaoying Lu,
• Bernd H. A. Rehm and
• Rohan A. Davis

Beilstein J. Org. Chem. 2024, 20, 3205–3214, doi:10.3762/bjoc.20.266

• aeruginosa biofilm inhibitors and antibiotic enhancers. Large-scale extraction and isolation studies resulted in the discovery of four new and minor natural products, ianthelliformisamines D–G (4–7) and the known steroid, aplysterol (8). Compounds 4–7 were fully characterised following 1D/2D NMR, MS and UV

• describe the large-scale extraction, isolation, and structure elucidation of four new metabolites, ianthelliformisamines D–G (4–7). Additionally, we report the isolation of the known natural products, aplysterol (8) and ianthelliformisamines A–C (1–3). Owing to the novelty of ianthelliformisamine D (4) we

• HPLC (RP-HPLC), which led to the purification of the known metabolites, ianthelliformisamines A–C (1–3) [7] and aplysterol (8) [13], and four new natural products, ianthelliformisamines D–G (4–7) (Figure 1). This extraction and isolation process was repeated twice to obtain sufficient quantities of the

Advances in the use of metal-free tetrapyrrolic macrocycles as catalysts

• Mandeep K. Chahal

Beilstein J. Org. Chem. 2024, 20, 3085–3112, doi:10.3762/bjoc.20.257

• conformational flexibility, allowing them to adopt four key conformations: 1,3-alternate, cone, partial cone, and 1,2-alternate [1][2]. Calix[4]pyrroles are one of the most studied hosts in supramolecular chemistry, finding use in applications of molecular recognition and extraction, drug delivery, ion transport

N-Glycosides of indigo, indirubin, and isoindigo: blue, red, and yellow sugars and their cancerostatic activity

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 2840–2869, doi:10.3762/bjoc.20.240

• material in Europe (Scheme 1). It is obtained by extraction and isolation of the colorless indole-O-glycoside indicane which is then hydrolyzed to give indoxyl. The latter undergoes oxidative dimerization to provide indigo. In the 19th century, syntheses of indigo were developed which made the pigment

Synthesis of benzo[f]quinazoline-1,3(2H,4H)-diones

• Ruben Manuel Figueira de Abreu,
• Peter Ehlers and
• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 2708–2719, doi:10.3762/bjoc.20.228

• ). Solvents for extraction and column chromatography were distilled prior employment. Synthesis of 4a–i The synthesis of 4a–f has been previously reported. Novel derivatives 4g–i were prepared according to our previously reported procedure [65]. 1,3-Dimethyl-5-phenyl-6-(phenylethynyl)pyrimidine-2,4(1H,3H

Computational design for enantioselective CO₂ capture: asymmetric frustrated Lewis pairs in epoxide transformations

• Maxime Ferrer,
• Iñigo Iribarren,
• Tim Renningholtz,
• Ibon Alkorta and
• Cristina Trujillo

Beilstein J. Org. Chem. 2024, 20, 2668–2681, doi:10.3762/bjoc.20.224

• oxygen atoms [6][7]. Carbon capture and utilisation (CCU) technologies involve the extraction of CO2 from the atmosphere of the Earth to generate value-added chemicals, which can serve as platform chemicals in other chemical processes [20][21]. This is achieved by inserting CO2 as a C1 building block

Visible-light-mediated flow protocol for Achmatowicz rearrangement

• Joachyutharayalu Oja,
• Sanjeev Kumar and
• Srihari Pabbaraja

Beilstein J. Org. Chem. 2024, 20, 2493–2499, doi:10.3762/bjoc.20.213

• transformations, then reaction extraction and separation, into a single process, which are typically performed individually/separately in batch methods. This enhances the overall efficiency for obtaining the desired product(s) from the reaction mixture. In continuation to our efforts on developing flow-based

• towards investigating for the selective elimination of the waste solvent using an integrated one-flow work-up procedure to generate 3a with maximum practicality. Initially, the individual stages of the liquid–liquid extraction was achieved using the droplet micro fluidic method for extracting the compound

• (see details in Supporting Information File 1, Table S2). In this context, our previously in-house-developed liquid–liquid extractor was utilized (see details in Supporting Information File 1, Figure S4) [27]. After few trials towards optimization of extraction and separation, the best yield (82%) was

Machine learning-guided strategies for reaction conditions design and optimization

• Lung-Yi Chen and
• Yi-Pei Li

Beilstein J. Org. Chem. 2024, 20, 2476–2492, doi:10.3762/bjoc.20.212

• of natural language processing (NLP) techniques to extract experimental data from unstructured text. For example, Vaucher et al. [69] combined rule-based models and deep-learning techniques to convert experimental procedures into standardized synthetic steps. They further used this data extraction

• machine-learning solutions for reaction diagram parsing [76][77], there are still some limitations. For instance, sometimes the reaction conditions are listed in tables, and certain functional groups in images are represented by abbreviations (e.g., R-groups). To achieve more complete data extraction

• , future efforts will need to employ multi-modal modeling approaches [78][79][80] that can collect information from different sources and provide robust results. Recently, Fan et al. developed the OpenChemIE toolkit [81], which integrates extraction methods from text, images, and tables, automating the

Efficient one-step synthesis of diarylacetic acids by electrochemical direct carboxylation of diarylmethanol compounds in DMSO

• Hisanori Senboku and
• Mizuki Hayama

Beilstein J. Org. Chem. 2024, 20, 2392–2400, doi:10.3762/bjoc.20.203

• triphenylmethanol (1n) was subjected to the electrochemical carboxylation, a small amount of carboxylic acid was obtained as a complex mixture. However, in the 1H NMR spectrum of the organic component after extraction with aqueous base, we observed a singlet at δ 5.55 ppm, which could be assigned to the methine

Asymmetric organocatalytic synthesis of chiral homoallylic amines

• Nikolay S. Kondratyev and
• Andrei V. Malkov

Beilstein J. Org. Chem. 2024, 20, 2349–2377, doi:10.3762/bjoc.20.201

• -diaminonaphthalene derivatives 42, which after hydrolysis and extraction into toluene, were reacted with indole, 3-methylindole, 3,4-dihydroisoquinoline, and benzoyl hydrazone ethyl glyoxylate ester to afford terminal (E)-trifluoromethyl homoallylic amines 44 with up to 3 adjacent stereocentres with high to

Catalysing (organo-)catalysis: Trends in the application of machine learning to enantioselective organocatalysis

• Stefan P. Schmid,
• Leon Schlosser,
• Frank Glorius and
• Kjell Jorner

Beilstein J. Org. Chem. 2024, 20, 2280–2304, doi:10.3762/bjoc.20.196

• number of experiments can be found in literature, as well as patents. Manual curation of this data is possible, but for larger amounts of data it is usually impractical. Therefore, automated extraction tools have been reported yielding the data in a structured format suitable for ML [37][38][39][40][41

Metal-free double azide addition to strained alkynes of an octadehydrodibenzo[12]annulene derivative with electron-withdrawing substituents

• Naoki Takeda,
• Shuichi Akasaka,
• Susumu Kawauchi and
• Tsuyoshi Michinobu

Beilstein J. Org. Chem. 2024, 20, 2234–2241, doi:10.3762/bjoc.20.191

• recorded on a JASCO FT/IR-4100 spectrometer in the range from 4000 to 600 cm−1. MALDI–TOF mass spectra were measured on a Shimadzu/Kratos AXIMACFR mass spectrometer equipped with a nitrogen laser (λ = 337 nm) and pulsed ion extraction, which was operated at an accelerating potential of 20 kV. THF solutions

Electrochemical allylations in a deep eutectic solvent

• Sophia Taylor and
• Scott T. Handy

Beilstein J. Org. Chem. 2024, 20, 2217–2224, doi:10.3762/bjoc.20.189

• recycled two times before incomplete conversion was noted. A more significant problem was the steady loss of DES during the product extraction stage. Using 3 mL of methoxycyclopentane in a single extraction, the amount of DES steadily decreased by roughly 0.5 mL for each recycling. This is likely due to

• partial solubility of ethylene glycol in methoxycyclopentane as ethylene glycol could be clearly seen in the 1H NMR spectrum of the crude reaction extracts. It should also be noted that the lower isolated yields most likely reflect mechanical losses during extraction and chromatographic separation as the

• starting material were recovered via extraction with methoxycyclopentane and the CC/EG used in another cycle. Through two recyclings, the reactions were similar in efficiency, although the DES became increasingly viscous as the tin byproducts built up and it became impractical to recycle the DES further

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

• , compounds 1–5 could be more potent in some other bioassays, which is a subject of future studies. Finally, these results supported that actinomycetes genera with little or no chemical study are a fruitful reservoir for discovering new natural molecules. Experimental Microorganism, fermentation, extraction

• , 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

• and 3 in CD3COCD3. 1H and 13C NMR data for 4 and 5. Supporting Information Supporting Information File 32: 1D and 2D NMR, MS, UV, and IR spectra of compounds 1–5; experimental section including general experimental procedures, microorganism, detailed procedures for fermentation, extraction, isolation

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

• % spectroscopic yield, when 10 was reacted with a large excess of Selectfluor (5.1 equivalents) in dry acetonitrile at 40 °C for 48 hours (Table 2, entry 1). More importantly, difluoroiodane 6 was isolated successfully in an excellent 91% yield by a simple extraction into dry dichloromethane providing an

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

• overnight with methanol using 200 g of ground root powder (Mountain Rose Herb Lot# 26356) and 1.5 L of methanol. After overnight extraction, vacuum filtration was used to separate the solids from the liquids. The methanol extract was dried and saved. The solids were extracted with methanol two more times

• . After the extractions were finished and dried by rotary evaporation, the extract was resuspended in basic water (pH 10 using NaOH) and vacuum filtered to remove insoluble particulates. Liquid–liquid extraction was performed three times with basic water and DCM. The DCM layer was collected and dried

• leaves, stems, and roots and lyophilized for extraction. G. jasminoides samples were prepared by extracting 89.24 g of dried leaf material over three days with 1 L of methanol each day yielding 19.10 g of crude extract. The root and stem extracts were prepared by extracting 180.6 mg and 145.2 mg of plant

Diameter-selective extraction of single-walled carbon nanotubes by interlocking with Cu-tethered square nanobrackets

• Guoqing Cheng and
• Naoki Komatsu

Beilstein J. Org. Chem. 2024, 20, 1298–1307, doi:10.3762/bjoc.20.113

• -TOF mass spectra. Upon extraction of SWNTs with the nanobracket and copper(II), in situ-formed square Cu-nanobrackets are found to interlock SWNTs to disperse them in 2-propanol. The interlocking is confirmed by Raman spectroscopy after thorough washing of the extracted SWNTs. Pristine SWNTs were

• diameter range. The diameter selectivity is supported by the theoretical calculations with the GFN2-xTB method, indicating that the most preferred SWNT diameter for the square Cu-nanobrackets is 1.04 nm. Keywords: complexation; diameter; extraction; interlock; nanobracket; single-walled carbon nanotubes

• depend on their structures [1]. To obtain specific structures, remarkable progress has been made in separation of SWNTs by various methods such as gel column chromatography [2][3], aqueous two-phase extraction (ATPE) [4][5], and polymer wrapping [6][7]. As compared with these methods, our separation by

Introduction of peripheral nitrogen atoms to cyclo-meta-phenylenes

• Koki Ikemoto and
• Hiroyuki Isobe

Beilstein J. Org. Chem. 2024, 20, 1207–1212, doi:10.3762/bjoc.20.103

• was first washed with CHCl3 (100 mL), and a residue comprising 3a and 3b was obtained. The residue was then suspended in CHCl3 (100 mL) and sonicated for 10 min. After separating the solid and the filtrate, each sample was purified as follows: The former was subjected to Soxhlet extraction with CHCl3

• overnight to give 3a in 6% yield (272 mg, 0.592 mmol) after the extraction. The latter was purified by silica gel short path and GPC (column: YMC-GPC T30000-40 + T4000-40 + T2000-40, eluent: CHCl3, flow rate: 30 mL/min) to give 3a in 1% yield (52.8 mg, 0.115 mmol) and 3b in 3% yield (118 mg, 0.193 mmol). In

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

• reaction time (Table 1, entry 7), giving total conversion and excellent selectivity toward 3a. Water is an essential constituent of the system, as its polar nature favours the extraction of HBr from the organic phase, resulting in a useful shift of the reversible hydrogen abstraction from the substrate

Structure–property relationships in dicyanopyrazinoquinoxalines and their hydrogen-bonding-capable dihydropyrazinoquinoxalinedione derivatives

• Tural N. Akhmedov,
• Ajeet Kumar,
• Daken J. Starkenburg,
• Kyle J. Chesney,
• Khalil A. Abboud,
• Novruz G. Akhmedov,
• Jiangeng Xue and
• Ronald K. Castellano

Beilstein J. Org. Chem. 2024, 20, 1037–1052, doi:10.3762/bjoc.20.92

• and charge injection/extraction processes [7]. The additional merits of H-bonding designs in organic optoelectronic materials include higher thermal stability, synergistic stabilizing effects with π-stacking interactions, etc. [8]. Acenes and N-heteroacenes are two prominent π-conjugated scaffolds for

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

• was performed on Merck Silica gel 60 (particle size 63–200 μm). Solvents for extraction and column chromatography were distilled prior employment. Representative method for the preparation of starting materials 5-Bromo-6-chloro-1,3-dimethyluracil (2). Uracil 1 (22.9 mmol; 4.00 g) was dissolved in

Research progress on the pharmacological activity, biosynthetic pathways, and biosynthesis of crocins

• Zhongwei Hua,
• Nan Liu and
• Xiaohui Yan

Beilstein J. Org. Chem. 2024, 20, 741–752, doi:10.3762/bjoc.20.68

• derivatives in microorganisms has been achieved by various teams. This article comprehensively reviews the research progress on the extraction, separation, pharmacological activity, biosynthesis, and synthetic biology of crocins. The biosynthesis of crocins is depicted in detail to shed light on the efficient

• extracting crocins include ultrasound-assisted extraction (UAE), supercritical fluid extraction, enzyme-linked extraction, and microwave-assisted extraction. Among these methods, the UAE exhibits a higher extraction yield [23][24]. Recently, Fiorito et al. developed a technique that utilizes cost-effective

Organic electron transport materials

• Joseph Cameron and
• Peter J. Skabara

Beilstein J. Org. Chem. 2024, 20, 672–674, doi:10.3762/bjoc.20.60

• transport materials for organic semiconductor devices due to their potential to be applied in various technologies. For example, such materials can be used to improve charge balance in the emissive layer of an organic light-emitting diode, charge extraction in perovskite solar cells or used as the