Transition-metal-catalyzed C–H bond activation as a sustainable strategy for the synthesis of fluorinated molecules: an overview

• Louis Monsigny,
• Floriane Doche and
• Tatiana Besset

Beilstein J. Org. Chem. 2023, 19, 448–473, doi:10.3762/bjoc.19.35

• pharmaceuticals and 30–40% of agrochemicals [3][4][5] contain at least one fluorine atom. Because of the exceptional features of fluorinated derivatives, tremendous developments and discoveries have been made in this blossoming research area, with a high interest for fundamental research as well as the industry

Continuous flow synthesis of 6-monoamino-6-monodeoxy-β-cyclodextrin

• János Máté Orosz,
• Dóra Ujj,
• Petr Kasal,
• Gábor Benkovics and
• Erika Bálint

Beilstein J. Org. Chem. 2023, 19, 294–302, doi:10.3762/bjoc.19.25

• processes in the pharmaceutical industry [1][27]. During continuous flow reactions, the target molecules can be produced with better purity, selectivity and in higher yields, as well as in consistent quality due to the precise parameter control, low volume ratio and small quantities. The temperature control

Insight into oral amphiphilic cyclodextrin nanoparticles for colorectal cancer: comprehensive mathematical model of drug release kinetic studies and antitumoral efficacy in 3D spheroid colon tumors

• Sedat Ünal,
• Gamze Varan,
• Juan M. Benito,
• Yeşim Aktaş and
• Erem Bilensoy

Beilstein J. Org. Chem. 2023, 19, 139–157, doi:10.3762/bjoc.19.14

• similarity factor (f2) were computed using a method outlined in the Guidance for Industry from the FDA's Center for Drug Evaluation and Research (CDER) [77]. These two factors can be calculated mathematically by the following equations [78]. R and T are the percentage dissolved of the reference and test

Modern flow chemistry – prospect and advantage

• Philipp Heretsch

Beilstein J. Org. Chem. 2023, 19, 33–35, doi:10.3762/bjoc.19.3

• stage in the last decades [1]. Originating from the petrochemical industry, where it enabled high productivity and scalability even for the most standard processes of heating, cracking, and refining of crude oil to bulk chemicals [2], it has since entered the production of pharmaceuticals and other fine

• - and postrun fractions are discarded [6], leading to loss of reagent and substrate as well as to increased waste. This is even less tolerable when small quantities of precious intermediates from multistep routes are to be employed, as is typically the case in projects of the pharmaceutical industry and

Inclusion complexes of the steroid hormones 17β-estradiol and progesterone with β- and γ-cyclodextrin hosts: syntheses, X-ray structures, thermal analyses and API solubility enhancements

• Alexios I. Vicatos,
• Zakiena Hoossen and
• Mino R. Caira

Beilstein J. Org. Chem. 2022, 18, 1749–1762, doi:10.3762/bjoc.18.184

• pharmaceutical industry for many decades. However, the complexation of APIs with cyclodextrins (cyclic oligosaccharides) resulting in the formation of inclusion complexes, has proven to be a versatile technology for overcoming not only the poor aqueous solubility of APIs, but also unfavourable properties such as

Inline purification in continuous flow synthesis – opportunities and challenges

• Jorge García-Lacuna and
• Marcus Baumann

Beilstein J. Org. Chem. 2022, 18, 1720–1740, doi:10.3762/bjoc.18.182

• and mass transfer, improved safety and scalability as well as the potential of reaction telescoping and automation [1][2]. Consequently, researchers from academia and the fine chemical industry have established flow technology as a complementary and oftentimes superior approach to traditional batch

• routinely employed in both industry and academia, examples of such systems integrated in continuous flow reactions are scarce. Recently, two protocols were reported that use an Advion puriFlash® 5.250 system for continuous purifications [37][38]. The puriFlash® system is an automated liquid chromatography

• expected that future refinements will lead to more robust and frequently exploited technologies. Inline extractions/separations Inline extractions are the most common type of workup performed in both industry and academia. They can be divided into two groups: those performed with semipermeable membranes

Navigating and expanding the roadmap of natural product genome mining tools

• Friederike Biermann,
• Sebastian L. Wenski and
• Eric J. N. Helfrich

Beilstein J. Org. Chem. 2022, 18, 1656–1671, doi:10.3762/bjoc.18.178

• Biodiversity Genomics (LOEWE TBG) and the German Chemical Industry Association. FB acknowledges funding from a Kekulé Fellowship of the German Chemical Industry Association.

Functionalization of imidazole N-oxide: a recent discovery in organic transformations

• Koustav Singha,
• Imran Habib and
• Mossaraf Hossain

Beilstein J. Org. Chem. 2022, 18, 1575–1588, doi:10.3762/bjoc.18.168

• Koustav Singha Imran Habib Mossaraf Hossain Synthetic Organic Research Laboratory, UGC-HRDC (Chemistry), University of North Bengal, Siliguri, Darjeeling, 734013, India 10.3762/bjoc.18.168 Abstract Nowadays heterocyclic compounds are widely used in medicinal chemistry and industry to develop life

Solid-phase total synthesis and structural confirmation of antimicrobial longicatenamide A

• Takumi Matsumoto,
• Takefumi Kuranaga,
• Yuto Taniguchi,
• Weicheng Wang and
• Hideaki Kakeya

Beilstein J. Org. Chem. 2022, 18, 1560–1566, doi:10.3762/bjoc.18.166

• Foundation, The Tokyo Biochemical Research Foundation, and the foundation of Tokyo Chemical Industry to T.K. are greatly appreciated.

Using UHPLC–MS profiling for the discovery of new sponge-derived metabolites and anthelmintic screening of the NatureBank bromotyrosine library

• Sasha Hayes,
• Aya C. Taki,
• Kah Yean Lum,
• Joseph J. Byrne,
• Merrick G. Ekins,
• Robin B. Gasser and
• Rohan A. Davis

Beilstein J. Org. Chem. 2022, 18, 1544–1552, doi:10.3762/bjoc.18.164

• sourced from the NatureBank open access compound library, is also reported. Results and Discussion While the unique NatureBank HTS-compatible natural product screening libraries (>21K extracts and >105K fractions) [14] have been regenerated for biodiscovery collaborations with industry and academia over

One-pot synthesis of 2-arylated and 2-alkylated benzoxazoles and benzimidazoles based on triphenylbismuth dichloride-promoted desulfurization of thioamides

• Arisu Koyanagi,
• Yuki Murata,
• Shiori Hayakawa,
• Mio Matsumura and
• Shuji Yasuike

Beilstein J. Org. Chem. 2022, 18, 1479–1487, doi:10.3762/bjoc.18.155

• benzazoles containing oxazole and imidazole skeletons are the most commonly used scaffolds [1][2][3][4][5]. Therefore, it is crucial for the drug industry to develop methods for their syntheses [1][2][4][6]. For example, conventional benzoxazole synthesis methods involve the condensation of 2-aminophenol

On drug discovery against infectious diseases and academic medicinal chemistry contributions

• Yves L. Janin

Beilstein J. Org. Chem. 2022, 18, 1355–1378, doi:10.3762/bjoc.18.141

• that, in many countries, academic research in medicinal chemistry should be more funded, especially in the therapeutic area neglected by the industry. At the least, such funds would provide the intensive to secure series of hopefully relevant chemical entities which appears to often lack when

• , medicinal chemistry is often not being considered as a true academic research domain. In many countries, the decision to delegate this aspect of drug discovery to the industry was instrumental in the policy choices made by their public funding agencies. However, at least in the research domains of anti

• pharmaceutical industry which certainly owe some of its origin to the academic world [34][35][36][37]. This perspective will not describe the true chemical challenges as well as the many environmental issues surrounding this last problem. All these are actually well described in books [38][39][40][41][42][43

Cyclodextrin-based Schiff base pro-fragrances: Synthesis and release studies

• Attila Palágyi,
• Jindřich Jindřich,
• Juraj Dian and
• Sophie Fourmentin

Beilstein J. Org. Chem. 2022, 18, 1346–1354, doi:10.3762/bjoc.18.140

• ; imine; kinetics; pro-fragrance; Schiff base; Introduction The fragrance and flavor industry is one of the most intensively developing sectors of the chemical industry. Encapsulation techniques are widely used in both food and cosmetic industries to control the delivery of the encapsulated guest

• industry, the covalent bond that links the fragrance to its substrate must be cleaved under environmental conditions found in everyday life, and the substrate should be non-volatile and non-toxic [17]. Typical triggers that may be used for mild chemical reactions are temperature, enzymatic or pH-dependent

• …) to attach the fragrance covalently with various functional groups. Additionally, CDs already occur in many daily products [16] and fulfill the requirements of biocompatibility and cost for designing pro-fragrances that could find applications in the flavor and fragrance industry [18]. In this article

Enantioselective total synthesis of putative dihydrorosefuran, a monoterpene with an unique 2,5-dihydrofuran structure

• Irene Torres-García,
• Josefa L. López-Martínez,
• Rocío López-Domene,
• Manuel Muñoz-Dorado,
• Ignacio Rodríguez-García and
• Miriam Álvarez-Corral

Beilstein J. Org. Chem. 2022, 18, 1264–1269, doi:10.3762/bjoc.18.132

• the perfumery industry [1]. In addition, A. pallens has been used in Indian traditional medicine (Ayurveda) for the treatment of measles, cough, cold, depression, diabetes, and high blood pressure [2]. More recently other biological activities have been reported, such as the blood glucose lowering

Heterogeneous metallaphotoredox catalysis in a continuous-flow packed-bed reactor

• Wei-Hsin Hsu,
• Susanne Reischauer,
• Peter H. Seeberger,
• Bartholomäus Pieber and
• Dario Cambié

Beilstein J. Org. Chem. 2022, 18, 1123–1130, doi:10.3762/bjoc.18.115

• 2008 – 390540038 – UniSysCat. B.P. acknowledges financial support by a Liebig Fellowship of the German Chemical Industry Fund (Fonds der Chemischen Industrie, FCI). W.-H. H. thanks the Taiwanese ministry of education for a scholarship.

First example of organocatalysis by cathodic N-heterocyclic carbene generation and accumulation using a divided electrochemical flow cell

• Daniele Rocco,
• Ana A. Folgueiras-Amador,
• Richard C. D. Brown and
• Marta Feroci

Beilstein J. Org. Chem. 2022, 18, 979–990, doi:10.3762/bjoc.18.98

• 1,3-diketones [21], etc. Electrosynthesis is considered as a more sustainable approach to perform chemical reactions, and an interesting alternative to conventional synthetic methods both in laboratory and industry processes. In fact, the electron may be considered to be a clean reagent, which

Electroreductive coupling of 2-acylbenzoates with α,β-unsaturated carbonyl compounds: density functional theory study on product selectivity

• Naoki Kise and
• Toshihiko Sakurai

Beilstein J. Org. Chem. 2022, 18, 956–962, doi:10.3762/bjoc.18.95

• . Starting materials. Methyl 2-formylbenzoate (1a) and methyl 2-benzoylbenzoate (1h) were purchased from Tokyo Chemical Industry Corporation. Methyl 2-acetylbenzoate (1g) [17] was prepared from commercially available 2-acetylbenzoic acids (Tokyo Chemical Industry Corporation) by usual esterification using

Synthesis of α-(perfluoroalkylsulfonyl)propiophenones: a new set of reagents for the light-mediated perfluoroalkylation of aromatics

• Durbis J. Castillo-Pazos,
• Juan D. Lasso and
• Chao-Jun Li

Beilstein J. Org. Chem. 2022, 18, 788–795, doi:10.3762/bjoc.18.79

• perfluoroalkylating reagent that participated in such condensation (around 30%), giving us the final yields of perfluoroalkylating reagents 1a–c displayed in Scheme 3. Afterward, to show the practicality of application of these reagents in industry, we proceeded to scale up their synthesis in gram-scale

• interest in academia and industry, namely, for the synthesis of molecules with novel properties in the fields of material and bioorganic chemistry. Envisioned Minisci perfluoroalkylation facilitated by “dummy group” reagents 1a–c. Control experiments for the nucleophilic substitution of

A trustworthy mechanochemical route to isocyanides

• Francesco Basoccu,
• Federico Cuccu,
• Federico Casti,
• Rita Mocci,
• Claudia Fattuoni and
• Andrea Porcheddu

Beilstein J. Org. Chem. 2022, 18, 732–737, doi:10.3762/bjoc.18.73

• industry such as TsCl (mechanochemical approach: EcoScale → 81; E-Factor → 9.5; in-solution approach: EcoScale → 55; E-Factor → 131.1; see Supporting Information File 1 for more details) [47][48]. Not only did we plummet the reaction expenditures, but we also undoubtedly proved that our method could be

Inductive heating and flow chemistry – a perfect synergy of emerging enabling technologies

• Conrad Kuhwald,
• Sibel Türkhan and
• Andreas Kirschning

Beilstein J. Org. Chem. 2022, 18, 688–706, doi:10.3762/bjoc.18.70

• chemistry, but also in medicine. Traditionally, inductive heating is used in industry, e.g., for heating large metallic objects including bending, bonding, and welding pipes. In addition, inductive heating has emerged as a partner for flow chemistry, both of which are enabling technologies for organic

• % yields, respectively, in a fraction of the time required for the corresponding batch processes. In a simplified purification protocol, potential metal impurities were then removed using a magnet. This approach could facilitate the use of metal oxides in industry for a broader range of oxidative

• reaction. Reactions with soluble metal complexes or metal nanoparticles, utilized in transition-metal catalysis, are often avoided, especially if the metal contamination in the product exceeds certain limits. This is particularly true for the pharmaceutical industry. A continuous flow protocol for

Shift of the reaction equilibrium at high pressure in the continuous synthesis of neuraminic acid

• Jannis A. Reich,
• Miriam Aßmann,
• Kristin Hölting,
• Paul Bubenheim,
• Jürgen Kuballa and
• Andreas Liese

Beilstein J. Org. Chem. 2022, 18, 567–579, doi:10.3762/bjoc.18.59

• Abstract The importance of a compound that helps fight against influenza is, in times of a pandemic, self-evident. In order to produce these compounds in vast quantities, many researchers consider continuous flow reactors in chemical industry as next stepping stone for large scale production. For these

• believe that this will be the next stepping stone for industry [25][26], the aim of this research was to first establish a continuous reactor at high pressure, and then to investigate the influence of pressure on the reaction sequence to produce Neu5Ac. While high-pressure processes that operate semi

• -continuously already exist in the food industry, continuous reactors containing a high-performance liquid chromatography (HPLC) pump and a fixed-bed reactor at high pressure are still a relatively new concept. The use of a back pressure regulator up to 10 MPa (100 bar) was already demonstrated by Ötvös et al

The asymmetric Henry reaction as synthetic tool for the preparation of the drugs linezolid and rivaroxaban

• Martin Vrbický,
• Karel Macek,
• Jaroslav Pochobradský,
• Jan Svoboda,
• Miloš Sedlák and
• Pavel Drabina

Beilstein J. Org. Chem. 2022, 18, 438–445, doi:10.3762/bjoc.18.46

• catalysts based on copper(II) complexes with chiral nitrogen ligands were chosen. Generally, chiral copper complexes possess many advantages valuable for the pharmaceutical industry. They exhibit low toxicity (compared to other metal-based complexes) and many of them exist in forms suitable for recycling

Flow synthesis of oxadiazoles coupled with sequential in-line extraction and chromatography

• Kian Donnelly and
• Marcus Baumann

Beilstein J. Org. Chem. 2022, 18, 232–239, doi:10.3762/bjoc.18.27

• significant development in continuous flow platforms, particularly in industry [16][17][18][19][20]. 1,3,4-Oxadiazoles are biologically relevant 5-membered heterocyclic compounds with various favourable pharmacokinetic properties and have been investigated as potential candidates for antiviral, antifungal and

Green synthesis of C5–C6-unsubstituted 1,4-DHP scaffolds using an efficient Ni–chitosan nanocatalyst under ultrasonic conditions

• Soumyadip Basu,
• Sauvik Chatterjee,
• Suman Ray,
• Suvendu Maity,
• Prasanta Ghosh,
• Asim Bhaumik and
• Chhanda Mukhopadhyay

Beilstein J. Org. Chem. 2022, 18, 133–142, doi:10.3762/bjoc.18.14

• delivery [11], biomedical uses [12], removal of toxic metals from wastewater [13], in manufacturing processes [14], in the food industry [15], in agriculture [16], and as catalyst in transesterification reactions [17]. Chitosan is regarded as one of the most effective bio-based polymers to chelate

Chemoselective N-acylation of indoles using thioesters as acyl source

• Tianri Du,
• Xiangmu Wei,
• Honghong Xu,
• Xin Zhang,
• Ruiru Fang,
• Zheng Yuan,
• Zhi Liang and
• Yahui Li

Beilstein J. Org. Chem. 2022, 18, 89–94, doi:10.3762/bjoc.18.9

• , heterocycles, such as carbazole, can also be used as nucleophiles in this reaction. Keywords: indole; N-acylation; nucleophilic substitution; thioesters; Introduction Molecules containing N-acylindoles have attracted wide attention in the synthetic polymers and pharmaceutical industry because of their unique