Reaction of indoles with aromatic fluoromethyl ketones: an efficient synthesis of trifluoromethyl(indolyl)phenylmethanols using K₂CO₃/n-Bu₄PBr in water

• Thanigaimalai Pillaiyar,
• Masoud Sedaghati and
• Gregor Schnakenburg

Beilstein J. Org. Chem. 2020, 16, 778–790, doi:10.3762/bjoc.16.71

• have been used as key precursors for the construction of complex indole derivatives that would be useful in pharmaceuticals as drugs and agrochemicals [2][3][4][5][6][7][8][9][10][11][12][13][14]. The simple (1H-indol-3-yl)methanol, a breakdown product of glucobrassicin, which can be found in

• into organic molecules can dramatically influence their physiochemical and biological properties in comparison with non-fluorinated analogs [18] (see compounds I and II in Figure 1). Many pharmaceuticals and agrochemicals developed in recent decades have either a fluorine atom or a trifluoromethyl

Recent advances in Cu-catalyzed C(sp³)–Si and C(sp³)–B bond formation

• Balaram S. Takale,
• Ruchita R. Thakore,
• Elham Etemadi-Davan and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2020, 16, 691–737, doi:10.3762/bjoc.16.67

Microwave-assisted efficient and facile synthesis of tetramic acid derivatives via a one-pot post-Ugi cascade reaction

• Yong Li,
• Zheng Huang,
• Jia Xu,
• Yong Ding,
• Dian-Yong Tang,
• Jie Lei,
• Hong-yu Li,
• Zhong-Zhu Chen and
• Zhi-Gang Xu

Beilstein J. Org. Chem. 2020, 16, 663–669, doi:10.3762/bjoc.16.63

• are privileged scaffolds that can be found in a wide variety of bioactive pharmaceuticals and natural products [1]. For this reason, research towards the development of novel and efficient strategies for the construction of these compounds represents one of the most active areas in synthetic organic

Asymmetric synthesis of CF₂-functionalized aziridines by combined strong Brønsted acid catalysis

• Xing-Fa Tan,
• Fa-Guang Zhang and
• Jun-An Ma

Beilstein J. Org. Chem. 2020, 16, 638–644, doi:10.3762/bjoc.16.60

• or fluoroalkyl groups into three-membered N-heterocycles has emerged as an attractive direction due to the unique fluorine effect in pharmaceuticals and biology [7][8][9][10][11]. In this context, it is not surprising that the syntheses of trifluoromethylaziridines have been pursued from versatile

Exploring the scope of DBU-promoted amidations of 7-methoxycarbonylpterin

• Anna R. Bockman and
• Jeffrey M. Pruet

Beilstein J. Org. Chem. 2020, 16, 509–514, doi:10.3762/bjoc.16.46

• molybdopterin [1]. Owing to this biological relevance, pterins are an attractive building block in the development of various pharmaceuticals, with methotrexate being the most well-known [2]. In addition to pteridine derivatives being used as inhibitors of dihydrofolate reductase and dihydropteroate synthase

Synthesis of 4-amino-5-fluoropyrimidines and 5-amino-4-fluoropyrazoles from a β-fluoroenolate salt

• Tobias Lucas,
• Jule-Philipp Dietz and
• Till Opatz

Beilstein J. Org. Chem. 2020, 16, 445–450, doi:10.3762/bjoc.16.41

• modern pharmaceuticals [1][2][3][4][5][6] and agrochemicals [7] contain at least one fluorine atom [8][9][10][11][12][13][14][15]. One of the approaches for their synthesis is the use of small fluorinated building blocks which avoids the often cumbersome regioselective fluorination at a later synthetic

• stage [15][16][17][18][19]. Fluorinated pyrimidines, pyrimidine analogues and pyrazoles [20][21] play a prominent role in several clinically important pharmaceuticals [22][23][24][25]. These compounds act against HIV or HIV-related diseases [26], such as opportunistic fungal infections, and represent

Visible-light-induced addition of carboxymethanide to styrene from monochloroacetic acid

• Kaj M. van Vliet,
• Nicole S. van Leeuwen,
• Albert M. Brouwer and
• Bas de Bruin

Beilstein J. Org. Chem. 2020, 16, 398–408, doi:10.3762/bjoc.16.38

• compound, with applications ranging from thickening agents (carboxymethyl cellulose, E466) [1][2], herbicides (2,4-dichlorophenoxyacetic acid), cosmetics (cocamidopropyl betaine), dyes (indigo vat dye) [3], to pharmaceuticals (ibuprofen, glycine, malonates) [4] (see Figure 1). Many reactions with

Allylic cross-coupling using aromatic aldehydes as α-alkoxyalkyl anions

• Akihiro Yuasa,
• Kazunori Nagao and
• Hirohisa Ohmiya

Beilstein J. Org. Chem. 2020, 16, 185–189, doi:10.3762/bjoc.16.21

• -catalyzed allylic substitution. Keywords: aldehyde; copper; copper catalysis; cross-coupling; palladium; synthetic method; Introduction α-Alkoxy-substituted carbanions (α-alkoxyalkyl anions) are useful C(sp3) nucleophiles for the construction of alcohol units found in a majority of pharmaceuticals

Reversible photoswitching of the DNA-binding properties of styrylquinolizinium derivatives through photochromic [2 + 2] cycloaddition and cycloreversion

• Sarah Kölsch,
• Heiko Ihmels,
• Jochen Mattay,
• Norbert Sewald and
• Brian O. Patrick

Beilstein J. Org. Chem. 2020, 16, 111–124, doi:10.3762/bjoc.16.13

• biological activity on and off due to the reversibility of the photoreaction [15]. Indeed, the application of light to induce and control bioactivity of pharmaceuticals or bio(macro)molecules has been convincingly demonstrated in the emerging field of photopharmacology [16][17][18]. Consequently, several

The interaction between cucurbit[8]uril and baicalein and the effect on baicalein properties

• Xiaodong Zhang,
• Jun Xie,
• Zhiling Xu,
• Zhu Tao and
• Qianjun Zhang

Beilstein J. Org. Chem. 2020, 16, 71–77, doi:10.3762/bjoc.16.9

• , baicalein contains three phenolic hydroxy groups, which are easily oxidized to the quinone derivative and appear green, therefore, it has limited use in pharmaceuticals on account of its poor aqueous solubility and stability [31]. The cucurbit[n]urils (Q[n]s n = 5–8, 10, …) are macrocyclic hosts with a

Light-controllable dithienylethene-modified cyclic peptides: photoswitching the in vivo toxicity in zebrafish embryos

• Sergii Afonin,
• Oleg Babii,
• Aline Reuter,
• Volker Middel,
• Masanari Takamiya,
• Uwe Strähle,
• Igor V. Komarov and
• Anne S. Ulrich

Beilstein J. Org. Chem. 2020, 16, 39–49, doi:10.3762/bjoc.16.6

• require the inclusion of in vivo toxicity studies using vertebrate animal models. (For example, toxicity studies of anticancer chemotherapeutics are requested by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) to include at least two mammalian

Functionalization of the imidazo[1,2-a]pyridine ring in α-phosphonoacrylates and α-phosphonopropionates via microwave-assisted Mizoroki–Heck reaction

• Damian Kusy,
• Agata Wojciechowska,
• Joanna Małolepsza and
• Katarzyna M. Błażewska

Beilstein J. Org. Chem. 2020, 16, 15–21, doi:10.3762/bjoc.16.3

• confirmed by the presence in a number of pharmaceuticals [2][3]. The imidazo[1,2-a]pyridine-ring modification via Pd-catalyzed reactions is broadly reported in the literature [3], however, such functionalizations for more complex molecules are not very common. On the other hand, the Mizoroki–Heck reaction

A green, economical synthesis of β-ketonitriles and trifunctionalized building blocks from esters and lactones

• Daniel P. Pienaar,
• Kamogelo R. Butsi,
• Amanda L. Rousseau and
• Dean Brady

Beilstein J. Org. Chem. 2019, 15, 2930–2935, doi:10.3762/bjoc.15.287

• the synthesis of heteroaromatic compounds and a wide variety of pharmaceuticals. A recent review by Kiyokawa et al. summarizes the applications of these valuable compounds and the abundant methods that have been developed over recent decades to prepare them [1], most of which still involve

An improved, scalable synthesis of Notum inhibitor LP-922056 using 1-chloro-1,2-benziodoxol-3-one as a superior electrophilic chlorinating agent

• Nicky J. Willis,
• Elliott D. Bayle,
• George Papageorgiou,
• David Steadman,
• Benjamin N. Atkinson,
• William Mahy and
• Paul V. Fish

Beilstein J. Org. Chem. 2019, 15, 2790–2797, doi:10.3762/bjoc.15.271

• , Figure 1) is an orally active inhibitor of Notum recently reported by Lexicon Pharmaceuticals [5][6]. Their research with 1 has shown that Notum is a potential drug target for stimulating bone formation and treating osteoporosis [7]. However, although 1 demonstrates low plasma clearance, the structure

Recent advances in transition-metal-catalyzed incorporation of fluorine-containing groups

• Xiaowei Li,
• Xiaolin Shi,
• Xiangqian Li and
• Dayong Shi

Beilstein J. Org. Chem. 2019, 15, 2213–2270, doi:10.3762/bjoc.15.218

• , carbon–fluorine bonds have become an integral part of pharmaceutical [2][3], agricultural [4], materials industries [5], and tracers for positron emission tomography [6]. According to statistics, about 35% of agrochemicals and 20% of pharmaceuticals contain fluorine [7]. Although the content of fluorine

Azologization and repurposing of a hetero-stilbene-based kinase inhibitor: towards the design of photoswitchable sirtuin inhibitors

• Christoph W. Grathwol,
• Nathalie Wössner,
• Sören Swyter,
• Adam C. Smith,
• Enrico Tapavicza,
• Robert K. Hofstetter,
• Anja Bodtke,
• Manfred Jung and
• Andreas Link

Beilstein J. Org. Chem. 2019, 15, 2170–2183, doi:10.3762/bjoc.15.214

• selective Sirt1 inhibitor, passed phase II clinical trials as a disease-modifying therapeutic for Huntington’s disease (HD) and was acquainted by AOP Orphan Pharmaceuticals AG for phase III trials in 2017 [9][10]. Its structure comprises a carboxamide moiety, which mimics the amide group of the endogenous

Reactions of 2-carbonyl- and 2-hydroxy(or methoxy)alkyl-substituted benzimidazoles with arenes in the superacid CF₃SO₃H. NMR and DFT studies of dicationic electrophilic species

• Dmitry S. Ryabukhin,
• Alexey N. Turdakov,
• Natalia S. Soldatova,
• Mikhail O. Kompanets,
• Alexander Yu. Ivanov,
• Irina A. Boyarskaya and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2019, 15, 1962–1973, doi:10.3762/bjoc.15.191

• –Crafts reaction; triflic acid; Introduction Imidazoles and benzimidazoles are important heterocyclic scaffolds in pharmaceuticals and agrochemicals [1][2][3][4][5][6][7][8][9][10]. They also have applications in the fields of dyes, chemo-sensing, and fluorescent materials [3]. (Benz)imidazoles are a

• superelectrophilic activation approach, we have developed a useful synthetically procedure for the modification of the benzimidazole structure. Examples of some commercially available pharmaceuticals and agrochemicals containing the benzimidazole scaffold. Formation of cationic species by protonation of 5-formyl-4

A metal-free approach for the synthesis of amides/esters with pyridinium salts of phenacyl bromides via oxidative C–C bond cleavage

• Kesari Lakshmi Manasa,
• Yellaiah Tangella,
• Namballa Hari Krishna and
• Mallika Alvala

Beilstein J. Org. Chem. 2019, 15, 1864–1871, doi:10.3762/bjoc.15.182

• chemistry. The occurrence of an amide and/or ester bond is widely realized in organic molecules, proteins, natural products, pharmaceuticals, polymers and agrochemicals [1][2][3][4][5]. The conventional synthesis of amides involves the reaction of carboxylic acids or their derivatives such as acyl halides

• and 13C NMR spectra of the compounds. Acknowledgements The authors thank the Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers Govt. of India, New Delhi for the award of NIPER fellowship.

Steroid diversification by multicomponent reactions

• Leslie Reguera,
• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Daniel G. Rivera

Beilstein J. Org. Chem. 2019, 15, 1236–1256, doi:10.3762/bjoc.15.121

• promise for the future development of peptide pharmaceuticals. 5 Multicomponent synthesis of steroidal macrocycles and cages Since the beginning of this century, the field of macrocycle synthesis has witnessed the emergence of MCRs as effective ring closing procedures, including the cyclization of large

Synthesis of aryl cyclopropyl sulfides through copper-promoted S-cyclopropylation of thiophenols using cyclopropylboronic acid

• Emeline Benoit,
• Ahmed Fnaiche and
• Alexandre Gagnon

Beilstein J. Org. Chem. 2019, 15, 1162–1171, doi:10.3762/bjoc.15.113

• was supported by Boehringer Ingelheim Pharmaceuticals, Inc. through a Scientific Advancement Grant, by a provincial Fonds de Recherche du Québec, Nature et Technologies (FRQNT) team grant and by the Centre in Green Chemistry and Catalysis (CGCC).

Switchable selectivity in Pd-catalyzed [3 + 2] annulations of γ-oxy-2-cycloalkenones with 3-oxoglutarates: C–C/C–C vs C–C/O–C bond formation

• Yang Liu,
• Julie Oble and
• Giovanni Poli

Beilstein J. Org. Chem. 2019, 15, 1107–1115, doi:10.3762/bjoc.15.107

• relevant pharmaceuticals and/or natural products (Figure 1) [34][35][36][37][38]. Indeed, we anticipated that the latter step might occur through either C-addition or O-addition (Scheme 2, products III (or V) vs IV) [32][39][40][41][42]. Therefore, an inherent challenge associated to this ambident

Synthesis of a novel category of pseudo-peptides using an Ugi three-component reaction of levulinic acid as bifunctional substrate, amines, and amino acid-based isocyanides

• Maryam Khalesi,
• Azim Ziyaei Halimehjani and
• Jürgen Martens

Beilstein J. Org. Chem. 2019, 15, 852–857, doi:10.3762/bjoc.15.82

• by acid catalysis from renewable resources, such as sugars, lignocellulosic biomass and waste materials [18]. It can be used as a bifunctional precursor for the synthesis of pharmaceuticals, plasticizers, and different additives [19]. Furthermore, it is recognized as an excellent starting material

Diastereo- and enantioselective preparation of cyclopropanol derivatives

• Marwan Simaan and
• Ilan Marek

Beilstein J. Org. Chem. 2019, 15, 752–760, doi:10.3762/bjoc.15.71

• are also important precursors in the synthesis of various biologically active molecules and pharmaceuticals such as antidepressants, antiviral and antibacterial drugs [4]. Cyclopropanols and their derivatives are considered to be carbocyclic homologues of enols presenting similar chemical properties

New sesquiterpenoids from the South China Sea soft corals Clavularia viridis and Lemnalia flava

• Qihao Wu,
• Yuan Gao,
• Meng-Meng Zhang,
• Li Sheng,
• Jia Li,
• Xu-Wen Li,
• Hong Wang and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2019, 15, 695–702, doi:10.3762/bjoc.15.64

• and Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou 310014, P. R. China 10.3762/bjoc.15.64 Abstract A detailed chemical investigation of the South China Sea soft corals Clavularia viridis and Lemnalia flava yielded four

Back to the future: Why we need enzymology to build a synthetic metabolism of the future

• Tobias J. Erb

Beilstein J. Org. Chem. 2019, 15, 551–557, doi:10.3762/bjoc.15.49

• the nature and reactivity of the chemical bond enabled chemists to use their knowledge to create new molecules and materials [3][4]. This development provided humankind with new chemical compounds, such as color dyes, pharmaceuticals, as well as polymers and plastics. Given its transforming nature, it