Diversity-oriented synthesis of 17-spirosteroids

• Benjamin Laroche,
• Thomas Bouvarel,
• Martin Louis-Sylvestre and
• Bastien Nay

Beilstein J. Org. Chem. 2020, 16, 880–887, doi:10.3762/bjoc.16.79

• biologically validated scaffolds [8][9][10], referred to as privileged structures in medicinal chemistry [11][12][13][14]. Spanning unexplored chemical space, DOS strategies have been successfully applied to the generation of biologically active libraries for screening, leading to the discovery of medicinally

• ) and lynestrenol (2). By using the sequence of RCEYM/Diels–Alder reaction, we rapidly synthesized "17-spirosteroid" compounds, orthogonally linking a non-steroidal polycyclic moiety to the steroid part at position 17. Spirocyclic systems play an important role in current medicinal chemistry thanks to

Efficient synthesis of piperazinyl amides of 18β-glycyrrhetinic acid

• Dong Cai,
• ZhiHua Zhang,
• Yufan Meng,
• KaiLi Zhu,
• LiYi Chen,
• ChangXiang Yu,
• ChangWei Yu,
• ZiYi Fu,
• DianShen Yang and
• YiXia Gong

Beilstein J. Org. Chem. 2020, 16, 798–808, doi:10.3762/bjoc.16.73

• fisch root. 18β-glycyrrhetinic acid (1, Figure 1) was then obtained by hydrolysis of glycyrrhizin. 18β-glycyrrhetinic acid and its derivatives have been extensively investigated in medicinal chemistry for their various biological activities, including anti-inflammatory [1], antiulcer [2], antioxidative

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

• Thanigaimalai Pillaiyar Masoud Sedaghati Gregor Schnakenburg PharmaCenter Bonn, Pharmaceutical Institute, Department of Pharmaceutical and Medicinal Chemistry, University of Bonn, An der Immenburg 4, D-53121 Bonn, Germany Institute of Inorganic Chemistry, University of Bonn, Gerhard-Domagk-Str. 1

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

• medicinal chemistry. Multicomponent reactions (MCRs) [22][23][24] are emerging tools for assembling complex molecules in a rapid and efficient manner. The four-component Ugi reaction followed by a suitable post modification of [25][26] has become a popular research field for diversity-oriented synthesis [27

Cascade trifluoromethylthiolation and cyclization of N-[(3-aryl)propioloyl]indoles

• Ming-Xi Bi,
• Shuai Liu,
• Yangen Huang,
• Xiu-Hua Xu and
• Feng-Ling Qing

Beilstein J. Org. Chem. 2020, 16, 657–662, doi:10.3762/bjoc.16.62

• )propioloyl]indole and N-propargylindoles, respectively. Inspired by these elegant results, we became interested in the preparation of SCF3-substituted pyrrolo[1,2-a]indol-3-ones, which might be potentially useful in medicinal chemistry. Radical cascade reactions constitute highly efficient strategies for the

Preparation and in situ use of unstable N-alkyl α-diazo-γ-butyrolactams in Rh^II-catalyzed X–H insertion reactions

• Maria Eremeyeva,
• Daniil Zhukovsky,
• Dmitry Dar’in and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2020, 16, 607–610, doi:10.3762/bjoc.16.55

• substantially expanded, thereby making this approach more useful for potential medicinal chemistry exploration of these disubstituted γ-lactams. Previously reported uses of α-diazo-γ-butyrolactams 1 and 4. Generation and in situ RhII-catalyzed X–H insertion reactions of the diazo compounds 4a–c. Conditions

Opening up connectivity between documents, structures and bioactivity

• Christopher Southan

Beilstein J. Org. Chem. 2020, 16, 596–606, doi:10.3762/bjoc.16.54

• accelerate the progress and impact of medicinal chemistry. To achieve this the community needs to increase the outward flow of experimental results locked-up in millions of published PDFs into structured open databases that explicitly capture the connectivity between structures, documents and bioactivity

• distillation. This report will outline the principles of connectivity capture, selected sources, progress, impediments and prospects for their amelioration. Review Defining terms It is necessary to outline the topics covered: Medicinal chemistry: As directed towards drug discovery this needs no introduction

• scale via an application programming interface (API) or a resource description framework (RDF). Papers as documents: This typically refers to research papers from journals but increasingly needs to encompass their associated supplementary data. Note also that by far the majority of medicinal chemistry

Regio- and stereoselective synthesis of new ensembles of diversely functionalized 1,3-thiaselenol-2-ylmethyl selenides by a double rearrangement reaction

• Svetlana V. Amosova,
• Andrey A. Filippov,
• Nataliya A. Makhaeva,
• Alexander I. Albanov and
• Vladimir A. Potapov

Beilstein J. Org. Chem. 2020, 16, 515–523, doi:10.3762/bjoc.16.47

• are important features of this approach. The obtained compounds represent novel ensembles of functionalized unsaturated five-membered heterocycles containing one sulfur atom and two selenium atoms of different nature (Schemes 8–11), which are valuable scaffolds for organic synthesis and medicinal

• chemistry. Monitoring the reaction of thiaselenole 1 with KSeCN by 1H NMR spectroscopy (in accordance with the data of Table 1). Reaction conditions: compound 1 (0.5 mmol), KSeCN (0.5 mmol), MeCN (2.5 mL), 0 °C. Possible formation of reaction products starting from 1 via seleniranium 2 or thiiranium cations

Recent developments in photoredox-catalyzed remote ortho and para C–H bond functionalizations

• Rafia Siddiqui and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 248–280, doi:10.3762/bjoc.16.26

• products was assembled with moderate to high yields using this powerful synthetic strategy, and the scope of the reaction can be seen in Scheme 12. C–H trifluoromethylation The introduction of a CF3 group into pharmaceutical agents can enhance their performance in medicinal chemistry [129][130][131]. In

• trifluoromethanesulfonyl chloride, which is easier to handle and cost-efficient. By using this methodology, they prepared diverse trifluoromethylated derivatives, which have applications in medicinal chemistry. The mechanism of the reaction involves the excitation of the photocatalyst 13, generating 92. The reduction of

Combination of multicomponent KA² and Pauson–Khand reactions: short synthesis of spirocyclic pyrrolocyclopentenones

• Riccardo Innocenti,
• Elena Lenci,
• Gloria Menchi and
• Andrea Trabocchi

Beilstein J. Org. Chem. 2020, 16, 200–211, doi:10.3762/bjoc.16.23

• structure in three single steps (Scheme 1b). This unprecedent molecular scaffold represents a valuable template for medicinal chemistry purpose, as the pyrrolocyclopentenone core is contained in a variety of bioactive molecules [49][50], and can serve as an advanced intermediate for the synthesis of

Synthesis of 3-alkenylindoles through regioselective C–H alkenylation of indoles by a ruthenium nanocatalyst

• Abhijit Paul,
• Debnath Chatterjee,
• Srirupa Banerjee and
• Somnath Yadav

Beilstein J. Org. Chem. 2020, 16, 140–148, doi:10.3762/bjoc.16.16

• -withdrawing and electron-donating groups on the indole moiety. Additionally, a “robustness screen” has also been employed to demonstrate the tolerance of several functional groups relevant to medicinal chemistry. With respect to the Ru nanocatalyst, it has been demonstrated that it is recoverable and

• tolerated several functional groups, including bromine and nitrile units, which provide ample scope for further manipulation of the products from the perspective of medicinal chemistry. The catalyst can be easily recovered and recycled in a colloidal solid form, enabling catalytic recycling and reusability

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

• of compounds from a common precursor and enables efficient generation of new chemical entities. Imidazo[1,2-a]pyridine constitutes an appealing scaffold in medicinal chemistry. It is present in a number of compounds, which exhibit many interesting biological properties. Its privileged character is

Synthesis and optoelectronic properties of benzoquinone-based donor–acceptor compounds

• Daniel R. Sutherland,
• Nidhi Sharma,
• Georgina M. Rosair,
• Ifor D. W. Samuel,
• Ai-Lan Lee and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2019, 15, 2914–2921, doi:10.3762/bjoc.15.285

• benzoquinones have found utility in a variety of different fields, such as medicinal chemistry [3], natural products [4], dyes [5], ligands [6][7][8][9], oxidation chemistry [10], functional materials [11], and molecular electronics [12][13]. Due to their myriad applications, one of our groups recently

Facile regiodivergent synthesis of spiro pyrrole-substituted pseudothiohydantoins and thiohydantoins via reaction of [e]-fused 1H-pyrrole-2,3-diones with thiourea

• Aleksandr I. Kobelev,
• Nikita A. Tretyakov,
• Ekaterina E. Stepanova,
• Maksim V. Dmitriev,
• Michael Rubin and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2019, 15, 2864–2871, doi:10.3762/bjoc.15.280

• in medicinal chemistry. Indeed, they are structurally related to rhodanine (2-thioxothiazolidin-4-one), and sometimes are classified as pan-assay interference compounds (PAINS), which are abhorrent in high-throughput screenings [6]. To clarify whether such compounds are privileged scaffolds or

• promiscuous binders, Mendgen and co-workers performed a systematic comparative study on rhodanines and related structures with respect to their medicinal chemistry properties [7]. As a result, it was shown that such structures could be suitable scaffolds for medicinal chemistry under proper conditions of

• biological evaluation, while their medicinal chemistry properties dramatically depend on the structure of the five-membered heterocyclic moiety and substituents in the C-5 position [7]. Some pseudothiohydantoins (2-iminothiazolidin-4-ones) are known to undergo a pseudothiohydantoin–thiohydantoin

Palladium-catalyzed synthesis and nucleotide pyrophosphatase inhibition of benzo[4,5]furo[3,2-b]indoles

• Hoang Huy Do,
• Saif Ullah,
• Alexander Villinger,
• Joanna Lecka,
• Jean Sévigny,
• Peter Ehlers,
• Jamshed Iqbal and
• Peter Langer

Beilstein J. Org. Chem. 2019, 15, 2830–2839, doi:10.3762/bjoc.15.276

• . The activities and selectivity of the compounds reported make them ideal targets for further applications in medicinal chemistry. Experimental General All reagents were obtained from commercial sources and used without further purification. Reactions were conducted in oven-dried glassware under an

A toolbox of molecular photoswitches to modulate the CXCR3 chemokine receptor with light

• Xavier Gómez-Santacana,
• Sabrina M. de Munnik,
• Tamara A. M. Mocking,
• Niels J. Hauwert,
• Shanliang Sun,
• Prashanna Vijayachandran,
• Iwan J. P. de Esch,
• Henry F. Vischer,
• Maikel Wijtmans and
• Rob Leurs

Beilstein J. Org. Chem. 2019, 15, 2509–2523, doi:10.3762/bjoc.15.244

• Xavier Gomez-Santacana Sabrina M. de Munnik Tamara A. M. Mocking Niels J. Hauwert Shanliang Sun Prashanna Vijayachandran Iwan J. P. de Esch Henry F. Vischer Maikel Wijtmans Rob Leurs Division of Medicinal Chemistry, Amsterdam Institute for Molecules Medicines and Systems (AIMMS), Vrije

• of medicinal chemistry and photochemistry. Classical medicinal chemistry approaches make use of small-molecule ligands binding a target protein, thereby modifying its activity. Photopharmacological approaches use light-sensitive photochromic ligands that provide an advantageous and more precise

Combining the Ugi-azide multicomponent reaction and rhodium(III)-catalyzed annulation for the synthesis of tetrazole-isoquinolone/pyridone hybrids

• Gerardo M. Ojeda,
• Prabhat Ranjan,
• Pavel Fedoseev,
• Lisandra Amable,
• Upendra K. Sharma,
• Daniel G. Rivera and
• Erik V. Van der Eycken

Beilstein J. Org. Chem. 2019, 15, 2447–2457, doi:10.3762/bjoc.15.237

• , which has been considered of interest for medicinal chemistry applications [7][8]. In recent years, the preparation of hybrid heterocyclic scaffolds including the tetrazole ring (either fused or linked to other heterocycles) has rendered potent bioactive compounds [9][10][11][12][13], which confirms the

Perspective isomorphs – a new classification of molecular structures based on artistic and chemical concepts

• Jannis Neumann,
• Ansgar Schnurr and
• Hermann A. Wegner

Beilstein J. Org. Chem. 2019, 15, 2319–2326, doi:10.3762/bjoc.15.224

• molecules in PI classes, the conceptual approach offers a novel way of categorizing for specific applications in medicinal chemistry, pharmacology or even in material sciences [21]. Conclusion With the proposal of perspective isomorphs, the transdisciplinary employment of artistic methods supports

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

• ]. Additionally, a diverse range of N-heterocycles, amides and motifs commonly encountered in medicinal chemistry were used as handles to direct C–H fluorination for the synthesis of pharmaceutical drugs (Scheme 24) [25]. Copper catalysis Despite the success of Pd-catalyzed fluorinations, the more widespread use

Cyclopropanation–ring expansion of 3-chloroindoles with α-halodiazoacetates: novel synthesis of 4-quinolone-3-carboxylic acid and norfloxacin

• Sara Peeters,
• Linn Neerbye Berntsen,
• Pål Rongved and
• Tore Bonge-Hansen

Beilstein J. Org. Chem. 2019, 15, 2156–2160, doi:10.3762/bjoc.15.212

• indoline cyclopropane intermediate and elimination of HX. The 4-quinolone-3-carboxylic acid scaffold (Figure 1) is regarded as a privileged scaffold in medicinal chemistry, due to the frequent appearance of this structural subunit in many commercial drugs [16][17][18][19][20][21], and a large variety of

• acidic removal of the Boc group (99%) gave norfloxacin as the hydrochloride salt (12) in an overall 35% yield from 8. Conclusion We have developed a novel and efficient synthetic route towards two privileged 4-quinolone-3-carboxylate scaffolds commonly used in medicinal chemistry. The highly attractive

A review of the total syntheses of triptolide

• Xiang Zhang,
• Zaozao Xiao and
• Hongtao Xu

Beilstein J. Org. Chem. 2019, 15, 1984–1995, doi:10.3762/bjoc.15.194

• Immunochemical Studies (SIAIS), ShanghaiTech University, Shanghai, 201210, China 10.3762/bjoc.15.194 Abstract Triptolide is a complex triepoxide diterpene natural product that has attracted considerable interest in the organic chemistry and medicinal chemistry societies due to its intriguing structural features

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

• common motif present in some components of human organisms, histidine, vitamin B12, purines, histamine, biotin, and in natural compounds such as lepidiline A and B [6]. Over the years of active research, benzimidazole derivatives have been involved in medicinal chemistry covering a wide range of

Installation of -SO₂F groups onto primary amides

• Jing Liu,
• Shi-Meng Wang,
• Njud S. Alharbi and
• Hua-Li Qin

Beilstein J. Org. Chem. 2019, 15, 1907–1912, doi:10.3762/bjoc.15.186

• medicinal chemistry and chemical biology. Synthesis background of N-fluorosulfonyl amides and fluorosulfates. Screening of the substrate scope of amides. Reaction conditions: a mixture of amides 1 (1.0 mmol), DBU (5.0 mmol, 5.0 equiv), and DMSO (1.0 mL) was added to a reaction flask before SO2F2 was

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

• Kesari Lakshmi Manasa Yellaiah Tangella Namballa Hari Krishna Mallika Alvala Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad-500 037, India Fluoro-Agrochemicals, CSIR-Indian Institute of Chemical Technology, Hyderabad-500 007, India

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

• been given much attention in various research fields, such as the discovery of lead compounds in medicinal chemistry, or combinatorial chemistry [95][96]. Copper-catalyzed synthetic protocols Ghosh and Mishra [97] have successfully reported the synthesis of imidazo[1,2-a]pyridines in a three-component