N-Boc-α-diazo glutarimide as efficient reagent for assembling N-heterocycle-glutarimide diads via Rh(II)-catalyzed N–H insertion reaction

• Grigory Kantin,
• Pavel Golubev,
• Alexander Sapegin,
• Alexander Bunev and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2023, 19, 1841–1848, doi:10.3762/bjoc.19.136

• ; Introduction Targeted protein degradation (TPD) has transformed the field of drug discovery [1][2]. Utilizing proximity-induced pharmacological strategies [3], this method has fostered the creation of numerous molecular glues and proteolysis-targeting chimeras (PROTACs). By manipulation of the internal

Trifluoromethylated hydrazones and acylhydrazones as potent nitrogen-containing fluorinated building blocks

• Zhang Dongxu

Beilstein J. Org. Chem. 2023, 19, 1741–1754, doi:10.3762/bjoc.19.127

• indispensable role in drug discovery and design since the hydrogen atom can act as lipophilic hydrogen-bond donor and act as a bioisostere for the alcohol moiety [81][82][83]. Thus, many effective difluoromethylation strategies have been developed in recent years. Difluoroacetohydrazonoyl bromides were chosen

Decarboxylative 1,3-dipolar cycloaddition of amino acids for the synthesis of heterocyclic compounds

• Xiaofeng Zhang,
• Xiaoming Ma and
• Wei Zhang

Beilstein J. Org. Chem. 2023, 19, 1677–1693, doi:10.3762/bjoc.19.123

• bioactive heterocyclic compounds in medicinal and drug discovery programs. Classification of AMYs. Biologically interesting pyrrolizidines. Biologically interesting spirooxindole-pyrrolizidines. Bioactive triazolobenzodiazepine derivatives. Bioactive pyrroloquinazolines and pyrrolobenzodiazepines. Bioactive

Morpholine-mediated defluorinative cycloaddition of gem-difluoroalkenes and organic azides

• Tzu-Yu Huang,
• Mario Djugovski,
• Sweta Adhikari,
• Destinee L. Manning and
• Sudeshna Roy

Beilstein J. Org. Chem. 2023, 19, 1545–1554, doi:10.3762/bjoc.19.111

• ; gem-difluoroalkenes; organic azides; Introduction gem-Difluoroalkenes and their synthetic preparations soared in the last decade, driven by the high demand for carbonyl mimics in medicinal chemistry and drug discovery [1]. Although a wide array of functionalization strategies for gem-difluoroalkenes

Synthesis and biological evaluation of Argemone mexicana-inspired antimicrobials

• Jessica Villegas,
• Bryce C. Ball,
• Katelyn M. Shouse,
• Caleb W. VanArragon,
• Ashley N. Wasserman,
• Hannah E. Bhakta,
• Allen G. Oliver,
• Danielle A. Orozco-Nunnelly and
• Jeffrey M. Pruet

Beilstein J. Org. Chem. 2023, 19, 1511–1524, doi:10.3762/bjoc.19.108

• drug discovery in recent years and an ever-growing prevalence of multidrug-resistant “superbugs”, there is a pressing need to explore alternative ways to combat pathogenic bacterial and fungal infections. Building upon our previous work in the field of medicinal phytochemistry, the present study is

• tumor cytotoxicity effects for a number of the berberine derivatives. Keywords: benzylisoquinoline; berberine; chelerythrine; drug discovery; plant-derived antimicrobials; Introduction The isolation, or creation of novel antimicrobial agents is currently at the forefront of modern healthcare due to

N-Sulfenylsuccinimide/phthalimide: an alternative sulfenylating reagent in organic transformations

• Fatemeh Doraghi,
• Seyedeh Pegah Aledavoud,
• Mehdi Ghanbarlou,
• Bagher Larijani and
• Mohammad Mahdavi

Beilstein J. Org. Chem. 2023, 19, 1471–1502, doi:10.3762/bjoc.19.106

• functional materials and indispensable synthetic intermediates in drug discovery [31][32][33]. Because of their value, constructing C–S bonds has attracted significant attention via metal-catalyzed cross-coupling reactions and metal-free C–S bond formation [34][35][36][37]. Direct sulfenylation of the C–H

Photoredox catalysis enabling decarboxylative radical cyclization of γ,γ-dimethylallyltryptophan (DMAT) derivatives: formal synthesis of 6,7-secoagroclavine

• Alessio Regni,
• Francesca Bartoccini and
• Giovanni Piersanti

Beilstein J. Org. Chem. 2023, 19, 918–927, doi:10.3762/bjoc.19.70

• synthetic route of ergot alkaloids and may offer new opportunities for drug discovery and biochemistry applications. As natural and unnatural tryptophan-derived redox-active N-hydroxyphthalimide esters have already been used in photoredox catalysis, we decided to use them as the initial substrates [77][78

Synthesis of aliphatic nitriles from cyclobutanone oxime mediated by sulfuryl fluoride (SO₂F₂)

• Xian-Lin Chen and
• Hua-Li Qin

Beilstein J. Org. Chem. 2023, 19, 901–908, doi:10.3762/bjoc.19.68

• the FDA for various indications and more than 140 additional nitrile-containing leads in clinical investigation [8]. Looking into changing the physicochemical properties, in the field of drug discovery, it is important to explore solutions to introduce nitrile groups into a molecule for enhancing the

Pyridine C(sp²)–H bond functionalization under transition-metal and rare earth metal catalysis

• Haritha Sindhe,
• Malladi Mounika Reddy,
• Karthikeyan Rajkumar,
• Akshay Kamble,
• Amardeep Singh,
• Anand Kumar and
• Satyasheel Sharma

Beilstein J. Org. Chem. 2023, 19, 820–863, doi:10.3762/bjoc.19.62

• biological activities. Hence, looking at the importance of azaindolines in drug discovery a protocol of rare earth metal-catalyzed intramolecular insertion of the pyridine C–H bond into unactivated vinyl C–H bonds has been developed by Chen and co-workers [108] (Scheme 38). Using this protocol azaindolines

Facile access to 3-sulfonylquinolines via Knoevenagel condensation/aza-Wittig reaction cascade involving ortho-azidobenzaldehydes and β-ketosulfonamides and sulfones

• Ksenia Malkova,
• Andrey Bubyrev,
• Stanislav Kalinin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2023, 19, 800–807, doi:10.3762/bjoc.19.60

• novel quinoline construction and functionalization techniques resulting in new or rare derivatives [17][18][19][20][21][22][23][24][25][26] is an important mission in the field of drug discovery and medicinal chemistry. The sulfonamide group is a known privileged motif in drug design often serving as a

Nostochopcerol, a new antibacterial monoacylglycerol from the edible cyanobacterium Nostochopsis lobatus

• Naoya Oku,
• Saki Hayashi,
• Yuji Yamaguchi,
• Hiroyuki Takenaka and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2023, 19, 133–138, doi:10.3762/bjoc.19.13

• ; Introduction Cyanobacteria are widely accepted as a prolific source of unique bioactive metabolites [1]. Some cyanobacterial species are consumed as food, nutritional supplements, or folk medicines in many parts of the world [2][3], and have offered attractive opportunities for drug discovery. Results from the

• detected by in vitro testings, which further raised the expectation of its richness as the source of bioactive metabolites. However, at present, only a single drug discovery attempt has been made on this alga [13], which prompted further chemical study. We evaluated the antimicrobial activity of the

Synthesis and characterisation of new antimalarial fluorinated triazolopyrazine compounds

• Kah Yean Lum,
• Jonathan M. White,
• Daniel J. G. Johnson,
• Vicky M. Avery and
• Rohan A. Davis

Beilstein J. Org. Chem. 2023, 19, 107–114, doi:10.3762/bjoc.19.11

• Kah Yean Lum Jonathan M. White Daniel J. G. Johnson Vicky M. Avery Rohan A. Davis Griffith Institute for Drug Discovery, School of Environment and Science, Griffith University, Nathan, QLD 4111, Australia School of Chemistry and Bio21 Institute, The University of Melbourne, Melbourne, VIC 3010

Practical synthesis of isocoumarins via Rh(III)-catalyzed C–H activation/annulation cascade

• Qian-Ci Gao,
• Yi-Fei Li,
• Jun Xuan and
• Xiao-Qiang Hu

Beilstein J. Org. Chem. 2023, 19, 100–106, doi:10.3762/bjoc.19.10

• and diverse functionalization of the isocoumarin products highlight the tremendous synthetic potential of this methodology in chemical synthesis and drug discovery. Experimental A 10 mL screw-cap vial was charged with enaminone 1 (0.2 mmol), iodonium ylide 2 (0.6 mmol), [Cp*RhCl2]2 (6.2 mg, 5 mol

Catalytic aza-Nazarov cyclization reactions to access α-methylene-γ-lactam heterocycles

• Bilge Banu Yagci,
• Selin Ezgi Donmez,
• Onur Şahin and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2023, 19, 66–77, doi:10.3762/bjoc.19.6

• -heterocycles [39][40][41][42][43][44][45] and specifically α-methylene-γ-lactams as a subset of this compound class, are popular targets in heterocyclic chemistry and drug discovery [46][47][48][49][50][51][52][53][54][55][56]. Against this background, we herein disclose a full account of our studies on the

Combining the best of both worlds: radical-based divergent total synthesis

• Kyriaki Gennaiou,
• Antonios Kelesidis,
• Maria Kourgiantaki and
• Alexandros L. Zografos

Beilstein J. Org. Chem. 2023, 19, 1–26, doi:10.3762/bjoc.19.1

• the latter, which is proven in the number of steps and the overall yield, hence establishing it as highly appealing for further development (Scheme 1). In order to identify the new pharmaceutical leads of tomorrow, drug discovery relies on the available chemical space rising from existing chemical

• libraries. But how big should this chemical space be, so as to actually address our needs? A general consensus has emerged, supporting that “it is not actually the library size but rather the library diversity in terms of molecular structure and function which is fundamental for a successful drug discovery

New cembrane-type diterpenoids with anti-inflammatory activity from the South China Sea soft coral Sinularia sp.

• Ye-Qing Du,
• Heng Li,
• Quan Xu,
• Wei Tang,
• Zai-Yong Zhang,
• Ming-Zhi Su,
• Xue-Ting Liu and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2022, 18, 1696–1706, doi:10.3762/bjoc.18.180

• Academy of Sciences, 555 Zu Chong Zhi Road, Zhangjiang Hi-Tech Park, Shanghai 201203, China Shandong Laboratory of Yantai Drug Discovery, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai, Shandong 264117, China Open Studio for Druggability Research of Marine Natural Products, Pilot

A novel bis-triazole scaffold accessed via two tandem [3 + 2] cycloaddition events including an uncatalyzed, room temperature azide–alkyne click reaction

• Ksenia Malkova,
• Andrey Bubyrev,
• Vasilisa Krivovicheva,
• Dmitry Dar’in,
• Alexander Bunev and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2022, 18, 1636–1641, doi:10.3762/bjoc.18.175

• ; Introduction 1,2,3-Triazoles are well-established heterocycles in drug discovery [1] and are even considered pharmacophores (i.e., structural motifs defining the compound’s biological activity profile) on their own [2]. Therefore, synthetic methods allowing to construct a 1,2,3-triazole heterocycle are a

• valuable part of the drug discovery chemistry toolbox. For the same reason, development of new methods [3] to either build 1,2,3-triazoles de novo and/or incorporate them into polycyclic scaffolds is a worthy undertaking which can help discover biological activity associated with hitherto unattainable

One-pot double annulations to confer diastereoselective spirooxindolepyrrolothiazoles

• Juan Lu,
• Bin Yao,
• Desheng Zhan,
• Zhuo Sun,
• Yun Ji and
• Xiaofeng Zhang

Beilstein J. Org. Chem. 2022, 18, 1607–1616, doi:10.3762/bjoc.18.171

• ; pyrrolothiazoles; spirooxindole; Introduction Nitrogen-containing heterocycles play a dominant role as a structural fragment of therapeutic agents in medicinal chemistry and drug discovery [1][2][3][4][5][6][7][8][9]. The nitrogen-containing heterocyclic moieties are currently discovered in more than 75% of the

• ]. Pyrrolothiazole and spirooxindole moieties occupy exclusive positions as valuable source of natural products and therapeutic agents in organic synthesis and drug discovery [60][61][62][63][64][65][66][67][68]. We have developed a number of asymmetric reactions to construct spirooxindole-based scaffolds through

• ][71]. With the promising applications of spirooxindolepyrrolothiazoles in drug discovery (Figure 1) [72][73][74], the structural integration of spirooxindole and pyrrolothiazole with diverse substituted groups via an efficient synthesis is a challengeable research in green chemistry. The corresponding

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

• and Technology, Japan [17H06401 (H.K.), 18K14396 (T.K.), 19H02840 (H.K.), 22K05112 (T.K.)], in addition to the Platform Project for Supporting Drug Discovery and Life Science Research from the Japan Agency for Medical Research and Development (AMED) (H.K.). Contributions from the Takeda Science

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

• Sasha Hayes Aya C. Taki Kah Yean Lum Joseph J. Byrne Merrick G. Ekins Robin B. Gasser Rohan A. Davis Griffith Institute for Drug Discovery, Griffith University, Don Young Road, Brisbane, 4111, Australia Department of Veterinary Biosciences, The University of Melbourne, Flemington Road, Parkville

• grade. H2O was filtered using a Sartorius Stedium Arium® Pro VF ultrapure water system. Sponge material The 39 Verongida sponge samples were obtained from the NatureBank biota library housed at the Griffith Institute for Drug Discovery, Griffith University, Australia [12]. All samples were collected and

• support towards NMR and MS equipment (grants LE0668477, LE140100119, and LE0237908). Research at The University of Melbourne was supported by the ARC and Yourgene Health Singapore (LP180101085). S.H. acknowledges the Griffith Institute for Drug Discovery (Griffith University) for scholarship support.

Mechanochemical synthesis of unsymmetrical salens for the preparation of Co–salen complexes and their evaluation as catalysts for the synthesis of α-aryloxy alcohols via asymmetric phenolic kinetic resolution of terminal epoxides

• Shengli Zuo,
• Shuxiang Zheng,
• Jianjun Liu and
• Ang Zuo

Beilstein J. Org. Chem. 2022, 18, 1416–1423, doi:10.3762/bjoc.18.147

• key organic intermediates in the drug discovery and process chemistry [4][5][6]. Chiral metal–salen complexes were designed for catalyzing reaction processes that resulted in good yield, high regioselective and enantioselective control for the asymmetric ring opening of terminal epoxides. Various

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

• , 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

• sciences: – The development of genetics and molecular biology leading, with or without the use of chemical probes [1], to the discovery of a near infinite number of biochemical processes, amenable to the design of assays as plausible targets for drug discovery programs. – The development of robotics and

• ][26][27][28][29][30][31][32]. As organic chemists, the main task at hand in a multidisciplinary drug discovery program starts with the initial problem of securing a compound endowed with a biological effect of interest: a “hit”. Then, the second problem arises as the program will require a “hit to

Synthesis of tryptophan-dehydrobutyrine diketopiperazine and biological activity of hangtaimycin and its co-metabolites

• Houchao Xu,
• Anne Wochele,
• Minghe Luo,
• Gregor Schnakenburg,
• Yuhui Sun,
• Heike Brötz-Oesterhelt and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2022, 18, 1159–1165, doi:10.3762/bjoc.18.120

• , Department of Microbial Bioactive Compounds, University of Tübingen, Auf der Morgenstelle 28, 72076 Tübingen, Germany Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, and School of Pharmaceutical Sciences, Wuhan University, No. 185 East Lake Road, Wuhan, 430071

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

• Berlin, Germany 10.3762/bjoc.18.115 Abstract Metallaphotoredox catalysis is a powerful and versatile synthetic platform that enables cross-couplings under mild conditions without the need for noble metals. Its growing adoption in drug discovery has translated into an increased interest in sustainable

New azodyrecins identified by a genome mining-directed reactivity-based screening

• Atina Rizkiya Choirunnisa,
• Kuga Arima,
• Yo Abe,
• Noritaka Kagaya,
• Kei Kudo,
• Hikaru Suenaga,
• Junko Hashimoto,
• Manabu Fujie,
• Noriyuki Satoh,
• Kazuo Shin-ya,
• Kenichi Matsuda and
• Toshiyuki Wakimoto

Beilstein J. Org. Chem. 2022, 18, 1017–1025, doi:10.3762/bjoc.18.102

• , Japan Global Station for Biosurfaces and Drug Discovery, Global Institution for Collaborative Research and Education, Hokkaido University, Sapporo 060-0812, Japan 10.3762/bjoc.18.102 Abstract Only a few azoxy natural products have been identified despite their intriguing biological activities

• Station for Biosurfaces and Drug Discovery, a project of Global Institution for Collaborative Research and Education in Hokkaido University, the Asahi Glass Foundation, the Naito Foundation, the Uehara Memorial Foundation, the Sumitomo Foundation−Grant for Basic Science Research Projects, Daiichi Sankyo