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

Anti-inflammatory aromadendrane- and cadinane-type sesquiterpenoids from the South China Sea sponge Acanthella cavernosa

• Shou-Mao Shen,
• Qing Yang,
• Yi Zang,
• Jia Li,
• Xueting Liu and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2022, 18, 916–925, doi:10.3762/bjoc.18.91

• Pharmaceutical Science, Nanchang University, Nanchang 330006, 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 National Laboratory for Marine Science

Synthesis of novel alkynyl imidazopyridinyl selenides: copper-catalyzed tandem selenation of selenium with 2-arylimidazo[1,2-a]pyridines and terminal alkynes

• Mio Matsumura,
• Kaho Tsukada,
• Kiwa Sugimoto,
• Yuki Murata and
• Shuji Yasuike

Beilstein J. Org. Chem. 2022, 18, 863–871, doi:10.3762/bjoc.18.87

• with potential bioactivity, has been reported [4][5][6][7]. Similarly, organoselenium compounds have also received increased attention in recent years due to their promising applications as bioactive substances in drug discovery [8]. Among these compounds, alkynyl selenides have attracted interest in

Synthesis of bis-spirocyclic derivatives of 3-azabicyclo[3.1.0]hexane via cyclopropene cycloadditions to the stable azomethine ylide derived from Ruhemann's purple

• Alexander S. Filatov,
• Olesya V. Khoroshilova,
• Anna G. Larina,
• Vitali M. Boitsov and
• Alexander V. Stepakov

Beilstein J. Org. Chem. 2022, 18, 769–780, doi:10.3762/bjoc.18.77

• substances. Many biologically active natural products have a spirocyclic skeleton in their structure [1][2]. In this regard, there is interest in studying heterocyclic spiro compounds for drug discovery. These compounds were found to exhibit a broad range of biological activities, including antioxidant [3

Structural basis for endoperoxide-forming oxygenases

• Takahiro Mori and
• Ikuro Abe

Beilstein J. Org. Chem. 2022, 18, 707–721, doi:10.3762/bjoc.18.71

• molecular insights into their remarkable chemistries. Finally, the detailed structural and mechanistic investigations of these enzymes will provide an excellent basis for the development of biocatalysts to generate novel compounds with endoperoxides for future drug discovery. Examples of endoperoxide

Synthesis of 3,4,5-trisubstituted isoxazoles in water via a [3 + 2]-cycloaddition of nitrile oxides and 1,3-diketones, β-ketoesters, or β-ketoamides

• Md Imran Hossain,
• Md Imdadul H. Khan,
• Seong Jong Kim and
• Hoang V. Le

Beilstein J. Org. Chem. 2022, 18, 446–458, doi:10.3762/bjoc.18.47

• prevalent scaffold in biomedical research and drug discovery programs. We also proposed a plausible mechanism for the selectivity of the [3 + 2]-cycloaddition reaction to produce 3,4,5-trisubstituted isoxazoles. Not to be overlooked are our optimized reaction conditions for the dimerization of hydroximoyl

• . Meanwhile, some of the starting material 2l remained unreacted and we suspected the lower solubility of compound 2l in water was responsible for the low yield of the reaction. Since trifluoromethyl-substituted isoxazoles are an important and prevalent scaffold in biomedical research and drug discovery

• similar 3,4,5-trisubstituted isoxazole structure to the synthesized compounds in this report. In addition, we optimized the reaction conditions to produce trifluoromethyl-substituted isoxazoles, a prevalent scaffold in biomedical research and drug discovery programs. We also proposed a plausible mechanism

Regioselective synthesis of methyl 5-(N-Boc-cycloaminyl)-1,2-oxazole-4-carboxylates as new amino acid-like building blocks

• Jolita Bruzgulienė,
• Greta Račkauskienė,
• Aurimas Bieliauskas,
• Vaida Milišiūnaitė,
• Miglė Dagilienė,
• Gita Matulevičiūtė,
• Vytas Martynaitis,
• Sonata Krikštolaitytė,
• Frank A. Sløk and
• Algirdas Šačkus

Beilstein J. Org. Chem. 2022, 18, 102–109, doi:10.3762/bjoc.18.11

• important class of heterocyclic compounds that plays a fundamental role in drug discovery [1][2][3][4][5][6][7]. Many amino-functionalized 1,2-oxazole derivatives are biologically active substances that include naturally occurring and synthetic neuroactive compounds. Specifically, natural products such as

Bifunctional thiourea-catalyzed asymmetric [3 + 2] annulation reactions of 2-isothiocyanato-1-indanones with barbiturate-based olefins

• Jiang-Song Zhai and
• Da-Ming Du

Beilstein J. Org. Chem. 2022, 18, 25–36, doi:10.3762/bjoc.18.3

• availability of these compounds will provide promising candidates for chemical biology and drug discovery. Experimental General information Commercially available compounds were used without further purification. Solvents were dried according to standard procedures. Column chromatography was performed with

Unsaturated fatty acids and a prenylated tryptophan derivative from a rare actinomycete of the genus Couchioplanes

• Shun Saito,
• Kanji Indo,
• Naoya Oku,
• Hisayuki Komaki,
• Masashi Kawasaki and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2021, 17, 2939–2949, doi:10.3762/bjoc.17.203

• the genus Streptomyces [11], non-Streptomyces actinomycetes, commonly referred to as rare actinomycetes [12], are attracting considerable attention as less tapped taxa for drug discovery. Those within the family Micromonosporaceae, represented by the second most prolific genus Micromonospora following

Selective sulfonylation and isonitrilation of para-quinone methides employing TosMIC as a source of sulfonyl group or isonitrile group

• Chuanhua Qu,
• Run Huang,
• Yong Li,
• Tong Liu,
• Yuan Chen and
• Guiting Song

Beilstein J. Org. Chem. 2021, 17, 2822–2831, doi:10.3762/bjoc.17.193

• chemists [7]. Therefore, merging the diarylmethane unit with the sulfonyl motif to assemble the sulfonyl diarylmethane skeleton has attractive potential application value and provides the possibility for drug discovery [8][9][10] (Figure 1). Consequently, the development of a rapid access to diarylmethyl

The PIFA-initiated oxidative cyclization of 2-(3-butenyl)quinazolin-4(3H)-ones – an efficient approach to 1-(hydroxymethyl)-2,3-dihydropyrrolo[1,2-a]quinazolin-5(1H)-ones

• Alla I. Vaskevych,
• Nataliia O. Savinchuk,
• Ruslan I. Vaskevych,
• Eduard B. Rusanov,
• Oleksandr O. Grygorenko and
• Mykhailo V. Vovk

Beilstein J. Org. Chem. 2021, 17, 2787–2794, doi:10.3762/bjoc.17.189

• of natural product-like compound libraries. Keywords: [bis(trifluoroacetoxy)iodo]benzene PIFA; nitrogen heterocycles; oxidative cyclization; pyrrolo[1,2-a]quinazolines; Introduction An important design concept in current drug discovery includes structural modifications of naturally occurring

• product 6. The structure of products 6 was confirmed by NMR spectroscopy; in addition to that, X-ray diffraction studies were performed with single crystals of compound 6f (see Figure 2). Since the application of the obtained compounds in early drug discovery is anticipated, it is important to assess

Recent advances in the asymmetric phosphoric acid-catalyzed synthesis of axially chiral compounds

• Alemayehu Gashaw Woldegiorgis and
• Xufeng Lin

Beilstein J. Org. Chem. 2021, 17, 2729–2764, doi:10.3762/bjoc.17.185

• considerable attention in recent years due to their wide application in the total synthesis of axially chiral natural products, functional materials, bioactive compounds, privileged chiral ligands, and have further potential applications in asymmetric catalysis and drug discovery. Accordingly, considerable

Direct C(sp³)–H allylation of 2-alkylpyridines with Morita–Baylis–Hillman carbonates via a tandem nucleophilic substitution/aza-Cope rearrangement

• Siyu Wang,
• Lianyou Zheng,
• Shutao Wang,
• Shulin Ning,
• Zhuoqi Zhang and
• Jinbao Xiang

Beilstein J. Org. Chem. 2021, 17, 2505–2510, doi:10.3762/bjoc.17.167

• Siyu Wang Lianyou Zheng Shutao Wang Shulin Ning Zhuoqi Zhang Jinbao Xiang The Center for Combinatorial Chemistry and Drug Discovery, School of Pharmaceutical Sciences, Jilin University, 1266 Fujin Road, Changchun, Jilin 130021, P. R. China 10.3762/bjoc.17.167 Abstract A base- and catalyst-free C

Exfoliated black phosphorous-mediated CuAAC chemistry for organic and macromolecular synthesis under white LED and near-IR irradiation

• Azra Kocaarslan,
• Zafer Eroglu,
• Önder Metin and
• Yusuf Yagci

Beilstein J. Org. Chem. 2021, 17, 2477–2487, doi:10.3762/bjoc.17.164

• Mendal [3], many studies have been dedicated to better understanding of the concept and expanding its scope to be applied in various fields of chemistry including bioconjugation [4], drug discovery [5], materials science [6][7][8][9] and so on [10]. The development of the use of light in click chemistry

Isolation and characterization of new phenolic siderophores with antimicrobial properties from Pseudomonas sp. UIAU-6B

• Emmanuel T. Oluwabusola,
• Olusoji O. Adebisi,
• Fernando Reyes,
• Kojo S. Acquah,
• Mercedes De La Cruz,
• Larry L. Mweetwa,
• Joy E. Rajakulendran,
• Digby F. Warner,
• Deng Hai,
• Rainer Ebel and
• Marcel Jaspars

Beilstein J. Org. Chem. 2021, 17, 2390–2398, doi:10.3762/bjoc.17.156

• -spectrum biological functions which include antifungal [9][10][11] and antibacterial activities [12][13][14]. Natural product scaffolds isolated from species of this genus have contributed immensely as leads to drug discovery and development [15]. For instance, clofazimine [16], the antimycobacterial agent

Phenolic constituents from twigs of Aleurites fordii and their biological activities

• Kyoung Jin Park,
• Won Se Suh,
• Da Hye Yoon,
• Chung Sub Kim,
• Sun Yeou Kim and
• Kang Ro Lee

Beilstein J. Org. Chem. 2021, 17, 2329–2339, doi:10.3762/bjoc.17.151

• on NO production and the stereoisomers 2 and 5 demonstrated the difference in activity according to the configuration. Compounds 8 and 16 exhibited neuroprotection effects. Thus, this study indicates that the active phenolic compounds from A. fordii would be potential candidates for drug discovery

Catalyzed and uncatalyzed procedures for the syntheses of isomeric covalent multi-indolyl hetero non-metallides: an account

• Ranadeep Talukdar

Beilstein J. Org. Chem. 2021, 17, 2102–2122, doi:10.3762/bjoc.17.137

• broad applications in organic electroluminescent devices [44]. Silanes Heteroaryl compounds containing silicon, an earth abundant and non-toxic element, are important in organic electronics or photonics and in the field of drug discovery and nuclear medicine [45][46][47][48][49][50]. The first property

Regioselective N-alkylation of the 1H-indazole scaffold; ring substituent and N-alkylating reagent effects on regioisomeric distribution

• Ryan M. Alam and
• John J. Keating

Beilstein J. Org. Chem. 2021, 17, 1939–1951, doi:10.3762/bjoc.17.127

• an improved and cost-effective approach to N-1 substituted indazole precursors as part of drug discovery and development campaigns. Results and Discussion Working towards the synthesis of a library of novel 1,3-disubstituted indazole derivatives necessitated us to develop a regioselective method that

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

Development of N-F fluorinating agents and their fluorinations: Historical perspective

• Teruo Umemoto,
• Yuhao Yang and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2021, 17, 1752–1813, doi:10.3762/bjoc.17.123

• , introduction of fluorine into selective positions of a bioactive compound can produce remarkable changes in efficacy. Fluorine-scan/fluorine editing of a lead molecule is now a routine step in drug discovery [8]. Organofluorine compounds are very rare in nature [9] and therefore without natural compounds

Sustainable manganese catalysis for late-stage C–H functionalization of bioactive structural motifs

• Jongwoo Son

Beilstein J. Org. Chem. 2021, 17, 1733–1751, doi:10.3762/bjoc.17.122

• strategy, is regarded as a crucial tactic in the area of natural products, drug discovery, and medicinal chemistry [7][8][9][10][11][12] as it confers an invaluable synthetic opportunity for the facile diversification of biologically active complex molecules at the late stage. In recent years, much effort

• protein–ligand binding properties as well as biological activities of small molecules, potentially leading to dramatic increases in potency, and thus has been widely explored in drug discovery [54][55][56]. Late-stage C–H methylation has recently been investigated using iron and cobalt catalysts as

• -economical approach to several tryptophan-containing peptides with significant potential for drug discovery and medicinal chemistry. Positional selectivity was observed at the C2 position due to the presence of the pyrimidine directing group. Interestingly, alkynylative conjugation of tryptophan to a steroid

Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

• Thiago S. Silva and
• Fernando Coelho

Beilstein J. Org. Chem. 2021, 17, 1565–1590, doi:10.3762/bjoc.17.112

• molecular complexity of drugs in drug discovery programs, aiming at molecules with better selectivity for biological targets [6][15][16]. One ideal way to achieve more complex molecular architectures is by hydroalkylation of olefins, a reaction that forms new C(sp3)–C(sp3) and C(sp3)–H bonds at the expense