Three-component N-alkenylation of azoles with alkynes and iodine(III) electrophile: synthesis of multisubstituted N-vinylazoles

• Jun Kikuchi,
• Roi Nakajima and
• Naohiko Yoshikai

Beilstein J. Org. Chem. 2024, 20, 891–897, doi:10.3762/bjoc.20.79

• motif in bioactive compounds and the synthetic utility of its olefinic C=C bond. The most extensively explored approach to this transformation is the transition metal-catalyzed C–N coupling between azoles and vinylating agents, including vinyl halides [4], boronates [5], sulfonium salts [6][7][8], and

SOMOphilic alkyne vs radical-polar crossover approaches: The full story of the azido-alkynylation of alkenes

• Julien Borrel and
• Jerome Waser

Beilstein J. Org. Chem. 2024, 20, 701–713, doi:10.3762/bjoc.20.64

• building blocks bearing two of the most versatile functional groups, allowing a rich panel of functionalization. They have been used as intermediates in numerous syntheses to access bioactive compounds [1][2][3][4] or materials [5][6][7]. In addition, azide reduction affords homopropargylic amines, which

Recent developments in the engineered biosynthesis of fungal meroterpenoids

• Zhiyang Quan and
• Takayoshi Awakawa

Beilstein J. Org. Chem. 2024, 20, 578–588, doi:10.3762/bjoc.20.50

• biosynthesis of bioactive compounds with still greater skeletal diversity. Conclusion In summary, many novel terpene cyclases and αKG-dependent dioxygenases were discovered by recent developments in genome mining approaches. Unique meroterpenoids have been generated by integrating these enzymes into

• cross-coupling between two aromatic rings [43]. In the future, further developments in bioinformatics, structural biology, and AI techniques will enable the design of biosynthetic enzymes and pathways to produce desired bioactive compounds, although understanding the chemistry catalyzed by individual

A new analog of dihydroxybenzoic acid from Saccharopolyspora sp. KR21-0001

• Rattiya Janthanom,
• Yuta Kikuchi,
• Hiroki Kanto,
• Tomoyasu Hirose,
• Arisu Tahara,
• Takahiro Ishii,
• Arinthip Thamchaipenet and
• Yuki Inahashi

Beilstein J. Org. Chem. 2024, 20, 497–503, doi:10.3762/bjoc.20.44

• Actinomycetes are well-known as the main producers of bioactive compounds such as antibiotics, anticancers, and immunosuppressants. Screening of natural products from actinomycetes has been an essential part of several drug discovery programs. Finding such novel biologically active metabolites is immensely

• but showed potent antioxidant activity. Keywords: antioxidant activity; dihydroxybenzoic acid analog; rare actinomycetes; Introduction Actinomycetes are Gram-positive bacteria with high GC content in their genome. They are well-known as the main producers of bioactive compounds such as antibiotic

• actinomycetes, which are believed to be rich sources of interestingly new compounds. Bioactive compounds are vastly beneficial in medicine, pharmaceutical industry, and agriculture [7][8]. The thoughtful exploration of novel sources for acquiring new compounds is crucial, and the strategies employed in this

Identification of the p-coumaric acid biosynthetic gene cluster in Kutzneria albida: insights into the diazotization-dependent deamination pathway

• Seiji Kawai,
• Akito Yamada,
• Yohei Katsuyama and
• Yasuo Ohnishi

Beilstein J. Org. Chem. 2024, 20, 1–11, doi:10.3762/bjoc.20.1

• particular, actinomycetes, a major source of bioactive compounds, have numerous BGCs in their genomes, but the majority of them are thought to be silent under laboratory conditions [2]. Because these orphan BGCs are often related to the production of unknown natural products, genome mining has been

Synthetic approach to 2-alkyl-4-quinolones and 2-alkyl-4-quinolone-3-carboxamides based on common β-keto amide precursors

• Yordanka Mollova-Sapundzhieva,
• Plamen Angelov,
• Danail Georgiev and
• Pavel Yanev

Beilstein J. Org. Chem. 2023, 19, 1804–1810, doi:10.3762/bjoc.19.132

• sensing; Introduction Among the vast number of biologically active quinoline derivatives [1][2], the subclass of 4-quinolones (also referred to as 4-oxo-1,4-dihydroquinolines, quinolin-4(1H)-ones, or 4-hydroxyquinolines) is of great importance with its rich variety of bioactive compounds. Perhaps the

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

• activation [108][109][110]. Besides, pyrazolidine and pyrazoline compounds are highly valuable hereocycles which are found in many natural products and bioactive compounds. Among them, CF3-substituted pyrazolidines have already been shown to be highly bioactive [111][112][113]. Thus, Hu et al. chose

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

• -type AMYs in multicomponent, one-pot, and stepwise reactions for the synthesis of diverse heterocycles related to some bioactive compounds and natural products. Keywords: [3 + 2] cycloaddition; decarboxylation; 1,3-dipolar; double cycloaddition; one-pot synthesis; multicomponent reaction; semi

• bioactive compounds and natural products such as PB1-5 [74], lixivaptan, and (+)-anthramycin (Figure 5) [73]. Stepwise synthesis of pyrrolo[2,1-a]isoquinolines A stepwise synthesis involving [3 + 2] cycloaddition, N-allylation and Heck reactions has been developed for the synthesis of pyrrolo[2,1-a

•  6) [75]. One-pot double annulations for the synthesis of tetrahydropyrrolothiazoles The unique tetrahydropyrrolothiazole and spiro[indole-tetrahydropyrrolothiazole] scaffolds are found in bioactive compounds such as those shown in Figure 7 [76][77]. Using cysteine as a key reactant, we developed a

Metal catalyst-free N-allylation/alkylation of imidazole and benzimidazole with Morita–Baylis–Hillman (MBH) alcohols and acetates

• Olfa Mhasni,
• Jalloul Bouajila and
• Farhat Rezgui

Beilstein J. Org. Chem. 2023, 19, 1251–1258, doi:10.3762/bjoc.19.93

• biological activities [1][2][3][4][5][6][7]. In this context, the imidazole moiety is widely known as one of the most important groups which plays efficient roles in bioactive compounds [8]. For instance, a number of N-substituted imidazole derivatives, such as miconazole, ketoconazole, genaconazole, and

Radical ligand transfer: a general strategy for radical functionalization

• David T. Nemoto Jr,
• Kang-Jie Bian,
• Shih-Chieh Kao and
• Julian G. West

Beilstein J. Org. Chem. 2023, 19, 1225–1233, doi:10.3762/bjoc.19.90

• alkyl C–H bond to a high valent iron oxo species, resulting in formation of iron hydroxo and alkyl radical intermediates [15]. Subsequent RLT of the hydroxo ligand to the alkyl radical produces a hydroxylated product, allowing for metabolism and excretion of previously diverse bioactive compounds

Two new lanostanoid glycosides isolated from a Kenyan polypore Fomitopsis carnea

• Winnie Chemutai Sum,
• Sherif S. Ebada,
• Didsanutda Gonkhom,
• Cony Decock,
• Rémy Bertrand Teponno,
• Josphat Clement Matasyoh and
• Marc Stadler

Beilstein J. Org. Chem. 2023, 19, 1161–1169, doi:10.3762/bjoc.19.84

• into the SARs of lanostanoid triterpenoids and expands the database of their bioactive compounds for subsequent studies. Conclusion The genus Fomitopsis remains to be a prolific source of several metabolites with health-promoting effects. We provide a new evidence of lanostanoid glycosides 1 and 2 from

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

• moiety (OCH2CF3), an important fluorinated group found in several bioactive compounds such as flecanide [154][155] and lansoprazole [156], as flagship molecules. Although the transition-metal-catalyzed hydroxylation and alkoxylation have been studied especially under palladium catalysis [157][158], the

Discrimination of β-cyclodextrin/hazelnut (Corylus avellana L.) oil/flavonoid glycoside and flavonolignan ternary complexes by Fourier-transform infrared spectroscopy coupled with principal component analysis

• Nicoleta G. Hădărugă,
• Gabriela Popescu,
• Dina Gligor (Pane),
• Cristina L. Mitroi,
• Sorin M. Stanciu and
• Daniel Ioan Hădărugă

Beilstein J. Org. Chem. 2023, 19, 380–398, doi:10.3762/bjoc.19.30

• solubility and bioaccessibility of the hazelnut oil components and antioxidants can be increased, as well as the controlled release of bioactive compounds (fatty acid glycerides and antioxidant flavonoids, namely hesperidin, naringin, rutin, and silymarin). The appropriate method for obtaining the ternary

• compounds [5]. The resulting supramolecular inclusion complexes provide enhanced water solubility and bioavailability/bioaccessibility of the nanoencapsulated bioactive compounds, higher oxidative and thermal stability or photostability of labile compounds, and their controlled release [6][7]. Vegetable oil

• provide the on-site protection of hazelnut oil components against oxidative degradation, in combination with a protection/stabilization through CD nanoencapsulation. Moreover, the apparent water solubility, bioaccessibility, bioavailability, and controlled release of the guest bioactive compounds can also

Synthesis and reactivity of azole-based iodazinium salts

• Thomas J. Kuczmera,
• Annalena Dietz,
• Andreas Boelke and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2023, 19, 317–324, doi:10.3762/bjoc.19.27

• underwent ring openings in this reaction. This reactivity demonstrates the highly stabilizing effect of N-heterocycles on hypervalent iodine species. Furthermore, the formed 2-aminobenzimidazoles reveal new access to potential bioactive compounds [46][47]. Even the formation of the free guanidine 16 via

Digyalipopeptide A, an antiparasitic cyclic peptide from the Ghanaian Bacillus sp. strain DE2B

• Adwoa P. Nartey,
• Aboagye K. Dofuor,
• Kofi B. A. Owusu,
• Anil S. Camas,
• Hai Deng,
• Marcel Jaspars and
• Kwaku Kyeremeh

Beilstein J. Org. Chem. 2022, 18, 1763–1771, doi:10.3762/bjoc.18.185

• as nystatin and nalidixic acid makes it easier to isolate them from a number of soil and sediment types using the spread plate method (SPM) in our laboratory. Therefore, in our continued research on the discovery of new bioactive compounds from Ghanaian microbes, we have started to study interesting

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

• : cyclodextrin; complexation; 17β-estradiol; progesterone; solubility; X-ray diffraction; Introduction The insolubility of active pharmaceutical ingredients (APIs) and other bioactive compounds in aqueous media and the associated challenges for effective drug delivery are well known to have beleaguered the

• their chemical instability, adverse side effects such as gastrointestinal irritation, and unpleasant tastes and odours [1][2][3][4][5]. Here we report an investigation of the cyclodextrin (CD) inclusion of two notable bioactive compounds (Figure 1), namely the most potent human estrogen, 17β-estradiol

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

• -cytotoxic which makes them suitable for interrogation of various biological targets. (a) Previously developed three-component approach to 1,5-disubstituted 1,2,3-triazoles; (b) double cycloaddition strategy investigated in this work. Diversely bioactive compounds based on scaffolds A and B. Aromatic azido

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

• longicatenamide A was confirmed. The developed solid-phase synthesis is expected to facilitate the rapid synthesis of diverse synthetic analogues. Keywords: antimicrobial; longicatenamides; peptidic natural product; solid-phase synthesis; total synthesis; Introduction Naturally occurring bioactive compounds can

Sinensiols H–J, three new lignan derivatives from Selaginella sinensis (Desv.) Spring

• Qinfeng Zhu,
• Beibei Gao,
• Qian Chen,
• Tiantian Luo,
• Guobo Xu and
• Shanggao Liao

Beilstein J. Org. Chem. 2022, 18, 1410–1415, doi:10.3762/bjoc.18.146

• activities [9][10][11]. However, chemical constituents responsible for its efficacy in treating various inflammatory diseases are still not clear. As part of our continuing research on the bioactive compounds from this genus [12][13], the chemical constituents of the whole plant of S. sinensis were

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

Facile and diastereoselective arylation of the privileged 1,4-dihydroisoquinolin-3(2H)-one scaffold

• Dmitry Dar’in,
• Grigory Kantin,
• Alexander Bunev and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2022, 18, 1070–1078, doi:10.3762/bjoc.18.109

• associated biological activities and relevance to the naturally occurring alkaloids [1], 1,4-dihydro-3(2H)-isoquinolones (1,4-DHIQs) undoubtedly represent a privileged scaffold [2] for drug design considering such diversely bioactive compounds documented in the literature as ligand for serotonin 5-HT1A

• anticancer cytotoxic agents. Diverse bioactive compounds based on the privileged 1,4-DHIQ scaffold. Strategy investigated in this work. Preparation of 3(2H)-isoquinolones 11. aObtained as a 10:1 mixture of regioisomers; purified by crystallization. bEmployed in the next step without purification (not

Understanding the competing pathways leading to hydropyrene and isoelisabethatriene

• Shani Zev,
• Marion Ringel,
• Ronja Driller,
• Bernhard Loll,
• Thomas Brück and
• Dan T. Major

Beilstein J. Org. Chem. 2022, 18, 972–978, doi:10.3762/bjoc.18.97

• main GGPP cyclization products, along with two minor compounds, namely the isoelisabethatrienes (IEs) A (13%) and B (9%), respectively. Interestingly, the elisabethatriene diterpene macrocycle and its isoforms can act as biosynthetic precursors of the bioactive compounds erogorgiaene and pseudopterosin

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

• attracting much attention, since bioactive compounds possessing these structures are known. This method has the potential to be applied to synthesize bioactive 2-cyanonaphthalen-1-ols [8][9] and 3-substituted phthalides [12][13][14][15][16]. The reaction mechanisms of the electroreductive coupling of 1 with

An isoxazole strategy for the synthesis of 4-oxo-1,4-dihydropyridine-3-carboxylates

• Timur O. Zanakhov,
• Ekaterina E. Galenko,
• Mikhail S. Novikov and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2022, 18, 738–745, doi:10.3762/bjoc.18.74

• represented among drugs [5][6][7][8][9][10][11][12]. Some of bioactive compounds, such as ciprofloxacin, levofloxacin, delafloxacin, and elvitegravir, contain the fragment of 4-oxo-1,4-dihydropyridine-3-carboxylic acid [6][8] and some others, ivacaftor, dolutegravir, bictegravir, aspernigrin B, and 4PYR

Menadione: a platform and a target to valuable compounds synthesis

• Acácio S. de Souza,
• Ruan Carlos B. Ribeiro,
• Dora C. S. Costa,
• Fernanda P. Pauli,
• David R. Pinho,
• Matheus G. de Moraes,
• Fernando de C. da Silva,
• Luana da S. M. Forezi and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 381–419, doi:10.3762/bjoc.18.43

• makes menadione a very interesting structural model for the development of new bioactive compounds. Considering the great potential of menadione, mainly in biological applications, in this review several applications involving its synthesis and its use as a versatile synthetic platform will be discussed