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

Tenacibactins K–M, cytotoxic siderophores from a coral-associated gliding bacterium of the genus Tenacibaculum

• Yasuhiro Igarashi,
• Yiwei Ge,
• Tao Zhou,
• Amit Raj Sharma,
• Enjuro Harunari,
• Naoya Oku and
• Agus Trianto

Beilstein J. Org. Chem. 2022, 18, 110–119, doi:10.3762/bjoc.18.12

• available on the secondary metabolites from this genus [17][18]. In our continuing search for bioactive compounds from underexplored marine bacteria [19][20][21], a Tenacibaculum strain, isolated from a stony coral, was found to produce three metabolites, which turned out to be new cytotoxic hydroxamate

1,2-Naphthoquinone-4-sulfonic acid salts in organic synthesis

• Ruan Carlos B. Ribeiro,
• Patricia G. Ferreira,
• Amanda de A. Borges,
• Luana da S. M. Forezi,
• Fernando de Carvalho da Silva and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 53–69, doi:10.3762/bjoc.18.5

• substituted at the C4 position of β-NQS. Despite great advances in the area, there are still many opportunities for the development of new bioactive compounds of great relevance to humanity. We hope this article will serve as a source of inspiration for current and future researchers in chemical

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

• mixture was stirred at 80 °C for 10 h and monitored by TLC. Then, the reaction mixture was concentrated under reduced pressure followed by column chromatography over silica gel using petroleum/EtOAc 10:1 to ≈5:1 as eluent to afford the desired product 4. Selected bioactive compounds. Crystal structure of

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

• scaffold for a variety of natural products, bioactive compounds and pharmacological agents [79] as well as for a variety of chiral phosphine ligands [80]. As a result, the preparation of axially chiral arylpyrroles has been one of the most important areas of investigation in synthetic chemistry. In the

• 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

The ethoxycarbonyl group as both activating and protective group in N-acyl-Pictet–Spengler reactions using methoxystyrenes. A short approach to racemic 1-benzyltetrahydroisoquinoline alkaloids

• Marco Keller,
• Karl Sauvageot-Witzku,
• Franz Geisslinger,
• Nicole Urban,
• Michael Schaefer,
• Karin Bartel and
• Franz Bracher

Beilstein J. Org. Chem. 2021, 17, 2716–2725, doi:10.3762/bjoc.17.183

• ), and identified 1-benzyl-1,2,3,4-tetrahydroisoquinolines bearing phenoxy and benzyloxy substituents (SG-005, SG-094; for structures of bioactive compounds mentioned in this text, see Figure S1 in Supporting Information File 1) on both aromatic rings as potent blockers with promising antitumor activity

• benzylisoquinolines 2a–f, 3a-c and 4 revealed that they possess neither antiproliferative nor P-glycoprotein blocking activity. Nevertheless, the results of this investigation represent a considerable contribution to the further development of benzyltetrahydroisoquinoline-derived bioactive compounds, since the here

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

• transporting system as a cellular entry gateway [31][32]. Thus far, a few Pseudomonas-derived siderophores including ferrocins [33], thioquinolobactin [34], and (+)-(S)-dihydroaeruginioc acid [35] have been reported as active antimicrobial agents. Our continued exploration of new bioactive compounds from

Nomimicins B–D, new tetronate-class polyketides from a marine-derived actinomycete of the genus Actinomadura

• Zhiwei Zhang,
• Tao Zhou,
• Taehui Yang,
• Keisuke Fukaya,
• Enjuro Harunari,
• Shun Saito,
• Katsuhisa Yamada,
• Chiaki Imada,
• Daisuke Urabe and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2021, 17, 2194–2202, doi:10.3762/bjoc.17.141

• cytotoxicity against P388 murine leukemia cells with IC50 values of 33 and 89 μM, respectively. Keywords: Actinomadura; nomimicin; polyketide; spirotetronate; Introduction Actinomycetes are a valuable source of bioactive compounds, accounting for approximately two thirds of all known antibiotics, and more

• plants, and marine invertebrates [6][7][8]. In the past 20 years, our laboratory studied the actinomycetes collected from the deep sea water (DSW) of the Sea of Japan and discovered diverse classes of bioactive compounds, such as lydicamycin congeners, γ-butyrolactones, and nyuzenamides [9][10][11

• 2 exhibited cytotoxicity against P388 murine leukemia cells with IC50 of 33 and 89 μM, respectively. Conclusion In summary, UV-based chemical screening of bioactive compounds from marine-derived actinomycetes led to the discovery of three new polyketides, nomimicins B (1), C (2), and D (3) along

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

• equally effective catalysts. First-row transition (3d) metals have shown to be important catalysts in this matter. This review summarizes the use of 3d metal catalysts in C–H activation processes to obtain potentially (or proved) biologically active compounds. Keywords: bioactive compounds; C–H

• bioactive molecules. They are also known to present valuable biological activities, such as anti-HBV (1) [44], anti-HIV (2) [45], antitumor (3) [46] and even antiplasmodial activities (4) [47] (Scheme 2A). Although these studied bioactive compounds do not directly represent the structural moieties obtained

• evidence for radical pathways involving vanadium-peroxo species [76], with a few exceptions [95]. Vanadium-based catalysts have been employed in carbon–carbon bond formation reactions, such as arene couplings, thereby proving especially useful in the synthesis of bioactive compounds, including natural

Natural products in the predatory defence of the filamentous fungal pathogen Aspergillus fumigatus

• Jana M. Boysen,
• Nauman Saeed and
• Falk Hillmann

Beilstein J. Org. Chem. 2021, 17, 1814–1827, doi:10.3762/bjoc.17.124

• , physiological adaptations and chemical defence mechanisms to optimize their living conditions and resist competitors, parasites and predators [3][4][5]. These bioactive compounds are often considered as secondary metabolites (SM) which are involved in communication, symbiotic interactions, pathogenicity or

• number of known metabolites and the interest of scientists to gain access to them remains high [7][8][9]. Genes associated with these bioactive compounds are often organized in biosynthetic gene clusters (BGCs) which are physically linked, commonly regulated and often belong to a few distinct classes of

• ecological trigger for the production and identification of new bioactive compounds in the future. Schematic overview of fungal interactions in the environment. Fungi can be found in essentially all terrestrial habitats comprising saprophytic, parasitic, symbiotic or predatory lifestyles [6]. Independent of

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

• synthesis of new bioactive compounds [1][2]. A careful view of the carbon backbone of these natural molecules reveals their high molecular complexity [3][4][5], which can be described by the presence of multiple stereogenic centers in the same molecule, a substantial fraction of sp3 hybridized carbons (Fsp3

Synthesis of trifluoromethyl ketones by nucleophilic trifluoromethylation of esters under a fluoroform/KHMDS/triglyme system

• Yamato Fujihira,
• Yumeng Liang,
• Makoto Ono,
• Kazuki Hirano,
• Takumi Kagawa and
• Norio Shibata

Beilstein J. Org. Chem. 2021, 17, 431–438, doi:10.3762/bjoc.17.39

• examined [46]. Trifluoromethyl ketones (TFMKs) are valuable fluorine-containing synthetic targets of bioactive compounds [55][56] that behave as mimics of the tetrahedral transition-state intermediate of enzymatic hydrolysis of esters and amides by stabilizing their hydrates (Figure 1a) [57]. In fact, the

Regioselective chemoenzymatic syntheses of ferulate conjugates as chromogenic substrates for feruloyl esterases

• Olga Gherbovet,
• Fernando Ferreira,
• Apolline Clément,
• Mélanie Ragon,
• Julien Durand,
• Sophie Bozonnet,
• Michael J. O'Donohue and
• Régis Fauré

Beilstein J. Org. Chem. 2021, 17, 325–333, doi:10.3762/bjoc.17.30

• preparation of bioactive compounds with potential antioxidant properties [2][3][4][5]. Operating via a two-step serine protease mechanism involving a conserved Ser-His-Asp/Glu catalytic triad [6][7], Faes catalyze the hydrolysis of ester bonds linking hydroxycinnamoyl groups to the glycosyl moieties of plant

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

Synthesis of aryl 2-bromo-2-chloro-1,1-difluoroethyl ethers through the base-mediated reaction between phenols and halothane

• Yukiko Karuo,
• Ayaka Kametani,
• Atsushi Tarui,
• Kazuyuki Sato,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2021, 17, 89–96, doi:10.3762/bjoc.17.9

• as monofluorinated and trifluoromethylated arenes or aliphatics [1][2][3][4]. Recent progress in difluoromethylene chemistry successfully led to the finding of bioactive compounds such as pantoprazole, a proton pump inhibitor [5], and AFP-07, a prostaglandin I2 receptor-selective agonist [6][7][8

An atom-economical addition of methyl azaarenes with aromatic aldehydes via benzylic C(sp³)–H bond functionalization under solvent- and catalyst-free conditions

• Divya Rohini Yennamaneni,
• Vasu Amrutham,
• Krishna Sai Gajula,
• Rammurthy Banothu,
• Murali Boosa and
• Narender Nama

Beilstein J. Org. Chem. 2020, 16, 3093–3103, doi:10.3762/bjoc.16.259

• ][4]. Among various nitrogen-containing heterocyclic compounds, pyridine and quinolines are readily found in bioactive compounds [5]. The functionalization of alkylpyridines and quinolines is significant and plays a remarkable role in the efficient drug design [6][7][8]. Due to their conformational

Bifurcated synthesis of methylene-lactone- and methylene-lactam-fused spirolactams via electrophilic amide allylation of γ-phenylthio-functionalized γ-lactams

• Tetsuya Sengoku,
• Koki Makino,
• Ayumi Iijima,
• Toshiyasu Inuzuka and
• Hidemi Yoda

Beilstein J. Org. Chem. 2020, 16, 2769–2775, doi:10.3762/bjoc.16.227

• carried out with 1 (1.2 equiv), 2 (1.0 equiv), and NaH (2.5 equiv) in THF (0.2 M for 2) at −10 °C for 1 h. aReactions were performed at −20 °C. Cytotoxicity of spirolactams on P388 cells (IC50 values). Examples of (a) bioactive compounds bearing an α-methylene-γ-butyrolactone structure, (b) syntheses of

Synthesis of purines and adenines containing the hexafluoroisopropyl group

• Viacheslav Petrov,
• Rebecca J. Dooley,
• Alexander A. Marchione,
• Elizabeth L. Diaz,
• Brittany S. Clem and
• William Marshall

Beilstein J. Org. Chem. 2020, 16, 2739–2748, doi:10.3762/bjoc.16.224

• ]. Benzimidazoles are an important class of organic materials, and many derivatives of these group are biologically active [6][7][8][9]. The benzimidazole moiety “ […] is isosteric with indole and purine nuclei, which are present in a number of fundamental cellular components and bioactive compounds. Indeed, a

Nocarimidazoles C and D, antimicrobial alkanoylimidazoles from a coral-derived actinomycete Kocuria sp.: application of ¹J_C,H coupling constants for the unequivocal determination of substituted imidazoles and stereochemical diversity of anteisoalkyl chains in microbial metabolites

• Md. Rokon Ul Karim,
• Enjuro Harunari,
• Amit Raj Sharma,
• Naoya Oku,
• Kazuaki Akasaka,
• Daisuke Urabe,
• Mada Triandala Sibero and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 2719–2727, doi:10.3762/bjoc.16.222

• of new bioactive compounds from actinomycetes, especially those from terrestrial sources, is likely reaching a plateau after intensive screening activities over several decades [3]. Actinomycetes also inhabit marine environments, including seashores, coastal waters, and bottom sediments or can be

Lipophilicity trends upon fluorination of isopropyl, cyclopropyl and 3-oxetanyl groups

• Benjamin Jeffries,
• Zhong Wang,
• Robert I. Troup,
• Anaïs Goupille,
• Jean-Yves Le Questel,
• Charlene Fallan,
• James S. Scott,
• Elisabetta Chiarparin,
• Jérôme Graton and
• Bruno Linclau

Beilstein J. Org. Chem. 2020, 16, 2141–2150, doi:10.3762/bjoc.16.182

• isopropyl substituent led to larger lipophilicity modulation compared to fluorination of the cyclopropyl substituent. Keywords: aliphatic fluorination; cyclopropane; isopropyl; isostere; lipophilicity; oxetane; Introduction The introduction of small alkyl groups onto bioactive compounds as space filling

• ][20][21][22]. However, there is comparatively less precedence of lipophilicity comparisons between fluorinated isopropyl groups, cyclopropanes and oxetanes. Examples of bioactive compounds are given in Figure 2. During the optimization of the LpxC inhibitor 7a [23], it was shown that fluorination to

Reactions of 3-aryl-1-(trifluoromethyl)prop-2-yn-1-iminium salts with 1,3-dienes and styrenes

• Thomas Schneider,
• Michael Keim,
• Bianca Seitz and
• Gerhard Maas

Beilstein J. Org. Chem. 2020, 16, 2064–2072, doi:10.3762/bjoc.16.173

• variety of nucleophiles to afford products containing a C(CF3)NR2 moiety. In particular C(CF3)NHR and C(CF3)NH2 groups are of interest as pharmacophores in the design of bioactive compounds [10][11][12][13]. Simple α-(trifluoromethyl)iminium salts (RCH(CF3)=N+Me2 X−, R= H, CF3) with weakly nucleophilic or

One-pot synthesis of 1,3,5-triazine-2,4-dithione derivatives via three-component reactions

• Gui-Feng Kang and
• Gang Zhang

Beilstein J. Org. Chem. 2020, 16, 1447–1455, doi:10.3762/bjoc.16.120

• . Selected examples of triazinethione-containing bioactive compounds. X-ray structure of 6-(methylthio)-4-phenyl-3,4-dihydro-1,3,5-triazine-2(1H)-thione (6aa) with thermal ellipsoids at 50% probability (CCDC 1991859). Strategies for the synthesis of triazinethiones. Aldehyde substrate scope of three

An overview on disulfide-catalyzed and -cocatalyzed photoreactions

• Yeersen Patehebieke

Beilstein J. Org. Chem. 2020, 16, 1418–1435, doi:10.3762/bjoc.16.118

• . In 1996, Burton and co-workers reported the stereoselective synthesis of cis-1,2-difluorotriethylsilyethylene and its conversion to a variety of cis-1,2-difluoroethylene synthons, which are important building blocks in the preparation of fluorine-containing pharmaceuticals, polymers, and bioactive

• compounds. In the synthesis of these synthons, the key transformation, the isomerization of the trans-1,2-difluorotriethylsilylethylene 57 to the cis isomer 58, is realized with phenyl disulfide under ultraviolet-light irradiation (Scheme 22) [29]. In 2009, Tsuboi and co-workers also reported a dendrimer

Highly selective Diels–Alder and Heck arylation reactions in a divergent synthesis of isoindolo- and pyrrolo-fused polycyclic indoles from 2-formylpyrrole

• Carlos H. Escalante,
• Eder I. Martínez-Mora,
• Carlos Espinoza-Hicks,
• Alejandro A. Camacho-Dávila,
• Fernando R. Ramos-Morales,
• Francisco Delgado and
• Joaquín Tamariz

Beilstein J. Org. Chem. 2020, 16, 1320–1334, doi:10.3762/bjoc.16.113

• -based heterocycles represent a varied and ubiquitous scaffold found in a large number of natural and synthetic bioactive compounds [22][23][24][25], such as isoindolocarbazoles (e.g., arcyriaflavins A–C (4a–c)) [26][27]. The challenge of the synthesis of this series of aza-heterocycles is associated

Synthesis, antiinflammatory activity, and molecular docking studies of bisphosphonic esters as potential MMP-8 and MMP-9 inhibitors

• Abimelek Cortes-Pacheco,
• María Adelina Jiménez-Arellanes,
• Francisco José Palacios-Can,
• José Antonio Valcarcel-Gamiño,
• Rodrigo Said Razo-Hernández,
• María del Carmen Juárez-Vázquez,
• Adolfo López-Torres and
• Oscar Abelardo Ramírez-Marroquín

Beilstein J. Org. Chem. 2020, 16, 1277–1287, doi:10.3762/bjoc.16.108

• a higher Pa value is desired. Thus, a Pa value of new bisphosphonates ≥ the Pa value of 1 and 2 was the applied inclusion criterion in this study. As can be seen in Figure 2, the Pa is greater for the new derivatives 3–6 (0.63–0.77) compared to the previous bioactive compounds 1 and 2 (0.51). In