Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules

• Valerian Dragutan,
• Ileana Dragutan,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2020, 16, 738–755, doi:10.3762/bjoc.16.68

• account surveys the current progress on the application of intra- and intermolecular enyne metathesis as main key steps in the synthesis of challenging structural motifs and stereochemistries found in bioactive compounds. Special emphasis is placed on ruthenium catalysts as promoters of enyne metathesis

• of known, in vivo effective substances but also for designing chemically modified analogs as valid alternatives for further therapeutic agents. Keywords: bioactive compounds; enyne metathesis; ring-closing metathesis; ruthenium catalysts; tandem reactions; Introduction Alkene and alkyne metathesis

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

• , especially those featuring medicinally promising scaffolds. Pyrrolo[1,2-a]indol-3-ones are prevalent scaffolds that widely exist in many bioactive compounds and natural products [17][18][19][20]. Representative examples of biologically active pyrrolo[1,2-a]indol-3-one derivatives are shown in Figure 1

Two antibacterial and PPARα/γ-agonistic unsaturated keto fatty acids from a coral-associated actinomycete of the genus Micrococcus

• Amit Raj Sharma,
• Enjuro Harunari,
• Naoya Oku,
• Nobuyasu Matsuura,
• Agus Trianto and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 297–304, doi:10.3762/bjoc.16.29

• association with higher organisms, such as fish, sponges, corals, molluscs, ascidians, seaweeds, and mangroves, and have kept attracting attention due to their ability to produce various bioactive compounds [2][4]. Among the isolation sources for marine actinobacteria, substantial amounts of studies were

Potent hemithioindigo-based antimitotics photocontrol the microtubule cytoskeleton in cellulo

• Alexander Sailer,
• Franziska Ermer,
• Yvonne Kraus,
• Rebekkah Bingham,
• Ferdinand H. Lutter,
• Julia Ahlfeld and
• Oliver Thorn-Seshold

Beilstein J. Org. Chem. 2020, 16, 125–134, doi:10.3762/bjoc.16.14

• here describe the photocharacterisation of HITub-4 as a representative example of the photoswitchable bioactive compounds (for more detailed analysis see Supporting Information File 1). In polar aprotic solvents, the HITub-4 Z-isomer (λmax ≈ 380, 460 nm) showed robust, reliable, and fully reversible

Reversible photoswitching of the DNA-binding properties of styrylquinolizinium derivatives through photochromic [2 + 2] cycloaddition and cycloreversion

• Sarah Kölsch,
• Heiko Ihmels,
• Jochen Mattay,
• Norbert Sewald and
• Brian O. Patrick

Beilstein J. Org. Chem. 2020, 16, 111–124, doi:10.3762/bjoc.16.13

• complementary approach toward the development of photoswitchable bioactive compounds. Absorption spectra and normalized emission spectrum (Abs. = 0.10, 3b: λex = 394 nm) of derivatives 3b (red) and 3d (black) in MeCN. Spectrophotometric titration upon the addition of ct DNA to the styrylquinolizinium

Pigmentosins from Gibellula sp. as antibiofilm agents and a new glycosylated asperfuran from Cordyceps javanica

• Soleiman E. Helaly,
• Wilawan Kuephadungphan,
• Patima Phainuphong,
• Mahmoud A. A. Ibrahim,
• Kanoksri Tasanathai,
• Suchada Mongkolsamrit,
• Janet Jennifer Luangsa-ard,
• Souwalak Phongpaichit,
• Vatcharin Rukachaisirikul and
• Marc Stadler

Beilstein J. Org. Chem. 2019, 15, 2968–2981, doi:10.3762/bjoc.15.293

• be a promising source of bioactive compounds [8][9][10]. Thus, during the current study, which is part of a project aiming to discover novel biofilm inhibitors from Thai fungi [11], a number of invertebrate-pathogenic fungi collected from various parts of Thailand were studied for production of

Two new aromatic polyketides from a sponge-derived Fusarium

• Mada Triandala Sibero,
• Tao Zhou,
• Keisuke Fukaya,
• Daisuke Urabe,
• Ocky K. Karna Radjasa,
• Agus Sabdono,
• Agus Trianto and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2019, 15, 2941–2947, doi:10.3762/bjoc.15.289

• polyketide; Fusarium; marine fungus; secondary metabolite; sponge; Introduction Marine organisms have been known as a potential source of prospective bioactive compounds, and sponges are particularly emphasized as the most promising source among all marine invertebrates [1][2]. However, the collection of

• structurally unique secondary metabolites with various biological activities [8][9]. Specifically, sponge-associated fungi are attracting substantial attention because of their high capability of producing a wide range of bioactive compounds [5][10][11]. As a tropical country, Indonesia is known as the second

A review of asymmetric synthetic organic electrochemistry and electrocatalysis: concepts, applications, recent developments and future directions

• Munmun Ghosh,
• Valmik S. Shinde and
• Magnus Rueping

Beilstein J. Org. Chem. 2019, 15, 2710–2746, doi:10.3762/bjoc.15.264

• chemistry. In this review, we aim to focus on methods for achieving stereocontrol in synthetic organic electrochemistry via a systematic description of the reported literature on chiral inductors, followed by their applications in the synthesis of natural products and bioactive compounds including late

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

• latter one. One of the main reasons is that an azobenzene has a relatively simple structure that can resemble various biaryl moieties of bioactive compounds: two aromatic rings linked with a bridge (e.g., amide, ether, alkane or alkyne) [8]. In the case of azobenzene the bridge is a diazene group (also

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

• . Keywords: C–H activation; cyclization; isoquinolone; multicomponent reaction; tetrazole; Introduction Pyridones and isoquinolones are relevant heterocyclic scaffolds present in numerous bioactive compounds and natural products [1][2][3][4]. Similarly, molecules containing a tetrazole ring exhibit a wide

• , 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

Current understanding and biotechnological application of the bacterial diterpene synthase CotB2

• Ronja Driller,
• Daniel Garbe,
• Norbert Mehlmer,
• Monika Fuchs,
• Keren Raz,
• Dan Thomas Major,
• Thomas Brück and
• Bernhard Loll

Beilstein J. Org. Chem. 2019, 15, 2355–2368, doi:10.3762/bjoc.15.228

• ], density functional theory calculations [33] as well as QM/MM simulations [37]. Variants of CotB2 open the route to a novel product portfolio with altered cyclic carbon skeletons, which can be converted into bioactive compounds by chemo-enzymatic methodologies. Modification descriptions are composed

Isolation and biosynthesis of an unsaturated fatty acid with unusual methylation pattern from a coral-associated bacterium Microbulbifer sp.

• Amit Raj Sharma,
• Enjuro Harunari,
• Tao Zhou,
• Agus Trianto and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2019, 15, 2327–2332, doi:10.3762/bjoc.15.225

• . Compound 1 showed weak growth inhibition against Saccharomyces cerevisiae. Keywords: biosynthesis; fatty acid; marine bacteria; methylation; Microbulbifer; Introduction Marine microbial symbionts are currently recognized as a reservoir of new bioactive compounds [1]. The most well-studied host animal is

Isolation of fungi using the diffusion chamber device FIND technology

• Benjamin Libor,
• Henrik Harms,
• Stefan Kehraus,
• Ekaterina Egereva,
• Max Crüsemann and
• Gabriele M. König

Beilstein J. Org. Chem. 2019, 15, 2191–2203, doi:10.3762/bjoc.15.216

• environment. Halotolerance was to date exclusively reported for members of the Cladosporium sphaerospermum complex [28]. Analysis of genes involved in secondary metabolite production suggested Cadophora malorum as a producer of bioactive compounds [29], as later confirmed by the results of Almeida et al. [30

Azologization and repurposing of a hetero-stilbene-based kinase inhibitor: towards the design of photoswitchable sirtuin inhibitors

• Christoph W. Grathwol,
• Nathalie Wössner,
• Sören Swyter,
• Adam C. Smith,
• Enrico Tapavicza,
• Robert K. Hofstetter,
• Anja Bodtke,
• Manfred Jung and
• Andreas Link

Beilstein J. Org. Chem. 2019, 15, 2170–2183, doi:10.3762/bjoc.15.214

• . Typically, it is not clear from the beginning, if the remodelling of the bioactive compounds will lead to an active diazeno derivative or not. The so-called azologization approach, moulded by Trauner et al., features a rational strategy for the design of photoswitchable compounds from established drug

Molecular basis for the plasticity of aromatic prenyltransferases in hapalindole biosynthesis

• Takayoshi Awakawa and
• Ikuro Abe

Beilstein J. Org. Chem. 2019, 15, 1545–1551, doi:10.3762/bjoc.15.157

• bioactive compounds, because the prenylated compounds exhibit better bioactivities due to their improved interactions with biological membranes [3]. The aromatic PTase superfamily involved in the secondary metabolism consists of the ABBA (α-β-β-α barrel)-type [4][5], the dimethylallyltryptophan synthase

• bioactive compounds. The reactions of aromatic PTases. The reactions catalyzed by AmbP1 (A) and AmbP3 (B). The overall structure of apo-AmbP1 (A), the Mg2+-free structure (B), and the Mg2+-bound structure (C). The active site structure of AmbP1. 1 and GSPP were bound in the active site without Mg2+ (A, Mg2

Synthesis of pyrrolo[1,2-a]quinolines by formal 1,3-dipolar cycloaddition reactions of quinolinium salts

• Anthony Choi,
• Rebecca M. Morley and
• Iain Coldham

Beilstein J. Org. Chem. 2019, 15, 1480–1484, doi:10.3762/bjoc.15.149

• rise to pyrrolidine rings, prevalent in a large number of natural products and bioactive compounds. Many methods have been used to prepare azomethine ylides that undergo cycloaddition with π-systems, especially electron-poor alkenes to give pyrrolidine products [1][2][3][4]. Azomethine ylides can be

Genomics-inspired discovery of massiliachelin, an agrochelin epimer from Massilia sp. NR 4-1

• Jan Diettrich,
• Hirokazu Kage and
• Markus Nett

Beilstein J. Org. Chem. 2019, 15, 1298–1303, doi:10.3762/bjoc.15.128

• recognition of a far greater taxonomic diversity of microbes that can produce bioactive compounds [1][2][3]. The exploration of previously neglected taxa has been demonstrated to bear significant potential for finding new natural products and is thus highly promising from a drug discovery perspective [4][5

Synthesis of non-racemic 4-nitro-2-sulfonylbutan-1-ones via Ni(II)-catalyzed asymmetric Michael reaction of β-ketosulfones

• Alexander N. Reznikov,
• Anastasiya E. Sibiryakova,
• Marat R. Baimuratov,
• Eugene V. Golovin,
• Victor B. Rybakov and
• Yuri N. Klimochkin

Beilstein J. Org. Chem. 2019, 15, 1289–1297, doi:10.3762/bjoc.15.127

• University, Leninskie Gory, 1, 119991, Mosсow, Russian Federation 10.3762/bjoc.15.127 Abstract Functionally substituted sulfones with stereogenic centers are valuable reagents in organic synthesis and key motifs in some bioactive compounds. The asymmetric Michael addition of β-ketosulfones to conjugated

Doebner-type pyrazolopyridine carboxylic acids in an Ugi four-component reaction

• Maryna V. Murlykina,
• Oleksandr V. Kolomiets,
• Maryna M. Kornet,
• Yana I. Sakhno,
• Sergey M. Desenko,
• Victoriya V. Dyakonenko,
• Svetlana V. Shishkina,
• Oleksandr A. Brazhko,
• Vladimir I. Musatov,
• Alexander V. Tsygankov,
• Erik V. Van der Eycken and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2019, 15, 1281–1288, doi:10.3762/bjoc.15.126

• synergetic application of several diversity-oriented synthesis (DOS) instruments allows an effective decoration of the privileged scaffolds for creating collections of unique, highly potent bioactive compounds [4][5]. The pyrazolopyridine scaffold can be regarded as a privileged motif as it exhibits various

Robust perfluorophenylboronic acid-catalyzed stereoselective synthesis of 2,3-unsaturated O-, C-, N- and S-linked glycosides

• Madhu Babu Tatina,
• Xia Mengxin,
• Rao Peilin and
• Zaher M. A. Judeh

Beilstein J. Org. Chem. 2019, 15, 1275–1280, doi:10.3762/bjoc.15.125

• molecular recognition, cell–cell interaction, immunological recognition and transmission of biological information [4][5][6]. They are easily transformed into important bioactive compounds such as oligosaccharides, glycopeptides, nucleosides, antibiotics, uronic acids and other natural products [1][2][3

Efficient synthesis of pyrazolopyridines containing a chromane backbone through domino reaction

• Razieh Navari,
• Saeed Balalaie,
• Saber Mehrparvar,
• Fatemeh Darvish,
• Frank Rominger,
• Fatima Hamdan and
• Sattar Mirzaie

Beilstein J. Org. Chem. 2019, 15, 874–880, doi:10.3762/bjoc.15.85

• tracazolate, cartazolate, and etazolate [22]. Other pyrazolopyridine-containing bioactive compounds include a GSK-3 inhibitor [23] and BAY 41-2272, [24][25] and could be used as cardiovascular therapeutic agents (Figure 1). Moreover, pyrazolopyridine derivatives also have industrial importance as fluorophores

Catalyst-free assembly of giant tris(heteroaryl)methanes: synthesis of novel pharmacophoric triads and model sterically crowded tris(heteroaryl/aryl)methyl cation salts

• Rodrigo Abonia,
• Luisa F. Gutiérrez,
• Braulio Insuasty,
• Jairo Quiroga,
• Kenneth K. Laali,
• Chunqing Zhao,
• Gabriela L. Borosky,
• Samantha M. Horwitz and
• Scott D. Bunge

Beilstein J. Org. Chem. 2019, 15, 642–654, doi:10.3762/bjoc.15.60

• ]. Furthermore, it is highly desirable to perform these reactions in environmentally friendly solvents such as water, ethanol, and PEG [6][7]. Motifs bearing triarylmethane (Ar3CH) [8][9][10] and their heterocyclic variants (Het-Ar)3CH [8][9][10][11][12], constitute an integral part of a number of bioactive

• compounds [13][14][15][16]. Due to their valuable properties, they are also well exploited by the chemical industry as dyes and photochromic agents [17][18], protective groups in organic synthesis [19] and as building blocks for dendrimers [20] and nonlinear optical (NLO) properties [21] (Scheme 1

Synthesis and selected transformations of 2-unsubstituted 1-(adamantyloxy)imidazole 3-oxides: straightforward access to non-symmetric 1,3-dialkoxyimidazolium salts

• Grzegorz Mlostoń,
• Małgorzata Celeda,
• Katarzyna Urbaniak,
• Marcin Jasiński,
• Vladyslav Bakhonsky,
• Peter R. Schreiner and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2019, 15, 497–505, doi:10.3762/bjoc.15.43

• , alkoxyamines are known not only as bioactive compounds [19][20] but also as important initiators of polymerization processes that have been extensively studied in the recent decade [21]. Among alkoxyamines, adamantyloxyamine (4) occupies a prominent position, and for that reason it was selected for experiments

• alkaloids, which found wide application in some regions as food-stuff and medical supply [33]. The method described in the present study opens a straightforward access to their benzyloxy analogues, potentially bioactive compounds, which have not been known yet. Experimental General information: Solvents and

Thiol-free chemoenzymatic synthesis of β-ketosulfides

• Adrián A. Heredia,
• Martín G. López-Vidal,
• Marcela Kurina-Sanz,
• Fabricio R. Bisogno and
• Alicia B. Peñéñory

Beilstein J. Org. Chem. 2019, 15, 378–387, doi:10.3762/bjoc.15.34

• role as precursors in the synthesis of bioactive compounds [13][26][27], substrates for multicomponent reactions [28], and lately, have successfully been applied in polymer photodecoration [29][30]. They can easily be reduced into chiral hydroxy derivatives [31] and properly oxidised at sulfur to

Sigmatropic rearrangements of cyclopropenylcarbinol derivatives. Access to diversely substituted alkylidenecyclopropanes

• Guillaume Ernouf,
• Jean-Louis Brayer,
• Christophe Meyer and
• Janine Cossy

Beilstein J. Org. Chem. 2019, 15, 333–350, doi:10.3762/bjoc.15.29

• alkylidenecyclopropanes are also synthetically useful [1][2][3][4][5][6]. The importance of this latter class of transformations is obviously related to the widespread occurrence of cyclopropanes in natural and/or bioactive compounds [7][8] and the great interest of the cyclopropyl core in new drugs development [9