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

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

• double bonds. Numerous natural compounds containing pyrans and benzopyrans (fused pyrans) are identified. Epicalyxin (45) is used as an anticancer agent against human HT-1080 fibrosarcoma and murine 26-L5 carcinoma. Laninamivir (46) is a pyran-based drug used as a neuraminidase inhibitor and zanamivir

Synthesis of dibenzosuberenone-based novel polycyclic π-conjugated dihydropyridazines, pyridazines and pyrroles

• Ramazan Koçak and
• Arif Daştan

Beilstein J. Org. Chem. 2021, 17, 719–729, doi:10.3762/bjoc.17.61

• ], and self-assembled supramolecular architectures [48]. On the other hand, many natural compounds that contain a pyrrole core, such as bilirubin, hemoglobin, chlorophyll a, and vitamin B12, are very important for life. In addition to being common in natural products and biological systems, the active

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

• into natural compounds has been widely accepted as a powerful tool for discovering new drugs and agrochemicals. The number of medicinal preparations containing at least one fluorine atom in the structure is now very high [3][4][5]. In this review we give an overview of the chemistry of 1,1

Pentannulation of N-heterocycles by a tandem gold-catalyzed [3,3]-rearrangement/Nazarov reaction of propargyl ester derivatives: a computational study on the crucial role of the nitrogen atom

• Giovanna Zanella,
• Martina Petrović,
• Dina Scarpi,
• Ernesto G. Occhiato and
• Enrique Gómez-Bengoa

Beilstein J. Org. Chem. 2020, 16, 3059–3068, doi:10.3762/bjoc.16.255

• of a triple bond, which has ultimately led to the total synthesis of several natural compounds [2][8]. The gold-catalyzed rearrangement of suitably substituted propargylic esters in particular provides a platform for cascade processes that involve a cationic or an allene intermediate generated in the

One-step route to tricyclic fused 1,2,3,4-tetrahydroisoquinoline systems via the Castagnoli–Cushman protocol

• Aleksandar Pashev,
• Nikola Burdzhiev and
• Elena Stanoeva

Beilstein J. Org. Chem. 2020, 16, 1456–1464, doi:10.3762/bjoc.16.121

• ]isoquinoline skeleton is incorporated in a large group of natural compounds such as crispines, trolline, and lamellarins, which are interesting due to their anticancer, antiviral, and antibacterial activities [7][8]. In the light of this broad array of biological activities, the development of novel methods

A simple and easy to perform synthetic route to functionalized thienyl bicyclo[3.2.1]octadienes

• Dragana Vuk,
• Irena Škorić,
• Valentina Milašinović,
• Krešimir Molčanov and
• Željko Marinić

Beilstein J. Org. Chem. 2020, 16, 1092–1099, doi:10.3762/bjoc.16.96

• numerous biologically active natural compounds (Figure 1) [4][5][6][7], their strenuous isolation procedures from plants, as well as their complicated multistage synthesis due to the complexity of their structure, encouraged us to develop a simple one-step synthetic procedure based on a photochemical

Copper-based fluorinated reagents for the synthesis of CF₂R-containing molecules (R ≠ F)

• Louise Ruyet and
• Tatiana Besset

Beilstein J. Org. Chem. 2020, 16, 1051–1065, doi:10.3762/bjoc.16.92

• turned out to be functional group tolerant. The same group extended their protocol to the functionalization of aryldiazonium salts [79]. Very recently, a similar protocol was applied to the pentafluoroethylation of (hetero)aryl halides as well as alkenyl iodides derived from natural compounds (e.g

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

• ) as the final product. Kempene diterpenes The first enantioselective synthesis of kempene diterpenes 14a–c, natural compounds exhibiting a significant antibiotic activity against B. subtilis, relying on the domino enyne metathesis of the adequate dienyne precursors as a key step, was disclosed by Metz

Copper-catalyzed enantioselective conjugate addition of organometallic reagents to challenging Michael acceptors

• Delphine Pichon,
• Jennifer Morvan,
• Christophe Crévisy and
• Marc Mauduit

Beilstein J. Org. Chem. 2020, 16, 212–232, doi:10.3762/bjoc.16.24

• neglected to varying degrees, probably owing to their particular reactivity, which led to less impressive results. Nevertheless, these substrates present a high potential in total synthesis, since the chiral products can be easily transformed into various natural compounds. For example, the aldehyde

• function, which is directly obtained from α,β-unsaturated aldehydes or is accessible through postderivatization of either acylimidazole or thioester functions, is present in many natural compounds and is also a key functional group for many synthetic strategies. Furthermore, some of the functional groups

Skeletocutins M–Q: biologically active compounds from the fruiting bodies of the basidiomycete Skeletocutis sp. collected in Africa

• Tian Cheng,
• Clara Chepkirui,
• Cony Decock,
• Josphat C. Matasyoh and
• Marc Stadler

Beilstein J. Org. Chem. 2019, 15, 2782–2789, doi:10.3762/bjoc.15.270

• source of unprecedented natural compounds showing a set of prominent biological activities [1][2][3]. The present study deals with the comparison of the secondary metabolites located in the basidiomes (fruiting bodies) of another, putatively new species belonging to the genus Skeletocutis, strain

Reactions of 2-carbonyl- and 2-hydroxy(or methoxy)alkyl-substituted benzimidazoles with arenes in the superacid CF₃SO₃H. NMR and DFT studies of dicationic electrophilic species

• Dmitry S. Ryabukhin,
• Alexey N. Turdakov,
• Natalia S. Soldatova,
• Mikhail O. Kompanets,
• Alexander Yu. Ivanov,
• Irina A. Boyarskaya and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2019, 15, 1962–1973, doi:10.3762/bjoc.15.191

• common motif present in some components of human organisms, histidine, vitamin B12, purines, histamine, biotin, and in natural compounds such as lepidiline A and B [6]. Over the years of active research, benzimidazole derivatives have been involved in medicinal chemistry covering a wide range of

Analysis of sesquiterpene hydrocarbons in grape berry exocarp (Vitis vinifera L.) using in vivo-labeling and comprehensive two-dimensional gas chromatography–mass spectrometry (GC×GC–MS)

• Philipp P. Könen and
• Matthias Wüst

Beilstein J. Org. Chem. 2019, 15, 1945–1961, doi:10.3762/bjoc.15.190

• aroma profile of grapes (Vitis vinifera L.) at the time of physiological ripening. To investigate these natural compounds, freshly harvested, ripe berries of the red wine variety Lemberger (Vitis vinifera subsp. vinifera L.) were analyzed using comprehensive two-dimensional gas chromatography (GC×GC

• ) coupled to a time-of-flight mass spectrometer (TOF–MS) after headspace-solid phase microextraction (HS-SPME). The identification of structurally complex natural compounds, such as sesquiterpenes from fruits and vegetables, is often reported as “tentative”, as authentic standards are not commercially

• , 25 sesquiterpene hydrocarbons were found in the exocarp of ripe grapes (Vitis vinifera L.) of the red wine variety Lemberger. The unequivocal identification of these structurally complex natural compounds was performed by combining multidimensional gas chromatography with in vivo labeling using the

Archangelolide: A sesquiterpene lactone with immunobiological potential from Laserpitium archangelica

• Silvie Rimpelová,
• Michal Jurášek,
• Lucie Peterková,
• Jiří Bejček,
• Vojtěch Spiwok,
• Miloš Majdl,
• Michal Jirásko,
• Miloš Buděšínský,
• Juraj Harmatha,
• Eva Kmoníčková,
• Pavel Drašar and
• Tomáš Ruml

Beilstein J. Org. Chem. 2019, 15, 1933–1944, doi:10.3762/bjoc.15.189

• , Czech Republic Department of Chemistry of Natural Compounds, University of Chemistry and Technology Prague, Technická 5, 166 28, Prague 6, Czech Republic Charles University in Prague, Faculty of Medicine in Pilsen, 301 66 Pilsen, Czech Republic Institute of Organic Chemistry and Biochemistry, Academy of

• cells, we synthesized a blue-emitting derivative employing a dansyl label. This fluorophore is convenient not only for its small size but also for its membrane permeability. Moreover, it was successfully used in other studies of visualizing other natural compounds [15][16][17]. The synthesis (Scheme 1

• . Immunobiological properties of compound 1 SLs, natural compounds predominantly isolated from the species Asteraceae and Apiaceae represent a rich source of small molecules with potential pharmacological effects. Indeed, some of them have reached clinical applications as antimalarial (artemisinin; [24]) or

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

• racemization, alternative three-carbon chirons would be of great value in enantioselective syntheses of natural compounds and/or drugs. This review article summarizes applications of N-(1-phenylethyl)aziridine-2-carboxylates, -carbaldehydes and -methanols in syntheses of approved drugs and potential

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

• frequently used in the synthesis of organic fine chemicals and natural compounds. In addition to using the sulfonyl group as an auxiliary, it is also included in some chiral bioactive molecules, such as remikiren (1, renin inhibitor for the treatment of hypertension) [5][6], eletriptan (2, Relpax®, serotonin

Phylogenomic analyses and distribution of terpene synthases among Streptomyces

• Lara Martín-Sánchez,
• Kumar Saurabh Singh,
• Mariana Avalos,
• Gilles P. van Wezel,
• Jeroen S. Dickschat and
• Paolina Garbeva

Beilstein J. Org. Chem. 2019, 15, 1181–1193, doi:10.3762/bjoc.15.115

• ]. Terpenoids are the largest and the most diverse class of natural compounds known to date and include the initial products of terpene synthases and all derivatives made from them in tailoring steps. This very diverse class of organic compounds is best known as plant metabolites. However, recent studies

Annulation of 1H-pyrrole-2,3-diones by thioacetamide: an approach to 5-azaisatins

• Aleksandr I. Kobelev,
• Ekaterina E. Stepanova,
• Maksim V. Dmitriev and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2019, 15, 364–370, doi:10.3762/bjoc.15.32

• heterocycles; thioamides; Introduction Omnipresent among natural compounds and drugs, the indole core is a privileged scaffold for library design and drug discovery [1]. Its dioxo derivative, isatin (1H-indole-2,3-dione), is an important building block for the construction of diverse indole-based compounds

N-Acylated amino acid methyl esters from marine Roseobacter group bacteria

• Hilke Bruns,
• Lisa Ziesche,
• Nargis Khakin Taniwal,
• Laura Wolter,
• Thorsten Brinkhoff,
• Jennifer Herrmann,
• Rolf Müller and
• Stefan Schulz

Beilstein J. Org. Chem. 2018, 14, 2964–2973, doi:10.3762/bjoc.14.276

• spectra often reveal key structural features. Furthermore, the availability of large cross-platform databases useful for dereplication allows focussing on new compounds. We are interested in natural compounds from Roseobacter group bacteria, an abundant class of marine bacteria occurring in diverse

• letters (Table 1). Mass spectrum of natural compound D, N-(13-methyltetradecanoyl)alanine methyl ester (iso-C15:0-NAME, 6). Mass spectra of natural compounds a) K (7, C16:0-NABME), b) J (8, C16:1-NABME), and c) N (9, C16:1-NAVME). TIC of an XAD extract of Loktanella sp. F14. Compound S is a minor

• component within the broad peak. Mass spectra of natural compounds a) R (11, C16:1-NAGME) and b) S (10, C16:0-NAGME). EI mass spectrometric fragmentation of N-acylated amino acid derivatives. The ions w–z allow identification of the respective amino acid residue. MS2 spectra in ESI positive mode of a) Z9

Synthesis of a leopolic acid-inspired tetramic acid with antimicrobial activity against multidrug-resistant bacteria

• Luce Mattio,
• Loana Musso,
• Leonardo Scaglioni,
• Andrea Pinto,
• Piera Anna Martino and
• Sabrina Dallavalle

Beilstein J. Org. Chem. 2018, 14, 2482–2487, doi:10.3762/bjoc.14.224

• -decyl-2,3-pyrrolidinedione ring linked to the ureido dipeptide L-Phe-L-Val. The 2,3-pyrrolidinedione ring is a quite unusual skeleton. A limited number of compounds containing this system have been synthesized so far [5][6][7] and, to the best of our knowledge, natural compounds with a 2,3

Microfluidic light-driven synthesis of tetracyclic molecular architectures

• Javier Mateos,
• Nicholas Meneghini,
• Marcella Bonchio,
• Nadia Marino,
• Tommaso Carofiglio,
• Xavier Companyó and
• Luca Dell’Amico

Beilstein J. Org. Chem. 2018, 14, 2418–2424, doi:10.3762/bjoc.14.219

• for the synthesis of biologically active natural compounds [16] and industrially relevant drugs [17] reminiscent of the bioactive tetralinolic pharmacophore core [18]. Acidic treatment of 4a generated, after a simple extraction, the corresponding α,β-unsaturated compound 7a in 97% yield. A further

One hundred years of benzotropone chemistry

• Arif Dastan,
• Haydar Kilic and
• Nurullah Saracoglu

Beilstein J. Org. Chem. 2018, 14, 1120–1180, doi:10.3762/bjoc.14.98

• and in a number of other natural compounds that have shown a highly diverse range of biological activity [1][2][3][4][5][6][7][8][9], like the inhibitory activity of inositol monophosphatase [10][11], antitumor [12], antibiotic [12][13], and antibacterial activity [14] and lipoxygenase inhibitor

Mannich base-connected syntheses mediated by ortho-quinone methides

• Petra Barta,
• Ferenc Fülöp and
• István Szatmári

Beilstein J. Org. Chem. 2018, 14, 560–575, doi:10.3762/bjoc.14.43

• reaction is an important, one-pot, multicomponent, C–C bond forming reaction that is widely used in the syntheses of many biologically active and natural compounds [1][2][3][4][5]. Originally, the Mannich product is formed through a three-component reaction containing a C–H acid, formaldehyde and a

• presence of a large excess of ethyl vinyl ether as o-QM trapping agent, they isolated several 2-ethoxychromane derivatives 16. However, yields as low as 36% were found in some cases. o-QMs derived from Mannich adducts also appear to be key intermediates in the syntheses of biologically active natural

• compounds. Wilson et al. successfully achieved the total synthesis of xyloketals 17 and 18, including cycloaddition of substituted dihydrofurans and 1-(2,4-dihydroxy-3-(morpholinomethyl)phenyl)ethanone via o-QM intermediates [69]. Osyanin et al. reported the synthesis of Uvaria scheffleri alkaloids

Vinylphosphonium and 2-aminovinylphosphonium salts – preparation and applications in organic synthesis

• Anna Kuźnik,
• Roman Mazurkiewicz and
• Beata Fryczkowska

Beilstein J. Org. Chem. 2017, 13, 2710–2738, doi:10.3762/bjoc.13.269

• performed a reaction of vinylphosphonium salts with a cyclic diketoester in the presence of sodium hydride which resulted in bicyclo[3.3.0]octenes 55 in 82–97% yield (Scheme 37) . The latter compounds were further used in the synthesis of natural compounds [50]. 2.3. Other synthetic uses of vinylphosphonium

• (104) led to the formation of 1,3-indanedione derivatives 105 in yields of 63–70% (Scheme 59) [72]. Nucleophilic displacement of the triphenylphosphonium group in α,β-di(alkoxycarbonyl)vinylphosphonium salts: Coumarins are an important class of natural compounds [73]. Yavari et al. developed a method

¹⁵N-Labelling and structure determination of adamantylated azolo-azines in solution

• Sergey L. Deev,
• Alexander S. Paramonov,
• Tatyana S. Shestakova,
• Igor A. Khalymbadzha,
• Oleg N. Chupakhin,
• Julia O. Subbotina,
• Oleg S. Eltsov,
• Pavel A. Slepukhin,
• Vladimir L. Rusinov,
• Alexander S. Arseniev and
• Zakhar O. Shenkarev

Beilstein J. Org. Chem. 2017, 13, 2535–2548, doi:10.3762/bjoc.13.250

• natural compounds is a widely used approach in medicinal chemistry [1]. The increased lipophilicity of adamantane-containing compounds compared with non-adamantylated derivatives [2] leads to considerably higher solubility of these compounds in blood plasma and their easier penetration through cell