Photosensitized direct C–H fluorination and trifluoromethylation in organic synthesis

• Shahboz Yakubov and
• Joshua P. Barham

Beilstein J. Org. Chem. 2020, 16, 2151–2192, doi:10.3762/bjoc.16.183

Naphthalene diimide–amino acid conjugates as novel fluorimetric and CD probes for differentiation between ds-DNA and ds-RNA

• Annike Weißenstein,
• Myroslav O. Vysotsky,
• Ivo Piantanida and
• Frank Würthner

Beilstein J. Org. Chem. 2020, 16, 2032–2045, doi:10.3762/bjoc.16.170

• ; Introduction The interplay of non-covalent interactions between nucleic acids and proteins or peptides is the basis of life and is also often used for the design of artificial small molecules, aiming for sensing or control of biorelevant processes. Many naturally occurring bioactive molecules contain a short

Controlling the stereochemistry in 2-oxo-aldehyde-derived Ugi adducts through the cinchona alkaloid-promoted electrophilic fluorination

• Yuqing Wang,
• Gaigai Wang,
• Anatoly A. Peshkov,
• Ruwei Yao,
• Muhammad Hasan,
• Manzoor Zaman,
• Chao Liu,
• Stepan Kashtanov,
• Olga P. Pereshivko and
• Vsevolod A. Peshkov

Beilstein J. Org. Chem. 2020, 16, 1963–1973, doi:10.3762/bjoc.16.163

• was successfully utilized for the synthesis of several bioactive molecules [79][80][81]. Herein we present its adaptation for the enantioselective fluorination of 2-oxo-aldehyde-derived Ugi adducts 8 leading to the installment of a fluorine-bound quaternary stereocenter at the peptidyl position. It

Et₃N/DMSO-supported one-pot synthesis of highly fluorescent β-carboline-linked benzothiophenones via sulfur insertion and estimation of the photophysical properties

• Dharmender Singh,
• Vipin Kumar and
• Virender Singh

Beilstein J. Org. Chem. 2020, 16, 1740–1753, doi:10.3762/bjoc.16.146

• ][29][30][31]. Moreover, these compounds were also used as synthetic intermediates for various sulfur-containing bioactive molecules (Figure 1) [32][33][34]. In organic synthesis, aromatic compounds having nitro groups play a vital role as building blocks for the synthesis of nitrogen-containing

4-Hydroxy-3-methyl-2(1H)-quinolone, originally discovered from a Brassicaceae plant, produced by a soil bacterium of the genus Burkholderia sp.: determination of a preferred tautomer and antioxidant activity

• Dandan Li,
• Naoya Oku,
• Yukiko Shinozaki,
• Yoichi Kurokawa and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 1489–1494, doi:10.3762/bjoc.16.124

• emerging source of bioactive molecules. Many new structure classes, even after being spun off as a new genus from Pseudomonas in 1992 [14], have been discovered from this group, which, along with their large genomes comparable to those of actinomycetes or myxobacteria, demonstrate a higher capacity of

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

• techniques. The reactions between 1-methyldihydroisoquinoline and glutaric, diglycolic and succinic anhydrides yielded unexpected isoquinoline derivatives containing an exocyclic double bond. The compounds prepared bear the potential to become building blocks for future synthetic bioactive molecules

An overview on disulfide-catalyzed and -cocatalyzed photoreactions

• Yeersen Patehebieke

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

• of visible light, oxygen, and disulfide [15]. The diaryl-1,2-diketone products can serve as an important structural component of many natural products and bioactive molecules. This method works for a broad range of substrates with high yields (77–97%). A plausible mechanism for this reaction is that

Anthelmintic drug discovery: target identification, screening methods and the role of open science

• Frederick A. Partridge,
• Ruth Forman,
• Carole J. R. Bataille,
• Graham M. Wynne,
• Marina Nick,
• Angela J. Russell,
• Kathryn J. Else and
• David B. Sattelle

Beilstein J. Org. Chem. 2020, 16, 1203–1224, doi:10.3762/bjoc.16.105

• ) and PubChem (NIH). Both focus on characterising drug-like molecules and providing information to the public domain. The former is a manually curated database of bioactive molecules, which aims to bring together chemical, bioactivity and genomic data to aid the translation of genomic information into

Copper-catalysed alkylation of heterocyclic acceptors with organometallic reagents

• Yafei Guo and
• Syuzanna R. Harutyunyan

Beilstein J. Org. Chem. 2020, 16, 1006–1021, doi:10.3762/bjoc.16.90

• chiral natural products and bioactive molecules. Hence, this review focuses on the progress made over the past 20 years for heterocyclic acceptors. Keywords: conjugate addition; copper catalysis; heterocyclic Michael acceptor; organometallics; Introduction The copper-catalysed asymmetric addition of

• organometallic reagents to various acceptors is a useful strategy for C–C bond-forming reactions [1][2][3][4]. These important transformations have been thoroughly developed in the last few decades and were widely used in the synthesis of chiral natural products and bioactive molecules [5][6][7][8]. The majority

• reagents and protecting groups were examined, providing the products with good yield (up to 90%) and ee (up to 95%). Copper-catalysed conjugate addition reactions to alkenyl-substituted heterocycles Chiral heterocyclic aromatic compounds are crucial motifs in natural products and bioactive molecules, and

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

• and technologies [21][22][23][24][25][26][27][28][29][30]. Thus, numerous multistep total syntheses of organic compounds, including bioactive molecules [31][32][33][34][35] and natural products [36][37], have been performed in a highly chemo- and stereoselective manner through metathesis routes [38

Asymmetric synthesis of CF₂-functionalized aziridines by combined strong Brønsted acid catalysis

• Xing-Fa Tan,
• Fa-Guang Zhang and
• Jun-An Ma

Beilstein J. Org. Chem. 2020, 16, 638–644, doi:10.3762/bjoc.16.60

• ; difluoromethyl compounds; fluorinated diazo reagents; strong Brønsted acids; Introduction Chiral aziridines are prevalently found in natural products and artificially made bioactive molecules, thus receiving significant attention in the past decades [1][2][3][4][5][6]. Among them, the introduction of fluorine

Copper-promoted/copper-catalyzed trifluoromethylselenolation reactions

• Clément Ghiazza and
• Anis Tlili

Beilstein J. Org. Chem. 2020, 16, 305–316, doi:10.3762/bjoc.16.30

• these methodologies was already demonstrated for the synthesis of bioactive analogs. To the best of our knowledge, to date there are no SeCF3-containing drug candidates or bioactive molecules in clinical trials. This could be explained by the lack of physicochemical data on the SeCF3 moiety. More

Combination of multicomponent KA² and Pauson–Khand reactions: short synthesis of spirocyclic pyrrolocyclopentenones

• Riccardo Innocenti,
• Elena Lenci,
• Gloria Menchi and
• Andrea Trabocchi

Beilstein J. Org. Chem. 2020, 16, 200–211, doi:10.3762/bjoc.16.23

• structure in three single steps (Scheme 1b). This unprecedent molecular scaffold represents a valuable template for medicinal chemistry purpose, as the pyrrolocyclopentenone core is contained in a variety of bioactive molecules [49][50], and can serve as an advanced intermediate for the synthesis of

AgNTf₂-catalyzed formal [3 + 2] cycloaddition of ynamides with unprotected isoxazol-5-amines: efficient access to functionalized 5-amino-1H-pyrrole-3-carboxamide derivatives

• Ziping Cao,
• Jiekun Zhu,
• Li Liu,
• Yuanling Pang,
• Laijin Tian,
• Xuejun Sun and
• Xin Meng

Beilstein J. Org. Chem. 2019, 15, 2623–2630, doi:10.3762/bjoc.15.255

• bioactive molecules, thus providing a practical method for the construction of similar skeleton compounds. Our next investigation will focus on the studies of the detailed reaction mechanism and the applications of this methodology for the synthesis of interesting molecules. Experimental General information

• –ESI (m/z): [M + H]+ calcd for C20H22N3O3S, 384.1376; found, 384.1375. Selected bioactive molecules containing the 5-amino-1H-pyrrole-3-carboxamide motif. Scope with regard to ynamide 4. All reactions were carried out with ynamide 4 (0.2 mmol), isoxazole 8 (0.22 mmol, 1.1 equiv) with AgNTf2 (5 mol

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

• reaction (checked by TLC), the mixture was diluted with AcOEt (10 mL), filtered through a Celite® pad and washed with additional AcOEt (10 mL). Then the solvent was removed under reduced pressure and the reaction crude was purified by LCC to get the title compound. Bioactive molecules containing a

Regioselective Pd-catalyzed direct C1- and C2-arylations of lilolidine for the access to 5,6-dihydropyrrolo[3,2,1-ij]quinoline derivatives

• Hai-Yun Huang,
• Haoran Li,
• Thierry Roisnel,
• Jean-François Soulé and
• Henri Doucet

Beilstein J. Org. Chem. 2019, 15, 2069–2075, doi:10.3762/bjoc.15.204

• ; Introduction Lilolidine (Figure 1, left), which is a commercially available compound, contains a 5,6-dihydropyrrolo[3,2,1-ij]quinoline skeleton found in several bioactive molecules. For example, tivantinib (Figure 1, middle) exhibits MET inhibitor properties [1]; whereas tarazepide (Figure 1, right) is being

Genome mining in Trichoderma viride J1-030: discovery and identification of novel sesquiterpene synthase and its products

• Xiang Sun,
• You-Sheng Cai,
• Yujie Yuan,
• Guangkai Bian,
• Ziling Ye,
• Zixin Deng and
• Tiangang Liu

Beilstein J. Org. Chem. 2019, 15, 2052–2058, doi:10.3762/bjoc.15.202

• ]. The C15 sesquiterpenoids constitute a large class of terpenoids with a wide range of industrial and commercial applications, including uses in flavours and perfumes, as bioactive molecules in the pharmaceutical industry, and in health care products [11]. Sesquiterpenoids are biosynthesised from the

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

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

• mixture was stirred at room temperature for 3–4 hours. The progress of the reaction was monitored by TLC (eluent ethyl acetate/n-hexane 1:2). After completion of the reaction, the yellow precipitate (5a–d) was filtered and washed with water and ethanol. Yields: 20–40%. Selected examples of bioactive

• molecules based on the pyrazolopyridine framework. ORTEP Structure of compound 4a and intermolecular hydrogen bonding; the ellipsoid probability level of each ORTEP diagram is 50%. Structures of synthesized pyrazolopyridines 4a–m. Reaction conditions: 3-formylchromone derivatives (1 mmol), primary amine

A diastereoselective approach to axially chiral biaryls via electrochemically enabled cyclization cascade

• Hong Yan,
• Zhong-Yi Mao,
• Zhong-Wei Hou,
• Jinshuai Song and
• Hai-Chao Xu

Beilstein J. Org. Chem. 2019, 15, 795–800, doi:10.3762/bjoc.15.76

• the biaryls with good to excellent central-to-axial chirality transfer. Keywords: axial chirality; biaryl; electrochemistry; oxidation; radical; Introduction Axially chiral biaryls are prevalent in natural products, bioactive molecules and organocatalysts [1][2]. Among the many methods that have

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

• of higher complexity by employing simpler, more efficient, catalytic methods that are also environmentally friendly. Molecular hybridization has emerged as an interesting strategy for the synthesis of bioactive molecules with improved properties by combining two or more pharmacophore fragments in a

Intramolecular cascade annulation triggered by rhodium(III)-catalyzed sequential C(sp²)–H activation and C(sp³)–H amination

• Liangliang Song,
• Guilong Tian,
• Johan Van der Eycken and
• Erik V. Van der Eycken

Beilstein J. Org. Chem. 2019, 15, 571–576, doi:10.3762/bjoc.15.52

• , we have developed a rhodium(III)-catalyzed sequential C(sp2)–H activation and C(sp3)–H amination of O-substituted N-hydroxyacrylamides for the synthesis of indolizinones. This method shows excellent functional-group tolerance. The family of indolizinone products represents potential bioactive

• molecules for further studies. Selected examples of natural products with a tricyclic indolizinone scaffold. Previous work and this approach. Reaction scope. Reaction conditions: 1 (0.3 mmol), [RhCp*Cl2]2 (0.015 mmol), CsOAc (0.6 mmol), 1,4-dioxane (3.0 mL), the ratio of isolated 3:2 was shown in

Design of indole- and MCR-based macrocycles as p53-MDM2 antagonists

• Constantinos G. Neochoritis,
• Maryam Kazemi Miraki,
• Eman M. M. Abdelraheem,
• Ewa Surmiak,
• Tryfon Zarganes-Tzitzikas,
• Beata Łabuzek,
• Tad A. Holak and
• Alexander Dömling

Beilstein J. Org. Chem. 2019, 15, 513–520, doi:10.3762/bjoc.15.45

• . The aforementioned artificial macrocycles combine the indole ring, a motif found in many bioactive molecules with the drug-like properties of a non-peptide macrocycle. We hypothesize that these chimeric derivatives of an indole and a macrocycle will offer new potential on specific PPIs and other

A chemoenzymatic synthesis of ceramide trafficking inhibitor HPA-12

• Seema V. Kanojia,
• Sucheta Chatterjee,
• Subrata Chattopadhyay and
• Dibakar Goswami

Beilstein J. Org. Chem. 2019, 15, 490–496, doi:10.3762/bjoc.15.42

• ]. Our group has been using lipases for the chemoenzymatic syntheses of several bioactive molecules [34][35][36][37][38][39]. The prevalence of PhCH(OH) in 2, and in many other biochemicals, attracted our attention to formulate an enantioselective lipase-catalyzed transacetylation strategy to obtain a

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

• moieties occurring in bioactive molecules, such as the immunosuppresor oxisurane [49], quinolone vasodilator flosequinan [50], and potential drugs for the treatment of diabetes [51]. As such, employing simple transformations, compound 2a was conveniently oxidised in moderate to good isolated yields (45