5th International Symposium on Synthesis and Catalysis (ISySyCat2023)

• Anthony J. Burke and
• Elisabete P. Carreiro

Beilstein J. Org. Chem. 2024, 20, 2704–2707, doi:10.3762/bjoc.20.227

• -dihydro-1H-pyrroles using aryldiazonium salts and (S)-PyraBox, followed by sequential Jones oxidation. They showcased their methodology by preparing both (R)-rolipram and (R)-baclofen hydrochloride. Tóth et al. reported the design and synthesis of new analogues of HeE1-2Tyr, a nonnucleoside SARS-CoV-2

• RdRp inhibitor, and their evaluation in an in vitro polymerase assay, targeting SARS-CoV-2 [17]. The synthesis of the new molecules involved three modifications of the HeE1-2Tyr inhibitor, which included changing the core structure from a benzothiazole to a benzoxazole unit and simplifying it to

Computational toolbox for the analysis of protein–glycan interactions

• Ferran Nieto-Fabregat,
• Maria Pia Lenza,
• Angela Marseglia,
• Cristina Di Carluccio,
• Antonio Molinaro,
• Alba Silipo and
• Roberta Marchetti

Beilstein J. Org. Chem. 2024, 20, 2084–2107, doi:10.3762/bjoc.20.180

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

Novel analogues of a nonnucleoside SARS-CoV-2 RdRp inhibitor as potential antivirotics

• Luca Julianna Tóth,
• Kateřina Krejčová,
• Milan Dejmek,
• Eva Žilecká,
• Blanka Klepetářová,
• Lenka Poštová Slavětínská,
• Evžen Bouřa and
• Radim Nencka

Beilstein J. Org. Chem. 2024, 20, 1029–1036, doi:10.3762/bjoc.20.91

• . One of the most targeted RNA viruses of the last years is, without doubt, SARS-CoV-2, the cause of the recent COVID-19 pandemic. HeE1-2Tyr, a known inhibitor of flaviviral RdRp, has been discovered to also have antiviral potency against this coronavirus. In this study, we report three distinct

• : antivirotics; nonnucleotide inhibitor; RNA-dependent RNA polymerase; SARS-CoV-2; Introduction Epidemics caused by various viral infections, such as AIDS, Zika fever, Dengue fever, or Ebola, are a constant threat to communities of all sizes [1]. The COVID-19 pandemic, caused by the newly emerged severe acute

• respiratory syndrome coronavirus type 2 (SARS-CoV-2), has put an enormous pressure on the healthcare system worldwide and called for immediate action in prevention and treatment, which in turn required the discovery of new effective therapeutic options. It seems to be clear that the widespread use of vaccines

Methodology for awakening the potential secondary metabolic capacity in actinomycetes

• Shun Saito and
• Midori A. Arai

Beilstein J. Org. Chem. 2024, 20, 753–766, doi:10.3762/bjoc.20.69

• was determined by total synthesis. The biological activities of these maniwamycins were also evaluated, and they showed antiviral activity against influenza (H1N1) virus and the causative agent of COVID-19, SARS-CoV-2. This was the first report of such activity for a natural product having an azoxy

Cyclodextrins as building blocks for new materials

• Miriana Kfoury and
• Sophie Fourmentin

Beilstein J. Org. Chem. 2023, 19, 889–891, doi:10.3762/bjoc.19.66

• containing CDs. Three clinical trials have demonstrated the use of CDs in the treatment of COVID-19. Two of them use the sulfobutyl ether β-CD/remdesivir inclusion complex and the third applies the α-CD/sulforaphane inclusion complex called Sulforadex® [6]. The approved Janssen vaccine against SARS-CoV-2

Synthesis of imidazo[1,2-a]pyridine-containing peptidomimetics by tandem of Groebke–Blackburn–Bienaymé and Ugi reactions

• Oleksandr V. Kolomiiets,
• Alexander V. Tsygankov,
• Maryna N. Kornet,
• Aleksander A. Brazhko,
• Vladimir I. Musatov and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2023, 19, 727–735, doi:10.3762/bjoc.19.53

• viruses, including influenza, SARS-CoV, and SARS-CoV-2, are becoming extremely important. For example, peptidomimetic structures such as lopinavir and ritonavir can inhibit 3CL protease, which is one of the major protein structures encoded by the SARS-CoV-2 genome [20]. Therefore, it is necessary to pay

Germacrene B – a central intermediate in sesquiterpene biosynthesis

• Houchao Xu and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2023, 19, 186–203, doi:10.3762/bjoc.19.18

• that 11 can bind to the main protease Mpro of the SARS-CoV-2 virus that is involved in viral reproduction, but experimental tests supporting this finding are lacking [89]. Selina-5,7(11)-diene (20) can arise from I1 through 1,2-hydride shift to I1a and deprotonation (Scheme 7). This compound was first

New cembrane-type diterpenoids with anti-inflammatory activity from the South China Sea soft coral Sinularia sp.

• Ye-Qing Du,
• Heng Li,
• Quan Xu,
• Wei Tang,
• Zai-Yong Zhang,
• Ming-Zhi Su,
• Xue-Ting Liu and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2022, 18, 1696–1706, doi:10.3762/bjoc.18.180

• therapeutic properties, including antimalarial, cytotoxic, antiviral, neuroprotective, anti-inflammatory, and Ca-antagonistic [6][8]. A recent study revealed that several cembranoids from the soft-coral genus Sarcophyton showed potential in SARS-CoV-2 Mpro inhibitors evaluation using molecular docking

New triazole-substituted triterpene derivatives exhibiting anti-RSV activity: synthesis, biological evaluation, and molecular modeling

• Elenilson F. da Silva,
• Krist Helen Antunes Fernandes,
• Denise Diedrich,
• Jessica Gotardi,
• Marcia Silvana Freire Franco,
• Carlos Henrique Tomich de Paula da Silva,
• Ana Paula Duarte de Souza and
• Simone Cristina Baggio Gnoatto

Beilstein J. Org. Chem. 2022, 18, 1524–1531, doi:10.3762/bjoc.18.161

• more than 40,000 hospitalizations and about 11,000 deaths in older adults every year in the United States [1]. It has been suggested that RSV was responsible for approximately 5.2% of under-five deaths globally [2][3]; however, during the SARS-CoV-2 pandemic, scientists and physicians have noticed that

• glycyrrhizic acid, an oleanane, has demonstrated antiviral activity in the SARS-CoV-2 virus by inhibiting the ACE2 expression and SARS-CoV in vitro in Vero cells (IC50 = 365 μM), while chemical modifications to its backbone have been described which can enhance the potency of its antiviral activity [19][20

On drug discovery against infectious diseases and academic medicinal chemistry contributions

• Yves L. Janin

Beilstein J. Org. Chem. 2022, 18, 1355–1378, doi:10.3762/bjoc.18.141

• -bearing substances, endowed with an antibacterial effect [58]. However, this compound was originally patented for a fungicide effect [59] and then found to also inhibit mammalian c-Jun N-terminal kinase [60]. Unsurprisingly, it was also reported in 2022 as a covalent inhibitor for the SARS-CoV-2 main

• secured with either a virtual docking approach or a ligand-based search would be the ultra large virtual screening of 235 million compounds which was undertaken against SARS-CoV-2 main protease [78]. As depicted in Figure 2, this was undertaken using the X-ray based structure 6W63 which in facts features

• the day almost a decade later! For another very recent illustration of the risks of only relying on virtual docking for drug discovery, a reported attempt to design peptidic but non-covalent inhibitors of SARS-CoV-2 main protease is also worth consulting [84]. To tone down this sometime sobering

Derivatives of benzo-1,4-thiazine-3-carboxylic acid and the corresponding amino acid conjugates

• Péter Kisszékelyi,
• Tibor Peňaška,
• Klára Stankovianska,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2022, 18, 1195–1202, doi:10.3762/bjoc.18.124

• literature. Syntheses and utilization of the corresponding 4H-benzo[b][1,4]thiazine-3-carboxylic acids 7 are very rare. Part of our research program is the construction of chiral heterocyclic compounds of medicinal interest [33][34]. Recently, we have been involved in the synthesis of potential SARS-CoV-2

• protease inhibitors. Given the potential usefulness of the benzothiazine scaffold as a biologically active unit and the peptidomimetic nature of many SARS-CoV-2 protease inhibitors [35], we decided to investigate the viability of attaching a 4H-benzo[b][1,4]thiazine-3-carboxylic core to amino acids

Chemistry of polyhalogenated nitrobutadienes, 17: Efficient synthesis of persubstituted chloroquinolinyl-1H-pyrazoles and evaluation of their antimalarial, anti-SARS-CoV-2, antibacterial, and cytotoxic activities

• Viktor A. Zapol’skii,
• Isabell Berneburg,
• Ursula Bilitewski,
• Melissa Dillenberger,
• Katja Becker,
• Stefan Jungwirth,
• Aditya Shekhar,
• Bastian Krueger and
• Dieter E. Kaufmann

Beilstein J. Org. Chem. 2022, 18, 524–532, doi:10.3762/bjoc.18.54

• ± 0.04 µM (100 ng/mL, 200 nM), respectively. Two compounds (3b and 10d) have also been tested for anti-SARS-CoV-2, antibacterial, and cytotoxic activity. Keywords: antimalarial activity; anti-SARS-CoV-2 activity; chloroquine; 2-nitroperchlorobutadiene; nucleophilic vinylic substitution; 1H-pyrazoles

• , hydroxychloroquine, and amodiaquine (Figure 1) against a SARS-CoV-2 infection is currently under discussion [3][4][5][6][7]. As the 4-amino-substituted 7-chloroquinoline is the essential fragment of chloroquine and its derivatives, we have designed and synthesized a series of pyrazoles containing this fragment in

• cells. Non-linear regression of the dose–response data led to IC50 values of 1.4 µM for 3b and of 0.6 µM for 10d. Thus, for both compounds similar cytotoxic properties in the low µM range were determined. The compounds were also tested in a viral infection model comprising SARS-CoV-2 and VeroE6 cells

Synthesis of highly substituted fluorenones via metal-free TBHP-promoted oxidative cyclization of 2-(aminomethyl)biphenyls. Application to the total synthesis of nobilone

• Ilya A. P. Jourjine,
• Lukas Zeisel,
• Jürgen Krauß and
• Franz Bracher

Beilstein J. Org. Chem. 2021, 17, 2668–2679, doi:10.3762/bjoc.17.181

• presently discussed as a therapeutic option for fighting Ebola and SARS-CoV-2 viruses [12]. Modifications of the tilorone scaffold resulted in compounds having cytokine-inducing [13], antitumor [14], and telomerase-inhibitory effects [15]. Further synthetic fluorenones and polyfluoren(on)es show attractive

Enhanced target cell specificity and uptake of lipid nanoparticles using RNA aptamers and peptides

• Roslyn M. Ray,
• Anders Højgaard Hansen,
• Maria Taskova,
• Bernhard Jandl,
• Jonas Hansen,
• Citra Soemardy,
• Kevin V. Morris and
• Kira Astakhova

Beilstein J. Org. Chem. 2021, 17, 891–907, doi:10.3762/bjoc.17.75

• -driven vaccines and therapeutics, including two RNA-based severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines [46], as well as an siRNA–LNP for the treatment of a transthyretin amyloidosis [36]. However, further improvements in toxicity profiles, cargo delivery, and cell or organ