Natural resorcylic lactones derived from alternariol

• Joachim Podlech

Beilstein J. Org. Chem. 2024, 20, 2171–2207, doi:10.3762/bjoc.20.187

• -methylalternariol derivative 15 was isolated from A. alternata and showed inhibitory activity against HCV NS3/4A protease (IC50: 52.0 μg/mL), cytotoxic activity against HEP-G2 cancer cells, and turned out to be antibacterial against Bacillus cereus, B. megaterium, and Escherichia coli with inhibition zones of 17

Non-noble metal-catalyzed cross-dehydrogenation coupling (CDC) involving ether α-C(sp³)–H to construct C–C bonds

• Hui Yu and
• Feng Xu

Beilstein J. Org. Chem. 2023, 19, 1259–1288, doi:10.3762/bjoc.19.94

• drugs are shown in Scheme 1c: Empagliflozin to treat type-2 diabetes [34][35][36], tegafur is used in medicine to treat a variety of cancers [37][38], lubazodone is an experimental antidepressant [39][40], and sofosbuvir is used to treat hepatitis C virus (HCV) infections [41][42]. For the synthesis of

Cyclometalated iridium complexes-catalyzed acceptorless dehydrogenative coupling reaction: construction of quinoline derivatives and evaluation of their antimicrobial activities

• Hongling Shui,
• Yuhong Zhong,
• Renshi Luo,
• Zhanyi Zhang,
• Jiuzhong Huang,
• Ping Yang and
• Nianhua Luo

Beilstein J. Org. Chem. 2022, 18, 1507–1517, doi:10.3762/bjoc.18.159

• , quinoline and its derivatives widely exist in natural products. They have a wide range of biological activities, such as antibacterial [1], anti-inflammatory [2], antitumor [3], antihepatitis C (HCV) [4], antituberculosis (TB) [5], antimalarial [6], and anti-Alzheimer's disease (AD) [7]. Among these

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

• ] developed the synthesis of naphtho[1,2-d]oxazole heterocycles from β-NQS as potential antiviral agents capable of inhibiting the HCV virus. Compound 45 was obtained from β-NQSNa (18) as shown above and reacted with substituted benzaldehyde or furfuryl aldehyde to form naphthoxazoles 51a–i and 53a–c

• , respectively. These compounds were then N-methylated, leading to the corresponding compounds 52a–i and 54a–c. Naphthoxazol 53c was the most effective anti-HCV agent, exhibiting an IC50 value of 0.63 μM, higher than that of the standard drug (ribavirin, IC50 13 μM) (Scheme 15). Naphthoxazoles stand out for

Beyond ribose and phosphate: Selected nucleic acid modifications for structure–function investigations and therapeutic applications

• Christopher Liczner,
• Kieran Duke,
• Gabrielle Juneau,
• Martin Egli and
• Christopher J. Wilds

Beilstein J. Org. Chem. 2021, 17, 908–931, doi:10.3762/bjoc.17.76

• by way of an HCV polymerase and extended to give a full-length oligonucleotide product, whereas 2',4'-diF-rUTP inhibited RNA synthesis at the early stages of dinucleotide-primed reactions [206]. Standard solid-phase synthesis allowed for the incorporation of this modified nucleoside into both RNA and

Synthesis of 3-alkenylindoles through regioselective C–H alkenylation of indoles by a ruthenium nanocatalyst

• Abhijit Paul,
• Debnath Chatterjee,
• Srirupa Banerjee and
• Somnath Yadav

Beilstein J. Org. Chem. 2020, 16, 140–148, doi:10.3762/bjoc.16.16

• the core of proposed anticancer compounds like MIPP and MOMIPP [10], fuligocandin B [2], the TDO inhibitor 680C91 [11], and a HCV NS5B polymerase inhibitor, which has been proposed as a drug against hepatitis C (Figure 1) [12]. The syntheses of 3-alkenylindoles can generally be classified into the

Lanyamycin, a macrolide antibiotic from Sorangium cellulosum, strain Soce 481 (Myxobacteria)

• Lucky S. Mulwa,
• Rolf Jansen,
• Dimas F. Praditya,
• Kathrin I. Mohr,
• Patrick W. Okanya,
• Joachim Wink,
• Eike Steinmann and
• Marc Stadler

Beilstein J. Org. Chem. 2018, 14, 1554–1562, doi:10.3762/bjoc.14.132

• their macrolactone ring was assigned based on NOE and vicinal 1H NMR coupling constants and by calculation of a 3D model. Lanyamycin inhibited HCV infection into mammalian liver cells with an IC50 value of 11.8 µM, and exhibited a moderate cytotoxic activity against the mouse fibroblast cell line L929

• and the human nasopharyngeal cell line KB3 with IC50 values of 3.1 and 1.5 μM, respectively, and also suppressed the growth of the Gram-positive bacterium Micrococcus luteus. Keywords: antimicrobial; HCV; lanyamycin; macrolide; Sorangium cellulosum; Introduction Viral hepatitis (HCV) has recently

• become a major concern of governments and health workers due to the economic and health burden it has brought. HCV has been found to be the main cause of liver associated deaths globally putting it in the same league of HIV and tuberculosis in terms of worldwide health challenges [1]. Approximately 71

Recent advances in synthetic approaches for medicinal chemistry of C-nucleosides

• Kartik Temburnikar and
• Katherine L. Seley-Radtke

Beilstein J. Org. Chem. 2018, 14, 772–785, doi:10.3762/bjoc.14.65

• ), respiratory syncytial virus (RSV, Pneumoviridae) and the hepatitis-C virus (HCV, Flaviviridae) family [63][65][69]. Through structure activity relationship studies, the 1'-CN compound 4 emerged as a compound with activity against EBOV, HCV and RSV [65][69]. It is active against EBOV in human microvascular

• endothelial cells and RSV with low cytotoxicity towards Huh-7, HEp-2 and MT4 cells. Moreover, the triphosphate of 4 selectively inhibits, HCV RdRp and RSV RdRp over human RNA Pol II and DNA polymerases (α, β, γ) [65]. The 2'-Me compound 7 as its triphosphate (TP) shows anti-HCV activity in replicon assays [77

• ]. However, 7-TP serves as a substrate for mitochondrial RNA polymerase, thereby causing toxicity in rats [63]. The 2'-F and 2'-β-Me compounds 8 and 9 are active against the HCV, but lack activity against EBOV and RSV in cell-based assays [65]. The pharmacokinetic properties of 4 were improved by converting

Synthesis of ribavirin 2’-Me-C-nucleoside analogues

• Fanny Cosson,
• Aline Faroux,
• Jean-Pierre Baltaze,
• Jonathan Farjon,
• Régis Guillot,
• Jacques Uziel and
• Nadège Lubin-Germain

Beilstein J. Org. Chem. 2017, 13, 755–761, doi:10.3762/bjoc.13.74

• promising as an anticancer drug [1][2][3]. The antiviral activity of ribavirin is ascribed to a combination of different mechanisms [4]. Although RBV causes some side effects [5][6][7] essentially due to its accumulation in red blood cells, it is indispensable in the treatment against hepatitis C virus (HCV

• against HCV as in the case of 2’-C-methylcytidine and 2’-C-methyladenosine [15]. The structure–activity studies of 2’-C-methylnucleosides showed that the methyl substituent must be in 2’-position and on the β face for an optimal efficacy that drops when the methyl is on the α face or in the 3’-position or

• untreated patients with HCV genotype 1, 2, or 3 infections with a combination of sofosbuvir (Gilead) and ribavirin for 12 weeks is considered as the most effective treatment at the moment [20]. Results and Discussion 2’-C-Methylnucleoside 2 was synthesized according to a seven step pathway starting from the

Synthesis of 1-indanones with a broad range of biological activity

• Marika Turek,
• Dorota Szczęsna,
• Marek Koprowski and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2017, 13, 451–494, doi:10.3762/bjoc.13.48

• , which inhibit HCV replication [9][10] (Figure 1). First publications concerning the preparation of 1-indanones appeared in the 1920s and since then this field has been intensively developed [11]. A huge interest in 1-indanones and their derivatives resulted in a considerable number of papers concerning

Rh-Catalyzed reductive Mannich-type reaction and its application towards the synthesis of (±)-ezetimibe

• Motoyuki Isoda,
• Kazuyuki Sato,
• Yurika Kunugi,
• Satsuki Tokonishi,
• Atsushi Tarui,
• Masaaki Omote,
• Hideki Minami and
• Akira Ando

Beilstein J. Org. Chem. 2016, 12, 1608–1615, doi:10.3762/bjoc.12.157

• –Pick C1 Like 1 Protein (NPC1L1), and is used as a strong cholesterol absorption inhibitor that reduces plasma low-density lipoprotein fraction (LDL-C) [28][29][30]. Recent studies on the function of NPC1L1 suggest that NPC1L1 may be involved with the internal uptake of the hepatitis C virus (HCV) and

Versatile synthesis and biological evaluation of novel 3’-fluorinated purine nucleosides

• Hang Ren,
• Haoyun An,
• Paul J. Hatala,
• William C. Stevens Jr,
• Jingchao Tao and
• Baicheng He

Beilstein J. Org. Chem. 2015, 11, 2509–2520, doi:10.3762/bjoc.11.272

• -lines [14][15][16]. Moreover, some 6-heterocyclic substituted purine ribonucleosides also demonstrate strong antiviral activities [17]. Purine derivatives such as, 2’-β-C-methyl-6-substituted purine nucleosides exhibit promising anti-HCV activity by blocking RNA dependent RNA polymerase [18][19][20

Facile synthesis of 1-alkoxy-1H-benzo- and 7-azabenzotriazoles from peptide coupling agents, mechanistic studies, and synthetic applications

• Mahesh K. Lakshman,
• Manish K. Singh,
• Mukesh Kumar,
• Raghu Ram Chamala,
• Vijayender R. Yedulla,
• Domenick Wagner,
• Evan Leung,
• Lijia Yang,
• Asha Matin and
• Sadia Ahmad

Beilstein J. Org. Chem. 2014, 10, 1919–1932, doi:10.3762/bjoc.10.200

• have been evaluated as inhibitors of respiratory syncytial virus [1], halogenated benzotriazoles have been shown to inhibit helicase activity of hepatitis C [2], N-alkylbenzotriazoles were shown to be active and selective towards HCV NTPase/helicase [3]. Benzotriazoles also possess anti-amoebic

Concise total synthesis of two marine natural nucleosides: trachycladines A and B

• Haixin Ding,
• Wei Li,
• Zhizhong Ruan,
• Ruchun Yang,
• Zhijie Mao,
• Qiang Xiao and
• Jun Wu

Beilstein J. Org. Chem. 2014, 10, 1681–1685, doi:10.3762/bjoc.10.176

• ), nucleoside 3 could be synthesized by using 1,2,3,5-tetra-O-benzoyl-2-C-methyl-D-ribofuranose (5) as a carbohydrate acceptor by a Vorbrüggen glycosylation with the corresponding silylated nucleobases and a Lewis acid as a catalyst. As the key intermediate for the preparation of the anti-HCV nucleoside

Chiral gold(I) vs chiral silver complexes as catalysts for the enantioselective synthesis of the second generation GSK-hepatitis C virus inhibitor

• María Martín-Rodríguez,
• Carmen Nájera,
• José M. Sansano,
• Abel de Cózar and
• Fernando P. Cossío

Beilstein J. Org. Chem. 2011, 7, 988–996, doi:10.3762/bjoc.7.111

• origin of the enantioselectivity of the chiral gold(I) catalyst was justified according to DFT calculations, the stabilizing coulombic interaction between the nitrogen atom of the thiazole moiety and one of the gold atoms being crucial. Keywords: BINAP; 1,3-dipolar cycloaddition; gold; HCV

• ; phosphoramidite; silver; viral inhibitor; Introduction The prevalence of chronic hepatitis C virus (HCV) infection is such that it is estimated to be suffered by around 200 million people worldwide [1]. This enveloped single-stranded RNA virus (belonging to the Flaviviridae family) is present in six major

• evaluation, the compounds targeting HCV replication being the most promising candidates to achieve a sustained virological response [1][4]. Several years ago, a high-throughput screening of the GlaxoSmithKline compound collection identified a series of small pyrrolidine molecules, e.g., 1 (Figure 1), able to

Metathesis access to monocyclic iminocyclitol-based therapeutic agents

• Ileana Dragutan,
• Valerian Dragutan,
• Carmen Mitan,
• Hermanus C.M. Vosloo,
• Lionel Delaude and
• Albert Demonceau

Beilstein J. Org. Chem. 2011, 7, 699–716, doi:10.3762/bjoc.7.81

• deoxygalactonojirimycin (DGJ). Five-membered iminocyclitols possessing N-alkyl and C1-alkyl substituents form a class of potent antiviral compounds active, e.g., against hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) [49][50][51][52]. Biological activity of this family of

An efficient synthesis of tetramic acid derivatives with extended conjugation from L-Ascorbic Acid

• Biswajit K. Singh,
• Surendra S. Bisht and
• Rama P. Tripathi

Beilstein J. Org. Chem. 2006, 2, No. 24, doi:10.1186/1860-5397-2-24

• and are potentially new tuberculosis drugs. 5-Alkenyl tetramic acids, being structurally similar to thiolactomycins, possess anti-HCV and anti-HIV activities [34][35] and are likely to yield new antitubercular prototype compounds active against tuberculosis in HIV cases. We have developed a one-pot