Synthesis of pyrrolidinedione-fused hexahydropyrrolo[2,1-a]isoquinolines via three-component [3 + 2] cycloaddition followed by one-pot N-allylation and intramolecular Heck reactions

• Xiaoming Ma,
• Suzhi Meng,
• Xiaofeng Zhang,
• Qiang Zhang,
• Shenghu Yan,
• Yue Zhang and
• Wei Zhang

Beilstein J. Org. Chem. 2020, 16, 1225–1233, doi:10.3762/bjoc.16.106

• ; Introduction Pyrrolo[2,1-a]isoquinoline and hexahydropyrrolo[2,1-a]isoquinoline are privileged heterocyclic rings existing in many natural products and synthetic compounds possessing antitumor, antibacterial, antiviral, antioxidizing, and other biological activities (Figure 1) [1][2]. For example, the alkaloid

Efficient synthesis of dipeptide analogues of α-fluorinated β-aminophosphonates

• Marcin Kaźmierczak and
• Henryk Koroniak

Beilstein J. Org. Chem. 2020, 16, 756–762, doi:10.3762/bjoc.16.69

• applications of fluorinated aminophosphonates and aminophosphonic acid derivatives, they exhibit antiviral [4][5], antibacterial [6] and antifungal [7] activities. Moreover, α-fluorinated phosphonates can be considered as hydrolytically stable mimics of naturally occurring phosphates [8]. Due to the fact that

Microwave-assisted efficient and facile synthesis of tetramic acid derivatives via a one-pot post-Ugi cascade reaction

• Yong Li,
• Zheng Huang,
• Jia Xu,
• Yong Ding,
• Dian-Yong Tang,
• Jie Lei,
• Hong-yu Li,
• Zhong-Zhu Chen and
• Zhi-Gang Xu

Beilstein J. Org. Chem. 2020, 16, 663–669, doi:10.3762/bjoc.16.63

• exhibit a wide range of biological activities, including antibiotic [8], antiviral [9], antifungal [10], phytotoxic [11], cytotoxic [12][13], and enzyme inhibitory activities against bacterial DNA-directed RNA polymerase [14]. The wide range of biological activity and structural variation of this class of

A systematic review on silica-, carbon-, and magnetic materials-supported copper species as efficient heterogeneous nanocatalysts in “click” reactions

• Pezhman Shiri and
• Jasem Aboonajmi

Beilstein J. Org. Chem. 2020, 16, 551–586, doi:10.3762/bjoc.16.52

• catalysts; Sharpless–Meldal C–N bond-forming reaction; silica/carbon/magnetic materials; Introduction Heterocycles are a class of organic compounds with significant biological activities [1][2][3][4][5][6][7][8][9][10], including antimicrobial [2], antibacterial [3], anti-HIV [4], antiviral [5

Regio- and stereoselective synthesis of new ensembles of diversely functionalized 1,3-thiaselenol-2-ylmethyl selenides by a double rearrangement reaction

• Svetlana V. Amosova,
• Andrey A. Filippov,
• Nataliya A. Makhaeva,
• Alexander I. Albanov and
• Vladimir A. Potapov

Beilstein J. Org. Chem. 2020, 16, 515–523, doi:10.3762/bjoc.16.47

• activity based on affordable and environmentally friendly materials is another important trend in organoselenium chemistry [17]. Reviews on the biological activity of organoselenium compounds reported examples exhibiting high antitumor, antiviral, antimicrobial, and neuroprotective activities [12][18][19

Ultrasonic-assisted unusual four-component synthesis of 7-azolylamino-4,5,6,7-tetrahydroazolo[1,5-a]pyrimidines

• Yana I. Sakhno,
• Maryna V. Murlykina,
• Oleksandr I. Zbruyev,
• Anton V. Kozyryev,
• Svetlana V. Shishkina,
• Dmytro Sysoiev,
• Vladimir I. Musatov,
• Sergey M. Desenko and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2020, 16, 281–289, doi:10.3762/bjoc.16.27

• importance, and they have attracted the attention of medicinal chemists because of their various biological activities [1]. Furthermore, tetrahydropyrimidines containing fused azole rings are a privileged class of heterocycles due to their antiviral [2], antitubercular, antitumor [3], antibacterial [4][5

Synthesis of 4-(2-fluorophenyl)-7-methoxycoumarin: experimental and computational evidence for intramolecular and intermolecular C–F···H–C bonds

• Vuyisa Mzozoyana,
• Fanie R. van Heerden and
• Craig Grimmer

Beilstein J. Org. Chem. 2020, 16, 190–199, doi:10.3762/bjoc.16.22

• ], anti-oxidant [7], antibacterial [8], hepatoprotective, anticoagulant, antiviral and antithrombotic activities [9]. The variety of uses of these compounds resulted in an increase in demand for large quantities of coumarins. Due to an insufficient natural supply to meet this demand for these compounds

Extension of the 5-alkynyluridine side chain via C–C-bond formation in modified organometallic nucleosides using the Nicholas reaction

• Renata Kaczmarek,
• Dariusz Korczyński,
• James R. Green and
• Roman Dembinski

Beilstein J. Org. Chem. 2020, 16, 1–8, doi:10.3762/bjoc.16.1

• only provide a biological impact but also create a synthetic handle for further functionalization/modification. Among others, alkynyl uridines undergo cycloisomerization to potent antiviral agents, furopyrimidines [13], related halofuropyrimidines [14], and can be converted into interstrand dimers [15

Construction of trisubstituted chromone skeletons carrying electron-withdrawing groups via PhIO-mediated dehydrogenation and its application to the synthesis of frutinone A

• Qiao Li,
• Chen Zhuang,
• Donghua Wang,
• Wei Zhang,
• Rongxuan Jia,
• Fengxia Sun,
• Yilin Zhang and
• Yunfei Du

Beilstein J. Org. Chem. 2019, 15, 2958–2965, doi:10.3762/bjoc.15.291

• anticholinergic agent for its antimuscarinic effects [3][17]; apigenin can function as an antiviral drug for the treatment of HIV [18][19], cancer [20][21][22], and other viral infections [23]; pranlukast [24] can be used in the treatment of allergic rhinitis [25] and asthma [26]; and khellin [27] has been proved

• to possess antiviral and antispasmodic effects (Figure 1) [28]. All of these pharmaceutical agents bear a chromone framework in their respective chemical structure. Since the chromone derivatives have a variety of biological activities, developing synthetic methods for efficient construction of the

Diversity-oriented synthesis of spirothiazolidinediones and their biological evaluation

• Sambasivarao Kotha,
• Gaddamedi Sreevani,
• Lilya U. Dzhemileva,
• Milyausha M. Yunusbaeva,
• Usein M. Dzhemilev and
• Vladimir A. D’yakonov

Beilstein J. Org. Chem. 2019, 15, 2774–2781, doi:10.3762/bjoc.15.269

• represent an important class of nitrogen-containing biologically active compounds which exhibit various biological properties, such as antiviral, antibacterial and anticancer, etc. [55][56][57][58]. Recently, the use of 1,2,3-triazole derivatives as drug candidates has been increased for clinical therapy of

Nanangenines: drimane sesquiterpenoids as the dominant metabolite cohort of a novel Australian fungus, Aspergillus nanangensis

• Heather J. Lacey,
• Cameron L. M. Gilchrist,
• Andrew Crombie,
• John A. Kalaitzis,
• Daniel Vuong,
• Peter J. Rutledge,
• Peter Turner,
• John I. Pitt,
• Ernest Lacey,
• Yit-Heng Chooi and
• Andrew M. Piggott

Beilstein J. Org. Chem. 2019, 15, 2631–2643, doi:10.3762/bjoc.15.256

• , sponges, molluscs and other fungi as well and possess a wide range of bioactivities [24]. The drimane sesquiterpenoids isolated from Aspergillus spp. have exhibited in vitro anti-inflammatory [5] and antiviral [22] activities as well as cytotoxicity against several mammalian cell lines [4][16][22

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

• [1][2][3]. Sesqui- and diterpenes are a diverse class of secondary metabolites derived predominantly from plants, marine invertebrates, fungi and some prokaryotes [4][5][6][7][8]. Properties of these natural products include antitumor, anti-oxidant, anti-inflammatory, antiviral, antimalarial

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

• antibiotics (e.g., cephalosporins), immunosuppressants (e.g., mycophenolic acid) and immunomodulators (e.g., fingolimod), as well as cholesterol lowering agents (statins). Generally, fungal metabolites were shown to have antiviral, cytotoxic, antineoplastic, cardiovascular, anti-inflammatory, immune

Harnessing enzyme plasticity for the synthesis of oxygenated sesquiterpenoids

• Melodi Demiray,
• David J. Miller and
• Rudolf K. Allemann

Beilstein J. Org. Chem. 2019, 15, 2184–2190, doi:10.3762/bjoc.15.215

• -derived sesquiterpenes β-sesquiphellandrene [38][39][40] and zingiberene [40], a hydrocarbon with antifertility, antiviral and anticancer activity [41], suggested that the major compound was 12-methoxy-β-sesquiphellandrene (26), while the minor product was identified as 12-methoxyzingiberene (27). The two

Cyclopropanation–ring expansion of 3-chloroindoles with α-halodiazoacetates: novel synthesis of 4-quinolone-3-carboxylic acid and norfloxacin

• Sara Peeters,
• Linn Neerbye Berntsen,
• Pål Rongved and
• Tore Bonge-Hansen

Beilstein J. Org. Chem. 2019, 15, 2156–2160, doi:10.3762/bjoc.15.212

• compounds with biological activities ranging from antitumor, antiviral, antibiotic and antiparasitic to cannabinoid receptor modulating [22][23][24][25][26][27][28]. Despite the attractive features of the quinolone-3-carboxylate scaffold, there are only four reported routes towards this valuable structural

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

• , antioxidant, antiprotozoal, antiviral and immunobiological activities (reviewed in [1][2]). Two SLs remarkable for their immunobiological potential are archangelolide (1) and trilobolide (2), depicted in Figure 1. Compound 2 exhibits strong induction of nitric oxide (NO) in eukaryotic cells, which in turn

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

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

• 5-HT1 receptor agonist for the treatment of migraine) [7], and apremilast (3, Otezla®, inhibitor of the PDE4 for the treatment of certain types of psoriasis and psoriatic arthritis) [8] (Figure 1). Recently we have shown that racemic sulfone 4 exhibits high antiviral activity against BVDV with low

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

• biological actions: antiproliferative [6][7][8][9], antimicrobial [10][11], anxiolytic [12], analgesic [13], hypnotic [13], antiviral [13], anti-HIV [13] activities, etc. Soural et al. [14] explored different data and showed the relevance of compounds composed of two or more heterocyclic rings for drug

Steroid diversification by multicomponent reactions

• Leslie Reguera,
• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Daniel G. Rivera

Beilstein J. Org. Chem. 2019, 15, 1236–1256, doi:10.3762/bjoc.15.121

• displaying biological activities such as antimicrobial, antiviral and anti-inflammatory, among others. Scheme 3 exemplifies the reaction of cholestan-6-one 7 with 2-aminopyridine and phenyl isocyanide to afford the heterocycle–steroid hybrid 8 in good yield and diastereoselectivity, whereas different

• compound class 18 was evaluated for the inhibition of the viral multiplication and for their implication in intracellular localization of viral glycoproteins [23]. Two compounds showed antiviral effects against herpes simplex virus 1 (HSV-1, KOS strain) and vesicular stomatitis virus (VSV). The key

• substitution pattern at the phenyl moiety (Figure 2A). The small library of compounds enabled a better understanding of the structural factors determining the antiviral activity versus the cytotoxic one, with the major effect found for substituents at the para-position [23]. Eventually, this work allowed the

Multicomponent reactions (MCRs): a useful access to the synthesis of benzo-fused γ-lactams

• Edorta Martínez de Marigorta,
• Jesús M. de Los Santos,
• Ana M. Ochoa de Retana,
• Javier Vicario and
• Francisco Palacios

Beilstein J. Org. Chem. 2019, 15, 1065–1085, doi:10.3762/bjoc.15.104

• , that shows antimalarial activity [40] and satavaptan, a selective V2-receptor antagonist that is useful for the treatment of cirrhosis (Figure 5) [41][42]. Additionally, methisazone is a 2-oxindole derivative that has been used as antiviral drug, especially for the prophylactic treatment of small-pox

An improved synthesis of adefovir and related analogues

• David J. Jones,
• Eileen M. O’Leary and
• Timothy P. O’Sullivan

Beilstein J. Org. Chem. 2019, 15, 801–810, doi:10.3762/bjoc.15.77

• Sciences, Cork Institute of Technology, Cork, Ireland 10.3762/bjoc.15.77 Abstract An improved synthesis of the antiviral drug adefovir is presented. Problems associated with current routes to adefovir include capricious yields and a reliance on problematic reagents and solvents, such as magnesium tert

• the versatility of our approach. Keywords: acyclic nucleoside phosphonate; adefovir; alkylation; antiviral; N-alkylation; purine; Introduction The acyclic nucleoside phosphonate adefovir (1) [1], administered as its dipivoxil prodrug form (2) [2], is used clinically for the treatment of infections

• was also isolated in 16% yield, which was readily separable from 6 by column chromatography. The synthesis of 20 has been reported only once before and the resulting phosphonic acid also possesses antiviral activity [54]. The authors report that 20 was prepared in four steps while our three step route

Diastereo- and enantioselective preparation of cyclopropanol derivatives

• Marwan Simaan and
• Ilan Marek

Beilstein J. Org. Chem. 2019, 15, 752–760, doi:10.3762/bjoc.15.71

• transformations [1]. The cyclopropane subunit is also present in many biologically important compounds such as pheromones, fatty acid metabolites, unusual amino acids and possess interesting herbicidal, insecticidal, antibiotic, antibacterial, antifungal, antiviral and antitumor activities [2]. For these reasons

• are also important precursors in the synthesis of various biologically active molecules and pharmaceuticals such as antidepressants, antiviral and antibacterial drugs [4]. Cyclopropanols and their derivatives are considered to be carbocyclic homologues of enols presenting similar chemical properties

Synthesis and biological investigation of (+)-3-hydroxymethylartemisinin

• Toni Smeilus,
• Farnoush Mousavizadeh,
• Johannes Krieger,
• Xingzhao Tu,
• Marcel Kaiser and
• Athanassios Giannis

Beilstein J. Org. Chem. 2019, 15, 567–570, doi:10.3762/bjoc.15.51

• sesquiterpene lactone is still unknown [5]. Whereas artemisinins are almost non-toxic to normal cells, several studies have confirmed their potent antitumor activity [6][7]. In addition, they have been reported to possess immunosuppressive, anti-inflammatory, antiviral, antifungal and antiparasitic activities

Study on the regioselectivity of the N-ethylation reaction of N-benzyl-4-oxo-1,4-dihydroquinoline-3-carboxamide

• Pedro N. Batalha,
• Luana da S. M. Forezi,
• Maria Clara R. Freitas,
• Nathalia M. de C. Tolentino,
• Ednilsom Orestes,
• José Walkimar de M. Carneiro,
• Fernanda da C. S. Boechat and
• Maria Cecília B. V. de Souza

Beilstein J. Org. Chem. 2019, 15, 388–400, doi:10.3762/bjoc.15.35

• antibacterial and antiviral. The presence of a carboxamide unit connected to carbon C-3 of the 4-oxoquinoline core has been associated with various biological activities. Experimentally, the N-ethylation reaction of N-benzyl-4-oxo-1,4-dihydroquinoline-3-carboxamide occurs at the nitrogen of the oxoquinoline

• been explored and were successfully described by researchers around the world [3][4], such as antiviral [5][6], antiplasmoidal [7][8], anticancer [9][10], and trypanocide [11] activities. 4-Oxoquinoline-3-carboxamide derivatives, more specifically, have shown to be a promising structural scaffold for

• work we described the synthesis and antiviral activity of some 4-oxoquinoline acyclonucleosides 3a and 3b [15] and studies on their anticancer activity are also underway. It is also worth mentioning that derivative 4 presented an excellent inhibitory profile for the enzyme hystone deacetylase (HDAC