Sequential Ugi reaction/base-induced ring closing/IAAC protocol toward triazolobenzodiazepine-fused diketopiperazines and hydantoins

• Robby Vroemans,
• Fante Bamba,
• Jonas Winters,
• Joice Thomas,
• Jeroen Jacobs,
• Luc Van Meervelt,
• Jubi John and
• Wim Dehaen

Beilstein J. Org. Chem. 2018, 14, 626–633, doi:10.3762/bjoc.14.49

• withdrawal, etc. [26][27][28][29][30][31][32][33][34]. In addition, these azaheterocycles also exhibit anti-inflammatory, antitumor, antiparasitic and anxiolytic activities [35][36][37][38][39][40][41][42]. In particular, 1,4-benzodiazepine derivatives are proposed to serve as a structural mimic of peptide β

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

• Ranjana Aggarwal and
• Suresh Kumar

Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15

• Pyrazolo[3,4-b]pyrazines have received great attention because of their interesting biological activities such as inhibition of protein kinases [137], blood platelet aggregation [138], bone metabolism improvers [139] as well as antifungal [140], antibacterial [141], antiparasitic [142] and antiviral [143

Preparation of imidazo[1,2-a]-N-heterocyclic derivatives with gem-difluorinated side chains

• Layal Hariss,
• Kamal Bou Hadir,
• Mirvat El-Masri,
• Thierry Roisnel,
• René Grée and
• Ali Hachem

Beilstein J. Org. Chem. 2017, 13, 2115–2121, doi:10.3762/bjoc.13.208

• , antiparasitic, hypnotic, etc. [1][2][3][4][5]. It is recognized as a key scaffold due to its broad occurrence in a number of drug candidates and drugs, such as zolpidem [6] (1a, used in the treatment of insomnia), and alpidem [6] (1b, an anxiolytic agent). Some imidazopyridine derivatives also act as β-amyloid

BODIPY-based fluorescent liposomes with sesquiterpene lactone trilobolide

• Ludmila Škorpilová,
• Silvie Rimpelová,
• Michal Jurášek,
• Miloš Buděšínský,
• Jana Lokajová,
• Roman Effenberg,
• Petr Slepička,
• Tomáš Ruml,
• Eva Kmoníčková,
• Pavel B. Drašar and
• Zdeněk Wimmer

Beilstein J. Org. Chem. 2017, 13, 1316–1324, doi:10.3762/bjoc.13.128

• defence mechanisms. This molecule is produced by macrophages and the antimicrobial and antiparasitic properties of NO have been well described [38]. Currently, the role of NO as a mediator between chronic inflammation and carcinogenesis is intensively studied [39]. The expression of inducible NO is under

Strategies in megasynthase engineering – fatty acid synthases (FAS) as model proteins

• Manuel Fischer and
• Martin Grininger

Beilstein J. Org. Chem. 2017, 13, 1204–1211, doi:10.3762/bjoc.13.119

• antineoplastic doxorubicin and by the antiparasitic avermectin (Figure 1a) [1]. PK are assembled from acyl-coenzyme A (acyl-CoA) units via a series of Claisen-type condensation reactions catalyzed by polyketide synthases (PKS) (Figure 1b). PKS occur as large multifunctional enzymes, termed megasynthases, which

First total synthesis of kipukasin A

• Chuang Li,
• Haixin Ding,
• Zhizhong Ruan,
• Yirong Zhou and
• Qiang Xiao

Beilstein J. Org. Chem. 2017, 13, 855–862, doi:10.3762/bjoc.13.86

• , antiparasitic and antitumor properties. Kipukasins A–G were firstly isolated from solid-substrate fermentation cultures of Hawaiian Aspergillus Versicolor in 2007 (Figure 1) [11]. Later on, kipukasins H, I [12] and J [13] were also isolated from the fungus Aspergillus flavus, which was collected at the South

Rearrangements of organic peroxides and related processes

• Ivan A. Yaremenko,
• Vera A. Vil’,
• Dmitry V. Demchuk and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2016, 12, 1647–1748, doi:10.3762/bjoc.12.162

Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides

• Franziska Hemmerling and
• Frank Hahn

Beilstein J. Org. Chem. 2016, 12, 1512–1550, doi:10.3762/bjoc.12.148

• polyketide with potent antitumor, antifungal, antiparasitic, pesticidal and antitrypanosomal activities (Scheme 13). In its biosynthesis, the furan-ring formation occurs on a late stage, catalysed in an unprecedented fashion by the cytochrome P450 oxidase AurH [13][62][63][64][65][66][67]. This enzyme

Microwave-assisted synthesis of (aminomethylene)bisphosphine oxides and (aminomethylene)bisphosphonates by a three-component condensation

• Erika Bálint,
• Ádám Tajti,
• Anna Dzielak,
• Gerhard Hägele and
• György Keglevich

Beilstein J. Org. Chem. 2016, 12, 1493–1502, doi:10.3762/bjoc.12.146

• antibacterial, antiparasitic, anticancer and herbicidal activities [5]. (Aminomethylene)bisphosphonates may be prepared in different ways [5]. One of the most convenient and widespread methods is the three-component condensation involving an amine, an orthoformate and a dialkyl phosphite. Usually, primary or

Three new trixane glycosides obtained from the leaves of Jungia sellowii Less. using centrifugal partition chromatography

• Luíse Azevedo,
• Larissa Faqueti,
• Marina Kritsanida,
• Antonia Efstathiou,
• Despina Smirlis,
• Gilberto C. Franchi Jr,
• Grégory Genta-Jouve,
• Sylvie Michel,
• Louis P. Sandjo,
• Raphaël Grougnet and
• Maique W. Biavatti

Beilstein J. Org. Chem. 2016, 12, 674–683, doi:10.3762/bjoc.12.68

• amastigotes with an IC50 value of 100 μg/mL. Except for compound 1 that exhibited a weak antileishmanial activity at 50 μM (20%) against L. amazonensis intracellular amastigotes, none of the other sesquiterpenes displayed antiparasitic activity. Compounds 1–3 showed less than 50% antiproliferative effect on

Biosynthesis of α-pyrones

• Till F. Schäberle

Beilstein J. Org. Chem. 2016, 12, 571–588, doi:10.3762/bjoc.12.56

• C (57, Figure 14), which have been isolated from different Pseudomonas strains [62][63]. Compounds 55 and 56 had been initially tested positive for antimycobacterial and antiparasitic activities and both inhibited fatty acid biosynthesis [62]. The new derivative 57, possessing a longer eastern acyl

Pyridinoacridine alkaloids of marine origin: NMR and MS spectral data, synthesis, biosynthesis and biological activity

• Louis P. Sandjo,
• Victor Kuete and
• Maique W. Biavatti

Beilstein J. Org. Chem. 2015, 11, 1667–1699, doi:10.3762/bjoc.11.183

• synthetic compounds, has been widely investigated. Many of them displayed cytotoxic activity in addition to other bioactivities such as antiviral, antifungal, antibacterial, antitumor and antiparasitic potential [41]. Several reviews on pyridoacridine alkaloids have been published between 1983–2015 [35][43

• subtilis, giving a MIC of 3.1 µg/mL [87]. 42 displayed in vitro antiparasitic activity against Plasmodium falciparum (K1, NF54), Leshmania donovani, Trypanosoma cruzi and T. rhodesiense but the effect was much lower than that of standard drugs artemisinin and chloroquine [88]. Ascididemin (42) displayed

A novel and widespread class of ketosynthase is responsible for the head-to-head condensation of two acyl moieties in bacterial pyrone biosynthesis

• Darko Kresovic,
• Florence Schempp,
• Zakaria Cheikh-Ali and
• Helge B. Bode

Beilstein J. Org. Chem. 2015, 11, 1412–1417, doi:10.3762/bjoc.11.152

• antimycobacterial and antiparasitic activity and they inhibit the fatty acid biosynthesis [29]. Natural and unnatural derivatives have also been synthesized in order to find more potent compounds [30]. We first analyzed the strain for pseudopyronine production and were able to detect three possible compounds. After

N-Alkyl derivatives of diosgenyl 2-amino-2-deoxy-β-D-glucopyranoside; synthesis and antimicrobial activity

• Agata Walczewska,
• Daria Grzywacz,
• Dorota Bednarczyk,
• Małgorzata Dawgul,
• Andrzej Nowacki,
• Wojciech Kamysz,
• Beata Liberek and
• Henryk Myszka

Beilstein J. Org. Chem. 2015, 11, 869–874, doi:10.3762/bjoc.11.97

• used as detergents, surfactants and emulsifiers. Moreover, they display a wide range of pharmacological activities, including antifungal, antiparasitic, antiinflammatory, antibacterial, and antitumor activities [2][3][4][5]. No wonder, saponins have been evaluated as vaccine adjuvants [6]. Despite the

Come-back of phenanthridine and phenanthridinium derivatives in the 21st century

• Lidija-Marija Tumir,
• Marijana Radić Stojković and
• Ivo Piantanida

Beilstein J. Org. Chem. 2014, 10, 2930–2954, doi:10.3762/bjoc.10.312

• - and RNA-fluorescent markers (ethidium bromide), probes for cell viability (propidium iodide), but also “ill-famed” for various toxic (genotoxic) and mutagenic effects. After two decades of low interest, the discovery of phenanthridine alkaloids and new studies of antiparasitic/antitumor properties of

• (propidium iodide) as a probe for cell viability. Besides, an antiparasitic activity for EB was reported and it possesses significant antitumor activity [2][3][4][5] both in vivo and in vitro. Nevertheless, phenanthridine derivatives were rather neglected regarding their human medicinal applications due to

• antiparasitic properties of phenanthridine derivatives resulted in a strong increase of the scientific interest about the turn of this century, consequently yielding many publications at high impact chemical and biomedicinal journals, and patents covering various chemical, biochemical and biomedical uses. These

(2R,1'S,2'R)- and (2S,1'S,2'R)-3-[2-Mono(di,tri)fluoromethylcyclopropyl]alanines and their incorporation into hormaomycin analogues

• Armin de Meijere,
• Sergei I. Kozhushkov,
• Dmitrii S. Yufit,
• Christian Grosse,
• Marcel Kaiser and
• Vitaly A. Raev

Beilstein J. Org. Chem. 2014, 10, 2844–2857, doi:10.3762/bjoc.10.302

• % yield, respectively (Scheme 7). Since the MeZ-protected cyclohexadepsipeptide core of the native hormaomycin was found to have a significant antiparasitic activity, N-acetylated 58 and N-trifluoroacetylated 59 derivatives were prepared by coupling the deprotected cyclic intermediate 52a with acetic and

• trifluoroacetic acid (Figure 6). Some antiparasitic activities of hormaomycin, its all-peptide analogue and the new analogues The syntheses of hormaomycin (1) itself and of its all-peptide aza-analogues 60 and 61 (Figure 6) as developed by Zlatopolskiy et al. [9][12], were reproduced in order to provide large

• enough quantities for biological tests of their antimalarial activities. Results of the in vitro tests of the antiparasitic activities of hormaomycin (1) [57], its analogues 8a, 52a, 58 and 59, as well as the aza-analogues 60 and 61 are presented in Table 3. All the newly prepared and tested hormaomycin

Encapsulation of biocides by cyclodextrins: toward synergistic effects against pathogens

• Véronique Nardello-Rataj and
• Loïc Leclercq

Beilstein J. Org. Chem. 2014, 10, 2603–2622, doi:10.3762/bjoc.10.273

• typical examples of CDs/biocide inclusion on textile are reported. In 2008, Wang et al. incorporated the miconazole nitrate (Figure 6) into the cavity of MCT-β-CD covalently bound onto cloth fibers. The miconazole salts are antifungal agents with additional antibacterial and antiparasitic actions [63

Multicomponent reactions in nucleoside chemistry

• Mariola Koszytkowska-Stawińska and
• Włodzimierz Buchowicz

Beilstein J. Org. Chem. 2014, 10, 1706–1732, doi:10.3762/bjoc.10.179

• moderate yields. Antiparasitic activities of the hybrid compounds 15 were evaluated; some of them showed moderate activities against trypomastigote forms of Trypanosoma brucei brucei GVR 35 (e.g., IC50 = 25 µM for Ar = C6H4-Cl-4). The Mannich reaction was also used to construct nucleoside scaffolds from

Synthesis of five- and six-membered cyclic organic peroxides: Key transformations into peroxide ring-retaining products

• Alexander O. Terent'ev,
• Dmitry A. Borisov,
• Vera A. Vil’ and
• Valery M. Dembitsky

Beilstein J. Org. Chem. 2014, 10, 34–114, doi:10.3762/bjoc.10.6

• -alkyl oximes 174 with ketones 175 (Scheme 45, Table 13). The selective synthesis of ozonides has attracted great interest because it allows the preparation of compounds exhibiting high antiparasitic activity. The Griesbaum method is widely applicable and allows the selective synthesis of symmetrical and

• 1,2,4-trioxalane 191 was synthesized by reductive amination of adamantane-2-spiro-3’-8’-oxo-1’,2’,4’-trioxaspiro[4.5]-decane 190 (Scheme 52). Ozonide 191 is an example of a combination of two known antiparasitic pharmacophores, viz. a peroxide and an aminoquinoline moiety [296]. Arterolane is a fully

• exhibit a broad spectrum of antiparasitic activities against causative agents of malaria, trypanosomiasis, and leishmaniasis [208][209][210][211][212]. 3.7. Methods for the synthesis of 1,2-dioxanes from hydroperoxides Compounds containing a С=С group and an oxygen-containing ring are convenient starting

Synthesis and biological activities of the respiratory chain inhibitor aurachin D and new ring versus chain analogues

• Xu-Wen Li,
• Jennifer Herrmann,
• Yi Zang,
• Philippe Grellier,
• Soizic Prado,
• Rolf Müller and
• Bastien Nay

Beilstein J. Org. Chem. 2013, 9, 1551–1558, doi:10.3762/bjoc.9.176

• some ring as opposed to chain analogues, allowing for the description of structure–activity relationships. Biological screening of the analogues showed antiparasitic, cytotoxic, antibacterial and antifungal activities, and depletion of the mitochondrial membrane potential. The strongest activity was

• (e.g., via enhanced ROS formation) [29]. However, at the highest assay concentration also shorter chain analogues 9–11 reduced the MMP to approximately 60–80% of the control value as exemplarily shown for geranyl analogue 9 (Figure 2B). Antiparasitic activities were evaluated on the chloroquine

• interesting antiparasitic activities for these compounds relative to the cytotoxicity on human Vero cells, with antiplasmodial and antitrypanosomal selectivity indexes of 345 and 35, respectively, for aurachin D (4), which still make it medicinally relevant for antiparasitic purposes [31]. In accordance with

Chemoenzymatic synthesis and biological evaluation of enantiomerically enriched 1-(β-hydroxypropyl)imidazolium- and triazolium-based ionic liquids

• Paweł Borowiecki,
• Małgorzata Milner-Krawczyk and
• Jan Plenkiewicz

Beilstein J. Org. Chem. 2013, 9, 516–525, doi:10.3762/bjoc.9.56

• . Imidazole rings are also frequently present in antibacterial [6][7][8], antifungal [9][10][11][12][13], antiparasitic [14][15], anticancer [16][17] and antiaggregatory [18] preparations. In turn, many 1,2,4-triazole derivatives exhibit antimicrobial [19][20], antifungal [21], antitumor [22], analgesic [23

Engineering of indole-based tethered biheterocyclic alkaloid meridianin into β-carboline-derived tetracyclic polyheterocycles via amino functionalization/6-endo cationic π-cyclization

• Piyush K. Agarwal,
• Meena D. Dathi,
• Mohammad Saifuddin and
• Bijoy Kundu

Beilstein J. Org. Chem. 2012, 8, 1901–1908, doi:10.3762/bjoc.8.220

• applications for these therapeutically relevant indole-based polyheterocycles includes protein kinase C inhibitors, 5-HT agonists, melatonin agonists, and glucocorticoid receptor modulators, displaying cytotoxic, antiviral, antimicrobial, antiparasitic, anti-inflammatory, antiserotonin, Ca2+/calmodulin

Mutational analysis of a phenazine biosynthetic gene cluster in Streptomyces anulatus 9663

• Orwah Saleh,
• Katrin Flinspach,
• Lucia Westrich,
• Andreas Kulik,
• Bertolt Gust,
• Hans-Peter Fiedler and
• Lutz Heide

Beilstein J. Org. Chem. 2012, 8, 501–513, doi:10.3762/bjoc.8.57

• antiparasitic activities, and as inhibitors of angiotensin converting enzyme (ACE) or testosterone-5-α-reductase [1]. The synthetic phenazine clofazimine has been approved for human therapy in the treatment of leprosy. Some of the other naturally occurring phenazines are bacterial virulence factors [1]. Natural

Recent progress on the total synthesis of acetogenins from Annonaceae

• Nianguang Li,
• Zhihao Shi,
• Yuping Tang,
• Jianwei Chen and
• Xiang Li

Beilstein J. Org. Chem. 2008, 4, No. 48, doi:10.3762/bjoc.4.48

• Annonaceae plants as pesticidal and antiparasitic agents [8]. The proven activities of the acetogenins now include (but are not limited to): pesticidal, antifeedant, antiprotozoal, immunosuppressive and probably most importantly, antitumor [3]. In this respect they are known to be very potent cytotoxic