Cyclisation mechanisms in the biosynthesis of ribosomally synthesised and post-translationally modified peptides

• Andrew W. Truman

Beilstein J. Org. Chem. 2016, 12, 1250–1268, doi:10.3762/bjoc.12.120

• are antibacterial towards Gram-positive species by inhibiting protein biosynthesis [75], but some members also exhibit biological activity towards a number of eukaryotic targets, which makes them promising anticancer [76][77] and antimalarial [78] compounds. Intriguingly, a recent study identified

Base metal-catalyzed benzylic oxidation of (aryl)(heteroaryl)methanes with molecular oxygen

• Hans Sterckx,
• Johan De Houwer,
• Carl Mensch,
• Wouter Herrebout,
• Kourosch Abbaspour Tehrani and
• Bert U. W. Maes

Beilstein J. Org. Chem. 2016, 12, 144–153, doi:10.3762/bjoc.12.16

• , benzyldiazines and benzyl(iso)quinolines was successfully oxidized to the corresponding benzylic ketones using a copper or iron catalyst and molecular oxygen as the stoichiometric oxidant. Application of the protocol in API synthesis is exemplified by the alternative synthesis of a precursor to the antimalarial

• acid as a promotor [25]. The resulting ketones are very valuable as they are intermediates in the synthesis of a variety of pharmaceuticals such as the antimalarial Mefloquine (Lariam®), the antihistamine Acrivastine, the β2-adrenergic agonist Rimiterol and the anxiolytic Bromazepam [26]. Furthermore

• oxidation of the methyl group was seen [25]. Applications An example of an important pharmaceutical which is industrially prepared from an azinyl benzoazinyl ketone, namely (2,8-bis(trifluoromethyl)quinolin-4-yl)(pyridin-2-yl)methanone (10), is the antimalarial Mefloquine (13) [36]. This drug is listed on

Copper-catalyzed intermolecular oxyamination of olefins using carboxylic acids and O-benzoylhydroxylamines

• Brett N. Hemric and
• Qiu Wang

Beilstein J. Org. Chem. 2016, 12, 22–28, doi:10.3762/bjoc.12.4

• -adrenergic receptor agonist [3]; lumefantrine, an antimalarial drug [4]; ifenprodil, an N-methyl-D-aspartate (NMDA) antagonist [5]; and tebuconazole, a commercial fungicide [6]. With the importance of 1,2-oxyamino motifs as privileged pharmacophores, the development of facile and efficient access to this

Bromotyrosine-derived alkaloids from the Caribbean sponge Aplysina lacunosa

• Qun Göthel,
• Thanchanok Sirirak and
• Matthias Köck

Beilstein J. Org. Chem. 2015, 11, 2334–2342, doi:10.3762/bjoc.11.254

• activities, including antiviral [2], antibiotic [3][4][5], Na+/K+ ATPase inhibition [6][7][8], anti-HIV [9][10], antifungal [11], histidine-H3 antagonist [12], cytotoxic [13][14], and antimalarial activities [15][16][17]. During our investigation of the chemical constituents of Aplysina lacunosa (Aplysinidae

Photoinduced 1,2,3,4-tetrahydropyridine ring conversions

• Baiba Turovska,
• Henning Lund,
• Viesturs Lūsis,
• Anna Lielpētere,
• Edvards Liepiņš,
• Sergejs Beljakovs,
• Inguna Goba and
• Jānis Stradiņš

Beilstein J. Org. Chem. 2015, 11, 2166–2170, doi:10.3762/bjoc.11.234

• ; photoinduced electron transfer; pyrrolidine; tetrahydropyridine; Introduction Increased attention has been paid to the chemistry of cyclic organic peroxides since it was found that naturally occurring representatives of this group possess biological activity, particular antimalarial [1][2]. Significantly less

Structure and conformational analysis of spiroketals from 6-O-methyl-9(E)-hydroxyiminoerythronolide A

• Ana Čikoš,
• Irena Ćaleta,
• Dinko Žiher,
• Mark B. Vine,
• Ivaylo J. Elenkov,
• Marko Dukši,
• Dubravka Gembarovski,
• Marina Ilijaš,
• Snježana Dragojević,
• Ivica Malnar and
• Sulejman Alihodžić

Beilstein J. Org. Chem. 2015, 11, 1447–1457, doi:10.3762/bjoc.11.157

• investigations have shown that beside their antibacterial activity, some macrolides exhibit anti-inflammatory/immunomodulatory [5][6][7][8][9][10], antitumor [11][12][13], antiviral [10] or antimalarial [14][15] activity. These discoveries have sparked a new interest in the structural modification of macrolides

Synthesis of the furo[2,3-b]chromene ring system of hyperaspindols A and B

• Danielle L. Paterson and
• David Barker

Beilstein J. Org. Chem. 2015, 11, 265–270, doi:10.3762/bjoc.11.29

• ]chromenes. Compound which contain this motif, such as albanol A and australisine A, display potent bioactive properties including hypotensive, anticancer, antimicrobial and antimalarial activity [10][11][12]. The unique ring system found in the hyperaspidinols combined with the potent biological activities

(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

• production of various streptomycetes including the producing strain itself, and an exceptionally selective inhibitory effect on coryneform bacteria [3][4], an interesting antimalarial activity was discovered [13]. It was this property that led us to consider the synthesis of even more analogues of 1. Bearing

• 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

• analogues and the native hormaomycin (1) [57] showed good and selective antimalarial activities. Compounds 8a and 1 additionally showed an activity against L. donovani. However, the activities of the (trifluoromethylcyclopropyl)alanine-containing hormaomycin analogue 8a against L. donovani and P. falciparum

Asymmetric Ugi 3CR on isatin-derived ketimine: synthesis of chiral 3,3-disubstituted 3-aminooxindole derivatives

• Giordano Lesma,
• Fiorella Meneghetti,
• Alessandro Sacchetti,
• Mattia Stucchi and
• Alessandra Silvani

Beilstein J. Org. Chem. 2014, 10, 1383–1389, doi:10.3762/bjoc.10.141

• spirohydantoin III [9], and the new antimalarial lead IV [10][11] (Figure 1). Giving the importance of this structural motif, the development of rapid synthetic methods for oxindoles bearing a nitrogen atom at the C3-stereogenic center is highly required [12][13][14][15]. In the course of our studies on new

Cyclization–endoperoxidation cascade reactions of dienes mediated by a pyrylium photoredox catalyst

• Nathan J. Gesmundo and
• David A. Nicewicz

Beilstein J. Org. Chem. 2014, 10, 1272–1281, doi:10.3762/bjoc.10.128

• bond engenders these compounds with a range of important biological functions, most notably, antimalarial and antitumor activity (e.g., artemisinin, yingzhaosu A and merulin C) [1][2][3][4]. From a synthetic standpoint, the installation of the endoperoxide moiety presents a significant challenge due to

First synthesis of meso-substituted pyrrolo[1,2-a]quinoxalinoporphyrins

• Dileep Kumar Singh and
• Mahendra Nath

Beilstein J. Org. Chem. 2014, 10, 808–813, doi:10.3762/bjoc.10.76

• subunit display a wide spectrum of biological profiles as antagonists [26][27], PARP-1 inhibitors [28], anticancer agents [29][30], anti-HIV agents [31], and antimalarial agents [32][33]. These molecules are also important intermediates for the construction of 5-HT3 receptor agonists [34][35] and are

Synthesis of complex intermediates for the study of a dehydratase from borrelidin biosynthesis

• Frank Hahn,
• Nadine Kandziora,
• Steffen Friedrich and
• Peter F. Leadlay

Beilstein J. Org. Chem. 2014, 10, 634–640, doi:10.3762/bjoc.10.55

• polyketide-derived thioesters suited for biosynthesis studies. Keywords: aldol reaction; coenzyme A; natural products; pig liver esterase; polyketide biosynthesis; protection groups; Introduction Borrelidin (1) is a macrolactone polyketide natural product with promising antibacterial, antimalarial

Concise, stereodivergent and highly stereoselective synthesis of cis- and trans-2-substituted 3-hydroxypiperidines – development of a phosphite-driven cyclodehydration

• Peter H. Huy,
• Julia C. Westphal and
• Ari M. P. Koskinen

Beilstein J. Org. Chem. 2014, 10, 369–383, doi:10.3762/bjoc.10.35

• other bioactive compounds [1][2][3][4][5][6][7]. Selected examples are given in Figure 1: The non-peptidic human neurokinin-1 (NK1) substance P receptor antagonists L-733,060 [15][16] and CP-99,994 [17][18][19], the natural product febrifugine (antimalarial) [20][21] and antiprotozoal agent halofuginone

Intermediates in monensin biosynthesis: A late step in biosynthesis of the polyether ionophore monensin is crucial for the integrity of cation binding

• Wolfgang Hüttel,
• Jonathan B. Spencer and
• Peter F. Leadlay

Beilstein J. Org. Chem. 2014, 10, 361–368, doi:10.3762/bjoc.10.34

• except in animal husbandry, but they are attracting renewed interest for their antimalarial [8][9], antiviral [10][11] and novel anticancer [12][13] activities. In turn, this has given impetus to current attempts to engineer polyether biosynthetic pathways to provide novel analogues with potentially

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

• fundamental organic reactions. Due to these properties, the molecular structures can be greatly modified to give peroxide ring-retaining products. The chemistry of cyclic peroxides has attracted considerable attention, because these compounds are used in medicine for the design of antimalarial, antihelminthic

• considerable role. In medicinal chemistry of peroxides, artemisinin a natural peroxide exhibiting high antimalarial activity, is the most important drug in use for approximately 30 years. Artemisinin was isolated in 1971 from leaves of annual wormwood (Artemesia annua) [49][50][51]; the 1,2,4-trioxane ring V

• , this compound is currently in phase III clinical trials [77][78][79][80][81]. The mechanism of antimalarial action of peroxides is unusual for pharmaceutical chemistry. According to the commonly accepted mechanism, peroxides diffuse into Plasmodium-infected erythrocytes, and the heme iron ion of the

Bidirectional cross metathesis and ring-closing metathesis/ring opening of a C₂-symmetric building block: a strategy for the synthesis of decanolide natural products

• Bernd Schmidt and
• Oliver Kunz

Beilstein J. Org. Chem. 2013, 9, 2544–2555, doi:10.3762/bjoc.9.289

• , antimalarial and antibacterial activity, which are a strong motivation for total synthesis [26][27]. In addition, several ambiguities in the structural assignment of some of these natural products still exist, and chemical synthesis has been proven to be a powerful and reliable tool for completing the

AgOTf-catalyzed one-pot reactions of 2-alkynylbenzaldoximes with α,β-unsaturated carbonyl compounds

• Qiuping Ding,
• Dan Wang,
• Puying Luo,
• Meiling Liu,
• Shouzhi Pu and
• Liyun Zhou

Beilstein J. Org. Chem. 2013, 9, 1949–1956, doi:10.3762/bjoc.9.231

• processes. Isoquinoline derivatives, an important class of nitrogen-containing polycyclic heteroarenes, have attracted considerable attention because of their pharmacological activities, including antitumor, antifungal, antimalarial, antihypertensive and antihistaminic activity, and their photo- and

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

• at an IC50 around 20 ng/mL (i.e., aurachins B, C and E, whereas aurachin D was 100- to 200-fold less active) [6]. This antimalarial activity was comparable to that of endochin (5) [13][14] and 2-methyl-4(1H)-quinolone analogues as determined in the course of important structure–activity optimization

Re₂O₇-catalyzed reaction of hemiacetals and aldehydes with O-, S-, and C-nucleophiles

• Wantanee Sittiwong,
• Michael W. Richardson,
• Charles E. Schiaffo,
• Thomas J. Fisher and
• Patrick H. Dussault

Beilstein J. Org. Chem. 2013, 9, 1526–1532, doi:10.3762/bjoc.9.174

• electron-poor amine in the presence of allyltrimethylsilane [15]. We now describe the Re2O7-promoted reactions of peroxyhemiacetals, hemiacetals, and alkoxyhydroperoxides with O-, S- and C-nucleophiles. Results In the course of investigations into potential antischistosomal and antimalarial agents [16][17

Synthesis of 2,3-dihydronaphtho[2,3-d][1,3]thiazole-4,9-diones and 2,3-dihydroanthra[2,3-d][1,3]thiazole-4,11-diones and novel ring contraction and fusion reaction of 3H-spiro[1,3-thiazole-2,1'-cyclohexanes] into 2,3,4,5-tetrahydro-1H-carbazole-6,11-diones

• Lidia S. Konstantinova,
• Kirill A. Lysov,
• Ljudmila I. Souvorova and
• Oleg A. Rakitin

Beilstein J. Org. Chem. 2013, 9, 577–584, doi:10.3762/bjoc.9.62

• -naphthoquinone structure is common for various natural products. It is associated with numerous biological activities, such as enzyme-inhibitory, antifungal, antibacterial, anticancer, antiproliferative, antiplatelet, anti-inflammatory, antiallergic, and antimalarial ones. Benzoquinones fused with heterocycles

Synthesis of meso-substituted dihydro-1,3-oxazinoporphyrins

• Satyasheel Sharma and
• Mahendra Nath

Beilstein J. Org. Chem. 2013, 9, 496–502, doi:10.3762/bjoc.9.53

• cancers [30]. Thorough literature search revealed that heterocycles containing a dihydro-1,3-oxazine ring system exhibit a wide spectrum of pharmacological activities, for example, acting as antimicrobial [31][32][33], anti-HIV [34], antimalarial [35] or antitumor agents [36][37]. By considering the

Zanthoxoaporphines A–C: Three new larvicidal dibenzo[de,g]quinolin-7-one alkaloids from Zanthoxylum paracanthum (Rutaceae)

• Fidelis N. Samita,
• Louis P. Sandjo,
• Isaiah O. Ndiege,
• Ahmed Hassanali and
• Wilber Lwande

Beilstein J. Org. Chem. 2013, 9, 447–452, doi:10.3762/bjoc.9.47

• , oxoaporphine and aporphine analogues have shown antimalarial, antitrypanosomal [24], cytotoxic [25], antioxidant [26] and larvicidal activities [20][21]. Despite the reported bioactivities, some of the oxoaporphines and aporphines have undesirable effects, for instance liriodenine is mutagenic [27] and induces

Synthesis of SF₅-containing benzisoxazoles, quinolines, and quinazolines by the Davis reaction of nitro-(pentafluorosulfanyl)benzenes

• Petr Beier and
• Tereza Pastýříková

Beilstein J. Org. Chem. 2013, 9, 411–416, doi:10.3762/bjoc.9.43

• co-workers have recently reported the synthesis of some SF5-substituted quinolines as intermediates towards analogues of the antimalarial agent mefloquine and found that some analogues had improved activity and selectivity against malaria parasites (Scheme 2) [29][30]. Results and Discussion We

The diketopiperazine-fused tetrahydro-β-carboline scaffold as a model peptidomimetic with an unusual α-turn secondary structure

• Francesco Airaghi,
• Andrea Fiorati,
• Giordano Lesma,
• Manuele Musolino,
• Alessandro Sacchetti and
• Alessandra Silvani

Beilstein J. Org. Chem. 2013, 9, 147–154, doi:10.3762/bjoc.9.17

• ]. Moreover, recently some tetracyclic β-carbolines have been described to act as selective inhibitors in the anticancer field [8][9], or to be endowed with antimalarial properties [10]. 2,5-Diketopiperazine (DKP)-based compounds are heterocyclic scaffolds structurally similar to peptides. They have attracted

• type 5 specific phosphodiesterase (PDE 5) for the treatment of erectile dysfunction (Tadalafil) [21], and the inhibition of plasmodial PDE activity for antimalarial drugs [22][23], to topoisomerase II inhibition [24], and oral antithrombotic properties [25] (Figure 1). In our ongoing program of design

Inclusion of the insecticide fenitrothion in dimethylated-β-cyclodextrin: unusual guest disorder in the solid state and efficient retardation of the hydrolysis rate of the complexed guest in alkaline solution

• Dyanne L. Cruickshank,
• Natalia M. Rougier,
• Raquel V. Vico,
• Susan A. Bourne,
• Elba I. Buján,
• Mino R. Caira and
• Rita H. de Rossi

Beilstein J. Org. Chem. 2013, 9, 106–117, doi:10.3762/bjoc.9.14

• form of a residual contact spray to control flies, mosquitoes and cockroaches. Fenitrothion has also been employed in antimalarial programmes, where spraying of houses and animal shelters with this insecticide over extended periods significantly reduced the incidence and prevalence of the disease [4