Reagent-controlled regiodivergent intermolecular cyclization of 2-aminobenzothiazoles with β-ketoesters and β-ketoamides

• Irwan Iskandar Roslan,
• Kian-Hong Ng,
• Gaik-Khuan Chuah and
• Stephan Jaenicke

Beilstein J. Org. Chem. 2017, 13, 2739–2750, doi:10.3762/bjoc.13.270

• regioselectively form this instead of 3a and 4. This tricyclic backbone can be found in compounds that possess a wide range of medicinal properties including those with antimalarial [74], anticancer [75][76], antiallergic [77][78], antibacterial [79], and antimicrobial properties [80][81]. In addition, they have

Phosphonic acid: preparation and applications

• Charlotte M. Sevrain,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2017, 13, 2186–2213, doi:10.3762/bjoc.13.219

• applications in biology and medicine to mimic the phosphate group leading to antiretroviral drugs (e.g., tenofovir (1)) [39], isoprenoid biosynthesis inhibitors [40][41], antibiotics (e.g., fosfomycin (2)) [42], tyrosine phosphatase inhibitors 3 [43], antimalarial 4 [44], antihypertensive drugs (e.g., K4 5 and

Synthesis of 2-aminosuberic acid derivatives as components of some histone deacetylase inhibiting cyclic tetrapeptides

• Shital Kumar Chattopadhyay,
• Suman Sil and
• Jyoti Prasad Mukherjee

Beilstein J. Org. Chem. 2017, 13, 2153–2156, doi:10.3762/bjoc.13.214

• antimalarial and histone deacetylase inhibitory (HDACi) properties [1][2]. It has been suggested [3] that the terminal carbonyl group in members of this family (e.g., in 2) functionally mimics the C-8 keto group of the acetylated lysine residue (3) of histones as a part of their biological activity and

Mechanochemical synthesis of thioureas, ureas and guanidines

• Vjekoslav Štrukil

Beilstein J. Org. Chem. 2017, 13, 1828–1849, doi:10.3762/bjoc.13.178

• . With the principal synthetic routes to (thio)ureas and guanidines in the solid-state now established, the next challenge of incorporation of these simple structural units into more complex molecular systems by mechanochemistry is expected. Antidiabetic (1–3) and antimalarial (4) drugs derived from

Opportunities and challenges for the sustainable production of structurally complex diterpenoids in recombinant microbial systems

• Katarina Kemper,
• Max Hirte,
• Markus Reinbold,
• Monika Fuchs and
• Thomas Brück

Beilstein J. Org. Chem. 2017, 13, 845–854, doi:10.3762/bjoc.13.85

• ), artemisinin [2] (antimalarial agent) and α-pinene [3] (antibiotic, anti-inflammatory). Apart from bioactive compounds with applications as drugs/pharmaceuticals [4] or in the nutrition or agricultural sector, isoprenoids of minor structural complexity are used as bulk chemicals or fuel additives [5][6]. To

• -pinene or limonene [78]. At present, 27.4 g/L of amorphadiene is the highest published titer for any reported terpenoid produced in E. coli. This result is of particular industrial relevance as amorphadiene constitutes the sesquiterpenoid scaffold of the antimalarial drug artemisinin [79]. In comparison

New approach toward the synthesis of deuterated pyrazolo[1,5-a]pyridines and 1,2,4-triazolo[1,5-a]pyridines

• Aleksey Yu. Vorob’ev,
• Vyacheslav I. Supranovich,
• Gennady I. Borodkin and
• Vyacheslav G. Shubin

Beilstein J. Org. Chem. 2017, 13, 800–805, doi:10.3762/bjoc.13.80

• antiviral [7][8], antimalarial [9] and antitubercular [10] agents. Also they were applied in the development of FIXa [11], PI3K [12], EGFR [13] and PDE [14] inhibitors and dopamine receptor ligands [15]. The nonselective PDE3,4 inhibitor ibudilast (MN-166) has been marketed in Japan for over 25 years for

Contribution of microreactor technology and flow chemistry to the development of green and sustainable synthesis

• Flavio Fanelli,
• Giovanna Parisi,
• Leonardo Degennaro and
• Renzo Luisi

Beilstein J. Org. Chem. 2017, 13, 520–542, doi:10.3762/bjoc.13.51

• is compatible with sensitive functional groups such as silyl ether, halogenes, and benzyl groups. A very nice application of this approach was the highly selective reduction of artemisinic acid to dihydroartemisinic acid, which are of interest in the synthesis of the antimalarial drug artemisinin

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

• , have been performed. This review also covers the most important studies on the biological activity of 1-indanones and their derivatives which are potent antiviral, anti-inflammatory, analgesic, antimalarial, antibacterial and anticancer compounds. Moreover, they can be used in the treatment of

• allowed the synthesis of 60 in yields ranged from 31 to 56%. 1-Indanones exhibit a broad spectrum of biological activity including anti-inflammatory [41], analgesic [42], antimicrobial [43], antiviral [5], anticancer [44] and antimalarial [45] activity. A combination of two or more biologically active

First DMAP-mediated direct conversion of Morita–Baylis–Hillman alcohols into γ-ketoallylphosphonates: Synthesis of γ-aminoallylphosphonates

• Marwa Ayadi,
• Haitham Elleuch,
• Emmanuel Vrancken and
• Farhat Rezgui

Beilstein J. Org. Chem. 2016, 12, 2906–2915, doi:10.3762/bjoc.12.290

• interesting antimicrobial and antimalarial properties [8][9], as well as useful substrates for the synthesis of valuable organic compounds [10][11][12]. Historically, the Michaelis−Arbuzov rearrangement [13] is the most widely and generally high yielding strategy for phosphonate synthesis. The current three

• derivatives were originally isolated from microorganisms [37][38], e.g., the fosmidomycin [39] is as an antimalarial drug that was isolated from broths of bacteria of the genus Streptomyces [40]. The γ-aminophosphonates were prepared through numerous synthetic methods [41][42][43][44][45]. For instance, they

Multicomponent synthesis of spiropyrrolidine analogues derived from vinylindole/indazole by a 1,3-dipolar cycloaddition reaction

• Manjunatha Narayanarao,
• Lokesh Koodlur,
• Vijayakumar G. Revanasiddappa,
• Subramanya Gopal and
• Susmita Kamila

Beilstein J. Org. Chem. 2016, 12, 2893–2897, doi:10.3762/bjoc.12.288

• [7][8][9][10]. Indole and indazolyl subunits are central to numerous alkaloids and are constituents of many classes of compounds that display a wide range of bioactivities such as antimycobacterial, anti-inflammatory, antihypertensive, anticancer, antidepressant, antidiabetic, antimalarial

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

• agents and initiators for free-radical reactions both in industry and in laboratory. These compounds are produced and involved in various natural and biological processes and were explored extensively as antimalarial agents, anthelmintics, and anticancer drugs. Organic peroxides, such as alkyl

• ][2][3][4][5][6][7][8][9]. Nowadays, the progress in the chemistry of organic peroxides is mainly a result of their biological activity and pharmaceutical application. The search of effective antimalarial and antihelminthic drugs is the main challenge of medicinal chemistry of peroxides. According to

• the World Health Organization (WHO) malaria is a widely distributed illness. About 3.2 billion people remain at risk of malaria and in 2015 214 million cases of malaria and 438 thousands deaths from it have been registered [10]. Compounds with high antimalarial [11][12][13][14][15][16][17][18][19][20

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