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

• example, in cases of calyculin and okadaic acid it has been proposed [18][19] that the spiroketal unit acts as a β-turn mimic. Naturally occurring spiroketals exhibit a wide spectrum of biological activity: anticancer [20][21][22], antibiotic [23][24], antifungal [25], anthelmintic [26] and anti-HIV [27

• sponges, which display extraordinary antitumor activity [29]. At the same time, the spiroketal-containing integramycin acts as an HIV-1 protease inhibitor [27]. The studies of Hayashi et al. have shown that the integrity of the spiroketal subunit is essential for the inhibition of telomerase by

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

• sensing; Introduction Chemical compounds containing an α-pyrone moiety are widespread in nature [1][2] and show a high diversity in their biological activity. Members of this class of compounds have been identified with antimicrobial, cytotoxic [3] and antitumor activities [4], as HIV protease inhibitors

DNA display of glycoconjugates to emulate oligomeric interactions of glycans

• Alexandre Novoa and
• Nicolas Winssinger

Beilstein J. Org. Chem. 2015, 11, 707–719, doi:10.3762/bjoc.11.81

• strand displacement thus allowing the glycosylated strand to adopt a folded structure. Affinity selection and reiteration of the cycle enables the in vitro evolution of glycan-functionalized aptamers. This technology was used to screen ligands for 2G12, an antibody that neutralizes HIV by binding to the

• 2G12, an antibody that neutralize HIV through tight binding with the glycan epitope, showed a clear distance–affinity relationship that was consistent with the proposed antibody–epitope interaction. Notably, neither of the PNA-tagged fragments making up the highest affinity assembly had measurable

• in the glycans. DC-SIGN is a tetrameric lectin implicated in interactions with a broad array of pathogens including HIV. A library of 37,485 assemblies was prepared by hybridization of two sets of PNA-tagged glycoconjugates onto a library of DNA templates (Figure 4). Screening the library by affinity

Novel stereocontrolled syntheses of tashiromine and epitashiromine

• Loránd Kiss,
• Enikő Forró and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2015, 11, 596–603, doi:10.3762/bjoc.11.66

• valuable physiological properties. A number of representatives of this class exhibit glycosidase inhibitory activity or antimetastatic, anticancer, antitumour or anti-HIV properties [1][2][3]. A large number of natural products contain an indolizidine framework, among them (−)-δ-coniceine, (−)-swainsonine

Enantioselective synthesis of polyhydroxyindolizidinone and quinolizidinone derivatives from a common precursor

• Nemai Saha and
• Shital K. Chattopadhyay

Beilstein J. Org. Chem. 2014, 10, 3104–3110, doi:10.3762/bjoc.10.327

• interest from both organic and medicinal chemists owing to their powerful biological activities [1][2][3]. For example, swainsonine (1, Figure 1) [4] and castanospermine (2) [5] obtained from natural sources have potent inhibitory effects towards various glycosidase enzymes and also exhibit anti-HIV

The Shono-type electroorganic oxidation of unfunctionalised amides. Carbon–carbon bond formation via electrogenerated N-acyliminium ions

• Alan M. Jones and
• Craig E. Banks

Beilstein J. Org. Chem. 2014, 10, 3056–3072, doi:10.3762/bjoc.10.323

• a linear peptide sequence was accomplished using an anodic oxidation step (Scheme 21). The stabilisation of linear peptides via inducing a stabilised secondary structure is of importance in mimicking protein–protein interactions (PPI) for diseases such as cancer and HIV [89][90]. The methoxylated

A one-pot multistep cyclization yielding thiadiazoloimidazole derivatives

• Debabrata Samanta,
• Anup Rana,
• Jan W. Bats and
• Michael Schmittel

Beilstein J. Org. Chem. 2014, 10, 2989–2996, doi:10.3762/bjoc.10.317

• bioactive compounds. For instance, thiadiazole containing heterocycles are known to exhibit important anti-inflammatory, antihypertensive, anti-HIV and antituberculosis activity [1]. Within this family, 1,2,4-thiadiazoles display notable medicinal properties as potent neuroprotectors [2

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

• various DNA and RNA. The ability of ethidium bromide analogues to inhibit the HIV-1 Rev–Rev Response Element (RRE) interaction, as well as their affinity to calf thymus (ct)DNA was analysed. One derivative (Figure 2, 1) displayed an enhanced affinity for HIV-1 RRE and a lower DNA affinity (i.e., lower

• respect to other nucleotides. In addition, the observed selectivity towards poly(G) and poly(A) can be beneficial in biological applications for instance to influence the mRNA-function via binding to the poly(A) tail [62][63][64] and inhibition of the HIV-1 replication by targeting recognition of the

• ligands that bind DNA:RNA hybrid structures. Latter play crucial roles in a number of biological processes (transcription, reverse transcription [79], the priming of DNA prior to replication [81], participating in different types of enzymatic activity, notably telomerases [82] and HIV RNase). Ethidium

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

New highlights of the syntheses of pyrrolo[1,2-a]quinoxalin-4-ones

• Emilian Georgescu,
• Alina Nicolescu,
• Florentina Georgescu,
• Florina Teodorescu,
• Daniela Marinescu,
• Ana-Maria Macsim and
• Calin Deleanu

Beilstein J. Org. Chem. 2014, 10, 2377–2387, doi:10.3762/bjoc.10.248

• constituent of several bioactive heterocyclic compounds that demonstrate interesting activity against Mycobacterium tuberculosis [1], anti-HIV [2], anticancer [3], and it modulates the estrogen receptor activity [4]. Synthetic methods towards pyrrolo[1,2-a]quinoxaline derivatives based on pyrroles [5], or

Pyrrolidine nucleotide analogs with a tunable conformation

• Lenka Poštová Slavětínská,
• Dominik Rejman and
• Radek Pohl

Beilstein J. Org. Chem. 2014, 10, 1967–1980, doi:10.3762/bjoc.10.205

• acyclic compounds 1a–c are currently in clinical use for the treatment of diseases caused by DNA viruses and retroviruses. Cyclic analogs 2 and 3 were reported to exhibit antiviral activity against HIV strains [3]. These examples show that the modification of the sugar-phosphate moiety in nucleotides is a

Synthesis of trifluoromethyl-substituted pyrazolo[4,3-c]pyridines – sequential versus multicomponent reaction approach

• Barbara Palka,
• Angela Di Capua,
• Maurizio Anzini,
• Gyté Vilkauskaité,
• Algirdas Šačkus and
• Wolfgang Holzer

Beilstein J. Org. Chem. 2014, 10, 1759–1764, doi:10.3762/bjoc.10.183

• the field of pyrazoles, pyridines and condensed systems thereof trifluoromethyl-substituted congeners can be found as partial structures in several pharmacologically active compounds. In the pyridine series the HIV protease inhibitor Tipranavir (Aptivus®) [6] may serve as an example, within the

Chemistry of polyhalogenated nitrobutadienes, 14: Efficient synthesis of functionalized (Z)-2-allylidenethiazolidin-4-ones

• Viktor A. Zapol’skii,
• Jan C. Namyslo,
• Mimoza Gjikaj and
• Dieter E. Kaufmann

Beilstein J. Org. Chem. 2014, 10, 1638–1644, doi:10.3762/bjoc.10.170

• focus on their anticancer [29][30][31] and anti-HIV potential [30][32]. Several 4-thiazolidinone derivatives such as ralitoline (anticonvulsant), etozoline (antihypertensive), pioglitazone (hypoglycemic) and thiazolidomycin (activity against streptomyces species) are already in the market [33]. Beyond

Glycosystems in nanotechnology: Gold glyconanoparticles as carrier for anti-HIV prodrugs

• Fabrizio Chiodo,
• Marco Marradi,
• Javier Calvo,
• Eloisa Yuste and
• Soledad Penadés

Beilstein J. Org. Chem. 2014, 10, 1339–1346, doi:10.3762/bjoc.10.136

• therapeutic approach for the treatment of HIV infection is based on the highly active antiretroviral therapy (HAART), a cocktail of antiretroviral drugs. Notwithstanding HAART has shown different drawbacks like toxic side effects and the emergence of viral multidrug resistance. Nanotechnology offers new tools

• to improve HIV drug treatment and prevention. In this scenario, gold nanoparticles are an interesting chemical tool to design and prepare smart and efficient drug-delivery systems. Here we describe the preparation and antiviral activity of carbohydrate-coated gold nanoparticles loaded with anti-HIV

• -containing glyconanoparticles were characterized and the pH-mediated release of the drug from the nanoparticle has been determined. The antiviral activity was tested by evaluating the replication of NL4-3 HIV in TZM-bl infected cells. The proof-of-principle presented in this work aims to introduce gold

Visible-light photoredox catalyzed synthesis of pyrroloisoquinolines via organocatalytic oxidation/[3 + 2] cycloaddition/oxidative aromatization reaction cascade with Rose Bengal

• Carlos Vila,
• Jonathan Lau and
• Magnus Rueping

Beilstein J. Org. Chem. 2014, 10, 1233–1238, doi:10.3762/bjoc.10.122

• of HIV integrase by lamellarin α-20-sulfate [6][7]. Moreover lamellarin I and lamellarin K also showed potential antitumor activities [8][9]. Due to their potential biological activities, the synthesis of pyrrolo[2,1-a]isoquinolines has become a very interesting, important and attractive goal in

Automated solid-phase peptide synthesis to obtain therapeutic peptides

• Veronika Mäde,
• Sylvia Els-Heindl and
• Annette G. Beck-Sickinger

Beilstein J. Org. Chem. 2014, 10, 1197–1212, doi:10.3762/bjoc.10.118

• Bivalirudin have been manufactured in multikilogram scale [10][19]. Enfuvirtide (T-20/ Fuzeon®), for example, is an efficient membrane fusion inhibitor for HIV treatment consisting of 36 amino acids [80]. The large-scale bulk production of Fuzeon® is performed by solution-phase fragment condensation from

Atherton–Todd reaction: mechanism, scope and applications

• Stéphanie S. Le Corre,
• Mathieu Berchel,
• Hélène Couthon-Gourvès,
• Jean-Pierre Haelters and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2014, 10, 1166–1196, doi:10.3762/bjoc.10.117

• shown for hydroquinone in Scheme 24 [76]. O,O-dialkyl thiophosphite was also engaged in AT reactions to produce dinucleotide designed as an anti-HIV prodrug [77]. H-phosphonothioates are intermediates considered for the synthesis of nucleotide analogues. This functional group can be used as a

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

Copper–phenanthroline catalysts for regioselective synthesis of pyrrolo[3′,4′:3,4]pyrrolo[1,2-a]furoquinolines/phenanthrolines and of pyrrolo[1,2-a]phenanthrolines under mild conditions

• Rupankar Paira,
• Tarique Anwar,
• Maitreyee Banerjee,
• Yogesh P. Bharitkar,
• Shyamal Mondal,
• Sandip Kundu,
• Abhijit Hazra,
• Prakas R. Maulik and
• Nirup B. Mondal

Beilstein J. Org. Chem. 2014, 10, 692–700, doi:10.3762/bjoc.10.62

• , antifungal, antitumor and anti-HIV candidates [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15]. We have also been pursuing the cycloaddition methodology for several years and established some synthetic routes towards indolizines, pyrrolo[1,2-a]quinolines/isoquinolines, oxazadicyclopenta[a,h]naphthalenes

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

• - [31], elastase- [32][33][34][35], and HIV-1 protease [36] and papain [37]. For the design of β-lactams, the Staudinger reaction involving a [2 + 2] cycloaddition of ketenes and imines is the most common method used [38]. However, Ugi reactions starting form β-amino acids are also described. In 2002

• numerous pharmaceutical and biological active compounds. For example, they are found in compounds used for the treatment of epilepsy [65][66], HIV [67][68], and depression [69]. Multicomponent reactions towards γ-lactam peptidomimetics were earlier described by Ugi [70], Mjalli [71] and Harriman [72

• of amide bonds by 1,2,3-triazoles, especially the 1,4-disubstituted isomer, provided a wide variety of biological active peptidomimetics. Peptidomimetics containing these triazole cores can serve as blood components [77], anticancer medications [78], inhibitors of cysteine [79] and HIV-1 proteases

A catalyst-free multicomponent domino sequence for the diastereoselective synthesis of (E)-3-[2-arylcarbonyl-3-(arylamino)allyl]chromen-4-ones

• Pitchaimani Prasanna,
• Pethaiah Gunasekaran,
• Subbu Perumal and
• J. Carlos Menéndez

Beilstein J. Org. Chem. 2014, 10, 459–465, doi:10.3762/bjoc.10.43

• ], antiviral [7], antihypertensive [8], anti-oxidant [9][10][11][12], HIV-inhibitory [13], anti-inflammatory [14][15], immunomodulatory [16], antithrombotic [17], and anticancer [18][19][20] activities. Furthermore, some chromone derivatives have been identified as suitable fluorophores for live cell imaging

Secondary amine-initiated three-component synthesis of 3,4-dihydropyrimidinones and thiones involving alkynes, aldehydes and thiourea/urea

• Jie-Ping Wan,
• Yunfang Lin,
• Kaikai Hu and
• Yunyun Liu

Beilstein J. Org. Chem. 2014, 10, 287–292, doi:10.3762/bjoc.10.25

• ; enamine activation; multicomponent reactions; Introduction DHPMs are well-known heterocyclic scaffolds with abundant biological relevance [1][2][3]. The DHPM backbone has been found in a class of marine natural products possessing anti-HIV activity [4]. What’s more, diversified other biological

Investigating the continuous synthesis of a nicotinonitrile precursor to nevirapine

• Ashley R. Longstreet,
• Suzanne M. Opalka,
• Brian S. Campbell,
• B. Frank Gupton and
• D. Tyler McQuade

Beilstein J. Org. Chem. 2013, 9, 2570–2578, doi:10.3762/bjoc.9.292

• . Box 842006 Richmond, Virginia 23284, United States 10.3762/bjoc.9.292 Abstract 2-Chloro-3-amino-4-picoline (CAPIC) is a strategic building block for the preparation of nevirapine, a widely-prescribed non-nucleosidic reverse transcriptase inhibitor for the treatment of HIV-infected patients. A

• other value added structures that contain complex pyridines. The route terminates in a batch crystallization yielding high purity CAPIC. This outcome is expected to facilitate regulatory implementation of the overall process. Keywords: continuous; flow chemistry; HIV; Knoevenagel; nevirapine

• ; nicotinonitriles; Introduction Nevirapine (3) was the first commercially available non-nucleoside reverse transcriptase inhibitor (NNRTI), and has remained an important medicine in the management of human immunodeficiency virus (HIV) [1][2]. Nevirapine combined with lamivudine (3TC) and azidothymidine (AZT) or

Synthesis of the spiroketal core of integramycin

• Evgeny. V. Prusov

Beilstein J. Org. Chem. 2013, 9, 2446–2450, doi:10.3762/bjoc.9.282

• Evgeny. V. Prusov Department of Medicinal Chemistry, Helmholtz Centre for Infection Research, Inhoffenstr. 7, 38124 Braunschweig, Germany 10.3762/bjoc.9.282 Abstract A concise synthetic strategy towards the spiroketal core of the HIV-integrase inhibitor integramycin (1) was developed. The

• ; hydrozirconation; natural products; spiroketals; total synthesis; Findings Integramycin is a polyketide natural product isolated from Actinoplanes sp. by the Singh group at Merck [1] (Figure 1). The compound was found to inhibit HIV-1 integrase coupled strand transfer reactions with IC50 values of 3 and 4 μM

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

• the presence of trimethylsilyl iodide together with oxathiolane 3.15 produces lamivudine (3.1) after reduction of the menthyl ester. Interestingly, the cis-(−)-enantiomer of structure 3.1 was reported to be much less cytotoxic although both cis-isomers are independently active against HIV. Recently, a

• important pyrimidine-based anti-HIV drug which was launched by Merck in 2008 [89]. Structurally, this HIV-integrase inhibitor consists of a fully substituted pyrimidone core flanked by an oxadiazole ring as well as an additional terminal para-fluorobenzyl unit. The central pyrimidone core was accessed in a