The chemistry of isoindole natural products

• Klaus Speck and
• Thomas Magauer

Beilstein J. Org. Chem. 2013, 9, 2048–2078, doi:10.3762/bjoc.9.243

• , Vedejs), the convergent approach reported by Myers allows a modular entry to diverse members of the cytochalasin alkaloid family [68]. As proof of concept, the macrolactone cytochalasin B (52) and the carbocyclic cytochalasin L-696,474 (78), a potent HIV-1 protease inhibitor [69][70][71][72], were

• interesting biological properties, such as high antiviral activity (156) [141], inhibition of the HIV-1 protease (157) [132], antibacterial and antifungal activities (159–160) [133] or neuritogenic properties (161) [134]. So far, only a few total syntheses were accomplished and the exact biosynthetic pathways

New tridecapeptides of the theonellapeptolide family from the Indonesian sponge Theonella swinhoei

• Annamaria Sinisi,
• Barbara Calcinai,
• Carlo Cerrano,
• Henny A. Dien,
• Angela Zampella,
• Claudio D’Amore,
• Barbara Renga,
• Stefano Fiorucci and
• Orazio Taglialatela-Scafati

Beilstein J. Org. Chem. 2013, 9, 1643–1651, doi:10.3762/bjoc.9.188

• oxazole or thiazole rings) [10], papuamides (HIV inhibitory macrocyclic depsipeptides) [11], polytheonamides (cytotoxic linear polypeptides) [12], cyclotheonamides (thrombin and serine protease inhibitors) [13], perthamides (anti-inflammatory cyclopeptides) [14][15], solomonamides [16] and

Efficient continuous-flow synthesis of novel 1,2,3-triazole-substituted β-aminocyclohexanecarboxylic acid derivatives with gram-scale production

• Sándor B. Ötvös,
• Ádám Georgiádes,
• István M. Mándity,
• Lóránd Kiss and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2013, 9, 1508–1516, doi:10.3762/bjoc.9.172

• in Figure 1) [8][9]. The 1,2,3-triazole moiety is a constituent part of many modified nucleosides or carbanucleosides with antiviral, anti-HIV or cytostatic activities [10][11][12]. However, the scope of triazole chemistry is not confined to drug discovery. There are an increasing number of

Amyloid-β probes: Review of structure–activity and brain-kinetics relationships

• Todd J. Eckroat,
• Abdelrahman S. Mayhoub and
• Sylvie Garneau-Tsodikova

Beilstein J. Org. Chem. 2013, 9, 1012–1044, doi:10.3762/bjoc.9.116

• . Between 2000 and 2008, the number of deaths caused by AD increased by 66%, a dramatic rise, especially when compared to other causes of death, such as heart disease, stroke, prostate and breast cancer, and HIV, which decreased by 3–29% during that time period [1]. As these numbers indicate, AD represents

Study on the total synthesis of velbanamine: Chemoselective dioxygenation of alkenes with PIFA via a stop-and-flow strategy

• Huili Liu,
• Kuan Zheng,
• Xiang Lu,
• Xiaoxia Wang and
• Ran Hong

Beilstein J. Org. Chem. 2013, 9, 983–990, doi:10.3762/bjoc.9.113

• of trans/cis of 1.9:1. Compound 25a can be easily converted into the key intermediate in the synthesis of indinavir, a protease inhibitor used as a component of a highly active antiretroviral therapy to treat HIV infection and AIDS [69]. When two alkene groups exist in 24b–d, the terminal alkene

A facile, rapid, one-pot regio/stereoselective synthesis of 2-iminothiazolidin-4-ones under solvent/scavenger-free conditions

• Murugan Sathishkumar,
• Sangaraiah Nagarajan,
• Poovan Shanmugavelan,
• Murugan Dinesh and
• Alagusundaram Ponnuswamy

Beilstein J. Org. Chem. 2013, 9, 689–697, doi:10.3762/bjoc.9.78

• ; scavenger-free; Introduction Thiazolidin-4-one derivatives are well known for their bioactivities such as antidiabetic [1], anticancer [2], calcium-channel blocker [3][4], platelet activating factor (PAF) antagonist [5] and anti-HIV [6] activity. In addition, 2-iminothiazolidin-4-ones exhibit remarkable

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

• ], anti-inflammatory [24], psychoactive [25][26][27], anticonvulsant [28], diuretic [29], and anti-HIV [30] activity. 1,2,4-Triazole derivatives also represent the most important group of herbicides and fungicides [31]. In recent years growing attention has been focused on imidazole- and 1,2,4-triazole

A one-pot catalyst-free synthesis of functionalized pyrrolo[1,2-a]quinoxaline derivatives from benzene-1,2-diamine, acetylenedicarboxylates and ethyl bromopyruvate

• Mohammad Piltan,
• Loghman Moradi,
• Golaleh Abasi and
• Seyed Amir Zarei

Beilstein J. Org. Chem. 2013, 9, 510–515, doi:10.3762/bjoc.9.55

• of various bioactive compounds that possess antibiotic, anti-inflammatory, antimicrobial [5], antidiabetic [6], and antiviral activity against retroviruses including HIV [7]. In addition, quinoxaline derivatives are also associated with a wide spectrum of biological effects including anticancer [8

Facile synthesis of benzothiadiazine 1,1-dioxides, a precursor of RSV inhibitors, by tandem amidation/intramolecular aza-Wittig reaction

• Krishna C. Majumdar and
• Sintu Ganai

Beilstein J. Org. Chem. 2013, 9, 503–509, doi:10.3762/bjoc.9.54

• and medicinal chemists, because this basic moiety is present in many natural products and biologically active substances [1][2][3][4][5][6][7][8]. Especially, benzothiadiazine-3-one 1,1-dioxide and its derivatives possess potential activity, including hypoglycemic [9], anticancer and anti-HIV activity

• activity [16][17][18][19][20][21][22], including hypoglycemic (1), anti-HIV (2), HIV-1 specific non-nucleoside reverse transcriptase inhibitor (3), sedative (4), and respiratory syncytial virus (RSV) inhibitory activity (5; Figure 1). A literature search revealed that the 1,2,4-benzothiadiazine 1,1

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

Asymmetric synthesis of host-directed inhibitors of myxoviruses

• Terry W. Moore,
• Kasinath Sana,
• Dan Yan,
• Pahk Thepchatri,
• John M. Ndungu,
• Manohar T. Saindane,
• Mark A. Lockwood,
• Michael G. Natchus,
• Dennis C. Liotta,
• Richard K. Plemper,
• James P. Snyder and
• Aiming Sun

Beilstein J. Org. Chem. 2013, 9, 197–203, doi:10.3762/bjoc.9.23

• impact on human health [2][3][4][5]. Although antivirals typically seek to disable viral proteins, cellular host proteins can also be targeted, as is the case with selzentry, which inactivates the coreceptor (CCR5) for human immunodeficiency virus (HIV) entry [6]. The former approach is likely to yield

Metal-mediated aminocatalysis provides mild conditions: Enantioselective Michael addition mediated by primary amino catalysts and alkali-metal ions

• Matthias Leven,
• Jörg M. Neudörfl and
• Bernd Goldfuss

Beilstein J. Org. Chem. 2013, 9, 155–165, doi:10.3762/bjoc.9.18

• -hydroxycoumarins to α,β-unsaturated ketones (Scheme 2) [19][20][21][22][23][24][25][26][27]. There is a wide spread of 4-hydroxycoumarins in pharmaceuticals such as anticoagulants and substances that inhibit HIV or malaria [28][29]. Among the most prominent chiral 4-hydroxycoumarins is warfarin, which works as a

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

• -HIV compounds [38]. Other examples of α-turn conformations are described in synthetic peptidomimetics [36][39][40][41][42]. Despite the growing interest in this kind of reverse turn and the need for all kinds of conformationally constrained mimics as tools for medicinal chemistry, the development of

Theoretical study on β-cyclodextrin inclusion complexes with propiconazole and protonated propiconazole

• Adrian Fifere,
• Narcisa Marangoci,
• Stelian Maier,
• Adina Coroaba,
• Dan Maftei and
• Mariana Pinteala

Beilstein J. Org. Chem. 2012, 8, 2191–2201, doi:10.3762/bjoc.8.247

• fungal diseases has dramatically increased during the past 20 years. Extremely rare ten years ago, nowadays, antifungal drug resistance has become an important problem in treatment of fungal diseases for various categories of patients, especially those infected with HIV. Excessive and prolonged treatment

• with azole-containing medicines has led to fungal resistance to this class of compounds, especially in the case of HIV patients with repeated recurrent episodes [1][2]. Today, the number of reported cases of clinic resistance to antifungal drugs is growing and mycologists have warned about an

Cyclodextrin-based nanosponges as drug carriers

• Francesco Trotta,
• Marco Zanetti and
• Roberta Cavalli

Beilstein J. Org. Chem. 2012, 8, 2091–2099, doi:10.3762/bjoc.8.235

• [38]. Nelfinavir is a protease inhibitor with low bioavailability, used to treat HIV infections. In this case, the drug was released more slowly from nanosponges than from a β-CD complex. This behaviour shows that nanosponges are able to prolong drug release over time and consequently could also be

Tricyclic flavonoids with 1,3-dithiolium substructure

• Lucian G. Bahrin,
• Peter G. Jones and
• Henning Hopf

Beilstein J. Org. Chem. 2012, 8, 1999–2003, doi:10.3762/bjoc.8.226

• unit. In addition to this, they are known to possess anti-inflammatory activity, inhibit the lens-aldose reductase, and decrease the blood glucose level [11][12]. Moreover, compound 3 was shown to inhibit HIV-1 integrase [13][14]. Several molybdenum and tungsten oxobisdithiolene complexes have been

Peptides presenting the binding site of human CD4 for the HIV-1 envelope glycoprotein gp120

• Julia Meier,
• Kristin Kassler,
• Heinrich Sticht and
• Jutta Eichler

Beilstein J. Org. Chem. 2012, 8, 1858–1866, doi:10.3762/bjoc.8.214

• Based on the structure of the HIV-1 glycoprotein gp120 in complex with its cellular receptor CD4, we have designed and synthesized peptides that mimic the binding site of CD4 for gp120. The ability of these peptides to bind to gp120 can be strongly enhanced by increasing their conformational stability

• -amino acids. Keywords: biomimetic synthesis; CD4; HIV entry; peptide; protein binding site; Introduction Synthetic molecules that have the ability to mimic binding and/or functional sites of proteins are useful tools for exploring and modulating protein function, as they interfere with binding events

• protein binding site mimics. We have previously developed strategies for the design and generation of scaffolded and assembled peptides to generate protein binding site mimics [1]. The interaction of the HIV-1 envelope glycoprotein gp120 with its cellular receptor CD4 is the first step in the process of

Automated three-component synthesis of a library of γ-lactams

• Erik Fenster,
• David Hill,
• Oliver Reiser and
• Jeffrey Aubé

Beilstein J. Org. Chem. 2012, 8, 1804–1813, doi:10.3762/bjoc.8.206

• been significant in the treatment of epilepsy [6][7], HIV [8][9], neurodegenerative disease and depression [10][11]. Having identified the lactam ring as a target of opportunity in chemical-screening efforts, we previously reported a method to prepare γ-lactams from readily available maleimides

Molecular solubilization of fullerene C₆₀ in water by γ-cyclodextrin thioethers

• Hai Ming Wang and
• Gerhard Wenz

Beilstein J. Org. Chem. 2012, 8, 1644–1651, doi:10.3762/bjoc.8.188

• synthesized and utilized for the inhibition of therapeutically important enzymes, such as HIV-1 protease [12], for the prevention of bacterial growth [13][14], or for photodynamic therapy of cancer by scission of DNA [3]. Despite these successes, there are still several issues relating to the chemical

• solvents will hopefully find interesting applications in biomedicine, such as in photodynamic therapy or HIV-protease inhibition. Experimental General Unless otherwise stated, all chemicals were used as received. Powdered fullerene C60 (> 99%) was purchased from Sigma Aldrich. Teflon syringe filters from

Design of a novel tryptophan-rich membrane-active antimicrobial peptide from the membrane-proximal region of the HIV glycoprotein, gp41

• Evan F. Haney,
• Leonard T. Nguyen,
• David J. Schibli and
• Hans J. Vogel

Beilstein J. Org. Chem. 2012, 8, 1172–1184, doi:10.3762/bjoc.8.130

• biological activity of antimicrobial peptides. This information was used to design a novel antimicrobial peptide sequence by using an intrinsically inactive membrane-associated peptide derived from the HIV glycoprotein, gp41, as a starting scaffold. This peptide corresponds to the tryptophan-rich membrane

• that does not possess intrinsic antimicrobial activity. Peptides derived from the envelope HIV-1 glycoproteins, gp120 and gp41, have previously been examined for their antimicrobial activity [10] and we chose to use the membrane-proximal region of gp41 as our starting peptide scaffold. This region of

• has four additional positive charges and is also antimicrobially inactive. The lack of antimicrobial activity may be related to the fact that the gp41w peptide appears to oligomerize in solution. When found in the HIV-1 Env glycoprotein complex, gp41 is known to exist as a trimer [26], and previous

Synthetic glycopeptides and glycoproteins with applications in biological research

• Ulrika Westerlind

Beilstein J. Org. Chem. 2012, 8, 804–818, doi:10.3762/bjoc.8.90

• hydrolysis reaction could be avoided [84][85]. A number of successful preparations of N-glycopeptides and N-glycoproteins have since then been successfully prepared by using oxazoline oligosaccharide donors; the synthesis of a HIV gp120 glycopeptide fragment, the HIV gp41 peptide, and the RNase B

Synthesis and antiviral activities of spacer-linked 1-thioglucuronide analogues of glycyrrhizin

• Christian Stanetty,
• Andrea Wolkerstorfer,
• Hassan Amer,
• Andreas Hofinger,
• Ulrich Jordis,
• Dirk Claßen-Houben and
• Paul Kosma

Beilstein J. Org. Chem. 2012, 8, 705–711, doi:10.3762/bjoc.8.79

• directed against a broad spectrum of viruses comprising herpes-, corona-, alpha-, and flaviviruses, HIV, Epstein–Barr virus, influenza A virus (IAV), vaccinia and polio type I viruses as examples [3][4][5][6][7][8]. In particular anti-influenza virus activities have been described, although the underlying

Investigation of the network of preferred interactions in an artificial coiled-coil association using the peptide array technique

• Raheleh Rezaei Araghi,
• Carsten C. Mahrenholz,
• Rudolf Volkmer and
• Beate Koksch

Beilstein J. Org. Chem. 2012, 8, 640–649, doi:10.3762/bjoc.8.71

• selectivity, forming stable multimers with strong interhelical interactions. Recently, their potential as drug targets has become the focus of medical research [3]. Their effectiveness in the successful inhibition of membrane fusion proteins of viruses, such as HIV [4] and avian influenza [5], also supports

Synthesis and characterization of new diiodocoumarin derivatives with promising antimicrobial activities

• Hany M. Mohamed,
• Ashraf H. F. Abd EL-Wahab,
• Ahmed M. EL-Agrody,
• Ahmed H. Bedair,
• Fathy A. Eid,
• Mostafa M. Khafagy and
• Kamal A. Abd-EL-Rehem

Beilstein J. Org. Chem. 2011, 7, 1688–1696, doi:10.3762/bjoc.7.199

• ]. Coumarins have also been reported to exhibit several biological activities, such as antimicrobial, anticancer, antifungal, anti-HIV and antioxidant properties [3][4][5][6], and they also served as versatile precursors for many organic transformations in the synthesis of a number of drug-like molecules [7][8

Marilones A–C, phthalides from the sponge-derived fungus Stachylidium sp.

• Celso Almeida,
• Stefan Kehraus,
• Miguel Prudêncio and
• Gabriele M. König

Beilstein J. Org. Chem. 2011, 7, 1636–1642, doi:10.3762/bjoc.7.192

• liver stages as described by Ploemen et al. [24]. Inhibition of the viral HIV-1- and HIV-2-induced cytopathogenic effect in MT-4 cells assays was performed according to Pannecouque et al. [25] and Zhan et al. [26]. Severe Acute Respiratory Syndrome coronavirus (SARS) assays were performed according to

• Phosphorylation & Disease, CNRS, Roscoff, France) for performing the protein kinases assays and Dr. C. Pannecouque (Rega Institute for Medical Research, Leuven, Belgium) for performing the HIV-1 and HIV-2 antiviral assays; we also kindly thank Indra Bergval (KIT Biomedical Research, Royal Tropical Institute