An improved synthesis of adefovir and related analogues

• David J. Jones,
• Eileen M. O’Leary and
• Timothy P. O’Sullivan

Beilstein J. Org. Chem. 2019, 15, 801–810, doi:10.3762/bjoc.15.77

• caused by the hepatitis B virus (HBV) [3][4][5] and the herpes simplex virus (HSV, Figure 1) [5][6]. While 1 possesses inhibitory activity against the human immunodeficiency virus (HIV) [1][5], it has not been approved by the FDA for the treatment of HIV as the dose required to elicit inhibition can

• form alcohol 4 and further base-mediated alkylation with tosylate 5 affords phosphonate ester intermediate 6. Subsequent dealkylation of 6 using trimethylsilyl bromide (TMSBr) gives adefovir (1). The related analogue tenofovir, developed as an anti-HIV agent, may be prepared in a similar manner [37][38

Synthesis of C₃-symmetric star-shaped molecules containing α-amino acids and dipeptides via Negishi coupling as a key step

• Sambasivarao Kotha and
• Saidulu Todeti

Beilstein J. Org. Chem. 2019, 15, 371–377, doi:10.3762/bjoc.15.33

• the complex interactions between cells and pathogens, e.g., the human immunodeficiency virus (HIV-1) [6]. The HIV-1 envelope protein is present as a C3-symmetric trimer on the viruses’ surface [7], and the virus entry into the cell is mediated by its interactions with cellular receptors. To explore

A novel and efficient synthesis of phenanthrene derivatives via palladium/norbornadiene-catalyzed domino one-pot reaction

• Yue Zhong,
• Wen-Yu Wu,
• Shao-Peng Yu,
• Tian-Yuan Fan,
• Hai-Tao Yu,
• Nian-Guang Li,
• Zhi-Hao Shi,
• Yu-Ping Tang and
• Jin-Ao Duan

Beilstein J. Org. Chem. 2019, 15, 291–298, doi:10.3762/bjoc.15.26

• used as fundamental building blocks or intermediates in the synthesis of complex natural products such as tuberosinone [1], aristolactam Ia [2] and (−)-R-tylophorine [3] (Figure 1). Meanwhile, they also demonstrate a wide range of biological activities including anticancer [4], anti-HIV [5

Quinolines from the cyclocondensation of isatoic anhydride with ethyl acetoacetate: preparation of ethyl 4-hydroxy-2-methylquinoline-3-carboxylate and derivatives

• Nicholas G. Jentsch,
• Jared D. Hume,
• Emily B. Crull,
• Samer M. Beauti,
• Amy H. Pham,
• Julie A. Pigza,
• Jacques J. Kessl and
• Matthew G. Donahue

Beilstein J. Org. Chem. 2018, 14, 2529–2536, doi:10.3762/bjoc.14.229

• acid residue required for the synthesis of key arylquinolines involved in an HIV integrase project. Keywords: cyclodehydration; HIV integrase; isatoic anhydride; masked acyl cyanide; quinoline; Introduction In stark contrast to the prevalence of the quinoline heterocycle in natural products [1

• ], quinolines are only present in approximately 2% of FDA approved prescription pharmaceuticals [2]. Recently, 2,3,4-trisubstituted arylquinolines such as BI 224436 1 [3][4] and 2 [5][6] have been shown to exhibit inhibitory activity against HIV-1 integrase that is essential for viral replication through

• [C13H12BrNO3 + Na]+ 331.989277; found: 331.988788; anal. calcd for C13H12BrNO3: C, 39.70; H, 1.67; found C, 39.51; H, 1.74. Investigational non-catalytic HIV-1 Integrase inhibitors. Boehringer Ingelheim retrosynthesis of quinoline 1. Quinoline ring condensation strategies. Isatoic anhydrides from anthranilic

Glycosylation reactions mediated by hypervalent iodine: application to the synthesis of nucleosides and carbohydrates

• Yuichi Yoshimura,
• Hideaki Wakamatsu,
• Yoshihiro Natori,
• Yukako Saito and
• Noriaki Minakawa

Beilstein J. Org. Chem. 2018, 14, 1595–1618, doi:10.3762/bjoc.14.137

• (PhI(OH)OTs) resulted in a decrease of the reaction yield (Table 2, entries 5–7). To prove the usefulness of the oxidative coupling reaction mediated by hypervalent iodine, the reaction was applied to the synthesis of a carbocyclic nucleoside derivative designed as a potential anti-HIV agent. As a

• cytosine analogues [63]. During the course of conversion, all the stereoisomers were separated. Among them, only the cytosine derivative 99 showed weak anti-HIV activity (Scheme 13 and Table 3). An oxidative coupling reaction for synthesizing carbocyclic nucleosides mediated by hypervalent iodine was

• ’-deoxy- and 2’,3’-dideoxydidehydronucleosides, some of which are known to have anti-HIV activity (Table 4). To reveal the scope of this reaction, we designed a new dihydropyranonucleoside as a potential anti-HIV agent and attempted to synthesize it by using the oxidative coupling reaction [70]. First

Lanyamycin, a macrolide antibiotic from Sorangium cellulosum, strain Soce 481 (Myxobacteria)

• Lucky S. Mulwa,
• Rolf Jansen,
• Dimas F. Praditya,
• Kathrin I. Mohr,
• Patrick W. Okanya,
• Joachim Wink,
• Eike Steinmann and
• Marc Stadler

Beilstein J. Org. Chem. 2018, 14, 1554–1562, doi:10.3762/bjoc.14.132

• become a major concern of governments and health workers due to the economic and health burden it has brought. HCV has been found to be the main cause of liver associated deaths globally putting it in the same league of HIV and tuberculosis in terms of worldwide health challenges [1]. Approximately 71

• of which were found to exert anti-HIV activity while sorazolones, argyrins and tubulysins showed antitumor activity or cytotoxicity [4][5][6][7][8]. In our studies on the secondary metabolites of Sorangium cellulosum (strain Soce 481), we observed strong antifungal activity in the raw extract. On RP

Synthesis of trifluoromethylated 2H-azirines through Togni reagent-mediated trifluoromethylation followed by PhIO-mediated azirination

• Jiyun Sun,
• Xiaohua Zhen,
• Huaibin Ge,
• Guangtao Zhang,
• Xuechan An and
• Yunfei Du

Beilstein J. Org. Chem. 2018, 14, 1452–1458, doi:10.3762/bjoc.14.123

• potential anti-HIV drug bearing a NCF3 moiety. 2H-Azirines are a class of highly strained and reactive molecules containing a C–N double bond. The exclusive framework can be found in some natural products [43][44][45][46][47], which were shown to possess antibiotic activities [43][44]. Furthermore

A selective removal of the secondary hydroxy group from ortho-dithioacetal-substituted diarylmethanols

• Anna Czarnecka,
• Emilia Kowalska,
• Agnieszka Bodzioch,
• Joanna Skalik,
• Marek Koprowski,
• Krzysztof Owsianik and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2018, 14, 1229–1237, doi:10.3762/bjoc.14.105

• ] or vasodilating activities (II) [6]. Other ones have been reported as inhibitors of HIV-1 integrase and viral replication in cells [7] or antitubercular agents (III) [8][9]. Various diarylmethane-based molecules, like tolterodine (IV) [10], podophyllotoxin (V) [11] and lasofoxifene (VI) [12] have

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

• ]. Gottesfeld et al. synthesized a series of Py/Im HP-polyamide–DNA alkylator (chlorambucil) (HP-Chl) conjugates in order to bind and alkylate within the HIV-1 promoter region, thereby blocking HIV-1 replication and screened them against human colon carcinoma cell lines [74][75]. It has been observed that

Stimuli-responsive oligonucleotides in prodrug-based approaches for gene silencing

• Françoise Debart,
• Christelle Dupouy and
• Jean-Jacques Vasseur

Beilstein J. Org. Chem. 2018, 14, 436–469, doi:10.3762/bjoc.14.32

• PNATAR fragment directed against the TAR RNA region of the HIV genome conjugated to TPP inhibited HIV replication in CEM cell lines with an IC50 of 1 μM, while the unconjugated 16-mer PNATAR was inactive in these tests. The anti-HIV activity confirmed that the PNATAR was not sequestered in mitochondria

One-pot preparation of 4-aryl-3-bromocoumarins from 4-aryl-2-propynoic acids with diaryliodonium salts, TBAB, and Na₂S₂O₈

• Teppei Sasaki,
• Katsuhiko Moriyama and
• Hideo Togo

Beilstein J. Org. Chem. 2018, 14, 345–353, doi:10.3762/bjoc.14.22

• ], antitumor [1], antiasthmatic [12], and antiviral including anti-HIV [13][14]. Comprehensive synthetic studies of coumarins and their derivatives have been carried out [15][16]. Typically, coumarins are prepared by the acid-catalyzed condensation of 2-alkynoic acids and phenols or the condensation of β

Fluorogenic PNA probes

• Tirayut Vilaivan

Beilstein J. Org. Chem. 2018, 14, 253–281, doi:10.3762/bjoc.14.17

• ), HIV and HVB (hepatitis B virus surface antigen) in a single tube was demonstrated [141]. Addition of a very low concentration of bovine serum albumin (BSA, 0.01%) was shown to enhance the performance of the PNA–GO-based DNA sensing platform by reducing the non-specific adsorption of PNA–DNA duplexes

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

• practical guidance to synthetic chemists for further research. Synthesis of pyrazolo[3,4-b]pyridines Pyrazolo[3,4-b]pyridines are important fused heterocycles due to their well-known synthetic and medicinal potential as good vasodilators [29], hypotensive [30], HIV reverse transcriptase inhibitors [31

• -aminopyrazolo[1,5-a]pyrimidine derivatives 155 (Scheme 43). All the synthesized compounds were screened for their anti-HIV activities in MT4 cell cultures and compound 155 (R1 = 2,4,6-trimethyl and R2 = 4-cyano) was found as most inhibiting for HIV-1 replication having an EC50 = 0.070 μM and the SI (selectivity

Nucleophilic dearomatization of 4-aza-6-nitrobenzofuroxan by CH acids in the synthesis of pharmacology-oriented compounds

• Alexey M. Starosotnikov,
• Dmitry V. Shkaev,
• Maxim A. Bastrakov,
• Ivan V. Fedyanin,
• Svyatoslav A. Shevelev and
• Igor L. Dalinger

Beilstein J. Org. Chem. 2017, 13, 2854–2861, doi:10.3762/bjoc.13.277

• hypertension. Dihydropyridine derivatives are relatively vascular selective in their mechanism of action in lowering blood pressure [31][32]. Dimeric dihydropyridines are used as the precursors for HIV-1 protease inhibitors [33][34]. The furoxan system is used in the design of new NO donors [35][36][37][38][39

Recent progress in the racemic and enantioselective synthesis of monofluoroalkene-based dipeptide isosteres

• Myriam Drouin and
• Jean-François Paquin

Beilstein J. Org. Chem. 2017, 13, 2637–2658, doi:10.3762/bjoc.13.262

• isomerization or epimerization, cyclic pseudopeptides using Fmoc SPPS [48][50]. Biological studies were conducted on monofluoroalkene-containing analogues of FC131, which is a known antagonist of the chemokine receptor CXCR4. The latter has implications in cancer metastasis and HIV 1 infection. Anti-HIV 1

• dipeptide isostere Lys-ψ[(Z)-CF=CH]-Lys into a fusion inhibitory peptide active against HIV 1, SC29EK, was investigated [49]. Weak to moderate anti-HIV activity was observed for the fluorinated analogues, but the potency was always lower than for SC29EK. This suggested than the H-bonding behaviour was

• mobilizing response in GPR103-transfected cells of different 26FRa analogues. Ki values of Phe-Gly and analogues based on inhibition of [3H]Gly-Sar uptake by PEPT1 in Caco-2 cells. Anti-HIV activities of FC131 and its fluorinated derivatives against three HIV strains. Anti-HIV activities of SC29EK and its

Regioselective decarboxylative addition of malonic acid and its mono(thio)esters to 4-trifluoromethylpyrimidin-2(1H)-ones

• Sergii V. Melnykov,
• Andrii S. Pataman,
• Yurii V. Dmytriv,
• Svitlana V. Shishkina,
• Mykhailo V. Vovk and
• Volodymyr A. Sukach

Beilstein J. Org. Chem. 2017, 13, 2617–2625, doi:10.3762/bjoc.13.259

• -dihydroquinazolin-2(1H)-ones and the anti-HIV drug DPC 083 [28]. No examples of any ketimines reacting directly with malonic acid have been reported so far. Here we present the results of the decarboxylative addition of malonic acid, malonic monoester 1a and thioester 1b to 4-trifluoromethylpyrimidin-2(1H)-ones 2

What contributes to an effective mannose recognition domain?

• Christoph P. Sager,
• Deniz Eriş,
• Martin Smieško,
• Rachel Hevey and
• Beat Ernst

Beilstein J. Org. Chem. 2017, 13, 2584–2595, doi:10.3762/bjoc.13.255

• Brewer reviewed the role of density and number of glycan epitopes involved in multivalent carbohydrate interactions for legume lectins as well as for lectins of the innate immune system [74]. As an example, HIV-1 establishes multivalent contacts to DC-SIGN (E)-decorated dendritic cells in order to bypass

• host immune attack. Thus, DC-SIGN plays a key role in the dissemination of HIV-1 by capturing of HIV-1 at entry sites of infection and subsequent transport of the virus to CD4+ T cells in lymphoid tissues. The weak monovalent binding affinity of DC-SIGN (E) is compensated for by a multivalent display

• of oligomannosides on viral envelop glycoprotein gp120, facilitating stronger adhesion between dendritic cells and HIV-1 [43][75][76]. This multivalent binding interaction results in an enhancement in binding by several orders of magnitude, from a KD of 26 μM for monovalent Man9GlcNAc2, as compared

A novel synthetic approach to hydroimidazo[1,5-b]pyridazines by the recyclization of itaconimides and HPLC–HRMS monitoring of the reaction pathway

• Dmitry Yu. Vandyshev,
• Khidmet S. Shikhaliev,
• Andrey Yu. Potapov,
• Michael Yu. Krysin,
• Fedor I. Zubkov and
• Lyudmila V. Sapronova

Beilstein J. Org. Chem. 2017, 13, 2561–2568, doi:10.3762/bjoc.13.252

• through the N1–C5 bond of the latter, have been studied to a lesser extent. So, for imidazo[1,5-b]pyridazines, inhibitory activity was found against the viruses of human immunodeficiency HIV-1 [12], influenza [13], and hepatitis C [14]. They also act as stimulators of guanylate cyclase [10], inhibitors of

Asymmetric synthesis of propargylamines as amino acid surrogates in peptidomimetics

• Matthias Wünsch,
• David Schröder,
• Tanja Fröhr,
• Lisa Teichmann,
• Sebastian Hedwig,
• Nils Janson,
• Clara Belu,
• Jasmin Simon,
• Shari Heidemeyer,
• Philipp Holtkamp,
• Jens Rudlof,
• Lennard Klemme,
• Alessa Hinzmann,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2017, 13, 2428–2441, doi:10.3762/bjoc.13.240

• structure of fluorinated propargylamines occurs in important drugs, like HIV protease inhibitor DPC 961 and its analogues [78][79][80][81][82][83], particular effort was put on the synthesis of N-sulfinyl propargylamine 7k. Because of the poor electrophilicity of imines 5, the nucleophilic addition of

Curcuminoid–BF₂ complexes: Synthesis, fluorescence and optimization of BF₂ group cleavage

• Henning Weiss,
• Jeannine Reichel,
• Helmar Görls,
• Kilian Rolf Anton Schneider,
• Mathias Micheel,
• Michael Pröhl,
• Michael Gottschaldt,
• Benjamin Dietzek and
• Wolfgang Weigand

Beilstein J. Org. Chem. 2017, 13, 2264–2272, doi:10.3762/bjoc.13.223

• curcuma longa, and its analogues, the curcuminoids, have attracted much attention regarding their biological activities [1]. These include antioxidant [2] and radical scavenging [3], antitumor [4] and anti-inflammatory [5] activities, as well as HIV inhibition [6]. Despite showing activity against several

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

• [28], to prepare oil/water emulsions [29], or to prevent corrosion [30][31][32]. The ionic interactions between phosphonic acid and lipophilic amine produced catanionic supramolecular aggregates that were assessed as HIV inhibitors [26][33]. Many phosphonic acids are present in nature and their

• addition of POCl3 or PCl3 [222] is a method that produces in one step the aminomethylene bis-phosphonic acid [228] (Figure 33A). This methodology was applied to prepare the compound 119 [229] that was assessed as HIV-1 integrase inhibitor. Compound 120 [230] was prepared simply by the refluxing

High-speed vibration-milling-promoted synthesis of symmetrical frameworks containing two or three pyrrole units

• Marco Leonardi,
• Mercedes Villacampa and
• J. Carlos Menéndez

Beilstein J. Org. Chem. 2017, 13, 1957–1962, doi:10.3762/bjoc.13.190

• proved to be useful include the protease of the human immunodeficiency virus HIV [1], cellular prion protein, PrPc [2], and the transient receptor potential melastatin 8 (TRPM8) channel receptor [3]. The synthesis of these symmetrical molecules normally relies on multistep sequences. Due to the special

Synthesis of benzothiophene and indole derivatives through metal-free propargyl–allene rearrangement and allyl migration

• Jinzhong Yao,
• Yajie Xie,
• Lianpeng Zhang,
• Yujin Li and
• Hongwei Zhou

Beilstein J. Org. Chem. 2017, 13, 1866–1870, doi:10.3762/bjoc.13.181

• in natural products and pharmacologically active compounds, thus economic and efficient methods to construct heterocycles are always highly desirable [1][2][3][4][5][6]. Benzothiophenes are important heterocycles that are one of the key motifs of anti-inflammatory, anti-estrogenic and anti-HIV drugs

Ni nanoparticles on RGO as reusable heterogeneous catalyst: effect of Ni particle size and intermediate composite structures in C–S cross-coupling reaction

• Debasish Sengupta,
• Koushik Bhowmik,
• Goutam De and
• Basudeb Basu

Beilstein J. Org. Chem. 2017, 13, 1796–1806, doi:10.3762/bjoc.13.174

• ; Introduction The formation of a carbon–sulfur bond is an imperative step for the synthesis of many biologically active chemical entities that have significant applications in different therapeutic areas such as HIV, cancer, diabetes, inflammation, Alzheimer’s and Parkinson’s diseases etc. [1][2][3][4]. The

Sustainable synthesis of 3-substituted phthalides via a catalytic one-pot cascade strategy from 2-formylbenzoic acid with β-keto acids in glycerol

• Lina Jia and
• Fuzhong Han

Beilstein J. Org. Chem. 2017, 13, 1425–1429, doi:10.3762/bjoc.13.139

• [3][4][5], exhibit a broad spectrum of pharmacological activity, such as antibacterial, anti-HIV, antifungal, antibiotic, antitumor and immunosuppressive effects [6][7][8][9][10]. In addition, the one-pot cascade transformation has proven to be the key step in organic syntheses because of its broad