N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

• alkaloids that were isolated in the mid-1990s from the Caribbean sponge bataella sp. From a biological point of view, the batzelladines have received attention due to their reported activity as inhibitors of HIV gp120-human CD4 binding. Chiral N-tert-butanesulfinyl aldimine (SS)-58 was used as a precursor

Beyond ribose and phosphate: Selected nucleic acid modifications for structure–function investigations and therapeutic applications

• Christopher Liczner,
• Kieran Duke,
• Gabrielle Juneau,
• Martin Egli and
• Christopher J. Wilds

Beilstein J. Org. Chem. 2021, 17, 908–931, doi:10.3762/bjoc.17.76

• targeted to proviral HIV DNA [68], and as a triplex-forming oligonucleotide that selectively binds a sequence within the chromatin structure of cell nuclei [69]. Remarkably, 3'-NP DNA can also act as an RNA mimic in interactions with binding proteins despite lacking a ribose moiety, making them useful

• incorporated into a DNA/RNA hybrid duplex it was shown to decrease the rate of both human and HIV reverse transcriptase-associated RNase H-mediated cleavage [208]. In 2018, the work was expanded to include 2',4'-diOMe-rU, 2'-OMe,4'-F-rU, and 2'-F,4'-OMe-araU nucleosides (Figure 9E,F,G) [209]. This work

Enhanced target cell specificity and uptake of lipid nanoparticles using RNA aptamers and peptides

• Roslyn M. Ray,
• Anders Højgaard Hansen,
• Maria Taskova,
• Bernhard Jandl,
• Jonas Hansen,
• Citra Soemardy,
• Kevin V. Morris and
• Kira Astakhova

Beilstein J. Org. Chem. 2021, 17, 891–907, doi:10.3762/bjoc.17.75

• LNPs that can cross the BBB, we developed and assessed two approaches. The first was centered on the BBB-penetrating trans-activator of transcription (Tat) peptide or the peptide T7, and the other on RNA aptamers targeted to glycoprotein gp160 from human immunodeficiency virus (HIV) or C-C chemokine

• receptor type 5 (CCR5), a HIV-1 coreceptor. We report herein a CCR5-selective RNA aptamer that acts to facilitate entry through a simplified BBB model and that drives the uptake of LNPs into CCR5-expressing cells, while the gp160 aptamer did not. We further observed that the addition of cell-penetrating

• the usefulness of aptamer-loaded LNPs to increase target cell specificity and potentially deliverability of central-nervous-system-active RNAi therapeutics across the BBB. Keywords: aptamer; blood–brain barrier; gene therapy; HIV-1; lipid nanoparticle; Introduction Lipid nanoparticles (LNPs

Total synthesis of pyrrolo[2,3-c]quinoline alkaloid: trigonoine B

• Takashi Nishiyama,
• Erina Hamada,
• Daishi Ishii,
• Yuuto Kihara,
• Nanase Choshi,
• Natsumi Nakanishi,
• Mari Murakami,
• Kimiko Taninaka,
• Noriyuki Hatae and
• Tominari Choshi

Beilstein J. Org. Chem. 2021, 17, 730–736, doi:10.3762/bjoc.17.62

• rearranged from a β-carboline skeleton (Figure 1). Additionally, the antihepatitis B virus (HBV) activity of the alkaloids was evaluated in vitro using an HBV-transfected HepG2 cell line. The antihuman immunodeficiency virus (HIV) properties were also investigated to determine whether trigonoine A and B

• could prevent the cytopathic effects of HIV-1IIIB in C8166 cells. Notably, it was found that both natural products exhibited anti-HIV activity. In addition to trigonoine B, aplidiopsamine A (2) [2] and marinoquinolines 3 [3] are natural products that possess the pyrrolo[2,3-c]quinoline skeleton (Figure

[2 + 1] Cycloaddition reactions of fullerene C₆₀ based on diazo compounds

• Yuliya N. Biglova

Beilstein J. Org. Chem. 2021, 17, 630–670, doi:10.3762/bjoc.17.55

• ]. Fullerene-containing compounds with antiviral (various forms of influenza, herpes, HIV) [28][29][30], antibacterial [31][32][33], and anticancer activity [34][35] have been found among them. An important approach in this area involves the synthesis of complex- and covalent-bound fullerene derivatives with

• diphenyldiazomethanes, available reagents carrying substituents on the phenyl rings. For example, covalent attachment of C60 to peptides is performed through a phenyl spacer, as it was demonstrated in a synthesis of fulleride 27 [89]. The latter compound was designed specifically for suppressing a HIV enzyme. The

The synthesis of chiral β-naphthyl-β-sulfanyl ketones via enantioselective sulfa-Michael reaction in the presence of a bifunctional cinchona/sulfonamide organocatalyst

• Deniz Tözendemir and
• Cihangir Tanyeli

Beilstein J. Org. Chem. 2021, 17, 494–503, doi:10.3762/bjoc.17.43

• outshined by sulfonamides in medicinal chemistry, they have a large array of biologic activities that show promising effects as potent anti-HIV-1 [34], anti-hepatitis C [35], antifungal [36], insecticidal/acaricial [37] and antimalarial [38] agents. Results and Discussion We have previously reported the

¹⁹F NMR as a tool in chemical biology

• Diana Gimenez,
• Aoife Phelan,
• Cormac D. Murphy and
• Steven L. Cobb

Beilstein J. Org. Chem. 2021, 17, 293–318, doi:10.3762/bjoc.17.28

• in studying the HIV-inactivating lectin cyanovirin-N protein as a model system (S52CCV-N). Single fluorine atoms were introduced at the 4-, 5-, 6- or 7-positions of Trp49 and the 4-position of Phe4, Phe54, and Phe80 (Figure 8). Simultaneously, the paramagnetic nitroxide spin label was chemically

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

An atom-economical addition of methyl azaarenes with aromatic aldehydes via benzylic C(sp³)–H bond functionalization under solvent- and catalyst-free conditions

• Divya Rohini Yennamaneni,
• Vasu Amrutham,
• Krishna Sai Gajula,
• Rammurthy Banothu,
• Murali Boosa and
• Narender Nama

Beilstein J. Org. Chem. 2020, 16, 3093–3103, doi:10.3762/bjoc.16.259

• diversity, these compounds constitute a motif in various natural alkaloid products, such as chimanine and those derived from lobelia, sedum, etc. These compounds act as anti-HIV and anti-asthma drugs [9][10][11]. Mainly, 2-substituted quinolines and their analogues exhibits magnificent bioactivity [12][13

Asymmetric Mannich reactions of (S)-N-tert-butylsulfinyl-3,3,3-trifluoroacetaldimines with yne nucleophiles

• Ziyi Li,
• Li Wang,
• Yunqi Huang,
• Haibo Mei,
• Hiroyuki Konno,
• Hiroki Moriwaki,
• Vadim A. Soloshonok and
• Jianlin Han

Beilstein J. Org. Chem. 2020, 16, 2671–2678, doi:10.3762/bjoc.16.217

• combined organic layers were dried with anhydrous Na2SO4, filtered and the solvent was removed to give the crude product 3, which was purified by column chromatography using hexane/EtOAc (4:1, v/v) as eluent. Anti-HIV compound containing a trifluoromethylpropargylamine moiety. ORTEP diagram showing of the

Water-soluble host–guest complexes between fullerenes and a sugar-functionalized tribenzotriquinacene assembling to microspheres

• Si-Yuan Liu,
• Xin-Rui Wang,
• Man-Ping Li,
• Wen-Rong Xu and
• Dietmar Kuck

Beilstein J. Org. Chem. 2020, 16, 2551–2561, doi:10.3762/bjoc.16.207

• attention for potential applications in host–guest recognition, such as gas storage and cationic complexation [31][32][33]. In the past years, the recognition of the biological and pharmaceutical relevance of fullerenes, such as their photodynamic activity, phototoxicity, HIV-1 protease inhibitor ability

NMR Spectroscopy of supramolecular chemistry on protein surfaces

• Peter Bayer,
• Anja Matena and
• Christine Beuck

Beilstein J. Org. Chem. 2020, 16, 2505–2522, doi:10.3762/bjoc.16.203

• [8][9][10][11][12], and inhibit enzyme function [13] in vitro, they also exhibit interesting effects in vivo like the reversal of Alzheimer plaques in mice [14], tumor inhibition [15], and reduction of HIV infectivity [16], all while showing almost no toxic side effects [14][17]. In calixarenes with

Photosensitized direct C–H fluorination and trifluoromethylation in organic synthesis

• Shahboz Yakubov and
• Joshua P. Barham

Beilstein J. Org. Chem. 2020, 16, 2151–2192, doi:10.3762/bjoc.16.183

• atoms, including drugs used to treat cancer, HIV, smallpox and malarial infections (Figure 1) [5][6]. Moreover, fluorine atoms and trifluoromethyl groups have dramatic effects on the biological activity of agrochemicals, such as herbicides, insecticides and fungicides, as reflected by a plethora of

Automated high-content imaging for cellular uptake, from the Schmuck cation to the latest cyclic oligochalcogenides

• Rémi Martinent,
• Javier López-Andarias,
• Dimitri Moreau,
• Yangyang Cheng,
• Naomi Sakai and
• Stefan Matile

Beilstein J. Org. Chem. 2020, 16, 2007–2016, doi:10.3762/bjoc.16.167

• reported cell-penetrating streptavidin, in which four asparagusic acids are covalently bound to the protein through irreversible triazole linkages [59]. The CP50 value of 7.3 ± 0.5 µM of 25 was not far above the CP50 value of 3.1 ± 0.5 µM of HIV Tat, the original CPP [55]. As the uptake efficiency

• CP50 value obtained for the COC–protein complex was in the range of the protein-free HIV Tat, and thus confirming the excellent activity of the COCs. Most importantly, with our refined HC CAPA, quantitative dose–response curves for the cytotoxicity could be obtained with the same HT screening

Metal-free synthesis of phosphinoylchroman-4-ones via a radical phosphinoylation–cyclization cascade mediated by K₂S₂O₈

• Qiang Liu,
• Weibang Lu,
• Guanqun Xie and
• Xiaoxia Wang

Beilstein J. Org. Chem. 2020, 16, 1974–1982, doi:10.3762/bjoc.16.164

• biological and pharmaceutical activities such as anticancer activities and anti-HIV activity among others (Figure 1) [1][2][3]. Therefore, the preparation of functionalized chroman-4-one derivatives has attracted great attention of experts and scientists in the field of organic synthesis and pharmaceutical

Tuneable access to indole, indolone, and cinnoline derivatives from a common 1,4-diketone Michael acceptor

• Dalel El-Marrouki,
• Sabrina Touchet,
• Abderrahmen Abdelli,
• Hédi M’Rabet,
• Mohamed Lotfi Efrit and
• Philippe C. Gros

Beilstein J. Org. Chem. 2020, 16, 1722–1731, doi:10.3762/bjoc.16.144

• drugs used as anticancer, antiemetic, antihypertensive, antidepressant, anti-inflammatory, or anti-HIV agents, among others [9]. In contrast, concerning indolone and cinnoline derivatives, there are very few marketed drugs, but many molecules are under investigations for their activities as

Microwave-assisted efficient one-pot synthesis of N²-(tetrazol-5-yl)-6-aryl/heteroaryl-5,6-dihydro-1,3,5-triazine-2,4-diamines

• Moustafa Sherief Moustafa,
• Ramadan Ahmed Mekheimer,
• Saleh Mohammed Al-Mousawi,
• Mohamed Abd-Elmonem,
• Hesham El-Zorba,
• Afaf Mohamed Abdel Hameed,
• Tahany Mahmoud Mohamed and
• Kamal Usef Sadek

Beilstein J. Org. Chem. 2020, 16, 1706–1712, doi:10.3762/bjoc.16.142

• [2], antitumor [3], anti-HIV [4], inhibitor of Trypanosoma brucei [5], angiogenesis inhibitor [6], antiplasmodial antifolates [7], and antimicrobial [8]. Moreover, and in particular N2,6-disubstituted-1,3,5-triazine-2,4-diamines possess a wide range of chemotherapeutic activities [8][9][10][11

Photocatalyzed syntheses of phenanthrenes and their aza-analogues. A review

• Alessandra Del Tito,
• Havall Othman Abdulla,
• Davide Ravelli,
• Stefano Protti and
• Maurizio Fagnoni

Beilstein J. Org. Chem. 2020, 16, 1476–1488, doi:10.3762/bjoc.16.123

• particular phenanthridines, are substructures present in a wide range of both natural and synthetic products, including trisphaeridine [12] (that exhibits an anti-HIV-I protease activity) and the antifungal sanguinarine [13]. Some phenantridinium derivatives are known as well, notably fagaronine (a DNA

Recent synthesis of thietanes

• Jiaxi Xu

Beilstein J. Org. Chem. 2020, 16, 1357–1410, doi:10.3762/bjoc.16.116

• of anal gland secretions of the stoat [1] and the ferret [2]. Some pharmaceutical and biological thietane-containing compounds include thiaanalogue thietanose nucleosides 1 and 2 [3][4], and the spiroannulated glyco-thietane nucleoside 3 [5] of the antiviral (anti-HIV and HSV) drug oxetanocin A, the

Synthesis of pyrrolidinedione-fused hexahydropyrrolo[2,1-a]isoquinolines via three-component [3 + 2] cycloaddition followed by one-pot N-allylation and intramolecular Heck reactions

• Xiaoming Ma,
• Suzhi Meng,
• Xiaofeng Zhang,
• Qiang Zhang,
• Shenghu Yan,
• Yue Zhang and
• Wei Zhang

Beilstein J. Org. Chem. 2020, 16, 1225–1233, doi:10.3762/bjoc.16.106

• crispine A isolated from Carduus crispus L has antitumor activity [3]. Erythrina alkaloids have curare-like neuromuscular blocking activities [4], and also antioxidant activity against DPPH free radicals [5]. Lamellarins isolated from marine invertebrates [6] are inhibitors for HIV-1 integrase and also

Synthesis of new asparagine-based glycopeptides for future scanning tunneling microscopy investigations

• Laura Sršan and
• Thomas Ziegler

Beilstein J. Org. Chem. 2020, 16, 888–894, doi:10.3762/bjoc.16.80

• example, in anti-HIV therapy, MUC1-based antitumor vaccines, or as antibiotics [12][13][14]. Especially glycans bearing noncanonical amino acids, which can only be introduced into a peptide by organic synthesis, are suitable for cancer therapy since they show better resistance to enzymatic degradation in

Reaction of indoles with aromatic fluoromethyl ketones: an efficient synthesis of trifluoromethyl(indolyl)phenylmethanols using K₂CO₃/n-Bu₄PBr in water

• Thanigaimalai Pillaiyar,
• Masoud Sedaghati and
• Gregor Schnakenburg

Beilstein J. Org. Chem. 2020, 16, 778–790, doi:10.3762/bjoc.16.71

• reported for their promising anti-HIV inhibitory activities [23], see for example compounds III and IV (Figure 1). However, these compounds were synthesized from multiple synthetic routes with the involvement of air sensitive conditions. Trifluoromethyl-substituted (1H-indol-3-yl)methanol derivatives can

• preparation of 3,3'-, and 3,6'-DIMs, which are known to possess a wide variety of biological activities, including anti-inflammatory, and anticancer effects. Additionally, trifluoromethyl(indolyl)phenylmethanols itselft have various biological properties including anti-HIV activity. The developed new

A systematic review on silica-, carbon-, and magnetic materials-supported copper species as efficient heterogeneous nanocatalysts in “click” reactions

• Pezhman Shiri and
• Jasem Aboonajmi

Beilstein J. Org. Chem. 2020, 16, 551–586, doi:10.3762/bjoc.16.52

• catalysts; Sharpless–Meldal C–N bond-forming reaction; silica/carbon/magnetic materials; Introduction Heterocycles are a class of organic compounds with significant biological activities [1][2][3][4][5][6][7][8][9][10], including antimicrobial [2], antibacterial [3], anti-HIV [4], antiviral [5

• ], antiparkinsonian [6], and anticancer [10] properties. Particularly, triazoles illustrate distinguished moieties well distributed in natural products with biological properties [2][3][4][9][10], including antimicrobial [2], antibacterial [3], antifungal [3], anti-HIV [4], and anticancer [10] activities. One of the

Synthesis of 4-amino-5-fluoropyrimidines and 5-amino-4-fluoropyrazoles from a β-fluoroenolate salt

• Tobias Lucas,
• Jule-Philipp Dietz and
• Till Opatz

Beilstein J. Org. Chem. 2020, 16, 445–450, doi:10.3762/bjoc.16.41

• stage [15][16][17][18][19]. Fluorinated pyrimidines, pyrimidine analogues and pyrazoles [20][21] play a prominent role in several clinically important pharmaceuticals [22][23][24][25]. These compounds act against HIV or HIV-related diseases [26], such as opportunistic fungal infections, and represent

• nucleoside analogues which can either act as antimetabolites or as nucleoside reverse transcriptase inhibitors (NRTIs). Two of the most common 5-fluoropyrimidines are the cytostatic 5-fluorouracil (1) [27] and the antimycotic prodrug 5-fluorocytosine (2) [28][29], which is also part of the anti-HIV agents

The reaction of arylmethyl isocyanides and arylmethylamines with xanthate esters: a facile and unexpected synthesis of carbamothioates

• Narasimhamurthy Rajeev,
• Toreshettahally R. Swaroop,
• Ahmad I. Alrawashdeh,
• Shofiur Rahman,
• Abdullah Alodhayb,
• Seegehalli M. Anil,
• Kuppalli R. Kiran,
• Chandra,
• Paris E. Georghiou,
• Kanchugarakoppal S. Rangappa and
• Maralinganadoddi P. Sadashiva

Beilstein J. Org. Chem. 2020, 16, 159–167, doi:10.3762/bjoc.16.18

• ) have been reported to have antimicrobial [1], antifungal (e.g., tolnaftate and tolciclate) [2], antimycobacterial [3], human leucocyte elastase inhibitory [4], TRPV1 antagonistic [5], and PPARα1γ dual antagonistic [6] properties, and also act as intermediates in the syntheses of HIV-1 integrase ligands