Cathodic generation of reactive (phenylthio)difluoromethyl species and its reactions: mechanistic aspects and synthetic applications

• Sadanobu Iwase,
• Shinsuke Inagi and
• Toshio Fuchigami

Beilstein J. Org. Chem. 2022, 18, 872–880, doi:10.3762/bjoc.18.88

• )difluoromethyl group (ArSCF2) have potential biological applications such as anti-HIV-1 reverse transcriptase inhibitors and agrochemical applications [3][4]. Reurakul and Pohmakotr et al. carried out the reaction of PhSCF2Br with SmI2 in THF/iPrOH to generate PhSCF2 radicals followed by trapping with various

Synthesis of 5-unsubstituted dihydropyrimidinone-4-carboxylates from deep eutectic mixtures

• Sangram Gore,
• Sundarababu Baskaran and
• Burkhard König

Beilstein J. Org. Chem. 2022, 18, 331–336, doi:10.3762/bjoc.18.37

• raltegravir, the first HIV-integrase inhibitor approved by the FDA for the treatment of HIV infection, derived from 5,6-dihydroxypyrimidine-4-carboxamide and N-methyl-4-hydroxypyrimidinone-carboxamide [18] and hydroxypyrimidinone carboxamide derivative P01, a potent inhibitor of Mycobacterium tuberculosis

Chemical and chemoenzymatic routes to bridged homoarabinofuranosylpyrimidines: Bicyclic AZT analogues

• Sandeep Kumar,
• Jyotirmoy Maity,
• Banty Kumar,
• Sumit Kumar and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2022, 18, 95–101, doi:10.3762/bjoc.18.10

• chemotherapeutic agents used for the treatment of cancer were nucleoside analogues and nucleobases [10]. Azidothymidine (1, AZT) was the first approved drug for the treatment of human immunodeficiency virus (HIV) [11][12]. Subsequently, a large number of sugar modified nucleosides, such as ddC (zalcitabine) [13

• ][14], ddI (didanosine) [15], d4T (stavudine) [16][17], 3TC (lamivudine) [18][19] and AZT analogues were synthesized and evaluated towards inhibition of HIV reverse transcriptase (HIV RT). However, the toxic side effects associated with these molecules and development of drug-resistant viruses

• eventually brought about the need for newly designed and improved anti-HIV drugs with respect to their improved pharmacological properties [20]. With an idea to keep the presence of azide functionality and to introduce structural rigidity, Marquez et al. [21] developed a methodology for the synthesis of

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• , the reactivity and applicability outperformed the racemic variant. Application of this methodology was applied towards the total synthesis of maraviroc, an anti-HIV drug, which was synthesized in 5 steps starting from styrene (115a) and CBr4 (20a). Carboamination In 2017, the Bao group investigated

Selective sulfonylation and isonitrilation of para-quinone methides employing TosMIC as a source of sulfonyl group or isonitrile group

• Chuanhua Qu,
• Run Huang,
• Yong Li,
• Tong Liu,
• Yuan Chen and
• Guiting Song

Beilstein J. Org. Chem. 2021, 17, 2822–2831, doi:10.3762/bjoc.17.193

• ; isonitrile diarylmethane; synthetic utility; Introduction Sulfones are ubiquitous units commonly found in marketed drugs and natural products. Because of their unique electronic and structural properties, they are often used in medicinal chemistry programs to search for anti-inflammatory, anti-HIV

Synthetic strategies toward 1,3-oxathiolane nucleoside analogues

• Umesh P. Aher,
• Dhananjai Srivastava,
• Girij P. Singh and
• Jayashree B. S

Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182

• ][4]. These compounds are the structural analogues of the naturally occurring 2’-deoxynucleosides, the building blocks of DNA. The World Health Organization (WHO) newsroom announced the primary statistics that HIV and cancer remain a significant global public health issue, having claimed over 47.6

• million lives so far [5][6]. The statistics confirm that 1 in 6 deaths happening globally are due to cancer [5]. In 2019, 690,000 people died from HIV-related causes worldwide and by the end of 2019, around 38 million people were living with HIV. From these, 1.7 million people were newly diagnosed [6

• natural nucleosides with β-ᴅ-configuration in the carbohydrate part. These molecules are known to have a common HIV transcriptase inhibition mechanism, in which cytoplasmic enzymes progressively phosphorylate the analogues to 5'-triphosphates. This then competes with the naturally occurring nucleoside

Synthesis of highly substituted fluorenones via metal-free TBHP-promoted oxidative cyclization of 2-(aminomethyl)biphenyls. Application to the total synthesis of nobilone

• Ilya A. P. Jourjine,
• Lukas Zeisel,
• Jürgen Krauß and
• Franz Bracher

Beilstein J. Org. Chem. 2021, 17, 2668–2679, doi:10.3762/bjoc.17.181

• of caulophine (1e) [7], and anti-HIV activity of gramniphenol D (1g) and related gramniphenol E (1h) [8]. For synthetic fluorenones antitumoral [9], antiviral [10], and trypanocidal [11] activities have been reported, and tilorone (1i), an antiviral fluorenone launched about 50 years ago, is

Recent advances in the tandem annulation of 1,3-enynes to functionalized pyridine and pyrrole derivatives

• Yi Liu,
• Puying Luo,
• Yang Fu,
• Tianxin Hao,
• Xuan Liu,
• Qiuping Ding and
• Yiyuan Peng

Beilstein J. Org. Chem. 2021, 17, 2462–2476, doi:10.3762/bjoc.17.163

• in many natural products, pharmaceuticals, and bioactive molecules. For instance, some pyridine derivatives have been used for therapy of HIV, cancer, inflammation, microbial infection and so on [1][2][3][4][5]. In addition, it is also an important synthetic unit, which is frequently used as catalyst

• -heterocycle that is widely used in pharmaceuticals, photoelectric materials, and functional materials [20][21][22][23]. Many pyrrole derivatives play a significant role in the life science and medicine domains due to the good bioactivities, such as antitumor, anti-HIV, and anti-HSV-1 activity [24][25][26][27

• % yield) and monodesulfonated nicotinate 17 (in 70% yield), respectively (Scheme 6). Selenyl- and sulfenylpyridine derivatives are gaining prominence due to the prospective biological activities. They could be used for treatment of HIV, cancer, inflammation, and microbial infection. Therefore, the

Strategies for the synthesis of brevipolides

• Yudhi D. Kurniawan and
• A'liyatur Rosyidah

Beilstein J. Org. Chem. 2021, 17, 2399–2416, doi:10.3762/bjoc.17.157

• immunodeficiency virus (HIV). The newly discovered brevipolides with interesting structural features in conjunction with promising biological activities have prompted the researchers to conduct synthetic studies. To date, there are six reported works in the literature for the syntheses of brevipolides, with the

• , brevipolides G–I (7–9) were found to inhibit the CCR5 receptor signaling as measured by a calcium mobilization assay with IC50 values of 15.5, 13.7, and 18.0 μM, respectively, which make them potential agents for treating HIV disease (Table 2, entries 7–9) [11]. Giménez and co-workers, in 2019, reported the

Catalyzed and uncatalyzed procedures for the syntheses of isomeric covalent multi-indolyl hetero non-metallides: an account

• Ranadeep Talukdar

Beilstein J. Org. Chem. 2021, 17, 2102–2122, doi:10.3762/bjoc.17.137

• -mediated coupling of N-silylated 6-hydroxyindole 174 with the corresponding boronic acid 173 (Scheme 24) [114]. For further synthetic transformations of 175, N-protection with bromo esters 176 followed by hydrolysis towards acids 177a and 177b were performed. The products 177a and 177b are potent anti-HIV

• . Syntheses of bis(indol-2-yl)selanes. Syntheses of bis(indol-3-yl)selanes. Synthesis of bis(indol-2-yl)tellane 147. Synthesis of tris(indolyl)borane 154. Synthesis of bis(indol-4-yl)amines 159. Synthesis of bis(indol-5-yl)amines. Synthesis of 6,5’/6,6’-bis(indolyl)amines. Synthesis of potent HIV-inhibitors

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

• against different types of diseases, such as cancer [1][2], malaria [3][4], Chagas disease [5][6], HIV [7][8], depression [9][10], amnesia [11], Alzheimer [12], and maybe even in a more recent scenario, COVID-19 [13]. Even though many compounds are found to present activity against these diseases, only a

• bioactive molecules. They are also known to present valuable biological activities, such as anti-HBV (1) [44], anti-HIV (2) [45], antitumor (3) [46] and even antiplasmodial activities (4) [47] (Scheme 2A). Although these studied bioactive compounds do not directly represent the structural moieties obtained

• catalyst to perform a regioselective scandium-catalyzed alkylation of 2-phenylquinoline derivatives (Scheme 3B) [38]. It is important to highlight the biological importance of quinoline derivatives, since several quinolines are known to present valuable biological activities, such as anti-HIV (5) [48

Cationic oligonucleotide derivatives and conjugates: A favorable approach for enhanced DNA and RNA targeting oligonucleotides

• Mathias B. Danielsen and
• Jesper Wengel

Beilstein J. Org. Chem. 2021, 17, 1828–1848, doi:10.3762/bjoc.17.125

• derivative group, when conjugated to the C-5 position on 2’-deoxyuridine (Table 1B, 12), improved antisense activity while reducing toxicity [39]. In addition, a 15-mer PS-ASO, modified with the C-5 tris-aminated 2’-deoxyuridine 12, improved anti-HIV activity and reduced cytotoxicity relative to the

Sustainable manganese catalysis for late-stage C–H functionalization of bioactive structural motifs

• Jongwoo Son

Beilstein J. Org. Chem. 2021, 17, 1733–1751, doi:10.3762/bjoc.17.122

• constitute an important structural modality in small-molecule drugs, such as levonorgestrel (birth control drug), efavirenz (HIV/AIDS treatment), and erlotinib (anticancer). Although step-economical C–H alkynylations have been investigated with 4d and 5d transition metals, 3d metal-catalyzed late-stage C–H

Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications

• Nikita Brodyagin,
• Martins Katkevics,
• Venubabu Kotikam,
• Christopher A. Ryan and
• Eriks Rozners

Beilstein J. Org. Chem. 2021, 17, 1641–1688, doi:10.3762/bjoc.17.116

• helix of the Antennapedia homeodomain) [167], Tat (14-amino acid peptide from HIV-1 TAT protein) [168], and transportan (chimeric 27-amino acid peptide derived from galanin and mastoparan) [169]. Corey and co-workers were the first to demonstrate that conjugation of an 11-mer PNA to penetratin peptide

A recent overview on the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles

• Pezhman Shiri,
• Ali Mohammad Amani and
• Thomas Mayer-Gall

Beilstein J. Org. Chem. 2021, 17, 1600–1628, doi:10.3762/bjoc.17.114

• screened for the synthesis of these rings [16][17]. Notably, triazole rings exhibit various medicinal applications, such as usages as anticancer [18] anti-HIV [19], antimalarial [20], antiplasmodial [21], and antibacterial agents [1][22]. Some significant triazole derivatives in this context are shown in

Double-headed nucleosides: Synthesis and applications

• Vineet Verma,
• Jyotirmoy Maity,
• Vipin K. Maikhuri,
• Ritika Sharma,
• Himal K. Ganguly and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2021, 17, 1392–1439, doi:10.3762/bjoc.17.98

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

• demonstrates the ease with which highly reactive reagents such as lithium bis(trimethylsilyl)amide can be used to effect sensitive aldol reactions in flow. Another recent example of an aldol reaction on a complex system originates from the group of Gauthier, which details the production of the HIV non

Synthesis of functionalized imidazo[4,5-e]thiazolo[3,2-b]triazines by condensation of imidazo[4,5-e]triazinethiones with DMAD or DEAD and rearrangement to imidazo[4,5-e]thiazolo[2,3-c]triazines

• Alexei N. Izmest’ev,
• Dmitry B. Vinogradov,
• Natalya G. Kolotyrkina,
• Angelina N. Kravchenko and
• Galina A. Gazieva

Beilstein J. Org. Chem. 2021, 17, 1141–1148, doi:10.3762/bjoc.17.87

• well as related thiazolo[3,2-b]-1,2,4-triazines and thiazolo[2,3-c]-1,2,4-triazines possessing antimicrobial, antidepressant, anti-HIV, and anticancer activities [10][11][12][13][14][15]. Modifications of the position 5 of the thiazolidine cycle often lead to an enhancement of the pharmacological

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