First total synthesis of hoshinoamide A

• Haipin Zhou,
• Zihan Rui,
• Yiming Yang,
• Shengtao Xu,
• Yutian Shao and
• Long Liu

Beilstein J. Org. Chem. 2021, 17, 2924–2931, doi:10.3762/bjoc.17.201

• achieved by solid-state synthesis. Our synthetic strategy could synthesize the target peptide in high yield with good purity Keywords: antimalarial; highly methylated polypeptides; hoshinoamides; total synthesis; Introduction Malaria is an insect-borne infectious disease caused by parasites of the genus

• artemisinin derivatives [7]. The emergence of drug resistance makes the efficacy of these drugs decline year by year, forcing scientists to constantly search for new antimalarial drugs [8][9][10]. In recent years, Iwasaki and co-workers have reported three novel linear lipopeptide natural products

• have a relatively simple structure and therefore make an attractive target for further medicinal chemistry studies. To enable these new SAR studies, we need to develop an efficient synthetic method to provide sufficient materials firstly. Hoshinoamide A shows a better antimalarial activity and less

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

• , antimicrobial, antimalarial, and anticancer activities [1][2]. Diarylmethane motifs are widely present in natural products and pharmaceuticals that exhibit extraordinary biological activity [3][4] (Figure 1). Among them, their anticancer activity is particularly attractive, demonstrated by drugs such as

Biological properties and conformational studies of amphiphilic Pd(II) and Ni(II) complexes bearing functionalized aroylaminocarbo-N-thioylpyrrolinate units

• Samet Poyraz,
• Samet Belveren,
• Sabriye Aydınoğlu,
• Mahmut Ulger,
• Abel de Cózar,
• Maria de Gracia Retamosa,
• Jose M. Sansano and
• H. Ali Döndaş

Beilstein J. Org. Chem. 2021, 17, 2812–2821, doi:10.3762/bjoc.17.192

• , antitumoral, antimalarial, antifungal, or antiviral activities [14]. In this study, as a continuation of our work related to organometallic compounds with very low/modest amphiphilic character [15][16][17], we propose the incorporation of a 3-indolylmethyl group in the ligand and compare the bioactivity

Photophysical, photostability, and ROS generation properties of new trifluoromethylated quinoline-phenol Schiff bases

• Inaiá O. Rocha,
• Yuri G. Kappenberg,
• Wilian C. Rosa,
• Clarissa P. Frizzo,
• Nilo Zanatta,
• Marcos A. P. Martins,
• Isadora Tisoco,
• Bernardo A. Iglesias and
• Helio G. Bonacorso

Beilstein J. Org. Chem. 2021, 17, 2799–2811, doi:10.3762/bjoc.17.191

• ). Quinolines are another important class of compounds and have numerous medicinal chemistry applications due to their biological applicability [9] and promising antimycobacterial [10], antimalarial [11][12], and antibacterial [13] activities. On the other hand, 6-aminoquinoline compounds demonstrate

Me₃Al-mediated domino nucleophilic addition/intramolecular cyclisation of 2-(2-oxo-2-phenylethyl)benzonitriles with amines; a convenient approach for the synthesis of substituted 1-aminoisoquinolines

• Krishna M. S. Adusumalli,
• Lakshmi N. S. Konidena,
• Hima B. Gandham,
• Krishnaiah Kumari,
• Krishna R. Valluru,
• Satya K. R. Nidasanametla,
• Venkateswara R. Battula and
• Hari K. Namballa

Beilstein J. Org. Chem. 2021, 17, 2765–2772, doi:10.3762/bjoc.17.186

• applications in medicinal chemistry such as antimalarial, anti-Parkinson and antitumor activity (Figure 1) [13][14][15][16][17]. They also display remarkable enzymatic inhibitory activities on topoisomerase I, [18] mutant B-Raf [19] and exhibit antagonistic activities towards adenosine A3 [20] and PDE4B [21

A visible-light-induced, metal-free bis-arylation of 2,5-dichlorobenzoquinone

• Pieterjan Winant and
• Wim Dehaen

Beilstein J. Org. Chem. 2021, 17, 2315–2320, doi:10.3762/bjoc.17.149

• salts; Green Chemistry; Meerwein arylation; photoredox; Introduction Quinones or quinoid-based structures are ubiquitous in nature [1][2][3]. These versatile structures have shown promising antimalarial [4][5], antibacterial [6], and chemotherapeutic [6][7][8] properties. Their inherent oxidative

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

• ], antiviral in general (6) [49], antituberculotic (7), and antimalarial (8) [50] (Scheme 3A). Using 2-phenylquinoline derivatives as substrates includes some intrinsic challenges, since there are two sites in the molecule where the C–H activation can take place. The authors were able to selectively obtain the

• authors used a bulky titanium catalyst, by which a desirable regioselectivity could be achieved (Scheme 7B and C). The obtained N-substituted anilines resemble some important compounds already known for their biological activities, such as antimalarial (17) [69] and anticancer (18) [70][71] properties

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

Synthetic accesses to biguanide compounds

• Oleksandr Grytsai,
• Cyril Ronco and
• Rachid Benhida

Beilstein J. Org. Chem. 2021, 17, 1001–1040, doi:10.3762/bjoc.17.82

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

• . Tacrine (1) is an acridine derivative used in the treatment of Alzheimer’s disease. A plethora of acridine derivatives have been synthesized and clinically proved with various biological activities such as ethacridine (antibacterial drug; 2), acranil (antiviral drug; 3) and quinacrine (antimalarial agent

• further studied for their antimicrobial, antituberculosis and antimalarial effects. Scheme 41 demonstrates the mechanism involving a direct Claisen–Schmidt condensation to intermediate A followed by a sequential [3 + 3] cycloaddition with 104 yields B. Finally, dehydration and hydrogen removal from B

• , antiulcer, anxiolytic, antiherpes agents [115][116][117][118][119]. Similarly, pyrazolo-pyridines are found to be potent antibacterial (131), cytotoxic (132), antiproliferative (133) and antimalarial (134) agents (Figure 10) [120][121]. 8.2.1 Imidazo[1,2-a]pyridine: Sun and co-workers [122] accomplished the

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

•  1). These pyrrolo[2,3-c]quinolines have been demonstrated to show antimalarial and antibacterial biological activities [2][3][4]. Thus, the development of a convenient and efficient synthetic route to the pyrrolo[2,3-c]quinoline skeleton has attracted considerable attention from organic and

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

Deoxygenative C2-heteroarylation of quinoline N-oxides: facile access to α-triazolylquinolines

• Geetanjali S. Sontakke,
• Rahul K. Shukla and
• Chandra M. R. Volla

Beilstein J. Org. Chem. 2021, 17, 485–493, doi:10.3762/bjoc.17.42

• natural products [1][2][3][4], agrochemicals and pharmaceuticals having potent biological activities, such as antimalarial, antibacterial and anticancer activities [5][6][7][8][9][10][11]. Due to their wide range of applications, selective functionalization of quinolines at various positions has gained

Synthetic strategies of phosphonodepsipeptides

• Jiaxi Xu

Beilstein J. Org. Chem. 2021, 17, 461–484, doi:10.3762/bjoc.17.41

• are derivatives of the new antimalarial drug fosmidomycin and inhibited the 1-deoxy-ᴅ-xylulose 5-phosphate reductoisomerase. The phosphonodepsipeptides 194 were synthesized as prodrugs with an increased activity after oral administration due to a chemical modification of the phosphonate moiety. For

Dawn of a new era in industrial photochemistry: the scale-up of micro- and mesostructured photoreactors

• Emine Kayahan,
• Mathias Jacobs,
• Leen Braeken,
• Leen C.J. Thomassen,
• Simon Kuhn,
• Tom van Gerven and
• M. Enis Leblebici

Beilstein J. Org. Chem. 2020, 16, 2484–2504, doi:10.3762/bjoc.16.202

• indigo carmine, diclofenac, and benzoylecgonine. The reactor volume was 0.15 mL [36]. The PSTY of the photodegradation of indigo carmine was calculated as 0.01 mol·day−1·kW−1 (Table 1, entry 8). In another study, those microcapillary films were used to synthesize ascaridole, an antimalarial drug, from α

Et₃N/DMSO-supported one-pot synthesis of highly fluorescent β-carboline-linked benzothiophenones via sulfur insertion and estimation of the photophysical properties

• Dharmender Singh,
• Vipin Kumar and
• Virender Singh

Beilstein J. Org. Chem. 2020, 16, 1740–1753, doi:10.3762/bjoc.16.146

• products [1][2][3][4] and pharmacologically active compounds endowed with anticancer [5][6][7][8][9], anti-inflammatory, antioxidant, antimalarial, antifungal, and antileishmanial activities (Figure 1) [10][11][12][13]. Notably, this privileged scaffold is incorporated in several marketed drugs such as

Heterogeneous photocatalysis in flow chemical reactors

• Christopher G. Thomson,
• Ai-Lan Lee and
• Filipe Vilela

Beilstein J. Org. Chem. 2020, 16, 1495–1549, doi:10.3762/bjoc.16.125

Anthelmintic drug discovery: target identification, screening methods and the role of open science

• Frederick A. Partridge,
• Ruth Forman,
• Carole J. R. Bataille,
• Graham M. Wynne,
• Marina Nick,
• Angela J. Russell,
• Kathryn J. Else and
• David B. Sattelle

Beilstein J. Org. Chem. 2020, 16, 1203–1224, doi:10.3762/bjoc.16.105

• arylpyrrole antimalarial series [82]. We are not aware of a similar real-time, fully open source effort being applied to anthelmintic discovery, but this would be an exciting prospect for the field. However, researchers have been freely releasing open tools useful for drug discovery, openly describing their

• to radically open up the drug development process, with the goal of increasing the efficiency, reducing the cost of research duplication, reducing the hoarding of data and creating collaborative communities [174]. This approach has been applied to the discovery of compounds with antimalarial activity

Synthesis and properties of quinazoline-based versatile exciplex-forming compounds

• Rasa Keruckiene,
• Simona Vekteryte,
• Ervinas Urbonas,
• Matas Guzauskas,
• Eigirdas Skuodis,
• Dmytro Volyniuk and
• Juozas V. Grazulevicius

Beilstein J. Org. Chem. 2020, 16, 1142–1153, doi:10.3762/bjoc.16.101

• , such as monitoring of specific biological activities and as antimalarial and anticancer agents [5][6]. However, electroactive properties of derivatives of this acceptor have been scarcely reported. Quinazoline-based compounds were used as hosts for red phosphorescent OLEDs with an external quantum

Recent applications of porphyrins as photocatalysts in organic synthesis: batch and continuous flow approaches

• Rodrigo Costa e Silva,
• Luely Oliveira da Silva,
• Aloisio de Andrade Bartolomeu,
• Timothy John Brocksom and
• Kleber Thiago de Oliveira

Beilstein J. Org. Chem. 2020, 16, 917–955, doi:10.3762/bjoc.16.83

• group publication [74] on new antimalarial drugs can be highlighted (Scheme 29). The authors report a 3.4 gram-scale preparation of ascaridole, in this case a synthetic intermediate, using TPP as photocatalyst. Another example of a scaled-up endoperoxide approach involves the stereoselective singlet

• -flow with O2). One very relevant example of a photooxygenation protocol is the Seeberger group’s semi-synthesis of the antimalarial API artemisinin (Scheme 32) [79]. They have established a gram-scale continuous protocol with a photooxygenation promoted by TPP starting from dihydroartemisinic acid

• oxygen and their mechanisms. Adapted from [67]. First scaled up ascaridole preparation from α-terpinene. Antimalarial drug synthesis using an endoperoxidation approach. Photooxygenation of colchicine. Synthesis of (−)-pinocarvone from abundant (+)-α-pinene. Seeberger’s semi-synthesis of artemisinin

Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules

• Valerian Dragutan,
• Ileana Dragutan,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2020, 16, 738–755, doi:10.3762/bjoc.16.68

• dihydroartemisinic acid (DHAA) [64][65]. Also, high efficient and recyclable catalytic systems based on metal-organic frameworks (MOFs) have also been reported for the tandem hemisynthesis of artemisinin [66]. In a remarkable work, this antimalarial drug was obtained by a new route involving enyne metathesis as the

Opening up connectivity between documents, structures and bioactivity

• Christopher Southan

Beilstein J. Org. Chem. 2020, 16, 596–606, doi:10.3762/bjoc.16.54

• (i.e., entombment) makes the ARC in result tables more difficult to extract. A specific example of the problem can be given for a 2017 article on new antimalarial compounds entering development [8]. Because the chemistry representations were restricted only to images in the PDF a blog post was

Pigmentosins from Gibellula sp. as antibiofilm agents and a new glycosylated asperfuran from Cordyceps javanica

• Soleiman E. Helaly,
• Wilawan Kuephadungphan,
• Patima Phainuphong,
• Mahmoud A. A. Ibrahim,
• Kanoksri Tasanathai,
• Suchada Mongkolsamrit,
• Janet Jennifer Luangsa-ard,
• Souwalak Phongpaichit,
• Vatcharin Rukachaisirikul and
• Marc Stadler

Beilstein J. Org. Chem. 2019, 15, 2968–2981, doi:10.3762/bjoc.15.293

• possess nonselective activities in biological systems and exhibit antimicrobial [28], cytotoxic [29], antimycobacterial [30], and antimalarial [31] effects. Pigmentosin A (1) and its new derivative pigmentosin B (2) exhibited weak activity against B. subtilis, with MIC values of 12.5 and 100 μg/mL

Bacterial terpene biosynthesis: challenges and opportunities for pathway engineering

• Eric J. N. Helfrich,
• Geng-Min Lin,
• Christopher A. Voigt and
• Jon Clardy

Beilstein J. Org. Chem. 2019, 15, 2889–2906, doi:10.3762/bjoc.15.283

• restricted members possess significant biological activities, like the anticancer agent taxol (1) [4] or the antimalarial agent artemisinin (2, Figure 1) [5][6]. The structural diversity and functional utility of this class of specialized metabolites have combined to encourage efforts to apply the tools of

Combining the Ugi-azide multicomponent reaction and rhodium(III)-catalyzed annulation for the synthesis of tetrazole-isoquinolone/pyridone hybrids

• Gerardo M. Ojeda,
• Prabhat Ranjan,
• Pavel Fedoseev,
• Lisandra Amable,
• Upendra K. Sharma,
• Daniel G. Rivera and
• Erik V. Van der Eycken

Beilstein J. Org. Chem. 2019, 15, 2447–2457, doi:10.3762/bjoc.15.237

• variety of pharmacological and antimicrobial properties [5][6], including analgesic, antihypertensive, anti-inflammatory, anticancer, antifungal and antimalarial activity (Figure 1). A key feature of the tetrazole ring is its bioisosteric character with the carboxylic acid and amide functional groups