Dipeptide analogues of fluorinated aminophosphonic acid sodium salts as moderate competitive inhibitors of cathepsin C

• Karolina Wątroba,
• Małgorzata Pawełczak and
• Marcin Kaźmierczak

Beilstein J. Org. Chem. 2023, 19, 434–439, doi:10.3762/bjoc.19.33

• in chemotherapies to support traditional anticancer drugs. Moreover, there is a growing interest in the topic of cathepsin C inhibition, which directly affects serine protease activity [5][6]. Inhibitors of cathepsin C can be cystatins that show activity against a large group of cysteine proteases [7

Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities

• Jorge de Lima Neto and
• Paulo Henrique Menezes

Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31

• bond of 28 leads to compounds of increasing activity, being the more polar hydroxy-substituted derivatives the most active (Table 2) [73]. One of the major obstacles in the development of highly potent drugs is the water solubility. Pettit and co-workers [55] conducted an extensive study in an attempt

Discrimination of β-cyclodextrin/hazelnut (Corylus avellana L.) oil/flavonoid glycoside and flavonolignan ternary complexes by Fourier-transform infrared spectroscopy coupled with principal component analysis

• Nicoleta G. Hădărugă,
• Gabriela Popescu,
• Dina Gligor (Pane),
• Cristina L. Mitroi,
• Sorin M. Stanciu and
• Daniel Ioan Hădărugă

Beilstein J. Org. Chem. 2023, 19, 380–398, doi:10.3762/bjoc.19.30

• -based ternary complexes, but they do not deal with triglyceride-based vegetable oils or with flavonoid glycosides/flavonolignans. Most of these studies are related to controlled release of various drugs from the CD complexes such as diosmin and polyethylene glycol, haloperidol and lactic acid

Continuous flow synthesis of 6-monoamino-6-monodeoxy-β-cyclodextrin

• János Máté Orosz,
• Dóra Ujj,
• Petr Kasal,
• Gábor Benkovics and
• Erika Bálint

Beilstein J. Org. Chem. 2023, 19, 294–302, doi:10.3762/bjoc.19.25

• complexation can lead to a significant solubility enhancement of poorly water-soluble molecules, and therefore it can enable the biological testing of drugs, which would otherwise not be possible by any other means [2][3]. Monosubstituted CDs contain only one hydroxy group modified with a functional group. In

An efficient metal-free and catalyst-free C–S/C–O bond-formation strategy: synthesis of pyrazole-conjugated thioamides and amides

• Shubham Sharma,
• Dharmender Singh,
• Sunit Kumar,
• Vaishali,
• Rahul Jamra,
• Naveen Banyal,
• Deepika,
• Chandi C. Malakar and
• Virender Singh

Beilstein J. Org. Chem. 2023, 19, 231–244, doi:10.3762/bjoc.19.22

• ], anticancer [13][14][15], antiviral [16], analgesic [17], antioxidants, antimicrobial [18], antidiabetic, anticonvulsant [19], antihelminthic [20], and antiarrhythmic activities. The pyrazole nucleus is a core unit in several FDA-approved marketed drugs such as sildenafil [21][22][23], celebrex [24][25

• linkage is present in several naturally occurring compounds and it is also one of the most productive functional groups in current pharmaceutical drugs [50][51]. As prime examples; atorvastatin [52], valsartan [53] and N-cyclohexylethyl-ETAsV are successfully utilized to treat various life challenging

Investigation of cationic ring-opening polymerization of 2-oxazolines in the “green” solvent dihydrolevoglucosenone

• Solomiia Borova and
• Robert Luxenhofer

Beilstein J. Org. Chem. 2023, 19, 217–230, doi:10.3762/bjoc.19.21

• clear bimodality, but the molar mass distribution was slightly lower (Ð = 1.45) compared to PBuOx obtained from EtOxMeOTf (Figure S14, Supporting Information File 1). POx-based block copolymers are well known to formulate poorly water soluble drugs and Haider et al. recently compared the drug loading

Insight into oral amphiphilic cyclodextrin nanoparticles for colorectal cancer: comprehensive mathematical model of drug release kinetic studies and antitumoral efficacy in 3D spheroid colon tumors

• Sedat Ünal,
• Gamze Varan,
• Juan M. Benito,
• Yeşim Aktaş and
• Erem Bilensoy

Beilstein J. Org. Chem. 2023, 19, 139–157, doi:10.3762/bjoc.19.14

• mathematically by release kinetic modeling for the first time. The overall findings indicated that the strategy of orally targeting anticancer drugs such as CPT with positively charged poly-β-CD-C6 nanoparticles to colon tumors for local and/or systemic efficacy is a promising approach. Keywords: colorectal

• is possible, chemotherapeutic treatment is still one of the most researched approaches in terms of tumor recurrence and the progression of the disease. In CRC chemotherapy, the most common approach is mainly an intravenous administration of anticancer drugs such as camptothecin (CPT) analogs

• (irinotecan, topotecan), 5-fluorouracil (5-FU), oxaliplatin (OXA) or the combination of these drugs. However, current treatment approaches frequently result in major adverse effects, non-specific biodistribution, poor patient compliance, and clinically inadequate results in terms of efficacy [3][4][5]. Today

Synthesis and characterisation of new antimalarial fluorinated triazolopyrazine compounds

• Kah Yean Lum,
• Jonathan M. White,
• Daniel J. G. Johnson,
• Vicky M. Avery and
• Rohan A. Davis

Beilstein J. Org. Chem. 2023, 19, 107–114, doi:10.3762/bjoc.19.11

• and death, as 80% of deaths in this region were children under five [1]. Whilst there are drugs available for the treatment of malaria infections, most have now succumbed to parasite drug resistance and thus reduced clinical efficacy [2][3]. Consequently, new antiplasmodial drugs with novel malaria

• promising leads within the OSM project [14]. Fluorine-containing compounds have exhibited wide applications in pharmaceuticals and agrochemicals – approximately 20% of marketed drugs are fluoro-pharmaceuticals, while for agrochemicals, 53% are fluoro-compounds [17][18]. In recent decades, the introduction

Revisiting the bromination of 3β-hydroxycholest-5-ene with CBr₄/PPh₃ and the subsequent azidolysis of the resulting bromide, disparity in stereochemical behavior

• Christian Schumacher,
• Jas S. Ward,
• Kari Rissanen,
• Carsten Bolm and
• Mohamed Ramadan El Sayed Aly

Beilstein J. Org. Chem. 2023, 19, 91–99, doi:10.3762/bjoc.19.9

• cholesterol biosynthesis (statins). However, the side effects of these drugs are controversial. Therefore, synthetic cholesterol derivatives came into focus for recent applications in chemical biology and materials science [6]. The advances have been summarized in comprehensive reviews [7][8]. In previous

Preparation of β-cyclodextrin/polysaccharide foams using saponin

• Max Petitjean and
• José Ramón Isasi

Beilstein J. Org. Chem. 2023, 19, 78–88, doi:10.3762/bjoc.19.7

• coronavirus vaccine chitosan–saponin coatings have been developed to study its immunogenic potential [32]. A complexation between saponin and cyclodextrins (native or derivative) is possible [33], and the resulting release kinetics is appropriate for the creation of new saponin-based drugs [34]. Their

NaI/PPh₃-catalyzed visible-light-mediated decarboxylative radical cascade cyclization of N-arylacrylamides for the efficient synthesis of quaternary oxindoles

• Dan Liu,
• Yue Zhao and
• Frederic W. Patureau

Beilstein J. Org. Chem. 2023, 19, 57–65, doi:10.3762/bjoc.19.5

• reactions constitute a powerful synthetic approach to construct multiple C–C or C–X bonds in one pot. As such, these tend to allow facile access to many complex natural molecules and drugs [1][2][3][4][5][6]. Recently, radical-initiated cascade cyclizations involving acrylamides have attracted considerable

Combining the best of both worlds: radical-based divergent total synthesis

• Kyriaki Gennaiou,
• Antonios Kelesidis,
• Maria Kourgiantaki and
• Alexandros L. Zografos

Beilstein J. Org. Chem. 2023, 19, 1–26, doi:10.3762/bjoc.19.1

• time, some members have been recognized as potent topoisomerase inhibitors and have been used as anticancer drugs [106]. To access the rich diversity of this class, Zhu’s group recently applied a Fukuzumi salt ([Mes–Acr–Me]BF4)-mediated photochemical oxidation of dicinnamyl ether derivative 225 in the

Inclusion complexes of the steroid hormones 17β-estradiol and progesterone with β- and γ-cyclodextrin hosts: syntheses, X-ray structures, thermal analyses and API solubility enhancements

• Alexios I. Vicatos,
• Zakiena Hoossen and
• Mino R. Caira

Beilstein J. Org. Chem. 2022, 18, 1749–1762, doi:10.3762/bjoc.18.184

• has already been published, the majority of the publications being focused on medicinal applications, for example, using formulations of these drugs with CDs for ophthalmic and nasal delivery [11][12][13][14][15][16][17][18][19][20][21]. The scientific literature abounds with reports featuring the use

• composition from the residual electron density peaks in the respective crystal structures. We carried out analogous studies on the four CD complexes to establish whether they might also display enhanced aqueous solubilities of the included steroids relative to those of the pure drugs. We also present here

Inline purification in continuous flow synthesis – opportunities and challenges

• Jorge García-Lacuna and
• Marcus Baumann

Beilstein J. Org. Chem. 2022, 18, 1720–1740, doi:10.3762/bjoc.18.182

• biocatalysts in view of recycling. This will likely see applications for generating small volume drugs or other high value entities where fast access to a high quality product is key, or where the isolation and handling of intermediates is not viable due to their properties. Thus, it can be concluded that many

A novel spirocyclic scaffold accessed via tandem Claisen rearrangement/intramolecular oxa-Michael addition

• Anastasia Vepreva,
• Alexander Yanovich,
• Dmitry Dar’in,
• Grigory Kantin,
• Alexander Bunev and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2022, 18, 1649–1655, doi:10.3762/bjoc.18.177

• . The resulting spirocyclic compounds are formed with a clear preference to the syn diastereomer over anti which can be rationalized by conformational analysis of the Claisen rearrangement precursors to their formation. Examples of approved spirocyclic drugs. (a) Earlier reported Rh(II)-catalyzed

One-pot double annulations to confer diastereoselective spirooxindolepyrrolothiazoles

• Juan Lu,
• Bin Yao,
• Desheng Zhan,
• Zhuo Sun,
• Yun Ji and
• Xiaofeng Zhang

Beilstein J. Org. Chem. 2022, 18, 1607–1616, doi:10.3762/bjoc.18.171

• drugs available in the market approved by the FDA. Thus, the reaction process with synthetic efficiency and operational simplification is a critical factor in the construction of nitrogen-based heterocycles. Normally, some advantageous approaches in green synthesis are in favor of innovating the

Functionalization of imidazole N-oxide: a recent discovery in organic transformations

• Koustav Singha,
• Imran Habib and
• Mossaraf Hossain

Beilstein J. Org. Chem. 2022, 18, 1575–1588, doi:10.3762/bjoc.18.168

• -saving drugs and medicines. Imidazole is one of the pharmacologically important heterocyclic motifs found in widely used and well-known medicines and bioactive molecules. The applications of imidazole derivatives displaying various biological activities, motivated researchers for the development of more

• potent and significant drugs containing imidazole moieties. The formation of imidazole derivatives can be achieved using imidazole N-oxide as starting material. In this review, the scope of substrates and reaction mechanisms of various synthetic approaches using imidazole N-oxides as substrates are

Simple synthesis of multi-halogenated alkenes from 2-bromo-2-chloro-1,1,1-trifluoroethane (halothane)

• Yukiko Karuo,
• Atsushi Tarui,
• Kazuyuki Sato,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2022, 18, 1567–1574, doi:10.3762/bjoc.18.167

• (s, 1F), −78.4 (s, 1F); EIMS m/z: 268, 270 [M]+; HREIMS: [M]+ calcd for C13H14ClFSi, 268.0486, 270.0457; found, 268.0490, 270.0452. Medicines containing a difluoromethylene group. Fluoroalkene analogs of some drugs. Reaction of phenol with polyfluoroalkanes. Proposed mechanism. Sonogashira cross

New triazole-substituted triterpene derivatives exhibiting anti-RSV activity: synthesis, biological evaluation, and molecular modeling

• Elenilson F. da Silva,
• Krist Helen Antunes Fernandes,
• Denise Diedrich,
• Jessica Gotardi,
• Marcia Silvana Freire Franco,
• Carlos Henrique Tomich de Paula da Silva,
• Ana Paula Duarte de Souza and
• Simone Cristina Baggio Gnoatto

Beilstein J. Org. Chem. 2022, 18, 1524–1531, doi:10.3762/bjoc.18.161

• drug for its treatment, however, its clinical use has been limited due to its side effects. Here, we designed two new nitroaryl-1,2,3-triazole triterpene derivatives as novel anti-RSV drugs. Their anti-RSV and cytotoxic activity were evaluated in vitro, RSV protein F gene effects by RT-PCR and

• , Figure 1), is one of the few licensed drugs for treating RSV infections [8][9]. Although there are many suggested mechanisms of action, the main mechanisms for RBV involve the inhibition of the enzymes RNA-dependent RNA polymerase and inosine monophosphate dehydrogenase (IMPDH). IMPDH is required for the

• forecast of increasing numbers of RSV infections in the future, and the medical requirements associated with severe RSV infections, no vaccine or effective drugs have been developed so far, which reinforces the urgency for the research and development of a new type of anti-RSV drugs that can be widely

Cyclometalated iridium complexes-catalyzed acceptorless dehydrogenative coupling reaction: construction of quinoline derivatives and evaluation of their antimicrobial activities

• Hongling Shui,
• Yuhong Zhong,
• Renshi Luo,
• Zhanyi Zhang,
• Jiuzhong Huang,
• Ping Yang and
• Nianhua Luo

Beilstein J. Org. Chem. 2022, 18, 1507–1517, doi:10.3762/bjoc.18.159

• antimicrobial effects of compounds 3ab, 3ad, 3ah, 3ck, 3an and other compounds were better than the parent drug norfloxacin. This method could be used to further synthesis of quinoline derivatives and provide theoretical support for the synthesis of new antibacterial drugs. Some new quinoline antibacterial

• drugs. Cyclometalated iridium-catalyzed ADC reaction of o-aminobenzyl alcohols and secondary alcohols. Gram-scale transformations. Mechanistic investigation. A speculated possible mechanism. Optimization of catalyst for ADC reaction of 2-aminobenzyl alcohol and 1-phenylethanol.a Studies of reaction

Synthesis of the biologically important dideuterium-labelled adenosine triphosphate analogue ApppI(d₂)

• Petri A. Turhanen

Beilstein J. Org. Chem. 2022, 18, 1466–1470, doi:10.3762/bjoc.18.153

• already in clinical use as antiviral or anticancer drugs [2][5][6]. Bisphosphonates (BPs), the stable analogues of the natural pyrophosphate (Figure 1) found in cells, have been used for decades in the treatment of bone-related diseases, such as osteoporosis [7][8]. BPs can be categorized by the chemical

Mechanochemical synthesis of unsymmetrical salens for the preparation of Co–salen complexes and their evaluation as catalysts for the synthesis of α-aryloxy alcohols via asymmetric phenolic kinetic resolution of terminal epoxides

• Shengli Zuo,
• Shuxiang Zheng,
• Jianjun Liu and
• Ang Zuo

Beilstein J. Org. Chem. 2022, 18, 1416–1423, doi:10.3762/bjoc.18.147

• ; mechanochemistry; phenolic KR; Introduction In the past decade, more than twenty chiral small molecule drugs were approved by the FDA, including ruxolitinib, afatinib, sonidegib, encorafenib, lorlatinib, darolutamide, alpelisib, artesunate, maribavir, ponesimod, daridorexant and others [1][2][3]. The

• enantioselective synthesis in modern chemistry turns out to be accumulatively essential for the preparation of chiral drugs, which is a huge growing market in the future. Indeed, the asymmetric ring opening of terminal epoxides is one of the most important strategies for synthesizing drug-like building blocks and

Characterization of a new fusicoccane-type diterpene synthase and an associated P450 enzyme

• Jia-Hua Huang,
• Jian-Ming Lv,
• Liang-Yan Xiao,
• Qian Xu,
• Fu-Long Lin,
• Gao-Qian Wang,
• Guo-Dong Chen,
• Sheng-Ying Qin,
• Dan Hu and
• Hao Gao

Beilstein J. Org. Chem. 2022, 18, 1396–1402, doi:10.3762/bjoc.18.144

• Jia-Hua Huang Jian-Ming Lv Liang-Yan Xiao Qian Xu Fu-Long Lin Gao-Qian Wang Guo-Dong Chen Sheng-Ying Qin Dan Hu Hao Gao Institute of Traditional Chinese Medicine & Natural Products, College of Pharmacy / Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs

On drug discovery against infectious diseases and academic medicinal chemistry contributions

• Yves L. Janin

Beilstein J. Org. Chem. 2022, 18, 1355–1378, doi:10.3762/bjoc.18.141

• -infectious or neglected diseases, such choices appear to have impacted the actual number of drugs discovered in these countries and this trend goes beyond the academic contributions of the considered country. Looking at the actual origins of the research entities who provided the anti-HIV1 drugs available

• chemistry culture caused by this lack of academic support. Indeed, virtual docking has yet to demonstrate that it was instrumental in preselecting a really successful hit out of chemical libraries and considering, for instance, anticancer drugs as potential antivirals is barely more relevant than assaying

• , amongst many other uses, provided the background for fragment-based drug design [2][3]. – An ever-increasing computer processing speed leading to an ever-growing list of software-based approaches to try to help in various aspects of drugs discovery. The neural network-based software AlphaFold [4], which

Cyclodextrin-based Schiff base pro-fragrances: Synthesis and release studies

• Attila Palágyi,
• Jindřich Jindřich,
• Juraj Dian and
• Sophie Fourmentin

Beilstein J. Org. Chem. 2022, 18, 1346–1354, doi:10.3762/bjoc.18.140

• of labile compounds is to prepare pro-fragrances in analogy with the concept of pro-drugs developed for pharmaceutical applications. The fragrance is linked covalently to a substrate that will release the fragrance under defined chemical conditions. For applications in the fragrance and flavor