Sequential Ugi reaction/base-induced ring closing/IAAC protocol toward triazolobenzodiazepine-fused diketopiperazines and hydantoins

• Robby Vroemans,
• Fante Bamba,
• Jonas Winters,
• Joice Thomas,
• Jeroen Jacobs,
• Luc Van Meervelt,
• Jubi John and
• Wim Dehaen

Beilstein J. Org. Chem. 2018, 14, 626–633, doi:10.3762/bjoc.14.49

• currently being evaluated for their biological properties, the results of which will be reported in due course. Triazolobenzodiazepine drugs. Generality in the synthesis of diketopiperazine-fused triazolobenzodiazepine 7. Reaction conditions: 1. 2-azidobenzaldehyde 1 (1.85 mmol), propargylamine 2 (1.85 mmol

Mannich base-connected syntheses mediated by ortho-quinone methides

• Petra Barta,
• Ferenc Fülöp and
• István Szatmári

Beilstein J. Org. Chem. 2018, 14, 560–575, doi:10.3762/bjoc.14.43

• ]. Their relatively easy accessibility and promising biological properties have led to the resurgence of their chemistry coming again into the focus of pharmacological research. The formation of aminonaphthols can be explained by two mechanisms. According to one possibility, first the reaction of the amine

• published about o-QM generation, applicability in organic syntheses and biological properties [11][12][13][14][15][16][17]. However, in this review we would like to focus on their role in syntheses connected to Mannich base chemistry as well as their wider applicability and properties. Formation of Mannich

• were also formed in around 90% yields under microwave irradiation (Scheme 7). Miscellaneous reactions It is also known that o-QMs could cross-link two biologically important molecules such as peptides, proteins or nucleic bases. (see section Biological properties) Achieving the reaction under

Synthesis of fluoro-functionalized diaryl-λ³-iodonium salts and their cytotoxicity against human lymphoma U937 cells

• Prajwalita Das,
• Etsuko Tokunaga,
• Hidehiko Akiyama,
• Hiroki Doi,
• Norimichi Saito and
• Norio Shibata

Beilstein J. Org. Chem. 2018, 14, 364–372, doi:10.3762/bjoc.14.24

• arylation reactions in synthetic organic chemistry, but their biological properties are not fully understood. Herein, after initially investigating 18 fluoro-functionalized reagents, we discovered that the ortho-fluoro-functionalized diaryliodonium salt reagents showed remarkable cytotoxicity in vitro

Continuous-flow retro-Diels–Alder reaction: an efficient method for the preparation of pyrimidinone derivatives

• Imane Nekkaa,
• Márta Palkó,
• István M. Mándity and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2018, 14, 318–324, doi:10.3762/bjoc.14.20

• antibiotics [41]. Our aim in the present study was to synthesize functionalized pyrimidinone systems through rDA reactions. Many of these products are of high importance in drug design due to their diverse biological properties including antimicrobial, antiviral, antioxidant and antitumor activities. In

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

• pharmacological activities such as: anticancer [1][2], anti-inflammatory [3][4], antioxidant [5], antibacterial [6][7][8], analgesic [9], antiviral [10][11], antimicrobial [12][13], antifungal [6], antiglycemic [14], antiamoebic [15] and antidepressive [16][17]. Considering the immense biological properties

Nucleophilic fluoroalkylation/cyclization route to fluorinated phthalides

• Masanori Inaba,
• Tatsuya Sakai,
• Shun Shinada,
• Tsuyuka Sugiishi,
• Yuta Nishina,
• Norio Shibata and
• Hideki Amii

Beilstein J. Org. Chem. 2018, 14, 182–186, doi:10.3762/bjoc.14.12

• synthesis of useful bioactive compounds. There is a growing interest in the usefulness of phthalides and their derivatives. Organofluorine compounds often show attractive physical, chemical, and biological properties and are widely used in many fields, such as pharmaceuticals, agrochemicals, and materials

The synthesis of the 2,3-difluorobutan-1,4-diol diastereomers

• Robert Szpera,
• Nadia Kovalenko,
• Kalaiselvi Natarajan,
• Nina Paillard and
• Bruno Linclau

Beilstein J. Org. Chem. 2017, 13, 2883–2887, doi:10.3762/bjoc.13.280

• opening; fluorinated building block; vicinal difluoride; Introduction The introduction of fluorine in organic compounds usually results in the modification of a range of chemical, physical and biological properties [1]. Fluorine incorporation is therefore a common strategy to optimise the properties of

Consecutive hydrazino-Ugi-azide reactions: synthesis of acylhydrazines bearing 1,5-disubstituted tetrazoles

• Angélica de Fátima S. Barreto,
• Veronica Alves dos Santos and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2017, 13, 2596–2602, doi:10.3762/bjoc.13.256

• and, in particular, it displays a wide range of biological properties such as analgesic, anti-inflammatory, antiviral, anticancer, among others [3][4][5]. The tetrazole nucleus most widely described in the literature is the 1,5-disubstituted tetrazole [6][7] because it presents a wide range of

Hydrolysis, polarity, and conformational impact of C-terminal partially fluorinated ethyl esters in peptide models

• Vladimir Kubyshkin and
• Nediljko Budisa

Beilstein J. Org. Chem. 2017, 13, 2442–2457, doi:10.3762/bjoc.13.241

• of fluorination, as these parameters strongly impact other important biological properties, such as the potential distribution in biochemical compartments and the metabolic stability [44][45]. Considering the variety of spectroscopic applications, a labeling strategy that allows specific

Exploring mechanochemistry to turn organic bio-relevant molecules into metal-organic frameworks: a short review

• Vânia André,
• Sílvia Quaresma,
• João Luís Ferreira da Silva and
• M. Teresa Duarte

Beilstein J. Org. Chem. 2017, 13, 2416–2427, doi:10.3762/bjoc.13.239

• centers, in order to obtain compounds with enhanced biological properties. New metal-organic frameworks, BioMOFs, for the use of controlled drug delivery and/or release or other biological applications, were successfully synthesized either by direct incorporation of the bioactive molecule in the framework

Synthesis, effect of substituents on the regiochemistry and equilibrium studies of tetrazolo[1,5-a]pyrimidine/2-azidopyrimidines

• Elisandra Scapin,
• Paulo R. S. Salbego,
• Caroline R. Bender,
• Alexandre R. Meyer,
• Anderson B. Pagliari,
• Tainára Orlando,
• Geórgia C. Zimmer,
• Clarissa P. Frizzo,
• Helio G. Bonacorso,
• Nilo Zanatta and
• Marcos A. P. Martins

Beilstein J. Org. Chem. 2017, 13, 2396–2407, doi:10.3762/bjoc.13.237

• great interest from a pharmacological point of view. A broader control and modulation of the equilibrium can lead to a specific compound to prevent undesirable pharmacokinetics and biological properties arising from the differences in the chemical structure. Our research group previously demonstrated an

Fluorination of some highly functionalized cycloalkanes: chemoselectivity and substrate dependence

• Attila Márió Remete,
• Melinda Nonn,
• Santos Fustero,
• Matti Haukka,
• Ferenc Fülöp and
• Loránd Kiss

Beilstein J. Org. Chem. 2017, 13, 2364–2371, doi:10.3762/bjoc.13.233

• dependence, neighboring group assistance and chemodifferentiation. Keywords: amino acids; chemoselectivity; fluorine; functionalization; stereoisomers; Introduction Fluorinated molecules exert an ever-increasing impact in medicinal chemistry thanks to their valuable biological properties. Numerous drugs

Diosgenyl 2-amino-2-deoxy-β-D-galactopyranoside: synthesis, derivatives and antimicrobial activity

• Henryk Myszka,
• Patrycja Sokołowska,
• Agnieszka Cieślińska,
• Andrzej Nowacki,
• Maciej Jaśkiewicz,
• Wojciech Kamysz and
• Beata Liberek

Beilstein J. Org. Chem. 2017, 13, 2310–2315, doi:10.3762/bjoc.13.227

• ]. They produce a soap-like foam when shaken in aqueous solutions, which makes them useful as detergents, foaming agents and emulsifiers. Saponins are known for their structural diversity and a wide range of biological properties [2]. Among others, they display different pharmacological activities

Preparation of imidazo[1,2-a]-N-heterocyclic derivatives with gem-difluorinated side chains

• Layal Hariss,
• Kamal Bou Hadir,
• Mirvat El-Masri,
• Thierry Roisnel,
• René Grée and
• Ali Hachem

Beilstein J. Org. Chem. 2017, 13, 2115–2121, doi:10.3762/bjoc.13.208

• widely recognized as a general strategy toward drug development in pharmaceutical research. This is connected to fluorine's electronegativity, size, and lipophilicity [15][16], which can strongly improve the biological properties of molecules through, for instance, increase of metabolic stability and

• fluorinated propargylic derivatives [21]. Thus, taking into account the known biological properties of the imidazo-fused N-heterocycles, we became interested in the preparation of new derivatives of this type possessing gem-difluorinated side chains as indicated in Figure 1. Such new fluorinated heterocycles

Difunctionalization of alkenes with iodine and tert-butyl hydroperoxide (TBHP) at room temperature for the synthesis of 1-(tert-butylperoxy)-2-iodoethanes

• Hao Wang,
• Cui Chen,
• Weibing Liu and
• Zhibo Zhu

Beilstein J. Org. Chem. 2017, 13, 2023–2027, doi:10.3762/bjoc.13.200

• and biological properties [26][27]. Organoperoxides have wide applications in the field of organic synthesis, as radical initiators, oxidants that replace transition metal oxidants, and key reactive intermediates in diverse organic synthesis reactions [28][29][30], as well as in medicinal chemistry

Mechanochemical enzymatic resolution of N-benzylated-β³-amino esters

• Mario Pérez-Venegas,
• Gloria Reyes-Rangel,
• Adrián Neri,
• Jaime Escalante and
• Eusebio Juaristi

Beilstein J. Org. Chem. 2017, 13, 1728–1734, doi:10.3762/bjoc.13.167

• resolution; mechanochemistry; Introduction β-Amino acids are rather interesting molecules that frequently exhibit exceptional biological properties [1][2][3]; for instance, some of them are efficient inhibitors of several enzymes [4][5]. Furthermore, β-amino acid residues can be used to protect peptides and

Switchable highly regioselective synthesis of 3,4-dihydroquinoxalin-2(1H)ones from o-phenylenediamines and aroylpyruvates

• Juraj Dobiaš,
• Marek Ondruš,
• Gabriela Addová and
• Andrej Boháč

Beilstein J. Org. Chem. 2017, 13, 1350–1360, doi:10.3762/bjoc.13.132

• . calcd for C17H11ClN2O4 (342.73): C, 59.57; H, 3.23; N, 8.17; found: C, 59.82; H, 3.10; N, 8.32. The structures including some of their physical and biological properties of 3,4-dihydroqunoxalin-2(1H)-ones 4–10. Abbreviations used: F-1,6-BP = fructose 1,6-bisphosphatase; Eya2 = eyes absent homolog 2; HNE

BODIPY-based fluorescent liposomes with sesquiterpene lactone trilobolide

• Ludmila Škorpilová,
• Silvie Rimpelová,
• Michal Jurášek,
• Miloš Buděšínský,
• Jana Lokajová,
• Roman Effenberg,
• Petr Slepička,
• Tomáš Ruml,
• Eva Kmoníčková,
• Pavel B. Drašar and
• Zdeněk Wimmer

Beilstein J. Org. Chem. 2017, 13, 1316–1324, doi:10.3762/bjoc.13.128

• encapsulation of construct 6 into the liposomes improved the drug distribution in cancer cells and was followed by cell death. This new liposomal trilobolide derivative not only retains the biological properties of pure trilobolide, but also enhances the bioavailability, and thus has potential for the use in

Biomimetic molecular design tools that learn, evolve, and adapt

• David A Winkler

Beilstein J. Org. Chem. 2017, 13, 1288–1302, doi:10.3762/bjoc.13.125

• parameters (network weights) and minimizing overfitting. While deep learning is attracting much attention in fields like image and voice recognition, it may not be superior to three layer ‘shallow’ neural networks for modelling chemical, molecular and biological properties. An important mathematical theorem

An eco-compatible strategy for the diversity-oriented synthesis of macrocycles exploiting carbohydrate-derived building blocks

• Sushil K. Maurya and
• Rohit Rana

Beilstein J. Org. Chem. 2017, 13, 1106–1118, doi:10.3762/bjoc.13.110

• rings and have shown important biological properties [5][6][7][8][9][10][11][12]. For example, macrocyclic aminoglycoside analogues have shown binding with the trans-activating region (TAR) RNA of the human immunodeficiency virus (HIV); an attractive target for RNA-based drug discovery [13]. Further

Total syntheses of the archazolids: an emerging class of novel anticancer drugs

• Stephan Scheeff and
• Dirk Menche

Beilstein J. Org. Chem. 2017, 13, 1085–1098, doi:10.3762/bjoc.13.108

• . The important biological properties in combination with their limited natural supply as well as their intriguing molecular architectures and initially unknown stereochemistry, have rendered the archazolids as highly attractive synthetic targets and so far, three total syntheses have been reported by

Transition-metal-free one-pot synthesis of alkynyl selenides from terminal alkynes under aerobic and sustainable conditions

• Adrián A. Heredia and
• Alicia B. Peñéñory

Beilstein J. Org. Chem. 2017, 13, 910–918, doi:10.3762/bjoc.13.92

• diseases, inflammatory processes, arthritis, and skin damage caused by exposure to UV radiation [1][2][3]. However, all these properties belong to organoselenides due to their ability to engage in enzymatic processes [4][5] and alkynyl selenides have demonstrated only limited biological properties [6][7

Metal-free hydroarylation of the side chain carbon–carbon double bond of 5-(2-arylethenyl)-3-aryl-1,2,4-oxadiazoles in triflic acid

• Anna S. Zalivatskaya,
• Dmitry S. Ryabukhin,
• Marina V. Tarasenko,
• Alexander Yu. Ivanov,
• Irina A. Boyarskaya,
• Elena V. Grinenko,
• Ludmila V. Osetrova,
• Eugeniy R. Kofanov and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2017, 13, 883–894, doi:10.3762/bjoc.13.89

• been paid to their synthesis and to the studies of their chemical, physical and biological properties (see numerous reviews [1][2][3][4][5][6][7][8]). The oxadiazole ring represents an essential part of the pharmacophore in many drugs. These compounds possess different kinds of biological activities

The effect of cyclodextrin complexation on the solubility and photostability of nerolidol as pure compound and as main constituent of cabreuva essential oil

• Joyce Azzi,
• Pierre-Edouard Danjou,
• David Landy,
• Steven Ruellan,
• Lizette Auezova,
• Hélène Greige-Gerges and
• Sophie Fourmentin

Beilstein J. Org. Chem. 2017, 13, 835–844, doi:10.3762/bjoc.13.84

• et Interactions sur le Vivant (UCEIV, EA 4492), SFR Condorcet FR CNRS 3417, ULCO, F-59140 Dunkerque, France 10.3762/bjoc.13.84 Abstract Nerolidol (Ner), a major component of many plant essential oils, is known for its various biological properties. However, the low solubility of Ner in water and its

• thus enhancing their biological properties [15][16]. To the best of our knowledge, no literature data reported the encapsulation of Ner in CDs. In this study, for the first time, CD/Ner inclusion complexes were characterized in solution and in solid state. Formation constants (Kf) were determined for

A practical and efficient approach to imidazo[1,2-a]pyridine-fused isoquinolines through the post-GBB transformation strategy

• Taofeng Shao,
• Zhiming Gong,
• Tianyi Su,
• Wei Hao and
• Chao Che

Beilstein J. Org. Chem. 2017, 13, 817–824, doi:10.3762/bjoc.13.82

• (Figure 1) [6]. Furthermore, the isoquinoline motif represents a privileged medicinal skeleton widely found in a number of natural alkaloids and pharmaceutically active compounds [7]. Some of them exhibit diversified biological properties, including anti-inflammatory [8], antibacterial [9], antiviral [10