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

• biologically active molecules on CD-coated polymers used in chromatography [62]. PCA was used for the evaluation of the similarity/dissimilarity of some pesticides, especially fungicides and herbicides, using the effect of a water-soluble β-CD polymer on the apparent pesticide’s lipophilicity [63]. Also

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

• ]. A survey of the evolution of commercially available chemical libraries is also of real interest [97]. It turns out that a low lipophilicity, a higher fraction of sp3 carbons [98] in the structures as well as a minimum of 20 compounds per scaffold are currently favored. A high sp3 proportion along

Identification of the new prenyltransferase Ubi-297 from marine bacteria and elucidation of its substrate specificity

• Jamshid Amiri Moghaddam,
• Huijuan Guo,
• Karsten Willing,
• Thomas Wichard and
• Christine Beemelmanns

Beilstein J. Org. Chem. 2022, 18, 722–731, doi:10.3762/bjoc.18.72

• prenyltransferase; Introduction Marine bacteria harbor an enormous potential to produce structurally diverse natural products, including prenylated aromatic metabolites [1][2]. Prenylation of metabolites most often confers increased biological activities due to enhanced lipophilicity, solubility, and improved

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

• electron-withdrawing group that enhances the effects of many bioactive molecules due to a significant improvement in stability, lipophilicity, and resistance to enzymatic degradation [17][18]. Also, it has been widely applied as a special alkyl substituent for ligands of phosphorescent heavy metal

Synthesis of new bile acid-fused tetrazoles using the Schmidt reaction

• Dušan Đ. Škorić,
• Olivera R. Klisurić,
• Dimitar S. Jakimov,
• Marija N. Sakač and
• János J. Csanádi

Beilstein J. Org. Chem. 2021, 17, 2611–2620, doi:10.3762/bjoc.17.174

• bile acids, derivatives with altered hydrophobicity are being studied [12][13][14]. The tetrazole moiety can be found in many biologically active compounds, and monosubstituted tetrazole is being used in medicinal chemistry as a bioisostere of carboxylic acid [15] because it increases the lipophilicity

(Phenylamino)pyrimidine-1,2,3-triazole derivatives as analogs of imatinib: searching for novel compounds against chronic myeloid leukemia

• Luiz Claudio Ferreira Pimentel,
• Lucas Villas Boas Hoelz,
• Henayle Fernandes Canzian,
• Frederico Silva Castelo Branco,
• Andressa Paula de Oliveira,
• Vinicius Rangel Campos,
• Floriano Paes Silva Júnior,
• Rafael Ferreira Dantas,
• Jackson Antônio Lamounier Camargos Resende,
• Anna Claudia Cunha,
• Nubia Boechat and
• Mônica Macedo Bastos

Beilstein J. Org. Chem. 2021, 17, 2260–2269, doi:10.3762/bjoc.17.144

• a side chain (R), derivatives with aliphatic side chains showed greater toxic activity against K562 cells (Figure 3). One hypothesis is that the derivatives that present higher lipophilicity (2c, 2d, and 2g) quantified by the octanol–water partition coefficient (cLogP, calculated by ALOGPS) as shown

A study on selective transformation of norbornadiene into fluorinated cyclopentane-fused isoxazolines

• Zsanett Benke,
• Attila M. Remete and
• Loránd Kiss

Beilstein J. Org. Chem. 2021, 17, 2051–2066, doi:10.3762/bjoc.17.132

• enhance the pharmacokinetic properties of lead candidates in drug research through the improvement in lipophilicity, absorption, distribution, hydrophobicity and metabolism. Considering the high importance of organofluorine chemistry and that of fluoroalkyl groups in pharmaceutical chemistry, a wide range

Synthesis of multiply fluorinated N-acetyl-D-glucosamine and D-galactosamine analogs via the corresponding deoxyfluorinated glucosazide and galactosazide phenyl thioglycosides

• Vojtěch Hamala,
• Lucie Červenková Šťastná,
• Martin Kurfiřt,
• Petra Cuřínová,
• Martin Dračínský and
• Jindřich Karban

Beilstein J. Org. Chem. 2021, 17, 1086–1095, doi:10.3762/bjoc.17.85

• modulating their protein affinity, metabolic stability, and lipophilicity. Here we described the synthesis of a series of mono-, di- and trifluorinated N-acetyl-ᴅ-glucosamine and ᴅ-galactosamine analogs. The key intermediates are the corresponding multiply fluorinated glucosazide and galactosazide

• molecules [12]. The fluorination of sugars is also a promising strategy to improve unfavorable pharmacokinetic properties of natural carbohydrates such as low lipophilicity [13][14][15][16] and fast metabolic degradation [17][18][19]. Over the last few years, considerable effort has been expended on the

Synthesis of 10-O-aryl-substituted berberine derivatives by Chan–Evans–Lam coupling and investigation of their DNA-binding properties

• Peter Jonas Wickhorst,
• Mathilda Blachnik,
• Denisa Lagumdzija and
• Heiko Ihmels

Beilstein J. Org. Chem. 2021, 17, 991–1000, doi:10.3762/bjoc.17.81

• compared to ct DNA. Since the ligands show essentially the same DNA binding properties as the parent berberine (1a), they have the potential to exhibit a similar DNA-targeted bioactivity. The latter may even be improved due to the higher lipophilicity and thus more balanced bioavailability of the ligands

Synthesis of bis(aryloxy)fluoromethanes using a heterodihalocarbene strategy

• Carl Recsei and
• Yaniv Barda

Beilstein J. Org. Chem. 2021, 17, 813–818, doi:10.3762/bjoc.17.70

• 5 h, with 85% hydrolysis observed after 20 hours. The relative stability of 11 to acidic hydrolysis and its presumably enhanced lipophilicity with respect to a des-fluoro acetal, might presage a role for compounds possessing the acyclic bis(aryloxy)fluoromethane moiety in medicinal or agrochemical

DNA with zwitterionic and negatively charged phosphate modifications: Formation of DNA triplexes, duplexes and cell uptake studies

• Yongdong Su,
• Maitsetseg Bayarjargal,
• Tracy K. Hale and
• Vyacheslav V. Filichev

Beilstein J. Org. Chem. 2021, 17, 749–761, doi:10.3762/bjoc.17.65

• supports the insignificant difference in the lipophilicity of the diastereomeric ONs. We hypothesised that, in comparison with native ONs, the N+ONs should hybridise with higher affinity to complementary single-stranded DNA (ssDNA) or RNA due to both a reduced repulsion between negatively charged

Metal-free visible-light-enabled vicinal trifluoromethyl dithiolation of unactivated alkenes

• Xiaojuan Li,
• Qiang Zhang,
• Weigang Zhang,
• Jinzhu Ma,
• Yi Wang and
• Yi Pan

Beilstein J. Org. Chem. 2021, 17, 551–557, doi:10.3762/bjoc.17.49

• by introducing fluorine-containing (such as -CF3, -CF2H, -C2F5, -SCF3, -OCF3) moieties has become a substantial strategy for medicinal research [2][7][8]. Among the fluorinated functionalities, the trifluoromethylthio group (SCF3) has strong electron-withdrawing properties and a higher lipophilicity

Biochemistry of fluoroprolines: the prospect of making fluorine a bioelement

• Vladimir Kubyshkin,
• Rebecca Davis and
• Nediljko Budisa

Beilstein J. Org. Chem. 2021, 17, 439–460, doi:10.3762/bjoc.17.40

• Lipophilicity The impact of fluorine substitution on the global polarity of the molecule is another parameter that should be considered. The global polarity can be typically analyzed by measurements of the molecular partitioning, e.g., the lipophilicity index logP. For aliphatic organofluorine compounds, this

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

Decarboxylative trifluoromethylthiolation of pyridylacetates

• Ryouta Kawanishi,
• Kosuke Nakada and
• Kazutaka Shibatomi

Beilstein J. Org. Chem. 2021, 17, 229–233, doi:10.3762/bjoc.17.23

• ]. Introducing a trifluoromethylthio group (CF3S–), which has high lipophilicity and strong electron-withdrawing properties, into medicinal compounds can improve their pharmacokinetic properties [7][8][9][10][11]. Hence, the development of a synthetic method for the preparation of trifluoromethyl thioethers has

Benzothiazolium salts as reagents for the deoxygenative perfluoroalkylthiolation of alcohols

• Armin Ariamajd,
• Nils J. Gerwien,
• Benjamin Schwabe,
• Stefan Dix and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2021, 17, 83–88, doi:10.3762/bjoc.17.8

• trifluoromethylthio group (SCF3), for example, is attracting considerable attention due to its strong lipophilicity-enhancing influence (Hansch constant π = 1.44) and electron-withdrawing properties (Hammett constants σp = 0.50 and σm = 0.40) [7][8][9][10][11][12]. On the other hand, longer-chain perfluoroalkylthio

Synthesis of tetrafluorinated piperidines from nitrones via a visible-light-promoted annelation reaction

• Vyacheslav I. Supranovich,
• Igor A. Dmitriev and
• Alexander D. Dilman

Beilstein J. Org. Chem. 2020, 16, 3104–3108, doi:10.3762/bjoc.16.260

• modify basicity, lipophilicity, as well as the hydrogen-bonding properties of amines [4][5] makes fluorinated piperidines [6][7] attractive targets in medicinal chemistry [8][9]. Previous efforts were mainly focused on the synthesis of mono- and difluorinated compounds. A single fluorine atom is

Synthesis of novel fluorinated building blocks via halofluorination and related reactions

• Attila Márió Remete,
• Tamás T. Novák,
• Melinda Nonn,
• Matti Haukka,
• Ferenc Fülöp and
• Loránd Kiss

Beilstein J. Org. Chem. 2020, 16, 2562–2575, doi:10.3762/bjoc.16.208

• lipophilicity, metabolism, binding, and bioavailability are often beneficial [1][2][3][4][5][6][7][8][9]. Fluorinated organic compounds are common amongst drugs [8][9], and the synthesis of fluorinated compounds has become a rapidly developing area [9][10][11][12][13][14][15][16][17][18]. In addition to

Conformational preferences of fluorine-containing agrochemicals and their implications for lipophilicity prediction

• Daniela Rodrigues Silva,
• Joyce K. Daré and
• Matheus P. Freitas

Beilstein J. Org. Chem. 2020, 16, 2469–2476, doi:10.3762/bjoc.16.200

• Daniela Rodrigues Silva Joyce K. Dare Matheus P. Freitas Department of Chemistry, Federal University of Lavras, 37200–900, Lavras–MG, Brazil 10.3762/bjoc.16.200 Abstract Molecular polarity governs lipophilicity, which in turn determines important agrochemical and environmental properties, such as

• lipophilicity with the molecular conformation. Keywords: dipole moment; fluorinated compounds; gauche effect; herbicides; log P; Introduction Whilst in the last years the agrochemical industry has encountered a period of downturn affected by new regulations, low crop prices, biochemical resistance, among

• expensive and time-consuming procedure [2]. Fluorination is a common strategy employed as part of the optimization process during the design of new chemical compounds, which includes the modulation of a variety of properties such as lipophilicity, biological half-life, and biosorption [3][4]. This role

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

• , metabolic stability, adsorption and excretion properties of the compound [16][17]. For example, the pharmacokinetics of drugs are mostly regulated by the balance of the lipophilicity, hydrophilicity and ionization state. Since C–H/C–F substitution in a drug molecule enhances the lipophilicity [18], this has

Lipophilicity trends upon fluorination of isopropyl, cyclopropyl and 3-oxetanyl groups

• Benjamin Jeffries,
• Zhong Wang,
• Robert I. Troup,
• Anaïs Goupille,
• Jean-Yves Le Questel,
• Charlene Fallan,
• James S. Scott,
• Elisabetta Chiarparin,
• Jérôme Graton and
• Bruno Linclau

Beilstein J. Org. Chem. 2020, 16, 2141–2150, doi:10.3762/bjoc.16.182

• Nantes, France Medicinal Chemistry, Oncology R&D, AstraZeneca, Cambridge CB4 0WG, UK 10.3762/bjoc.16.182 Abstract A systematic comparison of lipophilicity modulations upon fluorination of isopropyl, cyclopropyl and 3-oxetanyl substituents, at a single carbon atom, is provided using directly comparable

• , and easily accessible model compounds. In addition, comparison with relevant linear chain derivatives is provided, as well as lipophilicity changes occurring upon chain extension of acyclic precursors to give cyclopropyl containing compounds. For the compounds investigated, fluorination of the

• isopropyl substituent led to larger lipophilicity modulation compared to fluorination of the cyclopropyl substituent. Keywords: aliphatic fluorination; cyclopropane; isopropyl; isostere; lipophilicity; oxetane; Introduction The introduction of small alkyl groups onto bioactive compounds as space filling

Design, synthesis and application of carbazole macrocycles in anion sensors

• Alo Rüütel,
• Ville Yrjänä,
• Sandip A. Kadam,
• Indrek Saar,
• Mihkel Ilisson,
• Astrid Darnell,
• Kristjan Haav,
• Tõiv Haljasorg,
• Lauri Toom,
• Johan Bobacka and
• Ivo Leito

Beilstein J. Org. Chem. 2020, 16, 1901–1914, doi:10.3762/bjoc.16.157

• -life sensing, also influences binding [4]. Within an ion-selective electrode (ISE), lipophilicity is mostly contributed by the low polarity membrane, which is commonly based on plasticized PVC [5]. One possible receptor family for carboxylates is based on the biscarbazolylurea moiety (Figure 1). This

• functional groups in the 3,6-positions of the carbazole. High lipophilicity is achievable by using alkylation and leads to the possibility of using the receptor dissolved in the lipophilic polymeric sensor membrane, without the need for chemical linking. Cyclization of the receptor is possible via the

• ionophore clearly disrupted the Hofmeister selectivity pattern that could be seen in the control membrane where the lipophilicity of the interfering ion was the dominant factor in determining the selectivity. All of the ionophores had a greater affinity for pivalate than for benzoate based on the

On the hydrolysis of diethyl 2-(perfluorophenyl)malonate

• Ilya V. Taydakov and
• Mikhail A. Kiskin

Beilstein J. Org. Chem. 2020, 16, 1863–1868, doi:10.3762/bjoc.16.153

• to be one of the most powerful tools for fine tuning of chemical and physical properties [19][20]. For example, thermal stability, solubility, metabolic and oxidative stability, lipophilicity, membrane permeability, complexing ability, acid-base, and many other properties can be modified in a broad

Polarity effects in 4-fluoro- and 4-(trifluoromethyl)prolines

• Vladimir Kubyshkin

Beilstein J. Org. Chem. 2020, 16, 1837–1852, doi:10.3762/bjoc.16.151

• trifluoromethyl- or a difluoromethylene group. This orientation of the substituents explains the observed trends in the pKa values, lipophilicity, and the kinetics of the amide bond rotation. The study also provides a set of evidences that the transition state of the amide-bond rotation in peptidyl-prolyl favors

• orientation of the groups, while in the (trifluoromethyl)prolines the orientation is similar. This is reflected in the acidity values. Lipophilicity Another parameter, which may be sensitive to the orientation of the dipoles within a molecule is the lipophilicity. It is well known that single aliphatic

• make a molecule more polar, but also more lipophilic at the same time. In addition, interactions of these dipoles with the ones preexisting in the parent molecule should always be considered for predicting the molecular polarity [60][76]. Experimental lipophilicity values found for the model compounds

Pauson–Khand reaction of fluorinated compounds

• Jorge Escorihuela,
• Daniel M. Sedgwick,
• Alberto Llobat,
• Mercedes Medio-Simón,
• Pablo Barrio and
• Santos Fustero

Beilstein J. Org. Chem. 2020, 16, 1662–1682, doi:10.3762/bjoc.16.138

• strategic positions in a drug candidate may result in not only an increase in its potency, but also, perhaps more importantly, bring about an enhanced pharmacokinetic profile resulting in a more “drug-like” molecule [4]. Subtle changes in physicochemical properties such as acidity/basicity, lipophilicity