Diastereoselective synthesis of new O-alkylated and C-branched inositols and their corresponding fluoro analogues

• Charlotte Collet,
• Françoise Chrétien,
• Yves Chapleur and
• Sandrine Lamandé-Langle

Beilstein J. Org. Chem. 2016, 12, 353–361, doi:10.3762/bjoc.12.39

• (Figure 1). These new inositol members could represent attractive tools for the development of further inositol analogues. Indeed, this arm could improve some properties as the lipophilicity for example and should allow the easy anchoring of various groups or molecules, such as carbohydrates for example

• . Two arm lengths of two or three carbons were envisioned, on the C2 for the myo-series and on the C1 for the scyllo-series, ending with a hydroxy group or a fluorine atom. Indeed the addition of fluorine could improve chemical properties including lipophilicity, brain penetration, enhanced binding

Synthesis and nucleophilic aromatic substitution of 3-fluoro-5-nitro-1-(pentafluorosulfanyl)benzene

• Javier Ajenjo,
• Martin Greenhall,
• Camillo Zarantonello and
• Petr Beier

Beilstein J. Org. Chem. 2016, 12, 192–197, doi:10.3762/bjoc.12.21

• pentafluorosulfanyl (SF5) group are promising candidates in the development of new agrochemicals, pharmaceuticals and advanced materials [1][2][3]. This is due to an unusual combination of properties such as high stability [4], lipophilicity [5] and strong electron-withdrawing character [6] similar but more extreme

Synthesis and reactivity of aliphatic sulfur pentafluorides from substituted (pentafluorosulfanyl)benzenes

• Norbert Vida,
• Jiří Václavík and
• Petr Beier

Beilstein J. Org. Chem. 2016, 12, 110–116, doi:10.3762/bjoc.12.12

• applications ranging from advanced materials to bioactive compounds [1][2][3]. One such fluorinated functional group which has become the focus of systematic investigation only recently is the pentafluorosulfanyl (SF5) group [4][5]. The combination of high stability [6], lipophilicity [7] and strong electron

Carbon–carbon bond cleavage for Cu-mediated aromatic trifluoromethylations and pentafluoroethylations

• Tsuyuka Sugiishi,
• Hideki Amii,
• Kohsuke Aikawa and
• Koichi Mikami

Beilstein J. Org. Chem. 2015, 11, 2661–2670, doi:10.3762/bjoc.11.286

• ][2][3][4][5][6][7]. The characteristic size, strong electron-withdrawing ability, and the high lipophilicity of the trifluoromethyl group are key properties of biologically active CF3-containing molecules [8]. Perfluoroalkylcopper compounds (CnF2n+1Cu), which are soft and relatively stable

Versatile synthesis and biological evaluation of novel 3’-fluorinated purine nucleosides

• Hang Ren,
• Haoyun An,
• Paul J. Hatala,
• William C. Stevens Jr,
• Jingchao Tao and
• Baicheng He

Beilstein J. Org. Chem. 2015, 11, 2509–2520, doi:10.3762/bjoc.11.272

• for specific reasons. The fluorine atom possesses unique characteristics; it enhances the lipophilicity of organic compounds and C–F bonds have low chemical reactivity imparting high enzymatic stability and resistance to metabolic processes. The high electronegativity of fluorine and the lipophilicity

Efficient synthesis of π-conjugated molecules incorporating fluorinated phenylene units through palladium-catalyzed iterative C(sp²)–H bond arylations

• Fatiha Abdelmalek,
• Fazia Derridj,
• Safia Djebbar,
• Jean-François Soulé and
• Henri Doucet

Beilstein J. Org. Chem. 2015, 11, 2012–2020, doi:10.3762/bjoc.11.218

• dramatically influence both chemical properties and reactivities owing to its electronegativity, size, lipophilicity, and electrostatic interactions. For example, introduction of fluorine into natural products can result in beneficial biological properties [6]. On the other hand, fluorinated π-conjugated

Pyridine-promoted dediazoniation of aryldiazonium tetrafluoroborates: Application to the synthesis of SF₅-substituted phenylboronic esters and iodobenzenes

• George Iakobson,
• Junyi Du,
• Alexandra M. Z. Slawin and
• Petr Beier

Beilstein J. Org. Chem. 2015, 11, 1494–1502, doi:10.3762/bjoc.11.162

• from SF5-aliphatics have also been studied [28][29][30]. The unique combination of properties the SF5 group imparts includes high chemical, thermal, and metabolic stability, strong electron-acceptor property, and high lipophilicity. Furthermore, applications of SF5 compounds in catalysis [31][32], life

Antioxidant potential of curcumin-related compounds studied by chemiluminescence kinetics, chain-breaking efficiencies, scavenging activity (ORAC) and DFT calculations

• Adriana K. Slavova-Kazakova,
• Silvia E. Angelova,
• Timur L. Veprintsev,
• Petko Denev,
• Davide Fabbri,
• Maria Antonietta Dettori,
• Maria Kratchanova,
• Vladimir V. Naumov,
• Aleksei V. Trofimov,
• Rostislav F. Vasil’ev,
• Giovanna Delogu and
• Vessela D. Kancheva

Beilstein J. Org. Chem. 2015, 11, 1398–1411, doi:10.3762/bjoc.11.151

• saponified extracts of maize bran and grasses [14]. Ferulic acid and the corresponding ethyl ester protect primary neuronal cell cultures against oxidative damage [14]. The increased lipophilicity of ferulic acid ethyl ester improves the ability to cross cell membranes easier than the corresponding acid. The

• biphenylic structure provides lipophilicity to dimer 9 allowing for a strong effect against pests and plant diseases [15]. The different conformations of the biphenyl structure generated by selective functionalization of the aromatic rings led us to consider this moiety as a basic and valued framework for

Terminal lipophilization of a unique DNA dodecamer by various nucleolipid headgroups: Their incorporation into artificial lipid bilayers and hydrodynamic properties

• Emma Werz and
• Helmut Rosemeyer

Beilstein J. Org. Chem. 2015, 11, 913–929, doi:10.3762/bjoc.11.103

• lipophilicity but mainly the chemical structure and topology of the head group is of decisive importance for the optimal interaction of a lipo-oligonucleotide with an artificial lipid bilayer. Moreover, fluorescence half-live and diffusion time values were measured to determine the diffusion coefficients of the

• only loosely adsorbed at the bilayer surface. From these results, it can be stated that the insertion rate of a lipo-oligonucleotide into an artificial lipid bilayer as well as its stability within the bilayer does not exclusively depend on the lipophilicity of the head group but also (i) results from

• lipophilicity of the nucleolipid head group is of minor importance for the effectiveness of lipo-oligonucleotide binding within the artificial lipid bilayer with respect to (i) the maximal bilayer brightness, (ii) the binding rate to reach this maximum brightness, (iii) the stability of the LON within the

N-Alkyl derivatives of diosgenyl 2-amino-2-deoxy-β-D-glucopyranoside; synthesis and antimicrobial activity

• Agata Walczewska,
• Daria Grzywacz,
• Dorota Bednarczyk,
• Małgorzata Dawgul,
• Andrzej Nowacki,
• Wojciech Kamysz,
• Beata Liberek and
• Henryk Myszka

Beilstein J. Org. Chem. 2015, 11, 869–874, doi:10.3762/bjoc.11.97

• amine group, is able to work as a hydrogen bond acceptor. On the other hand, alkylation improves lipophilicity of the compound, which may be crucial for its biological activity. At the beginning, our experiences concerning the synthesis of the parent diosgenyl 2-amino-2-deoxy-β-D-glucopyranoside (7) are

Natural phenolic metabolites with anti-angiogenic properties – a review from the chemical point of view

• Qiu Sun,
• Jörg Heilmann and
• Burkhard König

Beilstein J. Org. Chem. 2015, 11, 249–264, doi:10.3762/bjoc.11.28

• antiproliferative activity of these acylphloroglucinols in HMEC-1 increases with increasing log P. Increasing the number of carbon atoms in the acyl group provides higher lipophilicity, which allows the compound to better penetrate across cellular membranes in the in vitro assay. In contrast, the activity of the

Encapsulation of biocides by cyclodextrins: toward synergistic effects against pathogens

• Véronique Nardello-Rataj and
• Loïc Leclercq

Beilstein J. Org. Chem. 2014, 10, 2603–2622, doi:10.3762/bjoc.10.273

• inclusion complexes is presented as a very attractive tool to modify the physicochemical properties of an organic biocide. Indeed, upon complexation, the lipophilicity can be disguised and the aqueous solubility can thus be enhanced. One of the most useful and widely applied analytical approaches to

Specific DNA duplex formation at an artificial lipid bilayer: fluorescence microscopy after Sybr Green I staining

• Emma Werz and
• Helmut Rosemeyer

Beilstein J. Org. Chem. 2014, 10, 2307–2321, doi:10.3762/bjoc.10.240

• paper which deals with the interaction of a defined oligonucleotide single strand, carrying nucleolipid head groups of different lipophilicity with lipid bilayer membranes, might be of importance for the optimization of the in vivo delivery of lipophilic siRNA [13] (e.g., by DNA trafficking as shown in

Synthesis of trifluoromethyl-substituted pyrazolo[4,3-c]pyridines – sequential versus multicomponent reaction approach

• Barbara Palka,
• Angela Di Capua,
• Maurizio Anzini,
• Gyté Vilkauskaité,
• Algirdas Šačkus and
• Wolfgang Holzer

Beilstein J. Org. Chem. 2014, 10, 1759–1764, doi:10.3762/bjoc.10.183

• lipophilicity [1][2]. Moreover, incorporation of fluorine often results in an increase of the binding affinity of drug molecules to the target protein [1][2]. As a consequence, a considerable amount – approximately 20% – of all the pharmaceuticals being currently on the market contain at least one fluorine

The search for new amphiphiles: synthesis of a modular, high-throughput library

• George C. Feast,
• Thomas Lepitre,
• Xavier Mulet,
• Charlotte E. Conn,
• Oliver E. Hutt,
• G. Paul Savage and
• Calum J. Drummond

Beilstein J. Org. Chem. 2014, 10, 1578–1588, doi:10.3762/bjoc.10.163

• , whilst the degree of lipophilicity, the polarity of the molecule, and the volume and shape of the molecule have all been attributed to controlling phase behaviour, the understanding of the interplay and relative contribution of these factors is still evolving. Therefore, in addition to discovering new

Syntheses of fluorooxindole and 2-fluoro-2-arylacetic acid derivatives from diethyl 2-fluoromalonate ester

• Antal Harsanyi,
• Graham Sandford,
• Dmitri S. Yufit and
• Judith A.K. Howard

Beilstein J. Org. Chem. 2014, 10, 1213–1219, doi:10.3762/bjoc.10.119

• biological activity [1], a growing number of commercially significant life science products, which owe their activity to the presence of fluorine atoms within their structures, have developed. Fluorine incorporation can lead, for example, to enhanced bioavailability, metabolic stability and lipophilicity of

Amino acid motifs in natural products: synthesis of O-acylated derivatives of (2S,3S)-3-hydroxyleucine

• Oliver Ries,
• Martin Büschleb,
• Markus Granitzka,
• Dietmar Stalke and
• Christian Ducho

Beilstein J. Org. Chem. 2014, 10, 1135–1142, doi:10.3762/bjoc.10.113

• derivatives 1a,b of the A- and B-series, respectively (Figure 1) [7]. This significant change in potency might be owed to increased lipophilicity and thus to improved cellular uptake, as muraymycins inhibit the transmembrane protein MraY (translocase I), an enzyme involved in peptidoglycan formation with its

• direct relation of the lipophilicity of semi-synthetic muraymycin C1 analogues and their biological activity [18]. They thus also postulated that the lipid structure might be involved in transporting the molecule to the active site of the target enzyme. The most recent SAR investigation on synthetic

A novel family of (1-aminoalkyl)(trifluoromethyl)- and -(difluoromethyl)phosphinic acids – analogues of α-amino acids

• Natalia V. Pavlenko,
• Tatiana I. Oos,
• Yurii L. Yagupolskii,
• Igor I. Gerus,
• Uwe Doeller and
• Lothar Willms

Beilstein J. Org. Chem. 2014, 10, 722–731, doi:10.3762/bjoc.10.66

• of its strong electronegativity. This enables modulation of the lipophilicity profile, of electrostatic interactions with the target structure and inhibition of some metabolic pathways [7][8][9]. Data concerning the biological activity and synthetic approaches toward fluorinated aminophosphonates

Flow microreactor synthesis in organo-fluorine chemistry

• Hideki Amii,
• Aiichiro Nagaki and
• Jun-ichi Yoshida

Beilstein J. Org. Chem. 2013, 9, 2793–2802, doi:10.3762/bjoc.9.314

• fluorine leads to the smallest steric perturbation available to us. In pharmaceuticals, fluorine is often introduced to increase lipophilicity, bioavailability, and metabolic stability; these unique properties are otherwise difficult to obtain. At present, nearly 15% of medicines and 20% of agrochemicals

• improves lipophilicity leading to enhanced solubility in fatty tissue and more efficient transport in the body. Nucleophilic introduction of perfluoroalkyl (RF) groups are one of the most effective and general methods for the synthesis of perfluoroalkylated compounds [77]. Perfluoroalkyllithiums, which are

Copper-catalyzed trifluoromethylation of alkenes with an electrophilic trifluoromethylating reagent

• Xiao-Ping Wang,
• Jin-Hong Lin,
• Cheng-Pan Zhang,
• Ji-Chang Xiao and
• Xing Zheng

Beilstein J. Org. Chem. 2013, 9, 2635–2640, doi:10.3762/bjoc.9.299

• pharmaceutically and agrochemically relevant molecules usually enhances their chemical and metabolic stability, lipophilicity and binding selectivity [1][2][3][4][5][6][7]. As a result, considerable effort has been directed towards the development of efficient and versatile trifluoromethylation methods [8][9][10

Recent advances in transition metal-catalyzed Csp²-monofluoro-, difluoro-, perfluoromethylation and trifluoromethylthiolation

• Grégory Landelle,
• Armen Panossian,
• Sergiy Pazenok,
• Jean-Pierre Vors and
• Frédéric R. Leroux

Beilstein J. Org. Chem. 2013, 9, 2476–2536, doi:10.3762/bjoc.9.287

• . Perfluoroalkyl substituents are particularly interesting as they often lead to a significant increase in lipophilicity and thus bioavailability albeit with a modified stability. Therefore, it is of continual interest to develop new, environmentally benign methods for the introduction of these groups into target

• important role in pharmaceutical [124] and agrochemical research [16][125]. The trifluoromethylthio group belongs to the most lipophilic substituents as expressed by the Hansch lipophilicity parameter (π = 1.44) [126][127][128][129] and the high electronegativity of the SCF3 group improves significantly the

Cu-catalyzed trifluoromethylation of aryl iodides with trifluoromethylzinc reagent prepared in situ from trifluoromethyl iodide

• Yuzo Nakamura,
• Motohiro Fujiu,
• Tatsuya Murase,
• Yoshimitsu Itoh,
• Hiroki Serizawa,
• Kohsuke Aikawa and
• Koichi Mikami

Beilstein J. Org. Chem. 2013, 9, 2404–2409, doi:10.3762/bjoc.9.277

• , biological, and physical properties [1][2][3][4][5][6]. Particularly, trifluoromethylated compounds can be widely employed as one of the most effective analogues of bioactive compounds, because the trifluoromethyl group enhances the metabolic stability, lipophilicity, and bioavailability of these compounds

Amyloid-β probes: Review of structure–activity and brain-kinetics relationships

• Todd J. Eckroat,
• Abdelrahman S. Mayhoub and
• Sylvie Garneau-Tsodikova

Beilstein J. Org. Chem. 2013, 9, 1012–1044, doi:10.3762/bjoc.9.116

• TgCRDN8 mouse brain sections by in vitro autoradiography [22]. [18F]-Labeled stilbene derivatives have enhanced brain kinetics rendering them appropriate for clinical use [23][24][25]. In order to control the lipophilicity and keep the partition coefficient (log P) value between 1 and 3, which reduces

• uptake rates (1.07–2.06% ID/g at 2 min) and slower washout rates (3.29–2.01% ID/g at 60 min) than their 1,3,4 counterparts [48]. These findings, together with the close structural similarities between compounds 50a–f and 51a–e, highlight the importance of lipophilicity as a factor in controlling brain

• radiotracers in which the ionic charge was removed to increase lipophilicity and to enhance in vivo BBB permeability. Overall, this class of compounds shows high affinity for Aβ aggregates with promising in vivo pharmacokinetics. One of the earliest radiolabeled benzothiazoles, [11C]6-Me-BTA-1 ([11C]56a; note

Synthesis and evaluation of cell-permeable biotinylated PU-H71 derivatives as tumor Hsp90 probes

• Tony Taldone,
• Anna Rodina,
• Erica M. DaGama Gomes,
• Matthew Riolo,
• Hardik J. Patel,
• Raul Alonso-Sabadell,
• Danuta Zatorska,
• Maulik R. Patel,
• Sarah Kishinevsky and
• Gabriela Chiosis

Beilstein J. Org. Chem. 2013, 9, 544–556, doi:10.3762/bjoc.9.60

• biotin directly or via a linker through an amide bond. We chose to make analogues of both 1a and 1b because the isopropyl group in 1a may result in considerable effects on cell-permeability properties due to its increased lipophilicity, while having little effect on the affinity for Hsp90. While it is

Synthesis of SF₅-containing benzisoxazoles, quinolines, and quinazolines by the Davis reaction of nitro-(pentafluorosulfanyl)benzenes

• Petr Beier and
• Tereza Pastýříková

Beilstein J. Org. Chem. 2013, 9, 411–416, doi:10.3762/bjoc.9.43

• various applications due to an unusual combination of the properties of the SF5 group, such as high lipophilicity, with strong electron-acceptor character. One important property of the SF5 group is its high thermal and chemical stability [14][15][16][17]. The main reason that prevents further development