Recent advances in synthetic approaches for medicinal chemistry of C-nucleosides

• Kartik Temburnikar and
• Katherine L. Seley-Radtke

Beilstein J. Org. Chem. 2018, 14, 772–785, doi:10.3762/bjoc.14.65

• employed in the design of drugs, most notably in the fields of virology and cancer research [13][14][15]. Variations in the nucleoside scaffold are typically accomplished by the insertion, deletion or transposition of functional groups or atoms [23][24][25][26][27][28][29]. The varied properties of such

Synthesis and in vitro biochemical evaluation of oxime bond-linked daunorubicin–GnRH-III conjugates developed for targeted drug delivery

• Sabine Schuster,
• Beáta Biri-Kovács,
• Bálint Szeder,
• Viktor Farkas,
• László Buday,
• Zsuzsanna Szabó,
• Gábor Halmos and
• Gábor Mező

Beilstein J. Org. Chem. 2018, 14, 756–771, doi:10.3762/bjoc.14.64

• preclinical and clinical studies, was zoptarelin-doxorubicin also known as AEZS-108 (previously AN-152) [16]. The anthracycline doxorubicin was conjugated to the ε-amino group of GnRH-I-[6D-Lys] by insertion of a glutaric acid linker. The resulting ester bond can be cleaved by carboxylesterases, leading to

Volatiles from the xylarialean fungus Hypoxylon invadens

• Jeroen S. Dickschat,
• Tao Wang and
• Marc Stadler

Beilstein J. Org. Chem. 2018, 14, 734–746, doi:10.3762/bjoc.14.62

• derivative to the corresponding aldehyde 12 that upon O-methylation (green), likely with S-adenosylmethionine, would result in 17. The alternative oxidation of 12 by a Baeyer–Villiger monooxygenase could result in the insertion of an oxygen (blue) to yield the formate ester 21, followed by ester hydrolysis

Synthesis and biological evaluation of RGD and isoDGR peptidomimetic-α-amanitin conjugates for tumor-targeting

• Lizeth Bodero,
• Paula López Rivas,
• Barbara Korsak,
• Torsten Hechler,
• Andreas Pahl,
• Christoph Müller,
• Daniela Arosio,
• Luca Pignataro,
• Cesare Gennari and
• Umberto Piarulli

Beilstein J. Org. Chem. 2018, 14, 407–415, doi:10.3762/bjoc.14.29

• and co-workers conjugated α-amanitin to pHLIP (pH low insertion peptide) via linkers of different hydrophobicities [7]. The results indicated that pHLIP could deliver α-amanitin into cells and induce cell death in 48 h by a pH-mediated direct translocation across the membrane and cleavage of the

Recent developments in the asymmetric Reformatsky-type reaction

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 325–344, doi:10.3762/bjoc.14.21

• -hydroxyalkanoates from the reaction of α-halocarbonyl compounds with aldehydes or ketones in the presence of zinc [1]. Today, the Reformatsky reactions are more generally defined as metal insertion into carbon–halogen bonds which are activated by carbonyl groups or related functions at vicinal or vinylogous

Transition-metal-free [3 + 3] annulation of indol-2-ylmethyl carbanions to nitroarenes. A novel synthesis of indolo[3,2-b]quinolines (quindolines)

• Michał Nowacki and
• Krzysztof Wojciechowski

Beilstein J. Org. Chem. 2018, 14, 194–202, doi:10.3762/bjoc.14.14

• ]. Several methods use prerequisite quinoline derivatives for the construction of the pyrrole ring of quindoline. 2-(2-Aminophenyl)-3-bromoquinoline cyclized to quindoline by reacting with pyridinium hydrochloride (d) [14]. Insertion of nitrene generated from 2-(2-nitrophenyl)quinoline by triethylphosphite

Polarization spectroscopy methods in the determination of interactions of small molecules with nucleic acids – tutorial

• Tamara Šmidlehner,
• Ivo Piantanida and
• Gennaro Pescitelli

Beilstein J. Org. Chem. 2018, 14, 84–105, doi:10.3762/bjoc.14.5

• chirality due to the structural changes caused by binding; b) an induced (I)CD as a result of ligand insertion into chiral binding sites; c) exciton coupling between multiple aggregated ligand molecules. The appearance of one or more isodichroic points (the CD equivalent of isosbestic points) during ECD

• indicated by the blue double-arrow in Figure 7) is most probably oriented at about 45° to the DNA chiral axis, thus matching the minor groove of the DNA [6][10]. For a planar molecule, this implies non-intercalative binding, whereas, for many potentially nonplanar or flexible molecules, a partial insertion

Photocatalytic formation of carbon–sulfur bonds

• Alexander Wimmer and
• Burkhard König

Beilstein J. Org. Chem. 2018, 14, 54–83, doi:10.3762/bjoc.14.4

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation. Part 1: Use of CF₃SO₂Na

• Hélène Guyon,
• Hélène Chachignon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2764–2799, doi:10.3762/bjoc.13.272

Recent progress in the racemic and enantioselective synthesis of monofluoroalkene-based dipeptide isosteres

• Myriam Drouin and
• Jean-François Paquin

Beilstein J. Org. Chem. 2017, 13, 2637–2658, doi:10.3762/bjoc.13.262

• -fluoro-2-phosphonoacetate (1) was converted into the α-fluoro-α,β-unsaturated carbonyl 3 using the HWE olefination. The (Z)-isomer was obtained with complete selectivity. Then, reduction of the ester into the corresponding alcohol followed by a Mitsunobu reaction allowed the insertion of the NH

Rh(II)-mediated domino [4 + 1]-annulation of α-cyanothioacetamides using diazoesters: A new entry for the synthesis of multisubstituted thiophenes

• Jury J. Medvedev,
• Ilya V. Efimov,
• Yuri M. Shafran,
• Vitaliy V. Suslonov,
• Vasiliy A. Bakulev and
• Valerij A. Nikolaev

Beilstein J. Org. Chem. 2017, 13, 2569–2576, doi:10.3762/bjoc.13.253

• produce thiophenes 4 through an ordinary N–H insertion process [6][7][8][9][10][11][12][13] (Scheme 5). To the best of our knowledge, the discovered processes are the first examples of intramolecular reactions of thiocarbonyl ylides with cyano groups, acting as an electrophile, with subsequent 1,3

Structure–property relationships and third-order nonlinearities in diketopyrrolopyrrole based D–π–A–π–D molecules

• Jan Podlesný,
• Lenka Dokládalová,
• Oldřich Pytela,
• Adam Urbanec,
• Milan Klikar,
• Numan Almonasy,
• Tomáš Mikysek,
• Jaroslav Jedryka,
• Iwan V. Kityk and
• Filip Bureš

Beilstein J. Org. Chem. 2017, 13, 2374–2384, doi:10.3762/bjoc.13.235

• approximately 50 °C higher melting point (e.g., 1a/1b with Tm = 261/215 °C). Thus, the insertion of an acetylene linker decreases the melting point and causes thermal instability in the liquid phase. Derivatives 1a/2a containing a 1,4-phenylene linker showed the highest Tm and Td values of 261/244 and 330/345

• be the strongest electron donor within the studied series of compounds. This is in accordance with our previous observations [9][35]. Except for chromophores 3a,b, insertion of an additional acetylene linker rather extended the electrochemical HOMO–LUMO gap (series a vs b). Linear optical properties

Dialkyl dicyanofumarates and dicyanomaleates as versatile building blocks for synthetic organic chemistry and mechanistic studies

• Grzegorz Mlostoń and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2017, 13, 2235–2251, doi:10.3762/bjoc.13.221

• converts into the orthoester 10 via insertion into the C–O bond. The reaction mechanism for the formation of 8 and 9 comprises the initial attack of the nucleophilic carbene onto the electron-deficient C atom of E-1b to give an intermediate zwitterion 11. The latter undergoes two competitive reactions. The

Phosphonic acid: preparation and applications

• Charlotte M. Sevrain,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2017, 13, 2186–2213, doi:10.3762/bjoc.13.219

• identified as metal organic framework (MOF) or coordination polymers that are synthesized by reaction with a metallic salts (e.g., copper [65], lanthanides [66]) under hydrothermal conditions [67][68] or by insertion of phosphonic acid in low dimensional inorganic materials like layered double hydroxide (LDH

Synthesis of benzannelated sultams by intramolecular Pd-catalyzed arylation of tertiary sulfonamides

• Valentin A. Rassadin,
• Mirko Scholz,
• Anastasiia A. Klochkova,
• Armin de Meijere and
• Victor V. Sokolov

Beilstein J. Org. Chem. 2017, 13, 1932–1939, doi:10.3762/bjoc.13.187

• latter transformation was a rhodium octanoate-catalyzed intramolecular carbenoid insertion into an ortho CAr–H bond (Scheme 1) [21][22], which proceeded with good yields in most cases. However, with non-equivalent aryl ortho-positions in the starting diazo compounds, mixtures of regioisomers – virtually

Mechanochemical synthesis of small organic molecules

• Tapas Kumar Achar,
• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2017, 13, 1907–1931, doi:10.3762/bjoc.13.186

• Coville and co-workers presented solvent-free organometallic transformations (e.g., migratory insertion and ligand substitution reactions) at elevated temperature (Scheme 44) which have close resemblance to mechanochemistry [173]. The examples of mechanochemical organometallic complex synthesis are

Mechanochemical synthesis of thioureas, ureas and guanidines

• Vjekoslav Štrukil

Beilstein J. Org. Chem. 2017, 13, 1828–1849, doi:10.3762/bjoc.13.178

• mechanochemical synthetic strategy and applied it to a previously unknown carbodiimide insertion into sulfonimides, resulting in two-atom ring expansion and chain extension reactions [51]. Saccharin was selected as a model cyclic sulfonimide substrate, while 4-methyl-N-tosylbenzamide was employed as an acyclic

• (Scheme 21), which was previously characterized as a simple guanidine adduct between saccharin and DCC, arose from the DCC insertion into the 5-membered saccharin ring. Under mechanochemical conditions, solvent-free or LAG milling of saccharin with N,N'-diisopropylcarbodiimide (DIC) failed to afford the

• desired product. However, the addition of 10 mol % of CuCl catalyst led to the quantitative formation of benzo[1,2,4]thiadiazepine 46a after 2 hours, as evidenced by FTIR-ATR and PXRD analyses of the crude reaction mixture. Other carbodiimides also smoothly underwent the mechanochemical insertion, e.g

NHC-catalyzed cleavage of vicinal diketones and triketones followed by insertion of enones and ynones

• Ken Takaki,
• Makoto Hino,
• Akira Ohno,
• Kimihiro Komeyama,
• Hiroto Yoshida and
• Hiroshi Fukuoka

Beilstein J. Org. Chem. 2017, 13, 1816–1822, doi:10.3762/bjoc.13.176

An efficient Pd–NHC catalyst system in situ generated from Na₂PdCl₄ and PEG-functionalized imidazolium salts for Mizoroki–Heck reactions in water

• Nan Sun,
• Meng Chen,
• Liqun Jin,
• Wei Zhao,
• Baoxiang Hu,
• Zhenlu Shen and
• Xinquan Hu

Beilstein J. Org. Chem. 2017, 13, 1735–1744, doi:10.3762/bjoc.13.168

• Mizoroki–Heck cross-coupling reactions [64][65]. These electron-donating groups could provide a flexible environment for the Pd center and thus favoring the complexation and the migratory insertion of an alkene. Cavell reported that a pyridine functionalized Pd–NHC complex showed outstanding catalytic

Oxidative dehydrogenation of C–C and C–N bonds: A convenient approach to access diverse (dihydro)heteroaromatic compounds

• Santanu Hati,
• Ulrike Holzgrabe and
• Subhabrata Sen

Beilstein J. Org. Chem. 2017, 13, 1670–1692, doi:10.3762/bjoc.13.162

• with alkyne M. This is facilitated by coordination of L with RuII, followed by C–H activation to afford N. Migratory insertion of M on N generate O and subsequent reductive elimination of O afforded the desired compounds (Scheme 26). In another example Yuan et al. [88] demonstrated that a catalytic

Molecular recognition of N-acetyltryptophan enantiomers by β-cyclodextrin

• Spyros D. Chatziefthimiou,
• Mario Inclán,
• Petros Giastas,
• Athanasios Papakyriakou,
• Konstantina Yannakopoulou and
• Irene M. Mavridis

Beilstein J. Org. Chem. 2017, 13, 1572–1582, doi:10.3762/bjoc.13.157

• studies in aqueous solution show that both enantiomers form similar, but not identical complexes with β-CD. L-NAcTrp induces larger shifts of β-CD cavity protons, suggesting stronger binding. For both enantiomers the prevailing complexation mode involves insertion in the cavity with the N-acetyl group in

Chemical systems, chemical contiguity and the emergence of life

• Terrence P. Kee and
• Pierre-Alain Monnard

Beilstein J. Org. Chem. 2017, 13, 1551–1563, doi:10.3762/bjoc.13.155

• explain its selection for the backbone of nucleic acids. Catalysis support The promotion of some complex catalyses was also shown to occur more readily in the presence of molecular assemblies, that is, in the context of a chemical system. Such effects could be either directly linked to the insertion into

• -tuned permeability to solutes and allow for the insertion of chemical species in their hydrophobic cores, thereby enabling a multiphase chemistry. This protocell development has focused on two types of processes required for self-maintenance and self-reproduction: the synthesis of protocell building

Glycoscience@Synchrotron: Synchrotron radiation applied to structural glycoscience

• Serge Pérez and
• Daniele de Sanctis

Beilstein J. Org. Chem. 2017, 13, 1145–1167, doi:10.3762/bjoc.13.114

• and ensure the closing of the orbit, or by insertion devices, such as undulators. Undulators are a much more efficient way to produce X-ray beams and force electrons along an oscillating path in the horizontal plane (Figure 3). In this manner, the X-ray emitted at one oscillation is in phase with the

• radiation from the following oscillations, resulting in an intrinsic higher brilliance. The improvements in insertion devices have made storage rings the most versatile intense X-ray sources, and many storage rings have been constructed around the world and planning for the construction and commissioning of

From chemical metabolism to life: the origin of the genetic coding process

• Antoine Danchin

Beilstein J. Org. Chem. 2017, 13, 1119–1135, doi:10.3762/bjoc.13.111

• membrane differs during states of growth and non-growth. The former implies a constructive function of the membrane. Proteins are the effectors of this function with the key operation of allowing protein insertion within the membrane. Studies investigating spontaneous evolution of lipid vesicles showed

Aggregation behaviour of a single-chain, phenylene-modified bolalipid and its miscibility with classical phospholipids

• Simon Drescher,
• Vasil M. Garamus,
• Christopher J. Garvey,
• Annette Meister and
• Alfred Blume

Beilstein J. Org. Chem. 2017, 13, 995–1007, doi:10.3762/bjoc.13.99

• ) [24]. However, the use of PC-C32-PC as “stabilizer” of phospholipid bilayers failed. In mixtures of PC-C32-PC with classical phospholipids, such as 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) or 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), no significant insertion of the bolalipid

• into the bilayer was observed [28]. The reason for this behaviour is that packing problems due to the mismatch between the large space requirement of the PC headgroup of PC-C32-PC and the small cross-sectional area of its single alkyl chain arise. The insertion of a PC-C32-PC molecule in a stretched

• alkyl chain of the bolalipid in order to fill the void volume. Besides heteroatoms [29][30], acetylene [31] or diacetylene groups [32], or methyl branches [31][33], also phenyl- or biphenyl rings were inserted into the long alkyl chain [34][35][36][37]. The insertion of a phenylene group led to PC