Synthesis of medronic acid monoesters and their purification by high-performance countercurrent chromatography or by hydroxyapatite

• Elina Puljula,
• Jouko Vepsäläinen and
• Petri A. Turhanen

Beilstein J. Org. Chem. 2016, 12, 2145–2149, doi:10.3762/bjoc.12.204

• unreported problem in the chlorination reaction of trimethyl methylene-BP with oxalyl chloride, i.e., we observed that the triester readily formed a dimer with itself during the chlorination reaction according to the 1H and 31P NMR spectra. Dimerization has been previously observed with clodronic acid

New furoisocoumarins and isocoumarins from the mangrove endophytic fungus Aspergillus sp. 085242

• Ze’en Xiao,
• Senhua Chen,
• Runlin Cai,
• Shao’e Lin,
• Kui Hong and
• Zhigang She

Beilstein J. Org. Chem. 2016, 12, 2077–2085, doi:10.3762/bjoc.12.196

• . The above evidences allowed us to conclude that compound 6 was a polyether dimer of stellatin as shown in Figure 2. In addition, the following known compounds were identified: ustusorane B (7) [20], penicisochroman A (8) [21], and TMC-120B (9) [22], on the basis of the spectroscopic comparison with

• isopentenyl substituent with two adjacent carbonyl groups seems to be rare in natural isocoumarin derivatives and asperisocoumarin F (6) presents as a scaffold with an ether dimer of isocoumarin. All isolates were evaluated for their α-glucosidase inhibitory activity using clinical acarbose (IC50 of 628.3 μM

Synthesis and NMR studies of malonyl-linked glycoconjugates of N-(2-aminoethyl)glycine. Building blocks for the construction of combinatorial glycopeptide libraries

• Markus Nörrlinger,
• Sven Hafner and
• Thomas Ziegler

Beilstein J. Org. Chem. 2016, 12, 1939–1948, doi:10.3762/bjoc.12.183

• quantitative yield by subjection 7 to a saturated solution of NH3 in MeOH (7 N) (Scheme 2). In addition to the monomeric glycoconjugates 1a–d and 2a–d we also prepared dimer 4 from the glucose containing conjugate 2a and the N-acetylglucosamine containing conjugate 1c. Treatment of 1c with 20% piperidine in

Mechanistic investigations on six bacterial terpene cyclases

• Patrick Rabe,
• Thomas Schmitz and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2016, 12, 1839–1850, doi:10.3762/bjoc.12.173

• -rich (DDXXD) motif near position 90 and the NSE triad (ND(L,I,V)XSXXXE) around position 230 [40][41]. Furthermore, usually 46 positions upstream of the NSE triad a highly conserved arginine (pyrophosphate sensor) and a RY dimer near the C-terminus are found that form hydrogen bonds to the diphosphate

• usual asparagine, obviously without effect on the enzyme function, the pyrophosphate sensor R-196 and the 327RY dimer. Terpene cyclases with close homology are encoded in more than 40 genome sequenced streptomycetes that all show an altered NSE triad starting with either proline or alanine. The closest

• [43]. The (+)-T-muurolol synthase from R. castenholzii DSM 13941 contains the aspartate-rich motif (81DDQCD), the NSE triad (221NDVLSYPKE), the pyrophosphate sensor R-175 and the 309RY dimer. Closely related is the (+)-T-muurolol synthase from Roseiflexus sp. RS-1 [29] with 69% identical residues

Reactivity studies of pincer bis-protic N-heterocyclic carbene complexes of platinum and palladium under basic conditions

• David C. Marelius,
• Curtis E. Moore,
• Arnold L. Rheingold and
• Douglas B. Grotjahn

Beilstein J. Org. Chem. 2016, 12, 1334–1339, doi:10.3762/bjoc.12.126

• temperature, an NMR spectrum was acquired that showed a new, unsymmetrical species, as expected for 5. Crystals were grown by vapor diffusion of pentanes into benzene and analyzed. Surprisingly, the data showed that the dimer 6-Pd had formed such that the open site was not filled with ethylene, but rather was

• occupied by an imidazolyl nitrogen from a second complex (Figure 2). The palladium and platinum dimer complexes, 6-Pd and 6-Pt, could be formed by addition of sodium tert-butoxide to the chloride analogs (Scheme 1), and isolated in 50–56% yields. The examination of the dimer crystal structure (see Figure 2

• other half of the dimer, which would be expected to shield the NH and cause a significant upfield chemical shift. Moreover, a ROESY experiment on 6-Pt (Figure S6, Supporting Information File 1) confirms that the NH (N5’, Figure 2) has a through-space interaction with the proton on the imidazole ring (C3

Modular synthesis of the pyrimidine core of the manzacidins by divergent Tsuji–Trost coupling

• Sebastian Bretzke,
• Stephan Scheeff,
• Felicitas Vollmeyer,
• Friederike Eberhagen,
• Frank Rominger and
• Dirk Menche

Beilstein J. Org. Chem. 2016, 12, 1111–1121, doi:10.3762/bjoc.12.107

• dimer in the crystal lattice, which is stabilized by two hydrogen bonds between the urea oxygen atoms and the tosyl-protected nitrogens. This also unambiguously confirms the absolute configuration of 39 and corroborates our prediction of the asymmetric adduct 31. We then attempted the installation of

The synthesis of functionalized bridged polycycles via C–H bond insertion

• Jiun-Le Shih,
• Po-An Chen and
• Jeremy A. May

Beilstein J. Org. Chem. 2016, 12, 985–999, doi:10.3762/bjoc.12.97

• –H bond insertion using Wilkinson’s catalyst (RhCl(PPh3)3) instead of the usual rhodium(II) dimer (Scheme 13) [68]. Rather than starting with a diazoketone, ester, or amide, Wilkinson’s catalyst may generate an active organorhodium intermediate through insertion into the acyl C–H bond of the aldehyde

• insertions, and inspiration for subsequent efforts of greater complexity. The transannular C–H bond insertion by an axially disposed carbene group that is needed for bridged-ring formation occurs readily, but pathways that lead to fused products having less ring strain or that lead to dimer formation must be

Enantioselective carbenoid insertion into C(sp³)–H bonds

• J. V. Santiago and
• A. H. L. Machado

Beilstein J. Org. Chem. 2016, 12, 882–902, doi:10.3762/bjoc.12.87

• reduce some type of steric strain on the transition state of the insertion reaction and avoid the dimer formation. For the insertion reaction of iridium carbenoid into the 1,4-cyclohexadiene (62) bis-allylic C(sp3)–H bond the authors observed the formation of two products, one resulting from iridium

A modular approach to neutral P,N-ligands: synthesis and coordination chemistry

• Vladislav Vasilenko,
• Torsten Roth,
• Clemens K. Blasius,
• Sebastian N. Intorp,
• Hubert Wadepohl and
• Lutz H. Gade

Beilstein J. Org. Chem. 2016, 12, 846–853, doi:10.3762/bjoc.12.83

• [2a-PdCl2] and [2a-PdCl]2(BF4)2, and molecular structure of the dimer [2a-PdCl]22+. Anisotropic displacement ellipsoids set at the 50% probability level. Hydrogen atoms have been omitted for clarity. (B) Formation of Pd(allyl) complexes of ligands 2a, 5, and 7. Reaction conditions: (i) DCM, [Pd(cod

Muraymycin nucleoside-peptide antibiotics: uridine-derived natural products as lead structures for the development of novel antibacterial agents

• Daniel Wiegmann,
• Stefan Koppermann,
• Marius Wirth,
• Giuliana Niro,
• Kristin Leyerer and
• Christian Ducho

Beilstein J. Org. Chem. 2016, 12, 769–795, doi:10.3762/bjoc.12.77

• the PNPT superfamily. MraYAA crystallised as a dimer and additional experiments showed that it also exists as a dimer in detergent micelles and membranes [71]. The previously proposed models are in agreement with the solved structure showing ten transmembrane helices and five cytoplasmic loops. The

From steroids to aqueous supramolecular chemistry: an autobiographical career review

• Bruce C. Gibb

Beilstein J. Org. Chem. 2016, 12, 684–701, doi:10.3762/bjoc.12.69

• way up to C50H102. In considering this we have found that for the octa-acid dimer the boundary between two or one guest encapsulation is C8H18 [47], but that guests longer than C12H26 must compress in some manner in order to be accommodated. There are three principle ways that such large guests

• together two octa-acid molecules. For this “dimer” host, guests smaller than n-heptadecane (C17H36) bind to the host in a similar manner as they do to the assembled capsule of octa-acid. However, guests larger than C18H38 do not adopt a U-shaped packing inside a 1:1 complex, but instead induce the

• capsular assemblies [49]. This unique property comes about because the four methyl groups reduce the relative stability of the dimer capsule so that guests such as C5H12 promote the formation of a 2:2 capsule, but near the transition point from two to one internalized guest, C7H16 destabilizes the capsular

Creating molecular macrocycles for anion recognition

• Amar H. Flood

Beilstein J. Org. Chem. 2016, 12, 611–627, doi:10.3762/bjoc.12.60

• their propensity to stack. This can be seen in the crystalline phase with dimer formation either around anionic guests like perchlorate [36] (Figure 14a) or, in the absence of an anion, around adventitious solvents of crystallization, like diglyme (Figure 14b) [37] . The π-surface was enhanced by

A journey in bioinspired supramolecular chemistry: from molecular tweezers to small molecules that target myotonic dystrophy

• Steven C. Zimmerman

Beilstein J. Org. Chem. 2016, 12, 125–138, doi:10.3762/bjoc.12.14

• for CUGexp by dimerizing ligands 27/28. Indeed, dimer 29 exhibited a bivalent effect of 133 and was an extremely potent inhibitor of the MBNL1N-(CUG)12 complex [86][87]. The possibility of off-target activity by the acridine ligands resulting from the unstacked conformation (Figure 8c) led Chun-Ho

Versatile deprotonated NHC: C,N-bridged dinuclear iridium and rhodium complexes

• Albert Poater

Beilstein J. Org. Chem. 2016, 12, 117–124, doi:10.3762/bjoc.12.13

• the pNHC leads to an equilibrium between a mononuclear complex containing a C-bound anionic imidazolide [42][43][44] and its dimer [45][46][47][48][49][50][51][52][53][54][55][56][57][58], where the NHC moiety binds in a µ-C,N bridging mode (see Scheme 1) [44]. Even though during the last two decades

• distances in Å). Equilibrium between the monoiridum complex bearing a C-bound anionic imidazolide and its corresponding dimer, once deprotonated a pNHC. Experimental routes to the “equilibrium” between 3H-H and 3H-T. Equilibrium between complexes 3–6, in the presence of CO, PMe3, and MeI. Supporting

Supramolecular structures based on regioisomers of cinnamyl-α-cyclodextrins – new media for capillary separation techniques

• Gabor Benkovics,
• Ondrej Hodek,
• Martina Havlikova,
• Zuzana Bosakova,
• Pavel Coufal,
• Milo Malanga,
• Eva Fenyvesi,
• Andras Darcsi,
• Szabolcs Beni and
• Jindrich Jindrich

Beilstein J. Org. Chem. 2016, 12, 97–109, doi:10.3762/bjoc.12.11

• -threaded supramolecular dimer in water, the 3-Cio-α-CD formed a soluble supramolecular oligomer in the same solvent. The mixture of both regioisomers led to the formation of a self-sorting oligomeric system, where only the heterosupramolecular interactions between the two isomers were present but the

• ) of structures at various concentrations. The D of the unmodified α-CD was previously reported by Avram and Cohen [13] and it was found to be 3.0 × 10-6 cm2 s−1. The D of a supramolecular dimer formed by the structurally similar 2-O-Cio-α-CD was measured in work [9] and its value was found to be 2.3

• 1.27 × 10−6 cm2 s−1 at 96 mM (Figure 6). These data indicate that the size of the supramolecular structures formed by the assembly of 2-O-Cin-α-CD or by 3-O-Cin-α-CD is apparently much larger than the size of the unmodified α-CD and also exceeds the size of the double threaded dimer formed by 2-O-Cio-α

Supramolecular polymer assembly in aqueous solution arising from cyclodextrin host–guest complexation

• Jie Wang,
• Zhiqiang Qiu,
• Yiming Wang,
• Li Li,
• Xuhong Guo,
• Duc-Truc Pham,
• Stephen F. Lincoln and
• Robert K. Prud’homme

Beilstein J. Org. Chem. 2016, 12, 50–72, doi:10.3762/bjoc.12.7

• presence of the two cyclodextrin annuli. Thus, such dimers may be used to form cross-links through the complexation of hydrophobic substituents on adjacent polymer chains and thereby generate a polymer network and hydrogel [74][75]. Variation of the length of the covalent-linker in the cyclodextrin dimer

• network formed when host–guest complexation occurs. In earlier studies, Auzély-Vetly et al. reported the substitution of chitosan (molecular weight 195 kDa) with adamantyl groups and characterized their complexation in the β-CD annuli of a singly octamethylene-linked β-CD dimer b and a doubly

• octamethylene-linked β-CD dimer c (Figure 10a, b and c) [78] and related β-CD [79][80] dimers in aqueous solution. It was determined from ITC experiments that while β-CD formed a 1:1 host–guest complex with adamantane carboxylate, only one annulus of the β-CD dimer b and β-CD dimer c complexed adamantane

New metathesis catalyst bearing chromanyl moieties at the N-heterocyclic carbene ligand

• Agnieszka Hryniewicka,
• Szymon Suchodolski,
• Agnieszka Wojtkielewicz,
• Jacek W. Morzycki and
• Stanisław Witkowski

Beilstein J. Org. Chem. 2015, 11, 2795–2804, doi:10.3762/bjoc.11.300

• compounds, e.g., methyl vinyl ketone (entry 3, Table 1) and acrylonitrile (entry 4, Table 1). The outcome of these reactions was also very promising for 9. It should be added that in all cases a dimer of the electron-deficient olefin was not observed. The homodimerisation product of allylbenzene (entries 1

Enantioselective additions of copper acetylides to cyclic iminium and oxocarbenium ions

• Jixin Liu,
• Srimoyee Dasgupta and
• Mary P. Watson

Beilstein J. Org. Chem. 2015, 11, 2696–2706, doi:10.3762/bjoc.11.290

• high levels of enantioselectivity. This lack is likely due to the multiple possibilities for copper acetylide structures (monomer, dimer, dicopper acetylide, etc.) [18][59][60][61][62][63][64][65]. Careful mechanistic studies to elucidate the structures of chiral copper acetylides and to provide

Assembly of synthetic Aβ miniamyloids on polyol templates

• Sebastian Nils Fischer and
• Armin Geyer

Beilstein J. Org. Chem. 2015, 11, 2646–2653, doi:10.3762/bjoc.11.284

• avoided only when two different reactive groups are employed; that is why the reversible esterification between boronic acids and diols appeared an attractive solution to us. In a first approach, we planned to condense short peptide boronic acids with polyol templates for the assembly of an Aβ-dimer. The

• diols on the template must be separated from each other far enough to exclude the simultaneous formation of mixtures of 5- and 6-membered boronic esters. However, the oligosaccharides, which are available with a consistent oligomerization degree of dimer, trimer, tetramer and higher, are known to have

• the protons NH(Hoti)-H8a(Hoti)-H3(Tapi+1)-NH(Hoti+2) trace in the same way as it is normally performed for NHi-Hαi-NHi+1 of peptides. Together with the chemical shift information about the esterification sites (Figure 2), a differentiation between the two possible monoesters of the Hot=Tap dimer 10

Comparison of the catalytic activity for the Suzuki–Miyaura reaction of (η⁵-Cp)Pd(IPr)Cl with (η³-cinnamyl)Pd(IPr)(Cl) and (η³-1-t-Bu-indenyl)Pd(IPr)(Cl)

• Patrick R. Melvin,
• Nilay Hazari,
• Hannah M. C. Lant,
• Ian L. Peczak and
• Hemali P. Shah

Beilstein J. Org. Chem. 2015, 11, 2476–2486, doi:10.3762/bjoc.11.269

• . As part of this work the Cp supported Pd(I) dimer (μ-Cp)(μ-Cl)Pd2(IPr)2 (CpDim) was synthesized and crystallographically characterized. It does not readily disproportionate to form monoligated Pd(0) and consequently CpDim is a poor catalyst for the Suzuki–Miyaura reaction. Keywords: cross-coupling

• between L-Pd(0) and the starting precatalyst, which generates a Pd(I) μ-cinnamyl dimer of the form (μ-cinnamyl)(μ-Cl)Pd2(L)2, and removes L-Pd(0) from the reaction mixture [13][14]. Furthermore, we used this mechanistic information to design an improved precatalyst scaffold featuring an η3-indenyl ligand

• [15]. In particular, precatalysts based on the (η3-1-t-Bu-indenyl)Pd(L)(Cl) scaffold were highly active because Pd(I) dimer formation was effectively suppressed and the rate of reduction from Pd(II) to Pd(0) was increased [16]. In organometallic chemistry, allyl and indenyl ligands are considered to

Friedel–Crafts-type reaction of pyrene with diethyl 1-(isothiocyanato)alkylphosphonates. Efficient synthesis of highly fluorescent diethyl 1-(pyrene-1-carboxamido)alkylphosphonates and 1-(pyrene-1-carboxamido)methylphosphonic acid

• Anna Wrona-Piotrowicz,
• Janusz Zakrzewski,
• Anna Gajda,
• Tadeusz Gajda,
• Anna Makal,
• Arnaud Brosseau and
• Rémi Métivier

Beilstein J. Org. Chem. 2015, 11, 2451–2458, doi:10.3762/bjoc.11.266

• , apart from the H1 atom which was involved in intermolecular hydrogen bond formation. (a) Dimers of π-stacked and hydrogen-bonded molecules of 3a represented in single figures; (b) network of weak C–H…O and C–H…π interactions stabilizing H-bonded dimer strings and (c) crystal packing along the

Copper-catalyzed stereoselective conjugate addition of alkylboranes to alkynoates

• Takamichi Wakamatsu,
• Kazunori Nagao,
• Hirohisa Ohmiya and
• Masaya Sawamura

Beilstein J. Org. Chem. 2015, 11, 2444–2450, doi:10.3762/bjoc.11.265

• -borabicyclo[3.3.1]nonane (9-BBN-H) dimer, and ethyl 3-phenylpropiolate (3a, 0.25 mmol) were treated with CuOAc (5 mol %), t-BuOK (5 mol %), P(OPh)3 (10 mol %), and t-BuOH (0.25 mmol) in 1,4-dioxane (1.2 mL) at 40 °C for 12 h. The reaction afforded a formal hydroalkylation product, β-disubstituted acrylate 4aa

Conformational equilibrium in supramolecular chemistry: Dibutyltriuret case

• Karina Mroczyńska,
• Małgorzata Kaczorowska,
• Erkki Kolehmainen,
• Ireneusz Grubecki,
• Marek Pietrzak and
• Borys Ośmiałowski

Beilstein J. Org. Chem. 2015, 11, 2105–2116, doi:10.3762/bjoc.11.227

• temperature is caused by fast in NMR time-scale equilibrium between various forms. The NOE experiments for 1 (and associated 1) at lowered temperatures did not gave any unequivocal data regarding the shift of equilibrium towards any form. This excludes the existence of the dimer or multimer of 1a as the major

• important to keep in mind that some rotational equilibrium may still be present. In 1d associated to 5 signals of H1/H7 protons are much sharper showing a triplet at 8.45 ppm. The signal of H1/H7 in associated 1e form at 8.21 ppm lies in the similar region as in 1 (dimer or polymer) at the same temperature

• /methanol shown in Supporting Information File 1 (Figure S38) confirms that dibutyltriuret also self-associates and forms singly charged cations of monomer [1 + H+]+ (m/zcalc = 259.1770, m/zmeas = 259.17675), dimer [12 + H+]+ (m/zcalc = 517.3461, m/z = 517.34636), and trimer [13 + H+]+ (m/zcalc = 775.5153

Supramolecular chemistry: from aromatic foldamers to solution-phase supramolecular organic frameworks

• Zhan-Ting Li

Beilstein J. Org. Chem. 2015, 11, 2057–2071, doi:10.3762/bjoc.11.222

• . Thus, I prepared compound 9, which bore a pyrene unit [17] (Scheme 4), based on previously published research by Sijbesma and co-workers, who had taken advantage of the excimer signal of the pyrene dimer to evaluate the stability of their famous quadruple hydrogen bonded 2-ureido-4[1H]-pyrimidinone

• dimers [18]. The excimer exhibits an emission band at 500–600 nm, which is separated from that of the monomer. I thus determined the Kdim of 9 as 3.0 × 107 M−1 in chloroform saturated with water ([water] ≈ 0.45 M) and 8.5 × 107 M−1 in freshly opened chloroform ([water] ≈ 17 mM). Dimer 8·8 had another

• found that the stacking of viologen radical cations could also drive a similar triangular molecule to form 2D SOF, which was further stabilized with CB[8] by encapsulating the stacking radical cation dimer [84]. Very recently, Zhao and co-workers reported that a donor–acceptor interaction could drive

The marine sponge Agelas citrina as a source of the new pyrrole–imidazole alkaloids citrinamines A–D and N-methylagelongine

• Christine Cychon,
• Ellen Lichte and
• Matthias Köck

Beilstein J. Org. Chem. 2015, 11, 2029–2037, doi:10.3762/bjoc.11.220

• alkaloids (PIAs), the citrinamines A–D (1–4) and the bromopyrrole alkaloid N-methylagelongine (5). All citrinamines are dimers of hymenidin (6) which was also isolated from this sponge as the major metabolite. Citrinamines A (1) and B (2) are derivatives of the PIA dimer mauritiamine (7), whereas

• citrinamine C (3) is derived from the PIA dimer nagelamide B (8). Citrinamine D (4) shows an uncommon linkage between the imidazole rings of both monomeric units as it is only observed in the benzocyclobutane ring moiety of benzosceptrins A–C (9–11). Compound 5 is the N-methyl derivative of agelongine (12