pinecone/core-2020-05-10-deduplication huggingface dataset:
Callipeltosides A, B & C: Total Syntheses and Structural Confirmation

Since their isolation almost 20 years ago, the callipeltosides have been of long standing interest to the synthetic community owing to their unique structural features and inherent biological activity. Herein we present our full research effort that has led to the synthesis of these molecules. Key aspects of our final strategy include a) synthesis of the C1–C9 pyran core (5) using a AuCl3-catalysed cyclisation; b) formation of C10–C22 vinyl iodide (55) via sequential bi-directional Stille reactions and c) diastereoselective union of these advanced fragments by means of an alkenylzinc addition (dr = 91:9 at C9). The common callipeltoside aglycon (4) was completed in a further 5 steps. Following this, all 3 sugar fragments were appended to provide the entire callipeltoside family. In addition to this, D-configured callipeltose B was synthesised and appended to the callipeltoside aglycon. The 1H NMR of this molecule was found to be significantly different to the natural isolate, further supporting our assignment of callipeltoside B (2).We thank Novartis for a research studentship (J.R.F) and also gratefully acknowledge the EPSRC (Award numbers: EP/F06985/1; EP/K009494/1; EP/K039520/1) for financial support (C.M.P., T.N.S., R.A.B., J.G. and D.M.S).This is the final version. It first appeared at http://dx.doi.org/10.1002/chem.20150187
Developing lithium chemistry of 1,2-dihydropyridines : from kinetic intermediates to isolable characterized compounds

Generally considered kinetic intermediates in addition reactions of alkyllithiums to pyridine, 1-lithio-2-alkyl-1,2-dihydropyridines have been rarely isolated or characterized. This study develops their "isolated" chemistry. By a unique stoichiometric (that is 1:1, alkyllithium:pyridine ratios) synthetic approach using tridentate donors we show it is possible to stabilize and hence crystallize monomeric complexes where alkyl is tert-butyl. Theoretical calculations probing the donor-free parent tert-butyl species reveal 12 energetically similar stereoisomers in two distinct cyclotrimeric (LiN)3 conformations. NMR studies (including DOSY spectra) and thermal volatility analysis compare new sec-butyl and iso-butyl isomers showing the former is a hexane soluble efficient hydrolithiation agent converting benzophenone to lithium diphenylmethoxide. Emphasizing the criticalness of stoichiometry, reaction of nBuLi/Me6TREN with two equivalents of pyridine results in non-alkylated 1-lithio-1,4-dihydropyridine·Me6TREN and 2-n-butylpyridine, implying mechanistically the kinetic 1,2-n-butyl intermediate hydrolithiates the second pyridine
Stereocontrolled annulations of indolo[2,3-a]quinolizidine-derived lactams with a silylated Nazarov reagent. Access to allo and epiallo yohimbine-type derivatives

The facial selectivity of double Michael addition reactions of the silylated Nazarov reagent 4 to unsaturated indolo[2,3-a]quinolizidine lactams 3 has been studied. Pentacyclic 3-H/15-H trans adducts 5 are generated from Nind -unsubstituted lactams, but the corresponding cis isomers 6 are formed when the indole nitrogen has a tert-butyloxycarbonyl (Boc) substituent. This reversal in the facial selectivity of the annulation has been rationalized by means of theoretical calculations, which indicate that the initial nucleophilic attack under stereoelectronic control is hampered by the presence of the bulky Boc group. The synthetic usefulness of the pentacyclic Nazarov-derived adducts is demonstrated by their conversion into allo and epiallo yohimbine-type targets
3D study of morphology and dynamics of zeolite nucleation

The principle aspects and constrains of the dynamics and kinetics of zeolite nucleation in hydrogel systems are analyzed on the basis of a model Na-rich aluminosilicate system. A detailed time-series EMT-type zeolite crystallization study in the model hydrogel system is performed in order to elucidate the topological and temporal aspects of zeolite nucleation. A comprehensive set\ud
of analytical tools and methods is employed to analyze the gel evolution complementing the primary methods of transmission electron microscopy (TEM) and nuclear magnetic resonance (NMR) spectroscopy. TEM tomography reveals that the initial gel particles exhibit a core-shell structure. Zeolite nucleation is topologically limited to this shell structure and the kinetics of\ud
nucleation is controlled by the shell integrity. The induction period extends to the moment when the shell is consumed and the bulk solution can react with the core of the gel particles. These new findings, in particular the importance of gel particle shell in zeolite nucleation, can be used to control the growth process and properties of zeolites formed in hydrogels
Mesoporous Silica Nanoparticles Decorated with Carbosilane Dendrons as New Non-viral Oligonucleotide Delivery Carriers

A novel nanosystem based on mesoporous silica nanoparticles covered with carbosilane dendrons grafted on the external surface of the nanoparticles is reported. This system is able to transport single-stranded oligonucleotide into cells, avoiding an electrostatic repulsion between the cell membrane and the negatively charged nucleic acids thanks to the cationic charge provided by the dendron coating under physiological conditions. Moreover, the presence of the highly ordered pore network inside the silica matrix would make possible to allocate other therapeutic agents within the mesopores with the aim of achieving a double delivery. First, carbosilane dendrons of second and third generation possessing ammonium or tertiary amine groups as peripheral functional groups were prepared. Hence, different strategies were tested in order to obtain their suitable grafting on the outer surface of the nanoparticles. As nucleic acid model, a single-stranded DNA oligonucleotide tagged with a fluorescent Cy3 moiety was used to evaluate the DNA adsorption capacity. The hybrid material functionalised with the third generation of a neutral dendron showed excellent DNA binding properties. Finally, the cytotoxicity as well as the capability to deliver DNA into cells, was tested in vitro by using a human osteoblast-like cell line, achieving good levels of internalisation of the vector DNA/carbosilane dendron-functionalised material without affecting the cellular viability
Formation of Foam-like Microstructural Carbon Material by Carbonization of Porous Coordination Polymers through a Ligand-Assisted Foaming Process.

Porous carbon material with a foam-like microstructure has been synthesized by direct carbonization of porous coordination polymer (PCP). In situ generation of foaming agents by chemical reactions of ligands in PCP during carbonization provides a simple way to create lightweight carbon material with a foam-like microstructure. Among several substituents investigated, the nitro group has been shown to be the key to obtain the unique foam-like microstructure, which is due to the fast kinetics of gas evolution during carbonization. Foam-like microstructural carbon materials showed higher pore volume and specific capacitance compared to a microporous carbon
Structural Characterization of the Complex between Hen Egg-White Lysozyme and Zr(IV) -Substituted Keggin Polyoxometalate as Artificial Protease

Successful co-crystallization of a noncovalent complex between hen egg-white lysozyme (HEWL) and the monomeric Zr(IV) -substituted Keggin polyoxometalate (POM) (Zr1 K1), (Et2 NH2 )3 [Zr(PW11 O39 )] (1), has been achieved, and its single-crystal X-ray structure has been determined. The dimeric Zr(IV) -substituted Keggin-type polyoxometalate (Zr1 K2), (Et2 NH2 )10 [Zr(PW11 O39 )2 ] (2), has been previously shown to exhibit remarkable selectivity towards HEWL hydrolysis. The reported X-ray structure shows that the hydrolytically active Zr(IV) -substituted Keggin POM exists as a monomeric species. Prior to hydrolysis, this monomer interacts with HEWL in the vicinity of the previously identified cleavage sites found at Trp28-Val29 and Asn44-Arg45, through water-mediated H-bonding and electrostatic interactions. Three binding sites are observed at the interface of the negatively charged Keggin POM and the positively charged regions of HEWL at: 1) Gly16, Tyr20, and Arg21; 2) Asn44, Arg45, and Asn46; and 3) Arg128.status: publishe
Synthesis of Ordered Mesoporous Carbon Materials by Dry Etching

A novel synthesis method for ordered mesoporous carbons is presented. The inverse replication of a silica template was achieved using the carbonization of sucrose within mesoporous KIT-6. Instead of liquid acid etching, as in classical nanocasting, a novel dry chlorine etching procedure for template removal is presented for the first time. The resultant ordered mesostructured carbon material outperforms carbons obtained by conventional hard templating with respect to high specific micro- and mesopore volumes (0.6 and 1.6 cm3 g−1, respectively), due to the presence of a hierarchical pore system. A high specific surface area of 1671 m2 g−1 was achieved, rendering this synthesis route a highly convenient method to produce ordered mesoporous carbons.Financial support from the Deutsche Forschungsgemeinschaft is gratefully acknowledged. M.O. thanks the German Academic Exchange Service (DAAD) for financial support
Rapid Asymmetric Transfer Hydroformylation (ATHF) of disubstituted alkenes using paraformaldehyde as a syngas surrogate

The authors thank Dr. Reddys (UK) and the Royal Society for an Industry Fellowship in the early stage of this work (2012–2014), and the EPSRC for funding (EP/M003868/1).As an alternative to conventional asymmetric hydroformylation (AHF), Asymmetric Transfer Hydroformylation (ATHF) using formaldehyde as a surrogate for syngas is reported. A catalyst derived from commercially available [Rh(acac)(CO)2] and Ph-BPE stands out in terms of both activity and enantioselectivity. Remarkably, not only are high selectivities achievable, the reactions are very simple to carry out, and can give higher enantioselectivity (up to 96% e.e.) and/or turnover frequencies than those that are achievable using the same catalyst (or other leading catalysts) using typical conditions for AHF.Publisher PDFPeer reviewe
Palladium-Catalyzed Zinc-Amide-Mediated C[BOND]H Arylation of Fluoroarenes and Heteroarenes with Aryl Sulfides.

Article first published online: 31 JUL 2015C[BOND]H arylation of polyfluoroarenes and heteroarenes with aryl sulfides proceeds smoothly with the aid of a palladium–N-heterocyclic carbene catalyst. A bulky zinc amide, TMPZnCl⋅LiCl, plays a key role as an effective base to generate the corresponding arylzinc species in situ. This arylation protocol is practically much easier to perform than our previous method, which necessitates preparation of the arylzinc reagents in advance from the corresponding aryl halides. Aryl sulfides that are prepared through sulfur-specific reactions, such as SNAr sulfanylation and extended Pummerer reactions, undergo this direct arylation, offering interesting transformations that are otherwise difficult to achieve with conventional halogen-based organic synthesis
Steric effects on the structures, reactivity and coordination chemistry of tris(2-pyridyl)aluminates

Introducing substituents in the 6-position of the 2-pyridyl rings of tris-pyridyl aluminate anions, of the type [EtAl(2-py´)3]-  (py´ = a substituted 2-pyridyl group), has a large impact on their metal coordination characteristics. This is seen most remarkably in the desolvation of the THF solvate [EtAl(6-Me-2-py)3Li•THF] to  give the monomer [EtAl(6-Me-2-py)3Li] (1), containing a pyramidal, three-coordinate Li+ cation. Similar monomeric complexes are observed for [EtAl(6-CF3-2-py)3Li] (2) and [EtAl(6-Br-2-py)3Li] (3), containing CF3 and Br substituents (R). This steric influence can be exploited in the synthesis of a new class of terminal Al-OH complexes, as is seen in the controlled hydrolysis of 2 and 3 to give [EtAl(OH)(6-R-2-py)2]- anions, as in the dimer [EtAl(OH)(6-Br-2-py)2Li]2 (5). Attempts to deprotonate the Al-OH group of 5 using Et2Zn led only to the formation of the zincate complex [LiZn(6-Br-py)3]2 (6), while reactions of the 6-Br substituted 3 and the unsubstituted complex [EtAl(2-py)3Li] with MeOH give [EtAl(OMe)(6-Br-2-py)2Li]2 (7) and [EtAl(OMe)(2-py)2Li]2 (8), respectively, having similar dimeric arrangements to 5. The combined studies presented here provide key synthetic tools for the functionalization and elaboration of tris-pyridyl aluminate ligands.We thank the EU for a Marie Curie Intra European Fellowship within the seventh European Community Framework Programme for R.G.-R. and an Advanced Investigator Award for D.S.W.This is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1002/chem.20150215
Brønsted Acid-Catalyzed Cascade Reactions Involving 1,2-Indole Migration

A cascade reaction of indoles with propargylic diols\ud
involving an unprecedented metal-free 1,2-indole migration onto an\ud
alkyne is here described. DFT calculations support a mechanism\ud
consisting in a concerted nucleophilic attack of the indole nucleus\ud
with loss of water followed by the 1,2-migration and subsequent\ud
Nazarov cyclization. This Brønsted acid-catalyzed protocol affords\ud
indole-functionalized benzofulvene derivatives in high yields.Junta de Castilla y León(BU237U13) and Ministerio de Economía y Competitividad (MINECO) and FEDER (CTQ2013-48937-C2-1P and 2-P
Activation of Hsp90 Enzymatic Activity and Conformational Dynamics through Rationally Designed Allosteric Ligands

Hsp90 is a molecular chaperone of pivotal importance\ud
for multiple cell pathways. ATP-regulated internal dynamics\ud
are critical for its function and current pharmacological\ud
approaches block the chaperone with ATP-competitive\ud
inhibitors. Herein, a general approach to perturb Hsp90\ud
through design of new allosteric ligands aimed at modulating\ud
its functional dynamics is proposed. Based on the characterization\ud
of a first set of 2-phenylbenzofurans showing\ud
stimulatory effects on Hsp90 ATPase and conformational dynamics,\ud
new ligands were developed that activate Hsp90 by\ud
targeting an allosteric site, located 65 æ from the active site.\ud
Specifically, analysis of protein responses to first-generation\ud
activators was exploited to guide the design of novel derivatives\ud
with improved ability to stimulate ATP hydrolysis. The\ud
molecules’ effects on Hsp90 enzymatic, conformational, cochaperone\ud
and client-binding properties were characterized\ud
through biochemical, biophysical and cellular approaches.\ud
These designed probes act as allosteric activators of the\ud
chaperone and affect the viability of cancer cell lines for\ud
which proper functioning of Hsp90 is necessary
Porphyrinylboranes Synthesized via Porphyrinyllithiums.

As the most nucleophilic porphyrins, meso- or β-lithiated porphyrins were generated by iodine-lithium exchange reactions of the corresponding iodoporphyrins with n-butyllithium at -98 °C. Porphyrinyllithiums thus prepared were used for synthesis of dimesitylporphyrinylboranes through reactions with fluorodimesitylborane. The boryl groups proved to serve as an electron-accepting unit to alter the photophysical and electrochemical properties. In addition, 5-diarylamino-15-dimesitylboryl-substituted donor-accepter porphyrins showed increased intramolecular charge-transfer character in the S1 state. Furthermore, the reaction of β-lithiated porphyrin with dichloromesitylborane provided a boron-bridged porphyrin dimer, which exhibited a conjugative interaction between two porphyrin units through the vacant p-orbital on the boron center
A photoactivatable PtIV anticancer complex conjugated to the RNA ligand guanidinoneomycin

A photoactivatable platinum(IV) complex, trans,trans,trans-[Pt(N3)2(OH)(succ)(py)2] (succ=succinylate, py=pyridine), has been conjugated to guanidinoneomycin to study the effect of this guanidinum-rich compound on the photoactivation, intracellular accumulation and phototoxicity of the pro-drug. Surprisingly, trifluoroacetic acid treatment causes the replacement of an azido ligand and the axial hydroxide ligand by trifluoroacetate, as shown by NMR spectroscopy, MS and X-ray crystallography. Photoactivation of the platinum-guanidinoneomycin conjugate in the presence of 5′-guanosine monophosphate (5′-GMP) led to the formation of trans-[Pt(N3)(py)2(5′-GMP)]+, as does the parent platinum(IV) complex. Binding of the platinum(II) photoproduct {PtN3(py)2}+ to guanine nucleobases in a short single-stranded oligonucleotide was also observed. Finally, cellular uptake studies showed that guanidinoneomycin conjugation improved the intracellular accumulation of the platinum(IV) pro-drug in two cancer cell lines, particularly in SK-MEL-28 cells. Notably, the higher phototoxicity of the conjugate in SK-MEL-28 cells than in DU-145 cells suggests a degree of selectivity towards the malignant melanoma cell line
A ratiometric fluorescent probe for gold and mercury ions

A fluorescent probe that displays a ratiometric fluorescence response towards gold and mercury ions has been devised. Emitting at a relatively longer wavelength, the conjugated form of the fluorescent dye transforms in the presence of the gold or mercury ions into a new dye, the molecular structure of which lacks the conjugation and consequently emits at a distinctly shorter wavelength. A fluorescent probe that displays a ratiometric fluorescence response towards gold and mercury ions has been devised. Emitting at a relatively longer wavelength, the conjugated form of the fluorescent dye transforms in the presence of the gold or mercury ions into a new dye (see figure).IZTECH and TUBITA
Adding a structural context to the deprotometalation and trans-metal trapping chemistry of phenyl-substituted benzotriazole

Organometallic bases are becoming increasingly complex, because mixing components can lead to bases superior to single-component bases. To better understand this superiority, it is useful to study metalated intermediate structures prior to quenching. This study is on 1-phenyl-1H-benzotriazole, which was previously deprotonated by an in situ ZnCl2• TMEDA/LiTMP (TMEDA=N,N,N′,N′-tetramethylethylenediamine; TMP=2,2,6,6-tetramethylpiperidide) mixture and then iodinated. Herein, reaction with LiTMP exposes the deficiency of the single-component base as the crystalline product obtained was [{4-R-1-(2-lithiophenyl)-1H-benzotriazole• 3THF}2], [R=2-C6H4(Ph)NLi], in which ring opening of benzotriazole and N2 extrusion had occurred. Supporting lithiation by adding iBu2Al(TMP) induces trans-metal trapping, in which C-Li bonds transform into C-Al bonds to stabilise the metalated intermediate. X-ray diffraction studies revealed homodimeric [(4-R′-1-phenyl-1H-benzotriazole)2], [R′=(iBu)2Al(μ-TMP)Li], and its heterodimeric isomer [(4-R′-1-phenyl-1H-benzotriazole){2-R′-1-phenyl-1H-benzotriazole}], whose structure and slow conformational dynamics were probed by solution NMR spectroscopy
Peripherally Silylated Porphyrins.

Article first published online: 19 AUG 2015Silylation of peripherally lithiated porphyrins with silyl electrophiles has realized the first synthesis of a series of directly silyl-substituted porphyrins. The meso-silyl group underwent facile protodesilylation, whereas the β-silyl group was entirely compatible with standard work-up and purification on silica gel. The meso-silyl group caused larger substituent effects to the porphyrin compared with the β-silyl group. Silylation of β-lithiated porphyrins with 1, 2-dichlorodisilane furnished β-to-β disilane-bridged porphyrin dimers. A doubly β-to-β disilane-bridged Ni(II)-porphyrin dimer was also synthesized from a β, β-dilithiated Ni(II)-porphyrin and characterized by X-ray crystallographic analysis to take a steplike structure favorable for interporphyrinic interaction. Denickelation of β-silylporphyrins was achieved upon treatment with a 4-tolylmagnesium bromide to yield the corresponding freebase porphyrins
Single-Molecule Magnetism, Enhanced Magnetocaloric Effect, and Toroidal Magnetic Moments in a Family of Ln4 Squares

Three cationic [Ln4] squares (Ln=lanthanide) were isolated as single crystals and their structures solved as [Dy4(μ4-OH)(HL)(H2L)3(H2O)4]Cl2·(CH3OH)4·(H2O)8 (1), [Tb4(μ4-OH)(HL)(H2L)3(MeOH)4]Cl2·(CH3OH)4·(H2O)4 (2) and [Gd4(μ4-OH)(HL)(H2L)3(H2O)2(MeOH)2]Br2·(CH3OH)4·(H2O)3 (3). The structures are described as hydroxo-centered squares of lanthanide ions, with each edge of the square bridged by a doubly deprotonated H2L2- ligand. Alternating current magnetic susceptibility measurements show frequency-dependent out-of-phase signals with two different thermally assisted relaxation processes for 1, whereas no maxima in χM" appears above 2.0 K for complex 2. For 1, the estimated effective energy barrier for these two relaxation processes is 29 and 100 K. Detailed ab initio studies reveal that complex 1 possesses a toroidal magnetic moment. The ab initio calculated anisotropies of the metal ions in complex 1 were employed to simulate the magnetic susceptibility by using the Lines model (POLY-ANISO) and this procedure yields J1=+0.01 and J2=-0.01 cm-1 for 1 as the two distinct exchange interactions between the DyIII ions. Similar parameters are also obtained for complex 1 (and 2) from specific heat measurements. A very weak antiferromagnetic super-exchange interaction (J1=-0.043 cm-1 and g=1.99) is observed between the metal centers in 3. The magnetocaloric effect (MCE) was estimated by using field-dependent magnetization and temperature-dependent heat-capacity measurements. An excellent agreement is found for the -ΔSm values extracted from these two measurements for all three complexes. As expected, 3 shows the largest -ΔSm variation (23 J Kg-1 K-1) among the three complexes. The negligible magnetic anisotropy of Gd indeed ensures near degeneracy in the (2S+1) ground state microstates, and the weak super-exchange interaction facilitates dense population of low-lying excited states, all of which are likely to contribute to the MCE, making complex 3 an attractive candidate for cryogenic refrigeration
Exceptionally inert lanthanide(III) PARACEST MRI contrast agents based on an 18-membered macrocyclic platform

[Abstract] We report a macrocyclic ligand based on a 3,6,10,13-tetraaza-1,8(2,6)-dipyridinacyclotetradecaphane platform containing four hydroxyethyl pendant arms (L1) that forms extraordinary inert complexes with Ln3+ ions. The [EuL1]3+ complex does not undergo dissociation in 1 M HCl over a period of months at room temperature. Furthermore, high concentrations of phosphate and Zn2+ ions at room temperature do not provoke metal-complex dissociation. The X-ray crystal structures of six Ln3+ complexes reveal ten coordination of the ligand to the metal ions through the six nitrogen atoms of the macrocycle and the four oxygen atoms of the hydroxyethyl pendant arms. The analysis of the Yb3+- and Pr3+-induced paramagnetic 1H NMR shifts show that the solid-state structures are retained in aqueous solution. The intensity of the 1H NMR signal of bulk water can be modulated by saturation of the signals of the hydroxy protons of Pr3+, Eu3+, and Yb3+ complexes following chemical-exchange saturation transfer (CEST). The ability of these complexes to provide large CEST effects at 25 and 37 °C and pH 7.4 was confirmed by using CEST magnetic resonance imaging experiments.España. Ministerio de Ciencia e Innovación (CTQ2011-24487)España. Ministerio de Economía y Competitividad (CTQ2013-43243-P