Synthesis,Dynamic Combinatorial Chemistry,and PCR Amplification of 3′–5′ and 3′–6′ Disulfide‐linked Oligonucleotides

Disulfide dithymidines linked 3′–5′ or 3′–6′ were synthesized and incorporated into oligonucleotides through a combined phosphotriester and phosphoramidite solid‐phase oligonucleotide synthesis approach. The disulfide links are cleaved and formed reversibly in the presence of thiols and oligonucleotides. This link was shown to be sequence‐adaptive in response to given templates in the presence of mercaptoethanol. The artificial 3′–5′ and 3′–6′ disulfide link was tolerated by polymerases in the polymerase chain reaction (PCR). By using sequencing analysis, we show that single mutations frequently occurred randomly in the amplification products of the PCR.     

Diels–Alder Additions,Ene Reactions,and Condensations of 4‐(Acylamino)‐5‐nitrosopyrimidines – Synthesis of 8‐Substituted Guanines and of 6‐Substituted Pteridinones

4‐(Acylamino)‐5‐nitrosopyrimidines react either by a reductive condensation to provide 8‐substituted guanines, or by a Diels–Alder cycloaddition, or an ene reaction, to provide 6‐substituted pteridinones, depending on the nature of the acyl group and the reaction conditions. Experimental details are provided for the transformation of (acylamino)‐nitrosopyrimidines to 8‐substituted guanines, and the scope of the reaction is further demonstrated by transforming the trifluoro acetamide 25 to the 8‐(trifluoromethyl)guanine ( 27 ), and the N,N′‐bis(nitrosopyrimidinyl)‐dicarboxamide 29 to the (R,R)‐1,2‐di(guan‐8‐yl)ethane‐1,2‐diol ( 32 ). An intramolecular Diels–Alder reaction of the N‐sorbyl (=N‐hexa‐2,4‐dienoyl) nitrosopyrimidine 10 , followed by a spontaneous elimination to cleave the N,O bond of the initial cycloaddition product provided the pteridinones 14 or 15 , characterized by a (Z)‐ or (E)‐3‐hydroxyprop‐1‐enyl group at C(6). Treatment of 10 with Ph₃P led to the C(8)‐penta‐1,3‐dienyl‐guanine 18 . The ene reaction of the N‐crotonyl (=N‐but‐2‐enoyl) nitrosopyrimidine 19 provided the 6‐vinyl‐pteridinone 20a that dimerized readily to 21a , while treatment of 19 with Ph₃P led in high yield to 8‐(prop‐1‐enyl)guanine ( 23 ). The structure of the dimer 21 was established by X‐ray analysis of its bis(N,N‐dimethylformamidine) derivative 21b . The crystal structure of the nitroso amide 10 is characterized by two molecules in the centrosymmetric unit cell. Intermolecular H‐bonds connect the amino group to the amide carbonyl and to N(1). The crystalline bis(purine) 30 forms a left‐handed helix with four molecules per turn and a pitch of 30.2 Å.     

Geometric and electronic structures of silicon fluorides (N = 4 – 6) and potential energy surfaces for dissociation reactions → SiF4 + F– and → + F–

The geometric and electronic structures of a series of silicon fluorides (n = 4 ? 6) were computationally studied with the aid of density functional theory (DFT) method with B3LYP and M06‐2X functionals and coupled cluster (CCSD and CCSD(T)) methods with 6‐311++G(d,p) basis set. The nature of the Si‐F bonds in these compounds was analyzed in the framework of the natural bond orbital theory and natural resonance theory. Energy characteristics (heats of reactions and energy barriers) of the dissociation reactions → SiF₄ + F^– and → + F^– were calculated using the DFT and CCSD methods. The potential energy surface of elimination of a fluoride anion from has a specific topology with valley‐ridge inflection points corresponding to bifurcations of the minimal energy reaction path. © 2016 Wiley Periodicals, Inc.     

From Blue Azulenes to Blue Heptalenes – New Strongly Polarized π‐Convertible Heptalenes

The 1,5,6,8,10‐pentamethylheptalene‐4‐carboxaldehyde ( 4b ) (together with its double‐bond‐shifted (DBS) isomer 4a ) and methyl 4‐formyl‐1,6,8,10‐tetramethylheptalene‐5‐carboxylate ( 15b ) were synthesized (Schemes 3 and 7, resp.). Aminoethenylation of 4a / 4b with N,N‐dimethylformamide dimethyl acetal (=1,1‐dimethoxy‐N,N‐dimethylmethanamine=DMFDMA) led in DMF to 1‐[(1E)‐2‐(dimethylamino)ethenyl]‐5,6,8,10‐tetramethylheptalene‐2‐carboxaldehyde ( 18a ; Scheme 9), whereas the stronger aminoethenylation agent N,N,N′,N′,N″,N″‐hexamethylmethanetriamine (=tris(dimethylamino)methane=TDMAM) gave an almost 1 : 1 mixture of 18a and 1‐[(1E)‐2‐(dimethylamino)ethenyl]‐5,6,8,10‐tetramethylheptalene‐4‐carboxaldehyde ( 20b ; Scheme 11). Carboxylate 15b delivered with DMFDMA on heating in DMF the expected aminoethenylation product 19b (Scheme 10). The aminoethenylated heptalenecarboxaldehydes were treated with malononitrile in CH₂Cl₂ in the presence of TiCl₄/pyridine to yield the corresponding malononitrile derivatives 23b, 24b , and 26a (Schemes 13 and 14). The photochemically induced DBS process of the heptalenecarboxaldehydes as ‘soft’ merocyanines and their malononitrile derivatives as ‘strong’ merocyanines of almost zwitterionic nature were studied in detail (Figs. 10–29) with the result that 1,4‐donor/acceptor substituted heptalenes are cleaner switchable than 1,2‐donor/acceptor‐substituted heptalenes.     

Simple,Efficient, and Catalyst‐Free Synthesis of (2‐Amino‐4H‐1‐benzopyran‐4‐yl)phosphonates in Polyethylene Glycol

Several (2‐amino‐4H‐1‐benzopyran‐4‐yl)phosphonates were efficiently synthesized by employing a multicomponent protocol involving a salicylaldehyde, malononitrile or ethyl cyanoacetate, and a trialkyl phosphite in polyethylene glycol. The latter could be recovered and re‐used. No additional solvent or catalyst was required. To the best of our knowledge, this is the first report of the one‐pot preparation of (2‐amino‐4H‐1‐benzopyran‐4‐yl)phosphonic acid dimethyl esters.     

Three novel topologically different metal–organic frameworks built from 3‐nitro‐4‐(pyridin‐4‐yl)benzoic acid

The design and synthesis of metal–organic frameworks (MOFs) have attracted much interest due to the intriguing diversity of their architectures and topologies. However, building MOFs with different topological structures from the same ligand is still a challenge. Using 3‐nitro‐4‐(pyridin‐4‐yl)benzoic acid (HL) as a new ligand, three novel MOFs, namely poly[[(N,N‐dimethylformamide‐κO)bis[μ₂‐3‐nitro‐4‐(pyridin‐4‐yl)benzoato‐κ³O,O′:N]cadmium(II)] N,N‐dimethylformamide monosolvate methanol monosolvate], {[Cd(C₁₂H₇N₂O₄)₂(C₃H₇NO)]·C₃H₇NO·CH₃OH}_n, ( 1 ), poly[[(μ₂‐acetato‐κ²O:O′)[μ₃‐3‐nitro‐4‐(pyridin‐4‐yl)benzoato‐κ³O:O′:N]bis[μ₃‐3‐nitro‐4‐(pyridin‐4‐yl)benzoato‐κ⁴O,O′:O′:N]dicadmium(II)] N,N‐dimethylacetamide disolvate monohydrate], {[Cd₂(C₁₂H₇N₂O₄)₃(CH₃CO₂)]·2C₄H₉NO·H₂O}_n, ( 2 ), and catena‐poly[[[diaquanickel(II)]‐bis[μ₂‐3‐nitro‐4‐(pyridin‐4‐yl)benzoato‐κ²O:N]] N,N‐dimethylacetamide disolvate], {[Ni(C₁₂H₇N₂O₄)₂(H₂O)₂]·2C₄H₉NO}_n, ( 3 ), have been prepared. Single‐crystal structure analysis shows that the Cd^II atom in MOF ( 1 ) has a distorted pentagonal bipyramidal [CdN₂O₅] coordination geometry. The [CdN₂O₅] units as 4‐connected nodes are interconnected by L^? ligands to form a fourfold interpenetrating three‐dimensional (3D) framework with a dia topology. In MOF ( 2 ), there are two crystallographically different Cd^II ions showing a distorted pentagonal bipyramidal [CdNO₆] and a distorted octahedral [CdN₂O₄] coordination geometry, respectively. Two Cd^II ions are connected by three carboxylate groups to form a binuclear [Cd₂(COO)₃] cluster. Each binuclear cluster as a 6‐connected node is further linked by acetate groups and L^? ligands to produce a non‐interpenetrating 3D framework with a pcu topology. MOF ( 3 ) contains two crystallographically distinct Ni^II ions on special positions. Each Ni^II ion adopts an elongated octahedral [NiN₂O₄] geometry. Each Ni^II ion as a 4‐connected node is linked by L^? ligands to generate a two‐dimensional network with an sql topology, which is further stabilized by two types of intermolecular OW—HW…O hydrogen bonds to form a 3D supramolecular framework. MOFs ( 1 )–( 3 ) were also characterized by powder X‐ray diffraction, IR spectroscopy and thermogravimetic analysis. Furthermore, the solid‐state photoluminescence of HL and MOFs ( 1 ) and ( 2 ) have been investigated. The photoluminescence of MOFs ( 1 ) and ( 2 ) are enhanced and red‐shifted with respect to free HL. The gas adsorption investigation of MOF ( 2 ) indicates a good separation selectivity (71) of CO₂/N₂ at 273 K (i.e. the amount of CO₂ adsorption is 71 times higher than N₂ at the same pressure).     

Phase separation and polymer crystallization in a poly(4‐methyl‐1‐pentene)–dioctylsebacate–dimethylphthalate system via thermally induced phase separation

The effects of the polymer concentration and quenching temperature on the phase separation, the membrane morphology and polymer crystallization behavior in a poly(4‐methyl‐1‐pentene) (TPX)‐dioctylsebacate (DOS)‐dimethylphthalate (DMP) system via thermally induced phase separation were studied with a pseudobinary phase diagram, with the weight ratio of DOS:DMP = 1:1. SEM was used to observe the membrane morphology and structure, whereas the TPX crystallization behavior was studied with DSC and WAXD. Liquid‐liquid phase separation occurred, although quenching under the crystallization temperature. As the quenching temperature decreased, the pore size decreased, with better connected pore structure formed. The membranes quenched at 333 and 363 K showed good cellular structures, with an average pore size of about 2.3μm, whereas the pores of the membranes quenched at 393 and 423 K were not well formed, with some lamellar crystals on the inner side. The diluent assisted the mobility of the polymer chain, which improved the polymer crystallization. Dual‐melting‐peak behavior occurred for all the samples studied here. As the quenching temperature increased, the first peak of the melting trace moved to a higher temperature, whereas the second one stayed almost the same. The flexibility of the TPX main chain was restricted by the side groups, which allowed liquid‐liquid phase separation to occur first when quenched below the equilibrium crystallization temperature. This allowed primary and secondary crystallization, which was responsible for the dual‐melting‐peak behavior. © 2006 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 45: 153–161, 2007     

Sodium Dithionite Initiated Addition‐lactonization of 2‐Acyl‐ amino‐4‐pentenoic Acids with Fluoroalkyl Iodides to Synthesize 4‐Fluoroalkyl‐2‐acylamino‐4‐butyrolactones

4‐Fluoroalkyl‐2‐acylamino‐4‐butyrolactones were afforded in moderate yields by the sodium dithionite initiated one‐pot addition‐lactonization reaction of polyfluoroalkyl iodides with 2‐acylamino‐4‐pentenoic acids.     

A Convenient Synthesis of 2,3‐Dihydro‐4H‐thiopyrano[2,3‐b]‐, ‐[2,3‐c]‐, or ‐[3,2‐c]pyridin‐4‐ones by the Reaction of the Corresponding 1‐(Chloropyridinyl)alk‐2‐en‐1‐ones with NaSH

2,3‐Dihydro‐4H‐thiopyrano[2,3‐b]pyridin‐4‐ones 4 were prepared by a three‐step sequence from commercially available 2‐chloropyridine ( 1 ). Thus, successive treatment of 1 with ⁱPr₂NLi (LDA) and α,β‐unsaturated aldehydes gave 1‐(2‐chloropyridin‐3‐yl)alk‐2‐en‐1‐ols 2 , which were oxidized with MnO₂ to 1‐(2‐chloropyridin‐3‐yl)alk‐2‐en‐1‐ones 3 . The reactions of 3 with NaSH?n H₂O proceeded smoothly at 0° in DMF to provide the desired thiopyranopyridinones. Similarly, 2,3‐dihydro‐4H‐thiopyrano[2,3‐c]pyridin‐4‐ones 8 and 2,3‐dihydro‐4H‐thiopyrano[3,2‐c]pyridin‐4‐ones 12 were obtained starting from 3‐chloropyridine ( 5 ) and 4‐chloropyridine ( 9 ), respectively.     

A novel azocompound, 2‐(4‐phenylazoaniline)‐4‐phenylphenol: Spectroscopic and quantum‐chemical approach

A novel azocompound with two nonequivalents azo groups, 2‐(4‐phenylazoaniline)‐4‐phenylphenol, was synthesized and characterized by spectroscopic and computational analysis. An intramolecular hydrogen bonding (HB), ? O₁? H₁ ··· N₁? , involving the ? N₁?N₂? group and the proton in a neighbor hydroxyl moiety, was identified. It was found responsible for a characteristic π‐conjugated H₁? O₁? C₁₈?C₁₃? N₂?N₁? six‐membered cyclic fragment. It is worth noting that this azo group is involved in an azo‐hydrazo equilibrium, being the azo form the most stable one. This resonance‐assisted HB was characterized using the OH‐related infrared bands and the corresponding signals in ¹H NMR. In addition, conformational studies and geometrical and electronic parameter calculations were performed using the density functional theory, at B3LYP/6‐311++G** level. Bond and ring critical points were identified using the atoms in molecules theory, which allowed confirming the intramolecular HB. The second azo‐group cannot be involved in HB, but it also presents two stereoisomerics forms corresponding to cis (Z) and trans (E) configurations, with the later being the one with the lowest energy. © 2013 Wiley Periodicals, Inc.     

2, 4‐Dimethylpenta‐1, 3‐dien‐ und 2, 4‐Dimethylpentadienyl‐Komplexe des Rhodiums und Iridiums

2, 4‐Dimethylpenta‐1, 3‐diene and 2, 4‐Dimethylpentadienyl Complexes of Rhodium and Iridium The complexes [(η⁴‐C₇H₁₂)RhCl]₂ ( 1 ) (C₇H₁₂ = 2, 4‐dimethylpenta‐1, 3‐diene) and [(η⁴‐C₇H₁₂)₂IrCl] ( 2 ) were obtained by interaction of C₇H₁₂ with [(η²‐C₂H₄)₂RhCl]₂ and [(η²‐cyclooctene)₂IrCl]₂, respectively. The reaction of 1 or 2 with CpTl (Cp = η⁵‐C₅H₅) yields the compounds [CpM(η⁴‐C₇H₁₂)] ( 3a : M = Rh; 3b : M = Ir). The hydride abstraction at the pentadiene ligand of 3a , b with Ph₃CBF₄ proceeds differently depending on the solvent. In acetone or THF the “half‐open” metallocenium complexes [CpM(η⁵‐C₇H₁₁)]BF₄ ( 4a : M = Rh; 4b : M = Ir) are obtained exclusively. In dichloromethane mixtures are produced which additionally contain the species [(η⁵‐C₇H₁₁)M(η⁵‐C₅H₄CPh₃)]BF₄ ( 5a : M = Rh; 5b : M = Ir) formed by electrophilic substitution at the Cp ring, as well as the η³‐2, 4‐dimethylpentenyl compound [(η³‐C₇H₁₃)Rh{η⁵‐C₅H₃(CPh₃)₂}]BF₄ ( 6 ). By interaction of 2, 4‐dimethylpentadienyl potassium with 1 or 2 the complexes [(η⁴‐C₇H₁₂)M(η⁵‐C₇H₁₁)] ( 7a : M = Rh; 7b : M = Ir) are generated which show dynamic behaviour in solution; however, attempts to synthesize the “open” metallocenium cations [(η⁵‐C₇H₁₁)₂M]⁺ by hydride abstraction from 7a , b failed. The new compounds were characterized by elemental analysis and spectroscopically, 4b and 5a also by X‐ray structure analysis.     

Hybrid 4‐Aminoquinoline‐1,3,5‐triazine Derivatives: Design,Synthesis, Characterization,and Antibacterial Evaluation

A series of novel 4‐aminoquinoline 1,3,5‐triazine derivatives were synthesized and characterized by FTIR, ¹H‐NMR, ¹³C‐NMR, MS, and elemental analysis. The antibacterial activities of synthesized compounds were tested against three Gram‐positive bacteria, namely Bacillus subtilis (NCIM‐2063), Bacillus cereus (NCIM‐2156), and Staphylococcus aureus (NCIM‐2079), and four Gram‐negative bacteria, namely Proteus vulgaris (NCIM‐2027), Proteus mirabilis (NCIM‐2241), Escherichia coli (NCIM‐2065), and Pseudomonas aeruginosa (NCIM‐2036), using ciprofloxacin as reference standard drug. Results showed compound 9a and 9e as potent antibacterial agents against all bacterial strains except Bacillus cereus (NCIM‐2156). Copyright © 2014 HeteroCorporation     

Experimental and Theoretical Conformational Analysis of 5‐Benzylimidazolidin‐4‐one Derivatives – a ‘Playground’ for Studying Dispersion Interactions and a ‘Windshield‐Wiper’ Effect in Organocatalysis

The PF₆ salts of 5‐benzyl‐1‐isopropylidene‐ and 5‐benzyl‐1‐cinnamylidene‐3‐methylimidazolidin‐4‐ones 1 (Scheme) with various substituents in the 2‐position have been prepared, and single crystals suitable for X‐ray structure determination have been obtained of 14 such compounds, i.e., 2 – 10 and 12 – 16 (Figs. 2–5). In nine of the structures, the Ph ring of the benzyl group resides above the heterocycle, in contact with the cis‐substituent at C(2) (staggered conformation A ; Figs. 1–3); in three structures, the Ph ring lies above the iminium π‐plane (staggered conformation B ; Figs. 1 and 4); in two structures, the benzylic C? C bond has an eclipsing conformation ( C ; Figs. 1 and 5) which places the Ph ring simultaneously at a maximum distance with its neighbors, the CO group, the N?C‐π‐system, and the cis‐substituent at C(2) of the heterocycle. It is suggested by a qualitative conformational analysis (Fig. 6) that the three staggered conformations of the benzylic C? C bond are all subject to unfavorable steric interactions, so that the eclipsing conformation may be a kind of ‘escape’. State‐of‐the‐art quantum‐chemical methods, with large AO basic sets (near the limit) for the single‐point calculations, were used to compute the structures of seven of the 14 iminium ions, i.e., 3, 4 / 12, 5 – 7, 13 , and 16 (Table) in the two staggered conformations, A and B , with the benzylic Ph group above the ring and above the iminium π‐system, respectively. In all cases, the more stable computed conformer (‘isolated‐molecule’ structure) corresponds to the one present in the crystal (overlay in Fig. 7). The energy differences are small (≤2 kcal/mol) which, together with the result of a potential‐curve calculation for the rotation around the benzylic C? C bond of one of the structures, 16 (Fig. 8), suggests that the benzyl group is more or less freely rotating at ambident temperatures. The importance of intramolecular London dispersion (benzene ring in ‘contact’ with the cis‐substituent in conformation A ) for DFT and other quantum‐chemical computations is demonstrated; the benzyl‐imidazolidinones 1 appear to be ideal systems for detecting dispersion contributions between a benzene ring and alkyl or aryl CH groups. Enylidene ions of the type studied herein are the reactive intermediates of enantioselective organocatalytic conjugate additions, Diels–Alder reactions, and many other transformations involving α,β‐unsaturated carbonyl compounds. Our experimental and theoretical results are discussed in view of the performance of 5‐benzyl‐imidazolidinones as enantioselective catalysts.     

D–π–A polysulfones for blue electroluminescence

Donor–π–acceptor type fluorene‐based copolymers with a sulfone unit were designed and synthesized for application in efficient pure‐blue light emitting. The electroluminescence behaviors of these copolymers were investigated by fabricating light‐emitting diodes and electrochemical cell devices. The former device little functioned but the latter worked well. The electrochemical cell devices having a configuration of ITO/PEDOT:PSS/copolymer:ionic liquid/Al exhibited purplish blue electroluminescence with an emission maximum at 434 nm (CIE coordinates (x, y) = (0.17, 0.10)) measured at 7 V. The initial positive scan of the D–π–A polysulfone based light emitting electrochemical cell with a sweep rate of 0.1 V s^?1 afforded a maximum luminance of 1080 cd m^?2 with a current efficiency of 1.96 cd A^?1 at an operating voltage of 12.5 V. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 3454–3461     

Model Construction for the A–B–C Ring System of Lysergic Acid via Vilsmeier–Haack‐Type Cyclization of 1H‐Indole‐4‐propanoic Acid Derivatives

Vilsmeier–Haack‐type cyclization of 1H‐indole‐4‐propanoic acid derivatives was examined as model construction for the A–B–C ring system of lysergic acid ( 1 ). Smooth cyclization from the 4 position of 1H‐indole to the 3 position was achieved by Vilsmeier–Haack reaction in the presence of K₂CO₃ in MeCN, and the best substrate was found to be the N,N‐dimethylcarboxamide 9 (Table 1). The modified method can be successfully applied to an α‐amino acid derivative protected with an N‐acetyl function, i.e., to 27 (Table 2); however, loss of optical purity was observed in the cyclization when a chiral substrate (S)‐ 27 was used (Scheme 5). On the other hand, the intramolecular Pummerer reaction of the corresponding sulfoxide 20 afforded an S‐containing tricyclic system 22 , which was formed by a cyclization to the 5 position (Scheme 3).     

Synthesis of Novel 3‐Acetyl‐2‐Aryl‐5‐(3‐Aryl‐1‐Phenyl‐Pyrazol‐4‐yl)‐2,3‐Dihydro‐1,3,4‐Oxadiazoles

A series of novel pyrazolyl‐substituted 1,3,4‐oxadiazole derivatives ( 4a‐4o ) were prepared by cyclization of the intermediate N′‐((3‐aryl‐l‐phenyl‐pyrazol‐4‐yl)methylene)arylhydrazide with acetic anhydride. The structures of the new compounds were confirmed by IR, ¹H NMR, MS and elemental analysis. Furthermore, preliminary bioassay of some of the title compounds indicated that they exhibited moderate inhibition against HIV‐1 PR.