Organic & Biomolecular Chemistry

Published by Royal Society of Chemistry
Online ISSN: 1477-0539
Print ISSN: 1477-0520
Publications
(Contd.)
A stereoselective and efficient method for free radical addition of benzyl thiol to aryl acetylene in the presence of Et(3)B-hexane has been developed for the synthesis of (Z) and (E)-styryl benzyl sulfides where base catalyzed hydrothiolations have failed. The scope of this reaction was successfully extended for the synthesis of (E)-ON 01910·Na, a phase III clinical stage anti-cancer agent and its inactive geometrical isomer (Z)-ON 01910·Na. It is interesting to note that all the E-isomers synthesized have shown better cytotoxicity profile on cancer cells compared to the Z-isomers.
 
JP4-039 is a lead structure in a series of nitroxide conjugates that are capable of accumulating in mitochondria and scavenging reactive oxygen species (ROS). To explore structure-activity relationships (SAR), new analogs with variable nitroxide moieties were prepared. Furthermore, fluorophore-tagged analogs were synthesized and provided the opportunity for visualization in mitochondria. All analogs were tested for radioprotective and radiomitigative effects in 32Dcl3 cells.
 
Enantioselective biohydrolysis of various substituted styrene oxides using whole fungus cells of Aspergillus nigerCGMCC 0496 are described. The results show not only para- but also some ortho- substituted styrene oxides can achieve high enantioselectivity during the hydrolysis.
 
Alkenylboranes R-CH[double bond, length as m-dash]CH-B(C6F5)2 undergo carbon-carbon coupling by means of 1,1-alkenylboration with diarylphosphino-enynes to give substituted conjugated hexatriene derivatives that bear a vicinal pair of B(C6F5)2 Lewis acid and PAr2 Lewis base functionalities at their central carbon portions. A series of six examples was prepared and all compounds were characterized by X-ray diffraction. Consecutive reactions of two selected examples were carried out.
 
1,1,3-Triarylpent-4-en-1-yn-3-ols, efficiently obtained in two steps from 1,1,3-triarylprop-2-yn-1-ols by a Meyer-Schuster rearrangement and subsequent addition of lithium trimethylsilylacetylide, react with either a 1- or 2- naphthol to afford photochromic 1,1-diarylvinyl substituted naphtho[1,2-b]- or naphtho[2,1-b]-pyrans respectively. Irradiation of solutions of these naphthopyrans results in reversible electrocyclic ring-opening to afford photomerocyanines which possess an extended conjugated system and show a bathochromically-shifted λ(max) relative to the non-vinyl substituted analogues.
 
Phosphine-catalyzed [4 + 2] annulation and vinylogous Michael addition reactions between 1,4-dien-3-ones and 1,1-dicyanoalkenes are presented. Under the catalysis of PBu(3) (20 mol %), 1,4-dien-3-ones like styryl ketones with 2-aryl 1,1-dicyanoalkenes as doubly activated alkenes readily undergo a formal [4 + 2] cycloaddition reaction, affording polysubstituted cyclohexanones in satisfactory yield and good diastereoselectivity; with the doubly activated alkenes bearing an acidic methyl or methylene at the 2-position, a vinylogous Michael addition of 1,4-dien-3-ones occurs under the same reaction conditions, giving a non-cyclized multifunctional adduct in good yield. These two phosphine-catalyzed transformations represent atom economical carbon-carbon bond forming reactions capable of rapid construction of molecular complexity. Based on experimental results, formation of the products has been mechanistically rationalized, and a phosphonium activation is proposed.
 
Incorporation in the dihydro[5]helicene framework prevents deprotonation of the title dications by steric factors, thus allowing their isolation as deeply colored stable salts. Based on the reversible interconversion with the electron-donating binaphthylic diolefins, they constitute a new class of electrochromic systems, in which C-C bond making/breaking is accompanied by two-electron transfer. Optically pure (R)-binaphthylic donors are interconvertible with the 1,4-dications with the R,R-configuration. The very large molar ellipticity makes it possible for them to be used as electrochiroptical response systems, by which the electrochemical input is transduced into two spectral outputs, i.e. UV-Vis and circular dichroism. Structurally related push-pull-type bis(quinonemethide)s also exhibit a similar multi-output electrochemical response.
 
Molecular modeling of the homo- and heterochiral dimeric self-associates of the enantiomers of 1,1'-bi-2-naphthol and 1-phenyl-2,2,2-trifluoroethanol in solution has been performed in order to understand their NMR behavior and in light of the phenomenon of "enantiomer self-disproportionation on achiral-phase chromatography" (ESDAC). For 1,1'-bi-2-naphthol in C(6)D(6), distinct NMR signals for each enantiomer arise for some spins in non-racemic mixtures-the phenomenon of self-induced diastereomeric anisochronism (SIDA). The linear divergence of these split signals across an enantiomeric titration (a series of samples in which the percentage of one enantiomer is varied from 50-100% whilst maintaining a constant total concentration), as well as the near linear migration of certain signals in CDCl(3) across a similar enantiomeric titration, where signals were not observed to be split, is consistent with the calculated small energy differences between the homo- and heterochiral associates. For an enantiomeric titration of 1-phenyl-2,2,2-trifluoroethanol in n-hexane, NMR signals also remained unsplit but the noticeable migration of some revealed a skew indicative of a preference for the heterochiral associate. This was duly reflected in the calculations which provided a DeltaG value favoring the heterochiral associate by 2.4 kJ mol(-1). The relevance of these results to evaluating the likely occurrence of ESDAC is considered.
 
Densely functionalized azoxabicyclo[3.3.1]nonanones were prepared by regio- and diastereoselective condensation of 1,1-bis(silyloxy)ketene acetals with isoquinolinium and quinolinium salts and subsequent regioselective and stereospecific iodolactonization.
 
The title diphenylethyne derivative with 4-methylphenyl (tolyl) groups at all the ortho positions was synthesized by the Stille or Sonogashira coupling from the corresponding iodide. The X-ray structure revealed that the two terminal phenyl groups at the sp carbons are twisted by 63 degrees out of the coplanar conformation to avoid steric interactions between the tolyl groups. The relative stabilities of possible conformers were analyzed by the PM3 calculations. The axially chiral derivative with two methoxymethyl groups showed no evidence of restricted rotation about the acetylenic axis by VT NMR measurements, its barrier being less than 35 kJ mol(-1). The spectroscopic features and reactivities of this sterically congested alkyne are also described.
 
We performed an efficient practical and systematic optical resolution method for gem-dihalo- and monohalocyclopropanecarboxylic acids and utilizing chiral 1,1'-binaphthol monomethyl ether (R)- as the key auxiliary. Direct esterification of with (R)- gave two 1R- and 1S-diastereomeric esters with marked different R(f) values, both of which were easily separated using simple column chromatography. Monodehalogenation of separated chiral esters using t-BuMgCl and cat. Co(dppe)(2)Cl(2) gave two 1,2-trans- and 1,2-cis-diastereomers with markedly different R(f) values, both of which were similarly separated using simple column chromatography. The obtained diastereomers and were easily hydrolyzed to the desired enantiopure acids (>99%) and (>99%), respectively, with recovery of (R)-, both in good to excellent yields. Utilizing the present method, important chiral agrochemicals, carpropamid and fencyclate , were readily synthesized. Pyrethroid with three asymmetric centers was efficiently synthesized in a much better yield compared with the reported method.
 
The reaction of readily accessible 1,1-dialkylhydrazones with commercially available o-(trimethylsilyl)aryl triflates provides a direct one-step route to pharmaceutically important 1-alkylindazoles. The products are obtained in high yields by one-pot NCS-chlorination/aryne annulation or Ac(2)O-acylation/deprotection/aromatization protocols.
 
A tandem reaction between N'-(2-alkynylbenzylidene)hydrazide and cycloprop-2-ene-1,1-dicarboxylate co-catalyzed by silver triflate and tris(triphenylphosphine)rhodium chloride is reported. The reaction proceeds through 6-endo-cyclization, [3 + 2] cycloaddition, cyclopropane opening, and aromatization, leading to pyrazolo[5,1-a]isoquinolines in moderate to good yields.
 
A type of 1,1'-binaphthyl-based imidazolium chemosensor module has been synthesized for the highly selective recognition of tryptophan (Trp) among the eleven alpha-amino acids investigated in aqueous solutions via synergistic effects of multiple hydrogen bonding and electrostatic interactions. These results have demonstrated that the C-2 hydrogen atom of the imidazolium ring plays a key role as a hydrogen bond donor. The UV/vis, fluorescence and mass spectral studies have indicated that a 1 : 1 complex is formed between the host and tryptophan. The binding affinity and selectivity of the cleft-like receptor (R)- with l-Trp are superior to those of (R)-. In spite of an inferior selectivity towards various aromatic amino acids, the macrocyclic (R)- displays a remarkable enantiodiscrimination for the two enantiomers of tryptophan with a K(D)/K(L) value as high as 6.2.
 
1,1'-bis(tert-butoxycarbonylamino)ferrocene (6), a protected derivative of 1,1'-diaminoferrocene, has been synthesized by a very convenient method and serves as a synthon for 1,1'-diaminoferrocene. Its structure in solid state and in solution has been studied by NMR and X-ray crystallography. 1,1'-bis(tert-butoxycarbonylamino)ferrocene serves as starting material for the synthesis of amino acid conjugates of L- and D-alanine. The structures of these bioconjugates have been studied by NMR and CD spectroscopy and X-ray crystallography and reveal that the chiral organization of the podant amino acid chains is controlled by the chirality of the attached amino acid. The substituents engage in strong intramolecular H-bonding generating 14-membered H-bonded rings, a motif previously unrealized in ferrocene-amino acid and peptide conjugates.
 
A series of C-shaped, 1,1'-alkyl-bridged 4,4'-diaryl-2,2'-bibenzimidazoles has been synthesized. The crystal structures of these compounds have been determined and packing diagrams demonstrate that these molecules either form linear intercalated molecular chains or include solvent molecules in the solid state. Crystal structures are compared to computational structures determined using density functional theory, with the BMK/DZV(2d,p) method. The C-shaped or tweezer-like geometry enables them to act as building blocks for supramolecular architectures.
 
Ferrocene-bridged bisporphyrins have been synthesized by the condensation of corresponding dipyrromethane-derived diols with a bisdipyrromethane. Purification of the final compounds has been achieved without chromatography. The specific geometry of these bisporphyrins makes them valuable starting points for building complex molecular and supramolecular structures. In particular it provides a core to which multiple sites of attractive intermolecular interactions can be attached thereby creating compounds predisposed to form complex networks by association. We have studied the structure of bis-1,1'-(porphyrinyl)ferrocenes by 1H NMR, UV-Vis and electrochemistry. Results have shown that complex dynamic processes occur in these molecules (which may involve conformers, formation of H-aggregates and tautomers) and that they have non-typical electrochemical behaviour.
 
cis-2,3-Disubstituted cyclopropane 1,1-diesters were found to be much more reactive than their corresponding trans-isomers in the AlCl3-promoted [3 + 2]-annulations with isothiocyanates. The reaction with the cis-cyclopropanes proceeded to completion within minutes, providing a variety of densely substituted diastereomerically pure 2-iminodihydrothiophenes in moderate to excellent yields.
 
The Friedel-Crafts benzylation of arenes using benzyl alcohols activated in situ with XtalFluor-E is described. A wide range of 1,1-diarylmethanes and 1,1,1-triarylmethanes were prepared under experimentally simple and mild conditions, without the need for a transition metal or a strong Lewis acid. Notably, the reactivity observed demonstrates the potential of XtalFluor-E to induce C-OH bond ionization and SN1 reactivity of benzylic alcohols.
 
The design of polymers with repeating [C(NR2)2CH2CH2] units which may simultaneously provide conformational control and contain repeating electroactive centres is discussed; (NR2)2 groups would be ideally provided by ortho-phenylenediamine derivatives, with 1,8-diaminonaphthalenes as alternatives. Oligomers containing 1,8-bis(methylamino)naphthalenes, up to the hexamer, were obtained by condensation of oligomers of CH3[COCH2CH2](n)COCH3 with 1,8-bis(methylamino)naphthalene, but attempts to prepare related oligomers from 1,2-bis(alkylamino)benzenes were unsuccessful, as only terminal ketone groups could be converted to aminals. Evidence for a strong preference for all-anti conformations of the main chain in the naphthalenediamine oligomers is provided by ring current effects on 1H NMR shifts, and by X-ray structures, which also provide evidence of intercalation in the solid state. Electrochemical studies of these oligomers show irreversible oxidation of oligomers in solution, but oxidation of longer oligomers leads to the deposition of a reddish-pink insoluble material which shows two reversible oxidation waves. Possible interpretation of these results is discussed.
 
An unusual ring-expansion reaction of 4-amino-1,1-dioxo-[1,2,3,5]-thiatriazoles has been identified that produces the relatively rare 5-amino-1,1-dioxo-[1,2,4,6]-thiatriazines and. Initial alkylation of the thiatriazole with alpha-halo-esters at N-3 produces alpha-substituted esters which, under basic reaction conditions, undergo opening of the thiatriazole ring and re-closure to a thiatriazine ring. Similar alkylations of with diethyl chloromalonate and ethyl dichloroacetate lead to the loss of SO2 and the production of triazine and triazole, apparently by an initial alkylation at N-5. The reaction of with phenacyl bromides or a phenacyl dibromide forms fully unsaturated 5-amino-1,1-dioxo-[1,2,4,6]-thiatriazines.
 
The absolute configuration of the (+)-1,1-dimethyl-2-phenylethyl phenyl sulfoxide is determined to be (R), using three different chiroptical spectroscopic methods, namely vibrational circular dichroism (VCD), electronic circular dichroism (ECD) and specific rotation. Four solution conformations are identified for 1,1-dimethyl-2-phenylethyl phenyl sulfoxide. In each of the methods used, experimental data for the enantiomers of 1,1-dimethyl-2-phenylethyl phenyl sulfoxide were measured in the solution phase and concomitant quantum mechanical calculations of corresponding properties were carried out using density functional theory with B3LYP functional and 6-31G* and 6-31+G basis sets. Additional VCD and ECD calculations were also undertaken with 6-311G(2d,2p) basis set. A comparison of theoretically predicted data with the corresponding experimental data has allowed us to elucidate the absolute configuration and predominant conformations of (+)-1,1-dimethyl-2-phenylethyl phenyl sulfoxide.
 
A tandem ring-opening-cyclization reaction of cyclopropanes with imines in the presence of 5 mol% of scandium triflate was developed for the highly diastereoselective synthesis of multi-substituted pyrrolidines.
 
Treatment of allyl-1,1-dichlorovinyl ethers with n-BuLi at -78 °C, followed by quenching with ketones, epoxides, and oxetanes, leads to highly substituted β-, γ-, and δ-lactones in good to excellent yields.
 
Treatment of 1,1-dichloroalk-1-enes with Cp2Ti[P(OEt)3]2 produced organotitanium species, which afford allenes on treatment with aldehydes and ketones.
 
A concise four-step synthesis of 9,9'-spirobixanthene-1,1'-diol is reported, featuring a practical preparation at large scale without the use of column chromatography purification. Co-crystallization with N-benzylcinchonidinium chloride and N-benzylquininium chloride rendered the optically pure product in both enantiomers.
 
A FeCl(3) promoted [3 + 2] annulation of dimethyl 2-vinyl and arylcyclopropane-1,1-dicarboxylate with aryl isothiocyanates has been developed to give pyrrolidine-2-thiones in good yields with high regioselectivity.
 
Effects of pressure on the enantiodifferentiating methanol addition to 1,1-diphenylpropene (1) sensitized by chiral naphthalenedicarboxylates (3 and 4) were investigated over 0.1–400 MPa. The logarithm of enantiomeric excess (ee) of photoadduct, i.e. 1,1-diphenyl-2-methoxypropane (2), was a linear function of both pressure (P) and temperature (T); further, the product chirality was switched by P in some cases. From the slope of P − ln(kR/kS) plot, the differential activation volume (ΔΔV‡) was determined for the first time for bimolecular asymmetric photoreactions. The ΔΔV‡ values obtained are mostly larger than those obtained for relevant unimolecular photoreactions, and are a critical function of the nature of the chiral auxiliary and solvent, indicating conformation changes of the intervening diastereomeric exciplex or transition state in different solvents. Indeed, fluorescence spectral examinations of the sensitizer and exciplex under high pressure revealed the existence of exciplexes of variable energy and structure, which may rationalize the different ΔΔV‡ and product ee obtained. A three-dimensional diagram, correlating the ee with P and T, was constructed from the pressure dependence data at different T, from which we may propose an idea of the multidimensional control of asymmetric reaction by the combined use of the entropy-related enviromental factors.
 
Palladium-catalyzed N-allylation of unprotected amino acids with 1,1-dimethylallyl alcohol were carried out. The reaction in the presence of Pd(OAc)(2) (5 mol%), sodium diphenylphosphinobenzene-3-sulfonate (TPPMS, 10 mol%), and AcONa (2 equiv) in water at 120 °C for 16 h in a sealed tube gave only mono-N-allylated amino acids in good yield.
 
α-Fluorinated-1,1-bisphosphonic acids derived from fatty acids were designed, synthesized and biologically evaluated against Trypanosoma cruzi, the etiologic agent of Chagas disease, and against Toxoplasma gondii, the agent responsible for toxoplasmosis, and also towards the target parasitic enzymes farnesyl pyrophosphate synthase of T. cruzi (TcFPPS) and T. gondii (TgFPPS). Interestingly, 1-fluorononylidene-1,1-bisphosphonic acid (compound 43) proved to be an extremely potent inhibitor of the enzymatic activity of TgFPPS at the low nanomolar range, exhibiting an IC(50) of 30 nM. This compound was two-fold more potent than risedronate (IC(50) = 74 nM) that was taken as a positive control. This enzymatic activity was associated with a strong cell growth inhibition against tachyzoites of T. gondii, with an IC(50) value of 2.7 μM.
 
The first asymmetric organocatalytic allylic alkylation of 1,2-dihydro-Reissert compounds and Morita-Baylis-Hillman (MBH) carbonates has been developed, which provided a novel protocol to construct enantioenriched functionalized 1,2-dihydroisoquinolines bearing vicinal quaternary and tertiary chiral centers at C-1 position (up to 94% ee, dr > 20 : 1).
 
Axially chiral, 3,5-dihydro-4H-dinaphtho[2,1-c:1',2'-e]azepine (dinaphthazepine) and 1,1'-binaphthyl-2,2'-disulfonimide (dinaphthosulfonimide) moieties were rigidly connected via N-p-phenylene linkers to photochemically (E)/(Z)-isomerisable 1,2-diethynylethene scaffolds. The chemical stability of the resulting systems was found to be critically related to the other substituents on the central π-conjugated scaffold. High helical twisting power (HTP), up to 315 μm(-1), for the induction of a cholesteric liquid-crystalline phase through doping of a nematic phase was measured, resulting from the introduction of the chiral, mesogenic 1,1'-binaphthyl motifs. Single crystal X-ray analysis revealed that the phenylene spacer is in π-conjugation with the N-atom of the dinaphthazepine but not with the N-atom of the dinaphthosulfonimide moiety. This difference in orientation results in visible-transparency in the electronic absorption spectrum and higher (E)/(Z)-photoisomerisation quantum yields of the dinaphthosulfonimide-derived chiral dopants, as compared to the dinaphthazepine systems, which feature intramolecular charge-transfer absorption in the visible region.
 
The complete resolution of 2,2[prime or minute]-dihydroxy-1,1[prime or minute]-binaphthyl into its enantiomers by inclusion complexation with a commercially available derivative of choline, is reported. The two enantiomers are recovered in >99% ee from the inclusion complexes by simple dissolution in a diethyl ether-water medium and the resolving agent can be recycled.
 
Ethyl 2-diazo-4,4,4-trifluoroacetoacetate (1a) and 3-diazo-1,1,1-trifluoro-2-oxopropane (1b) exhibit a deviating behavior in solution photolysis (hydrogen abstraction for 1a; Wolff rearrangement for 1b) [(a) F. Weygand, W. Schwenke and H. J. Bestmann, Angew. Chem., 1958, 70, 506; (b) F. Weygand, H. Dworschak, K. Koch and S. Konstas, Angew. Chem., 1961, 73, 409]. As shown by 13C-labelling of 1b this difference is not caused by rearrangement of the primarily formed alpha-oxocarbene to an isomeric alpha-oxocarbene presenting a hydrogen atom as a migrating substituent for the Wolff rearrangement. It is discussed that the singlet alpha-oxocarbene generated from 1a rapidly undergoes spin equilibration followed by hydrogen abstraction of the triplet alpha-oxocarbene. In contrast, due to a larger singlet-triplet splitting in the singlet alpha-oxocarbene generated from 1b, the intramolecular Wolff rearrangement on the singlet surface can efficiently compete with the singlet-triplet interconversion.
 
An efficient and straightforward approach towards the synthesis of 1-alkyl-2-(trifluoromethyl)aziridines starting from 1,1,1-trifluoroacetone via imination, α-chlorination, hydride reduction and ring closure was developed. In addition, novel primary β-iodo amines were obtained by regioselective ring opening of these 2-(trifluoromethyl)aziridines using alkyl iodides, and their synthetic potential was demonstrated by converting them into novel α-CF(3)-β-phenylethylamines upon treatment with lithium diphenylcuprate.
 
A calix[4]phyrin-(1,1,1,1) substituted with a 4-isothiocyanatophenyl group has been synthesised and used to attach the macrocycle to a solid support. The NCS group can also be used to further functionalise the calix[4]phyrin-(1,1,1,1) by reaction with amines and amino acids. Stability constants for anion binding by the calix[4]phyrin-(1,1,1,1) are reported and these show a clear ability to differentiate F(-) and HSO(4)(-) from Cl(-), Br(-), I(-) which can be detected by both NMR and UV-visible spectroscopy.
 
A method to prepare highly conjugated indenes efficiently by iron(III) chloride-catalysed dimerisation of trisubstituted propargylic alcohols under very mild conditions at room temperature is described. The reactions are rapid and operationally straightforward, giving the indene products in good yields and regioselectivity.
 
Here we describe the synthesis and characterisation of a new isoindole-based nitrone spin trap, 1,1,3-trimethylisoindole N-oxide (TMINO). This nitrone and its radical adducts (isoindoline nitroxides) exhibit enhanced stability with respect to other commonly used spin traps and their adducts. We also report EPR trapping studies of this new nitrone with some carbon- and oxygen-centred radicals including alkyl, aryl, hydroxyl and benzoyloxyl systems. The narrow EPR line-widths and stability of the resulting nitroxide spin adducts allowed the detection of the expected radicals as well as secondary and minor radical components in the reaction mixtures.
 
The new EPR spin trap, 1,1,3-trimethylisoindole N-oxide (TMINO), very efficiently scavenges several Fenton-derived carbon- and oxygen-centred radicals including hydroxyl, formyl and alkyl radicals. The adducts display good stability and narrow EPR line-widths, allowing the detection of the expected radicals as well as two-dimensional (time-resolved) EPR experiments. Trapping experiments were also undertaken with superoxide radicals (giving no EPR signals) and nitric oxide (which gave strong EPR signals attributed to the action of higher oxides of nitrogen). The selectivity of TMINO towards HO. with respect to superoxide radicals demonstrates its potential as a useful spin-trap.
 
A 3 x 3 matrix of manisyl (4-methoxy-2,6-dimethylphenyl) substituted pyridyl-1,10-phenanthrolines has been synthesized by utilizing a general palladium catalyzed cross-coupling procedure. The directionality of these terdentate ligands will generate chiral octahedral ML(2) complexes, potentially useful for the metal templated synthesis of topologically chiral structures.
 
Organic semiconductors containing metal binding sites within their molecular backbones are of a general interest in organic materials chemistry. In this paper, we describe a straightforward synthetic procedure, which gives access to a series of 2-(oligothienyl)-[1,10]phenanthrolines (nT-phen), 2,9-bis(oligothienyl)-[1,10]phenanthrolines (nT-phen-nT) and 2,2'-(oligothienyl)bis-[1,10]phenanthrolines (phen-nT-phen). By a Negishi-type cross coupling of 2-iodo-[1,10]phenanthroline or 2,9-diiodo-[1,10]phenanthroline with in situ generated alpha-zinc derivatives of different mono-, ter-, and quinquethiophenes we were able to synthesize the corresponding oligothienyl-phenanthrolines in medium to excellent yields. Furthermore, characterization of the optical properties of the new materials indicated that the two subunits, oligothiophene and phenanthroline, are in pi-conjugation. Characterization of the redox properties revealed additional evidence for the role of [1,10]phenanthroline as a pi-bridging unit in the nT-phen-nT series.
 
Screening of the reaction conditions for decarboxylation of 2,3-diaryl- acrylic acid (1a) a
(Contd.) 
Decarboxylation of 2,3-diaryl acrylic acids (1a–1t) under optimized conditions a 
A series of trans- or cis-stilbenes have been synthesized in good to excellent yields via a functional group-dependent decarboxylation process from the corresponding 2,3-diaryl acrylic acids in a neutral CuI/1,10-phen/PEG-400 system under microwave conditions. The in situ generation of the recyclable catalytic complex, the use of environmentally benign solvent PEG-400, the operational simplicity, the short reaction times, as well as the functional group-dependent chemo- and stereo-selectivity have made the decarboxylation process a highly efficient and applicable protocol.
 
Photographs of 1% agarose gels showing photocleavage of 38 l M bp pUC19 plasmid DNA by 35 l M of compounds 3 , 4 and 6 (from top to bottom), in the absence and presence of 35 l M CuCl 2 (20 mM sodium phosphate buffer, pH 7.0). Prior to electrophoresis, all reactions were equilibrated in the dark (1 h, 22 ◦ C) and were then either irradiated with 13 RPR-3500 A  ̊ 24 W Rayonet lamps at specific time intervals up to 25 min or kept in the dark for 25 min. Lane 1: DNA control irradiated for 25 min; lane 2: 35 l M CuCl 2 irradiated for 25 min; 
We report the syntheses and characterization of a series of compounds based on 1,10-phenanthroline covalently tethered, at the 2 and 9 positions, to either two benzene, naphthalene, acridine or anthracene chromophores. The acridine and anthracene derivatives are shown to efficiently cleave pUC19 plasmid DNA upon irradiation with ultraviolet light (pH = 7.0, 22 degrees C, 350 nm). Furthermore, photocleavage levels are markedly increased by the addition of Cu2+ to the DNA photolysis reactions. Interestingly, when the concentrations of the anthracene compounds are lowered from 35 microM to 0.25 microM, the reverse trend is observed. DNA photocleavage is markedly reduced in the presence of copper(II).
 
S Molecular structures of the compounds 5a-5d showing the atom labeling scheme and 20% probability displacement ellipsoids viewed approximately parallel in the central phenantroline ring (a) and viewed approximately perpendicular to the central phenantroline ring (b). C-H···π hydrogen bonds are represented by dotted lines (H atoms not involved in these interactions have been omitted). Cg1, Cg2 and Cg3 denote the ring centroids. The solvent molecule (CH 2 Cl 2 ) for 5a has been omitted.
S Molecular structure showing the atom labeling scheme and 20% probability displacement ellipsoids (a) and crystal packing of the complex 5c·6a (b) (the layers are highlighted in grey). O–H···Se, O–H···O and C–H···Se hydrogen bonds are represented by dashed lines. Cg1 denote the ring centroid. 
S Molecular structure of the bisamide 7 showing the atom labeling scheme and 20% probability displacement ellipsoids (a,) meso-helical structure of 7 (b) and crystal packing of bisamide 7 (c). The intramolecular C–H···π interactions are represented by dotted lines and (H atoms not involved in these interactions have been omitted, as well as solvent molecule (CHCl 3 )) and C–H···O hydrogen bonds are represented by dashed lines. Cg1, Cg2 and Cg3 denote the ring centroids. 
X-ray crystallographic analysis of the title compounds revealed that they assume a folded helical conformation of an approximate C2 symmetry in the solid state. Dithioamide , diselenoamide and monoselenoamide were resolved to enantiomers by inclusion crystallization with optically active diols (TADDOLs). The absolute configuration of the guest molecules in the complexes , and was assigned as P. The optical activity of the resolved compounds is manifested by their CD spectra showing relatively strong Cotton effects in the region of thionoamide and selenoamide n-π* transition. The optically active thiono- and selenoamides are configurationally labile compounds and gradually racemize in solution but they are stable in the form of the inclusion complexes. The first-order kinetics of the racemization in solution allowed us to assign the racemization barriers by the spectropolarimetric measurements.
 
Anionic aromatic ipso-substitution has allowed an aziridine ring to be fused onto pyrrolo[1,2-a]benzimidazole. This diazole analogue of aziridinomitosene, and N-[(aziridinyl)methyl]-1H-benzimidazole are shown to be significantly more cytotoxic towards the human breast cancer cell lines MCF-7 and HCC1937 than towards a human normal fibroblast cell line (GM00637). The aziridinyl fused pyrrolo[1,2-a]benzimidazole is less cytotoxic than the non-ring fused aziridinyl analogue towards all three cell lines. The BRCA1-deficient HCC1937 cells are more sensitive to mitomycin C (MMC) compared to GM00637 and MCF-7 cells. The evidence provided indicates that different pathways may mediate cellular response to benzimidazole-containing aziridine compounds compared to MMC.
 
A bis-bisurea receptor () based on the R,R-cyclohexane-1,2-diamino scaffold forms an uncommon 2 : 2 complex () with the monohydrogen phosphate ion (HPO(4)(2-)) and a 1 : 1 complex () with the sulfate ion (SO(4)(2-)). Solution binding properties of the two anions were studied by (1)H NMR, UV-vis, and circular dichroism (CD) methods.
 
N-(2-azidomethyl)phenyl ketenimines and N-(2-azidomethyl)phenyl-N'-alkyl(aryl) carbodiimides undergo, under mild thermal conditions, intramolecular [3 + 2] cycloaddition reactions between the azido group and either the C=C or the distal C=N double bonds of the ketenimine and carbodiimide functions respectively. The reaction products are indolo[1,2-a]quinazolines and/or indolo[2,1-b]quinazolines in the case of azido-ketenimines, and tetrazolo[5,1-b]quinazolines in the case of azido-carbodiimides. The formation of the two classes of indoloquinazolines implies the ulterior dinitrogen extrusion from the non-isolated, putative [3 + 2] cycloadducts between the azide and ketenimine functions, whereas in the case of azido-carbodiimides the initial cycloadducts, tetrazoloquinazolines, were cleanly isolated and further converted into 2-aminoquinazolines by thermally induced dinitrogen extrusion.
 
A novel synthesis of 1,2-disubstituted 1,2-dihydroquinazoline 3-oxides 8 and the first ever examples of 1,3-dipolar trapping of these nitrones to homonuclear dipolarophiles is described. The new dipoles 8 reacted with N-methyl maleimide, generating diastereomeric adducts 14-16. In the reaction between 8 and dimethyl acetylenedicarboxylate, primary cycloadducts 17 and/or stable rearrangement products, azomethine ylides 18, are formed depending on the substitution pattern of the dipole. The structure of 18c is unambiguously assigned by X-ray crystallographic analysis. An X-ray crystal structure determination is also presented for the cyclopropylisoxazoloquinazoline 22 formed by a [3 + 2] addition of 8a to 21, the dimethyl acetylenedicarboxylate tetramer.
 
Reactions of aldehydes, 1,3-indanedione and enaminones were successfully carried out using p-toluene sulfonic acid (p-TsOH) as a catalyst and high-temperature water as a solvent under microwave irradiation. This method provided several advantages such as rapid reaction times, high yields, and a simple workup procedure. In addition, a possible mechanism to account for the reaction was proposed.
 
(4E,8E,10E)-9-Methyl-4,8,10-sphingatrienine, a core component of marine sphingolipids, was synthesised for the first time using a copper(I)-mediated 1,2-metallate rearrangement of a lithiated glycal as a key step. It was converted to phalluside-1, a cerebroside isolated from the ascidian Phallusia fumigate. By an analogous route, (4E,8E)-9-methyl-4,8-sphingadiene was synthesised and converted to Sch II, a cerebroside that induces fruiting body formation in the basidiomycete Schizophyllum commune.
 
Top-cited authors
Luis Ramon Domingo
  • University of Valencia
Steven V Ley
  • University of Cambridge
Ian R Baxendale
  • Durham University
Dhevalapally B Ramachary
  • University of Hyderabad
John Ralph
  • University of Wisconsin–Madison