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At least 19 recordsLinked to original sources
PubMed2002

Study of the conformational profile of the norbornane analogues of phenylalanine.

The conformational profile of the eight stereoisomeric 2-amino-3-phenylnorbornane-2-carboxylic acids (2-amino-3-phenylbicyclo[2.2.1]heptane-2-carboxylic acids) has been assessed by computational methods. These molecules constitute a series of four enantiomeric pairs that can be considered as rigid analogues of either L- or D-phenylalanine. The conformational space of their N-acetyl methylamide derivatives has been explored within the molecular mechanics framework, using the parm94 set of parameters of the AMBER force field. Local minimum energy conformations have been further investigated at the ab initio level by means of the Hartree-Fock and second order Moller-Plesset perturbation energy calculations using a 6-31G(d) basis set. The results of the present work suggest that the bulky norbornane structure induces two kinds of conformational constraints on the residues. On one hand, those of a steric nature directly imposed by the bicycle on the peptide backbone and, on the other hand, those that limit the orientations attainable by the phenyl ring which, in turn, reduces further the flexibility of the peptide backbone. A comparative analysis of the conformational profile of the phenylnorbornane amino acids with that of the norbornane amino acids devoid of the beta-phenyl substituent suggests that the norbornane system hampers the residue to adopt extended conformations in favour of C7-like structures. However, the bicycle itself does not impart a clear preference for any of the two possible C7 minima. It is the aromatic side chain, which is forced to adopt an almost eclipsed orientation, that breaks this symmetry introducing a marked preference for a single region of the (phi, psi) conformational space in each of the phenylalanine norbornane analogues investigated.

Cyclization↗
PubMed1997

Mobility of norbornane-type substrates and water accessibility in cytochrome P-450cam.

The behaviour of norbornane-type substrates bound to oxidised cytochrome P-450cam (CYP 101) in 60% (w/w) glycerol-containing phosphate buffer was investigated using electronic absorption spectroscopy. The high-pressure dependence study revealed that the value of the spin-state reaction-volume change decreased from -70 to -22.8 cm3/mol with decreasing high-spin state content from 99 to 63%. Simultaneously, the values for the enthalpy and entropy determined from the low-temperature dependence of the spin-state transition decreased from 73.7 to 24.3 kJ/mol and from 310.4 to 88.9 J/mol K, respectively. Under our experimental conditions the pH-value of the buffer remained at low temperatures and high pressures in the range of pH 7-8, in which no pH-value-induced spin-state conversion occurred. Therefore, the secondary effect of the temperature and pressure-induced pH change can be disregarded as being responsible for the observed spin-state transition effects. Substrate dissociation constants were determined. From the temperature-jump experiments (297 K to 180 K) we found a higher mobility in the active site for the substrates in the sequence (1R)-camphor, (1S)-camphor, camphane, (1R)- and (1S)-camphorquinone, norcamphor, and norbornane. Our findings can be explained by the incomplete fit of the methyl groups of the norbornane-type substrate to the protein, in particular to the I-helix, predominantly determining the substrate mobility and water accessibility to the protein.

Binding Sites↗
PubMed2005

The band 12 issue in the electron momentum spectra of norbornane: a comparison with additional Green's Function calculations and ultraviolet photoemission measurements.

In continuation of a recent study of the electronic structure of norbornane [J. Chem. Phys., 2004, 121, 10525] by means of electron momentum spectroscopy (EMS), we present Green's Function calculations of the ionization spectrum of this compound at the ADC(3) level using basis sets of varying quality, along with accurate evaluations at the CCSD(T) level of the vertical (26.5 eV) and adiabatic (22.1 eV) double ionization thresholds under C(2v) symmetry. The obtained results are compared with newly recorded ultraviolet photoemission spectra (UPS), up to binding energies of 40 eV. The theoretical predictions are entirely consistent with experiment and indicate that, in a vertical depiction of ionization, shake-up states at binding energies larger than approximately 26.5 eV tend to decay via emission of a second electron in the continuum. A band of s-type symmetry that has been previously seen at approximately 25 eV in the electron impact ionization spectra of norbornane is entirely missing in the UPS measurements and theoretical ADC(3) spectra. With regard to these results and to the time scales characterizing electron-electron interactions in EMS (10(-17) s) as compared with that (10(-13) s) of photon-electron interactions in UPS, and considering the p-type symmetry of the electron momentum distributions for the nearest 1b(1) and 1b(2) orbitals, this additional band can certainly not be due to adiabatic double ionization processes starting from the ground electronic state of norbornane, or to exceptionally strong vibronic coupling interactions between cationic states derived from ionization of the latter orbitals. It is therefore tentatively ascribed to autoionization processes via electronically excited and possibly dissociating states.

Cations↗
PubMed2004

Conformational studies by dynamic NMR. 97. Structure, conformation, stereodynamics and enantioseparation of aryl substituted norbornanes.

The structure of a 1,7,7-triaryl norbornane (compound 3) has been determined by X-ray diffraction and was found essentially equal to that predicted by molecular mechanics calculations. Restricted rotation of the aryl groups also has been observed by dynamic NMR spectroscopy in this compound and in a number of analogously substituted norbornanes. The aryl-norbornane bond rotation barriers were measured by line shape analysis of the (13)C NMR spectra obtained at temperatures lower than -100 degrees C and were found to cover the range 6.0 to 7.9 kcal mol(-1). An exception was the rotation involving the o-anisyl group in compound 5, which occurs near ambient temperature since the corresponding barrier is much higher (14.4 kcal mol(-1)). In one case (compound 4) configurational enantiomers could be separated by chiral HPLC and the corresponding CD spectra recorded.

Journal Article↗
PubMed2004

Norbornane: an investigation into its valence electronic structure using electron momentum spectroscopy, and density functional and Green's function theories.

We report on the results of an exhaustive study of the valence electronic structure of norbornane (C(7)H(12)), up to binding energies of 29 eV. Experimental electron momentum spectroscopy and theoretical Green's function and density functional theory approaches were all utilized in this investigation. A stringent comparison between the electron momentum spectroscopy and theoretical orbital momentum distributions found that, among all the tested models, the combination of the Becke-Perdew functional and a polarized valence basis set of triple-zeta quality provides the best representation of the electron momentum distributions for all of the 20 valence orbitals of norbornane. This experimentally validated quantum chemistry model was then used to extract some chemically important properties of norbornane. When these calculated properties are compared to corresponding results from other independent measurements, generally good agreement is found. Green's function calculations with the aid of the third-order algebraic diagrammatic construction scheme indicate that the orbital picture of ionization breaks down at binding energies larger than 22.5 eV. Despite this complication, they enable insights within 0.2 eV accuracy into the available ultraviolet photoemission and newly presented (e,2e) ionization spectra, except for the band associated with the 1a(2) (-1) one-hole state, which is probably subject to rather significant vibronic coupling effects, and a band at approximately 25 eV characterized by a momentum distribution of "s-type" symmetry, which Green's function calculations fail to reproduce. We note the vicinity of the vertical double ionization threshold at approximately 26 eV.

Journal Article↗
PubMed1995

Investigation of cytotoxic effects of 8 norbornane derivatives on 4 human cancer cell lines using the MTT assay.

A group of 8 structurally modified norbornane analogs, selected on basis of water solubility, was tested for its potential cytotoxic effects using a modified MTT assay. Four tumor cell lines, three hematological and a hepatocellular one were used as an experimental model system. Some analogs exhibited an antitumor effect which was shown to be tissue specific. The cytotoxic effect is most likely due to the nature of the side chains rather than to the basic bicyclic norbornane structure of the molecule. These results not only provide a basis for the synthesis of derivatives with effective antitumor activity, but also give some indication of the the molecular target of these compounds.

Antineoplastic Agents↗
PubMed2002

Thermal isomerization of (3-butenyl)cyclopropane to norbornane.

[reaction: see text] (3-Butenyl)cyclopropane isomerizes thermally to norbornane and gives rise to many other products. Deuterium and carbon-13-labeled versions of (3-butenyl)cyclopropane have been prepared and isomerized, establishing that the formation of norbornane involves cleavage of the cyclopropyl C2-C3 bond.

Journal Article↗
PubMedDate not supplied

Development of neural network simulator for structure--activity correlation of molecules (NECO). Prediction of endo/exo substitution of norbornane derivatives and of carcinogenic activity of PAHs from 13C-NMR shifts.

A perceptron type neural network simulator for structure--activity correlation of molecules has been developed with two different learning methods, i.e., back-propagation and reconstruction methods. First by use of the back-propagation method the exo/endo branching of norbornane and norbornene derivatives was correctly predicted from the set of 13C NMR chemical shifts for various ring carbon atoms. Then the obtained correlation was analyzed by the reconstruction learning method. It was shown in this case that the NMR shifts for two carbon atoms out of seven have strong correlation with the exo/endo branching. Further, structure--activity correlation between the 13C NMR chemical shifts and carcinogenicity of 11 polycyclic aromatic hydrocarbons was also analyzed using the reconstruction method. It was demonstrated that neural network analysis is suitable for the elucidation of complicated structure--activity problems where many factors are nonlinearly entangled.

Animals↗
PubMed2004

General synthesis of unsymmetrical norbornane scaffolds as inducers for hydrogen bond interactions in peptides.

Starting from readily accessible endo-cis-(2S,3R)-norbornene dicarboxylic acid benzyl monoester, a general and efficient synthetic approach toward unsymmetrical two-stranded peptidic structures was developed. In these structures the peptide strands are oriented in a parallel geometry. Their synthesis is easily applicable to a variety of amino acids and peptides. Specifically, a norbornane template as molecular scaffold induces hydrogen bonding between the adjacent peptide strands. The specific hydrogen bonding patterns between these strands were revealed by detailed NMR analysis including TOCSY/NOE experiments.

Amino Acids↗
PubMed1983

[Norbornane compounds in pharmaceutical research].

This review compiles the literature about norbornanes which already are used as medicaments and such bicyclo [2.2.1]heptanes, which are connected with drug research in some way. As is shown for the period from 1967 until 1980 the occupation with these bicyclic compounds has gained some importance in drug research, not only because they are used medicinally but also because they are used as suitable test molecules for studying structure-activity-relationships by reason of their special molecular shape, their voluminous, bicyclic carbon skeleton and the sterically fixed position of their substituents.

Amines↗
PubMed1999

Electron impact fragmentation patterns of 3,3-dimethyl-1, 2-norbornane derivatives

The electron impact mass spectra of several 3,3-dimethyl-1, 2-norbornanediols, diamines, amino alcohols and related derivatives have been studied and their fragmentation pathways discussed. Different fragmentation patterns were observed, depending not only on the nature of the substituents, but also on their relative positions on the norbornane framework. In general, the dominant peaks in the spectra of these compounds originate from initial C1-C2 bond cleavage (alpha-cleavage) with charge retention on the heteroatom (oxygen or nitrogen) attached at the bridgehead position, followed by hydride shift and loss of the C2-C3 fragment by homolytic cleavage of the C3-C4 bond. This fragmentation pathway leads to a highly stabilized cyclopentenylimmonium or cyclopentenyloxonium ion, which constitutes the base peak in the spectra in most of the studied compounds. Copyright 1999 John Wiley & Sons, Ltd.

Journal Article↗
PubMed1990

[Synthesis of the isocamphene series. 33. The synthesis of fungicidal norbornane derivatives].

Starting from the corresponding amines the syntheses of various norbornyl ureas with potential fungicidal activity are described. These new compounds possess a tricyclo[5.2.1.0(2,6)]decane, or an isocamphenilane, a camphenilane, an exo- and endo- dimethylnorbornane or a bicyclo[2.2.2]octane carbon skeleton. With the exception of the first class all other derivatives bear a geminal dimethyl group--important because of its shielding effect--at C-3 of the bicyclus. Some ureas, especially 6 and the acetamide 5, are active against phytopathogenic fungi.

Ascomycota↗
PubMed2006

Anticancer thiopyrano[2,3-d][1,3]thiazol-2-ones with norbornane moiety. Synthesis, cytotoxicity, physico-chemical properties, and computational studies.

A series of novel 9-substituted-3,7-dithia-5-azatetracyclo[9.2.1.0(2,10).0(4,8)]tetradecen-4(8)-ones-6 have been synthesized by a stereoselective hetero-Diels-Alder reaction of 5-ylidene-4-thioxo-2-thiazolidone derivatives with norbornene-2. All the compounds have been evaluated for antitumor activity in in vitro human tumor cell lines, and 10 of them possessed significant and selective cytotoxicity (MGM logGI50 approximately -4.17 to -4.98, for individual cell lines logGI50 up to -8). COMPARE analyses of differential growth inhibition patterns of compounds at the GI50 level showed high correlations with some of the antitubulin agents. The lipophilicity of the compounds was studied by RP-TLC and found to correlate well with calculated logP values. Docking and structure-activity relationship studies produced seven QSAR models with 2 or 3 variables, with correlation coefficients r2>0.9 and leave-one-out cross-validation correlation coefficients, q2>0.8.

Antineoplastic Agents↗
PubMed2004

Preparation of enantiopure norbornane ligands bearing both (2S,3S)-bis(phosphinomethyl) and 7-syn-oxygen functional groups and an application to rhodium-catalyzed asymmetric hydrogenation.

Enantiopure bicyclo[2.2.1]heptane derivatives having both (2S,3S)-bis[(diphenylphosphino)methyl] and 7-syn-oxygen functional groups were synthesized by using diastereoselective Diels-Alder reaction of di-(1R)-menthyl fumarate and 5-trimethylsilylcyclopentadiene followed by silver-promoted stereospecific frame rearrangement of a bromolactone intermediate. Rhodium-catalyzed asymmetric hydrogenations were carried out using the diphosphines as a chiral ligand.

Catalysis↗