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71.
72.
The recently discovered intramolecular aza-xylylene Diels-Alder reaction, based on a 1,4-dehydrohalogenation reaction, was extended in terms of substrates and leaving groups allowing the assembly of tetrahydroquinolines in two synthetic steps. Intramolecular cleavage of a thiocarbamate using triphenylphosphine and tetrachloromethane (Appel conditions) to give chloromethyl phenylisocyanate has been presented for the first time. The synthetic feasibility of this process was demonstrated in the first total syntheses of the alkaloids rac-Angustureine and 1-methyl-2-propyltetrahydroquinoline. 相似文献
73.
The synthesis of a biotinated amphiphile assembled from d-(+)-biotin, ethylene diamine as spacer, galactaric acid and 1-dodecylamine was achieved in six steps. The key step was the synthesis of a bisacetonide protected galactaric ester, the structure of which was determined by X-ray analysis. Aminolysis, spacer attachment, coupling with biotin and deprotection led to the amphiphilic galactaramide. 相似文献
74.
Gerhard Klebe Thomas Mietzner Frank Weber 《Journal of computer-aided molecular design》1994,8(6):751-778
Summary A relative comparison of the binding properties of different drug molecules requires their mutual superposition with respect to various alignment criteria. In order to validate the results of different alignment methods, the crystallographically observed binding geometries of ligands in the pocket of a common protein receptor have been used. The alignment function in the program SEAL that calculates the mutual superposition of molecules has been optimized with respect to these references. Across the reference data set, alignments could be produced that show mean rms deviations of approximately 1 Å compared to the experimental situation. For structures with obvious skeletal similarities a multiple-flexible fit, linking common pharmacophoric groups by virtual springs, has been incorporated into the molecular mechanics program MOMO. In order to combine conformational searching with comparative alignments, the optimized SEAL approach has been applied to sets of conformers generated by MIMUMBA, a program for conformational analysis. Multiple-flexible fits have been calculated for inhibitors of ergosterol biosynthesis. Sets of different thrombin and thermolysin inhibitors have been conformationally analyzed and subsequently aligned by a combined MIMUMBA/SEAL approach. Since for these examples crystallographic data on their mutual alignment are available, an objective assessment of the computed results could be performed. Among the generated conformers, one geometry could be selected for the thrombin and thermolysin inhibitors that approached reasonably well the experimentally observed alignment. 相似文献
75.
Jan F. Keij Jan Th . M. Jansen Frank W. Schultz Jan W. M. Visser 《Photochemistry and photobiology》1994,60(5):503-509
Abstract-During the development of a photodamage cell sorter several photosensitizers were tested for their ability to photoinactivate more than 90% of the sensitized cells after a brief irradiation with a fluence of 10 kJ/m2 . In pilot experiments, yeast cells sensitized with 10-dodecyl acridine orange (DAO) were effectively photoinactivated after receiving a fluence of 10 kJ/m2 delivered in 8 s. However, when the same fluence was delivered in 3 μ s during passage through a focused laser beam in the cell sorter, all cells survived.
Computer simulations of the relevant photophysical and chemical reactions inside the irradiated cell were used to investigate the cause of this phenomenon. The results indicated that the absence of photoinactivation by DAO, after flash irradiations, was caused by the combined effects of (1) limited oxygen diffusion into the cell and (2) a reduced number of collisions between photosensitizer triplet and oxygen molecules during the irradiation due to saturation of the intracellular photosensitizer triplet concentration. The contributions of triplet-triplet annihilation and triplet quenching by ground state photosensitizer molecules were found to be minimal and not significant. These findings indicate that Type II photosensitizers are incapable of rapid selective photoinactivation in cell sorters. 相似文献
Computer simulations of the relevant photophysical and chemical reactions inside the irradiated cell were used to investigate the cause of this phenomenon. The results indicated that the absence of photoinactivation by DAO, after flash irradiations, was caused by the combined effects of (1) limited oxygen diffusion into the cell and (2) a reduced number of collisions between photosensitizer triplet and oxygen molecules during the irradiation due to saturation of the intracellular photosensitizer triplet concentration. The contributions of triplet-triplet annihilation and triplet quenching by ground state photosensitizer molecules were found to be minimal and not significant. These findings indicate that Type II photosensitizers are incapable of rapid selective photoinactivation in cell sorters. 相似文献
76.
Vanommeslaeghe K Van Alsenoy C De Proft F Martins JC Tourwé D Geerlings P 《Organic & biomolecular chemistry》2003,1(16):2951-2957
Histone deacetylase (HDAC) inhibitors have recently attracted considerable interest because of their therapeutic potential for the treatment of cell proliferative diseases. An X-ray structure of a very potent inhibitor, Trichostatin A (TSA), bound to HDLP (an HDAC analogue isolated from Aquifex aeolicus), is available. From this structure, an active site model (322 atoms), relevant for the binding of TSA and structural analogues, has been derived, and TSA has been minimized in this active site at HF 3-21G* level. The resulting conformation is in excellent accordance with the X-ray structure, and indicates a deprotonation of the hydroxamic acid in TSA by His 131. Also, a water molecule was minimized in the active site. In addition to a similar deprotonation, in accordance with a possible catalytic mechanism of HDAC as proposed by Finnin et al. (M. S. Finnin, J. R. Donigian, A. Cohen, V. M. Richon, R. A. Rifkind and P. A. Marks, Nature, 1999, 401, 188-193), a displacement of the resulting OH- ion in the active site was observed. Based on these results, the difference in energy of binding between TSA and water was calculated. The resulting value is realistic in respect to experimental binding affinities. Furthermore, the mechanism of action of the His 131-Asp 166 charge relay system was investigated. Although the Asp residue in this motif is known to substantially increase the basicity of the His residue, no proton transfer from His 131 to Asp 166 was observed on binding of TSA or water. However, in the empty protonated active site, this proton transfer does occur. 相似文献
77.
Both, dielectric continuum solvation models as well as surface or group based methods using polarity and lipophilicity parameters have been proven to be useful tools for the analysis of solvation and partition questions. For the first time, COSMO-RS provides an integrated theory, which combines the aspects of continuum solvation and surface interactions, and which ends up with chemical potentials of molecules in almost arbitrary solvents and mixtures. Due to its sound theoretical basis, COSMO-RS does not only provide a new quantitative access to solvation and partition properties in well defined solvents, but it also opens a novel view and gives a better understanding of the general problem of solvation. Finally, this allows for a generalisation of COSMO-RS to sophisticatedphysiological partition problems involving as complex phases as blood, brain, or cell membranes. The use of COSMO-RS for drug discovery and design is demonstrated by applications to blood-brain partition coefficients, and water solubility. 相似文献
78.
The electron repulsion integrals arising in LCAO-MO theory are approximated by replacement of the product of two orbitals on different centers by linear combinations of one-center products. The approximation differs from those previously proposed in that the coefficients of the various terms are determined by requiring agreement for certain integrals, and in the emphasis of the role of symmetry in selecting the one-center products. For two-center integrals, the new approximation is significantly better than older approximate methods. Reasons are given for expecting this improvement to extend also to multi-center integrals.
Zusammenfassung Es wird ein Verfahren zur näherungsweisen Berechnung von Elektronenwechselwirkungsintegralen der LCAO-MO-Theorie beschrieben, bei welchem das Produkt zweier Zustandsfunktionen an verschiedenen Zentren durch eine Linearkombination von Produkten am gleichen Zentrum ersetzt wird. Der Unterschied zu ähnlichen Ansätzen liegt in der Justierung der Koeffizienten. Für Zweizentrenintegrale liefert die hier vorgeschlagene Methode bedeutend bessere Ergebnisse als das Mulliken-Verfahren.
Résumé Les intégrales de répulsion électroniques intervenant dans la théorie LCAO MO sont calculées d'une manière approchée en remplaçant le produit de deux orbitales sur des centres différents par des combinaisons linéaires de produits à un centre. Cette approximation diffère de celles proposées auparavant par la détermination des coefficients des différents termes au moyen de l'ajustement de certaines intégrales et par l'importance du rôle de la symétrie dans le choix des produits monocentriques. Cette nouvelle approximation est bien meilleure que les anciennes en ce qui concerne les intégrales bi-centriques. Nous donnons des raisons d'espérer que cette amélioration s'étendra aux intégrales polycentriques.相似文献
79.
Jörn Müller Helmuth Menig Gottfried Huttner Albin Frank 《Journal of organometallic chemistry》1980,185(2):251-263
The complexes [Ir(COD)(η5-C7H9)] and [Ir(COD)(η5-C8H11)] are obtained by the isoprophyl Grignard synthesis of [Ir(COD)Cl]2 (COD = η4-1,5-cyclooctadiene) in the presence of cycloheptatriene, and cyclooctatriene, respectively. The later reaction yields [IrH(COD)(δ4-1,3,6-C8H10)] as a by-product which, in contrast to other [IrH(η4-cyclodiene)2] complexes, does not show H-addition-elimination equilibria. Reduction of [Ir(1,3-C7H10)2Cl] with C2H5OH/Na2CO3 yields [Ir(η4-1,3-C7H10)](η5-C7H9)] which was characterized by X-ray analysis. [Ir(COD)Cl]2 reacts with Na2C8H8, and after hydrolysis unstable [Ir(COD)(η5-C8H9)] is formed which by protonation with HPF6 is converted into the [Ir(COD)(η6-1,3,5-C8H10)]+ cation. All these compounds are fluxional in solution. 相似文献
80.
Abdolhassen Talebian Alem Ghiorghis Charles F. Hammer Evelyn A. Murril Frank Pallas 《Journal of heterocyclic chemistry》1992,29(4):979-984
The syntheses and spectroscopic properties (ir, 1H nmr, 13C nmr, uv and ms) of pure samples of 2-chloro-4,6-bis(dimethylamino)-s-triazine 1 , 4,6-dichloro-2-dimethylamino-s-triazine 2 , 4,6-bis(dimethylamino)-s-triazin-2(lH)-one 3 , 4-chloro-6-dimethylamino-s-triazin-2(1H)-one 4 , 6-dimethylamino-s-triazine-2,4(1H,3H)-dione 5 , and 2,4,6-tris(dimethylamino)-s-triazine (altretamine, HMM) are reported. Evidence for enol-keto equilibria are also presented for 3 , in which the enol form exhibits as an H-bonded dimer structure similar to the dimer of organic carboxylic acids. 相似文献