The synthesis of benzofuroquinolines. V. Some benzofuro[3,2-B]quinoline derivatives

Some benzofuro[3,2-b]quinoline derivatives 1a-d and 3a were synthesized by condensation of 2-amino-benzaldehyde, 2-aminoacetophenone, 2-aminobenzophenone, isatin, or 2-aminobenzoic acid with 3(2H)-benzofuranone. The benzofuroquinolinone 3a was also obtained from 2-aminobenzoic acid and phenoxy-acetyl chloride in two steps and converted to 10-chloro derivative 1e . Similarly, some 8-halobenzofuro[3,2-b]-quinoline derivatives 1d,e and 3a (X = F, Cl, Br, I) were synthesized from 5-haloisatin or 2-amino-5-halo-benzoic acid. And benzofuro[3,2-b]quinolines 1a-e thus obtained were converted to corresponding N-oxides 2 .     

Manganese(III) acetate oxidation of 1-acetylindole derivatives

In the presence of malonic acid, the reaction of 1-acetylindole ( 2 ) with manganese(III) acetate resulted in the formation of 4-acetyl-3,3a,4,8b-tetrahydro-2H-furo[3,2-b]indol-2-one ( 5 ). The same reaction of 1-acetyl-2,3-dimethylindole yielded a mixture of 2-acetoxymethyl-1-acetyl-3-methylindole and 4-acetyl-3a,8b-dimethyl-3,3a,4,8b-tetrahydro-2H-furo[3,2-b]indol-2-one, furthermore, the oxidation of 1-acetylindoline proceeded to the formation of 2, 5 and 1-acetylindoline-5-carboxylic acid.     

Development of hardware accelerator for molecular dynamics simulations: a computation board that calculates nonbonded interactions in cooperation with fast multipole method

Evaluation of long-range Coulombic interactions still represents a bottleneck in the molecular dynamics (MD) simulations of biological macromolecules. Despite the advent of sophisticated fast algorithms, such as the fast multipole method (FMM), accurate simulations still demand a great amount of computation time due to the accuracy/speed trade-off inherently involved in these algorithms. Unless higher order multipole expansions, which are extremely expensive to evaluate, are employed, a large amount of the execution time is still spent in directly calculating particle-particle interactions within the nearby region of each particle. To reduce this execution time for pair interactions, we developed a computation unit (board), called MD-Engine II, that calculates nonbonded pairwise interactions using a specially designed hardware. Four custom arithmetic-processors and a processor for memory manipulation ("particle processor") are mounted on the computation board. The arithmetic processors are responsible for calculation of the pair interactions. The particle processor plays a central role in realizing efficient cooperation with the FMM. The results of a series of 50-ps MD simulations of a protein-water system (50,764 atoms) indicated that a more stringent setting of accuracy in FMM computation, compared with those previously reported, was required for accurate simulations over long time periods. Such a level of accuracy was efficiently achieved using the cooperative calculations of the FMM and MD-Engine II. On an Alpha 21264 PC, the FMM computation at a moderate but tolerable level of accuracy was accelerated by a factor of 16.0 using three boards. At a high level of accuracy, the cooperative calculation achieved a 22.7-fold acceleration over the corresponding conventional FMM calculation. In the cooperative calculations of the FMM and MD-Engine II, it was possible to achieve more accurate computation at a comparable execution time by incorporating larger nearby regions.     

Chemistry and biology of khafrefungin. Large-scale synthesis, design, and structure-activity relationship of khafrefungin, an antifungal agent

Large-scale synthesis, design, and structure-activity relationships of khafrefungin are reported. Khafrefungin is an antifungal agent that inhibits inositol phosphorylceramide (IPC) synthase, an enzyme involved in fungal sphingolipid biosynthesis. Unlike other inhibitors that inhibit the corresponding enzyme in fungi and mammals to the same extent, khafrefungin does not impair sphingolipid synthesis in mammals. We have developed an efficient method for large-scale synthesis of khafrefungin, and various khafrefungin derivatives were synthesized based on this method. While most of the khafrefungin derivatives lost antifungal activity, a lactone-type derivative had almost the same activity as khafrefungin. We also designed and synthesized derivatives which contain a five- or six-membered ring at the central part of the structure based on NOE experiments of khafrefungin. A macrocyclic khafrefungin derivative was also synthesized, but the antifungal activity was lost. These results suggest that the structure of khafrefungin might be strictly recognized in fungi.     

Flavor mixing in the low energy hadron dynamics: Interplay of theSU f (3) breaking and theU A (1) anomaly

We extend our previous investigation about the flavor mixing or the OZI violating process in the light quark systems with the use of the generalized Nambu-Jona-Lasinio model incorporating theU _A (1) anomaly. The OZI breaking effects newly studied in the meson sector include the and meson decay constants, their couplings with nucleon as well as the masses and the mixing property of the scalar mesons. As for the baryon sector, we reexamine the strangeness content of the proton and the -N sigma term _N by taking into account the interactions between the constituent quarks. It is found that the short-range spin-spin interaction between the quarks gives anO(10 MeV)-enhancement for the theoretical value of the sigma term. Anomalous quark contents of other octet and decuplet baryons (hyperons) are also examined. It is shown that the axial anomaly induces the anomalous quark contents which are not expected in the naive quark model, while the short-range interaction between the quarks acts to suppress (enhance) the quark contents of the decuplet (octet) baryons. All the results indicate that the following picture holds systematically:m _s is so large that (i) the strangeness mixing induced by the anomaly is considerably suppressed and that (ii) the naive chiral perturbation does not work in the strange sector even in the tree level of the meson fields (largeN _c limit). The spin problem of nucleon, which is another subject related to the flavor mixing, is also examined with the use of our effective model.This paper is a modified version of the paper SUNY-NTG-89-49, RYU-THP-89-2 (August 1989)     

Immobilization of enzymes with use of photosensitive polymers having the stilbazolium group

Reaction of the homopolymer of 2-chloroethyl vinyl ether and the copolymer of N-vinylpyrrolidone with stilbazole produced photosensitive polymers. The photocrosslinking mechanism is discussed. Irradiation of a film of the water-soluble photosensitive polymer yielded insolubilized material in which the enzymes were entrapped. The activity of entrapped invertase, glucoamylase, and catalase was 30, 60, and 35%, respectively.     

A novel parallel algorithm for large-scale Fock matrix construction with small locally distributed memory architectures: RT parallel algorithm

We developed a novel parallel algorithm for large-scale Fock matrix calculation with small locally distributed memory architectures, and named it the "RT parallel algorithm." The RT parallel algorithm actively involves the concept of integral screening, which is indispensable for reduction of computing times with large-scale biological molecules. The primary characteristic of this algorithm is parallel efficiency, which is achieved by well-balanced reduction of both communicating and computing volume. Only the density matrix data necessary for Fock matrix calculations are communicated, and the data once communicated are reutilized for calculations as many times as possible. The RT parallel algorithm is a scalable method because required memory volume does not depend on the number of basis functions. This algorithm automatically includes a partial summing technique that is indispensable for maintaining computing accuracy, and can also include some conventional methods to reduce calculation times. In our analysis, the RT parallel algorithm had better performance than other methods for massively parallel processors. The RT parallel algorithm is most suitable for massively parallel and distributed Fock matrix calculations for large-scale biological molecules with more than thousands of basis functions.     

Surface-mediated photoalignment of discotic liquid crystals on azobenzene polymer films

This paper describes a simple strategy for the formation of photoaligned and micropatterned discotic liquid crystal (DLC) film on the surface of photoirradiated azobenzene-containing polymer thin film. The key material for the surface-mediated photoalignment of the DLCs was poly[4-(4-cyanophenylazo)phenyl methacrylate] (pMAzCN). Optical anisotropy was generated in a pMAzCN film by oblique exposure to nonpolarized light which resulted in angle-selective photoisomerization and reorientation of the azobenzenes. Subsequent annealing of the film at 240 degrees C enhanced the photoaligned state of the p-cyanoazobenzenes due to strong intermolecular dipole-dipole interaction and semicrystalline nature of the pMAzCN. This combination of photoirradiation and subsequent annealing of the pMAzCN film made it possible to realize the surface-assisted orientation control of a DLC molecule, which displays both columnar (Col) and discotic nematic (N(D)) phases over 152 degrees C. When the pMAzCN film was exposed to linearly polarized light from the surface normal, the DLC molecules showed homeotropic orientation with the director perpendicular to the substrate surface. In the contrast, oblique irradiation of the pMAzCN film with nonpolarized light gave rise to tilted DLC orientation with well-ordered optical birefringence at the N(D) phase. Rapid cooling from the N(D) phase produced a well-aligned glassy N(D) state at room temperature, which was adequately stable for 10 months even though no covalent cross-linking among the DLCs was performed. The spatial orientation of photoaligned DLCs in both their bulk film and in their interface region was characterized by means of optical birefringence, X-ray diffraction, and fluorescence measurements. At the N(D) phase, the DLC molecules were aligned in a hybrid manner such that their tilt angles varied throughout the thickness of DLC film. The direction of tilted DLCs was opposite to the propagation of the actinic nonpolarized light. The photoaligned DLC films exhibited polarized fluorescence emission with an s-polarized/p-polarized intensity ratio of 4.1, despite the nonpolarized excitation of only DLC at outmost surface. These results indicate that the three-dimensionally aligned azobenzene moieties of the pMAzCN thin film were transferred to the tilted DLC molecules at air/DLC interface. Finally, we demonstrated micrometer-scale photopatterned orientation of DLC molecules on the pMAzCN surface by oblique nonpolarized irradiation of the film through a photomask.     

Some chemical transformations of 7a-cyanohexahydro-1H-pyrrolizine into 7a-substituted hexahydro-1H-pyrrolizines

Chemical transformations of 7a-cyanohexahydro-1H-pyrrolizine ( 2 ) into 7a-substituted hexahydro-1H-pyrrolizines are described. In the reaction of 2 with lithium aluminum hydride, the orientation of the lone pair of the bridgehead nitrogen against C-CN bond can be regarded as significant.     

Solubilization of fullerene into water with fluoroalkyl end-capped amphiphilic oligomers-novel fluorescence properties

Solubilization of fullerene into water was studied by the use of fluoroalkyl end-capped acryloylmorpholine oligomers, N,N-dimethylacrylamide oligomers, and acrylic acid oligomers. In these fluorinated oligomers, fluoroalkyl end-capped acryloylmorpholine oligomers were more effective in solubilizing fullerene into water. Interestingly, the aqueous solutions of fullerene were applicable to fluorescence analyses.