Ion-exchange selectivity of anion exchange resin modified with polystyrenesulfonic acid.

In order to change the ion-exchange selectivity of anion-exchange resin, the surface of a gel-type anion exchange resin was modified with anionic polyelectrolyte, polystyrenesulfonic acid. Using this modified resin, the ion-exchange rate of nitrate was little decreased, but that of sulfate was evidently decreased. It is considered that the ion-exchange reaction of the multivalent anion is suppressed by the greater electrostatic repulsive force against the modification layer than that against the monovalent anion. Thus, this modified resin may be suitable for the selective separation of monovalent anions. The influence of the modified condition on the ion-exchange rate was examined. Furthermore, this modified resin was used to separate nitrate ions from sulfate ions in the aqueous solution.     

Diastereoselective synthesis of new psi[(E)-CH=CMe]- and psi[(Z)-CH=CMe]-type alkene dipeptide isosteres by organocopper reagents and application to conformationally restricted cyclic RGD peptidomimetics

Diastereoselective synthesis of new psi[(E)-CH=CMe]- and psi[(Z)-CH=CMe]-type alkene dipeptide isosteres corresponding to dipeptides having one N-methylamino acid, and application to bioactive peptides, are described. In a key reaction introducing the chiral alpha-alkyl group of the isosteres, organocopper-mediated alkylation of syn-beta-methylated gamma-mesyloxy-alpha,beta-enoate 26a afforded E- and Z-isomers of anti-S(N)2' products in a solvent-dependent manner. The resulting two isosteres, D-Phe-psi[(E)-CH=CMe]-L-Val 27a and D-Phe-psi[(Z)-CH=CMe]-L-Val 28b, which corresponded to trans- and cis-conformers of D-Phe-L-MeVal, respectively, were utilized in a structure-activity relationship study on cyclic RGD peptides 1 and 2, in company with a psi[(E)-CH=CH]-type alkene dipeptide isostere, D-Phe-psi[(E)-CH=CH]-L-Val. The cyclic isostere-containing pseudopeptides 3, 4, and 40 were synthesized and biological activity against integrin alpha(V)beta(3) and alpha(IIb)beta(3) receptors were also evaluated.     

Excited states of porphyrin isomers and porphycene derivatives: a SAC-CI study

Excited states of free-base porphyrin isomers, porphycene (Pc), corrphycene (Cor), and hemiporphycene (hPc), were studied by the Symmetry-Adapted Cluster (SAC)/SAC-Configuration Interaction (CI) method. The absorption peaks of the porphyrin isomers were assigned on the basis of the SAC-CI spectra. The X, Y, X', and Y' bands of the porphyrin isomers, which have weak intensities, are identified. The differences in the Q-band absorptions among the isomers were clearly explained by the four-orbital model. In Cor and hPc, the wave function of the B-band corresponds to the mixture of the four-orbital excitations and the optically forbidden excitation of free-base porphin (P), due to the molecular symmetry lowering in the isomers. The B-band character is described by the five-orbital model in Pc and the six-orbital model in Cor and hPc. Two tetrazaporphycenes and two ring-extended (dibenzo) porphycenes were designed, and the Q-band transition moment was successfully controlled. These examples show that the control of the four-orbital energy levels is the guiding principle for pigment design in porphyrin compounds.     

Spirostane derivatives highly oxygenated at A and B rings from the rhizomes of rohdeajaponica roth and of campylandra aurantiaca baker

Two steroidal compounds BR-1 (I) and ?2 (II) which had been obtained from the rhizomes of $\text{Campylandra aurantiaca}$ Baker, were isolated also from those of $\text{Rohdea japonica}$ Roth. They were identified, respectively, by X-ray analysis and chemical correlation as 1β,2β,3β,4β,5β,7α-hydroxy-spirost-25(27)-en-6-one and its corresponding 6β-hydroxy compound.     

Application of samarium diiodide (SmI2)-induced reduction of gamma-acetoxy-alpha,beta-enoates with alpha-specific kinetic electrophilic trapping for the synthesis of amino acid derivatives

Gamma-acetoxy-alpha,beta-enoates were easily reduced by samarium diiodide (SmI2) in THF to generate samarium dienolates which were kinetically trapped with ease at their alpha-positions by electrophiles (proton, aldehydes or ketones) to yield (E)-alkene dipeptide isosteres or gamma-amino acid derivatives in high chemical yields.     

SmI2-mediated reduction of gamma,gamma-difluoro-alpha,beta-enoates with application to the synthesis of functionalized (Z)-fluoroalkene-type dipeptide isosteres

A samarium diiodide (SmI(2))-mediated reduction of gamma,gamma-difluoro-alpha,beta-enoates (15, 29, and 34) was successfully applied to the synthesis of (Z)-fluoroalkene dipeptide isosteres (23, 30, and 35), which have served as potential dipeptide mimetics. Reduction of the gamma,gamma-difluoro-alpha,beta-enoates by SmI(2) proceeded via successive two-electron transfers to form dienolate species which upon kinetically controlled trapping with t-BuOH yielded Xaa-Gly-type fluoroalkene isosteres exemplified by 23, 30, and 35. Replacement of the t-BuOH kinetic trapping agent with aldehydes or ketones provided access to alpha-substituted fluoroalkene isosteres (43 and 45) through aldol reactions of Sm-dienolates with the carbonyl compounds. Of particular note, the use of the SmI(2)-HCHO reagent system with chiral enoate 34 provided D-Phe-psi[(Z)-CF[double bond]CH]-D/L-Ser isosteres (45), which could be converted to enantiomerically pure isosteres (49-52) that bore a variety of side chain functionalities at the alpha-position. This was achieved by a sequence of manipulations consisting of beta-lactone formation followed by chromatographic separation and ring-opening with soft nucleophiles. Included in the present work is the first utilization of a Rh-catalyzed Reformatsky reaction of chiral imines for the stereoselective preparation of alpha,alpha-difluoro-beta-amino acid derivatives (28 and 33). The appropriate choice of reagents (carbonyl compounds for kinetic trapping or ring-opening nucleophiles and imines for Reformatsky reactions) allows the presented methodology to yield various fluoroalkene isosteres possessing a wide range of side chain functionalities.     

Diastereoselective synthesis of psi[(E)-CH=CMe]- and psi[(Z)-CH=CMe]-type dipeptide isosteres by organocopper-mediated anti-S(N)2' reaction

[reaction: see text] Acyclic psi[(E)-CH=CMe]- and psi[(Z)-CH=CMe]-type dipeptide isosteres were efficiently synthesized. In a key reaction, alpha-alkylation of gamma-mesyloxy-beta-methyl-alpha,beta-unsaturated esters with organocyanocuprates in diethyl ether or tetrahydrofuran preferentially afforded the psi[(E)-CH=CMe]- or psi[(Z)-CH=CMe]-isomer, respectively, via anti-S(N)2' mechanism.     

Dynamics of order formation by colloidal adsorption onto a substrate studied with Brownian dynamics

Colloidal adsorption and spontaneous ordering of adsorbed particles on a substrate was simulated using a three-dimensional simulation model for colloidal dispersion system with an adsorptive surface under a specified bulk concentration, where the particle-particle and particle-substrate interactions were modeled on the DLVO theory. The key process for order formation is considered to be the adsorption of a particle that induces the transition from incomplete order to perfect order, and is found to involve a stochastic nature due to an energy barrier which must be overcome for the system to reach ordered state. Also, a model was developed to predict the energy barrier for order formation based on direct observation of the key process. Further, a model to describe the stochastic nature of the process was developed and its quantitative validity was demonstrated. Through the examination of the key process, it is concluded that the mechanism of the order formation is composed of two successive processes and the rate-determining step varies depending on the ionic strength.     

Synthesis of potent beta-secretase inhibitors containing a hydroxyethylamine dipeptide isostere and their structure-activity relationship studies

Several beta-secretase inhibitors were designed based on hydroxyethylamine dipeptide isostere (HDI) structures and were synthesized by a methodology using the aza-Payne rearragement and O,N-acyl transfer reactions to study their structure-activity relationships. Among these pseudopeptides, effective compounds were developed as the first beta-secretase inhibitors containing the HDI transition state mimic with potent enzyme inhibitory activity (IC50 < 100 nM).