Evaluation of the abilities of ��-cyclodextrin to form complexes by surface plasmon resonance with a Biacore? system

Although phase-solubility studies have often been used to evaluate the interaction of cyclodextrins (CDs) with various drugs, hundreds of milligrams of both CD and drug are required to prepare a phase diagram. A method that would require considerably less material for evaluating complex formation between a CD and guest compound is therefore needed. We previously reported the detection of the interactions between ??-CD and various drugs using a Biacore^® system. In this study, we succeeded in immobilizing 6-monodeoxy-6-monoamino-??-CD on the gold surface of a sensor chip and in detecting the interactions between the immobilized ??-CD and various drugs. The interaction processes were kinetically analyzed using Biacore^®. The surface plasmon resonance sensorgrams indicated that the association and dissociation rates of the interactions between ??-CD and drugs were faster than those between ??-CD and drugs. Although the association constants calculated from the sensorgrams were smaller than those calculated from phase-solubility studies, good correlation was shown between these data.     

Bioinert surface to protein adsorption with higher generation of dendrimer SAMs

Interactions between proteins and biomaterial surfaces correlate with many important phenomena in biological systems. Such interactions have been used to develop various artificial biomaterials and applications, in which regulation of non-specific protein adsorption has been achieved with bioinert properties. In this research, we investigated the protein adsorption behavior of polymer brushes of dendrimer self-assembled monolayers (SAMs) with other generations. The surface adsorption properties of proteins with different pI values were examined on gold substrates modified with poly(amidoamine) dendrimer SAMs. The amount of fibrinogen adsorption was greater than that of lysozyme, potentially because of the surface electric charge. However, as the generations increased, protein adsorption decreased regardless of the surface charge, suggesting that protein adsorption was also affected by density of terminal group.     

Synthesis of aspergillide A via proline-catalyzed trans-to-cis isomerization of a substituted tetrahydropyran

The transformation of a common synthetic intermediate of aspergillides B and C into aspergillide A, a cytotoxin produced by a marine-derived fungus, has been accomplished in an eleven-step sequence involving an efficient proline-catalyzed isomerization of a 2,6-trans-substituted tetrahydropyran-2-acetaldehyde intermediate into the corresponding cis isomer and the Yamaguchi macrolactonization as the key steps.     

Enhancement of water solubility of fullerene by cogrinding with mixture of cycloamyloses, novel cyclic alpha-1,4-glucans, via solid-solid mechanochemical reaction

Improvement of solubility for fullerene (C60) was studied by cogrinding with cycloamyloses using a ball mill in the solid state. Cycloamylose is a novel cyclic alpha-1,4-glucan produced from synthetic amylose by enzymatic reaction. Although sample solutions showed a pale yellow for the initial period of cogrinding with cycloamyloses and C60, the color varied to brown after 48 h. Subsequently, the solubility of C60 was improved markedly to 560 (microg/ml) at 96 h. From powder X-ray diffraction analysis, the peak intensity of crystalline C60 decreased as the cogrinding time was extended. The UV-VIS absorption spectrum of C60 shows absorption bands at 262 and 340 nm in water with cycloamyloses, and 258 and 328 nm in n-hexane. These results suggested that C60 molecules were dispersed into cycloamyloses micellar system and the red-shift of the UV-VIS spectra was due to an intermolecular interaction between C60 and cycloamyloses.     

Concise synthesis of anti-HIV-1 active (+)-inophyllum B and (+)-calanolide A by application of (-)-quinine-catalyzed intramolecular oxo-Michael addition

(-)-Quinine-catalyzed intramolecular oxo-Michael addition (IMA) of 7-hydroxy-5-methoxy-8-tigloylcoumarins was developed for the enantioselective construction of 2,3-dimethyl-4-chromanone systems in the context of the asymmetric synthesis of anti-HIV-1 active Calophyllum coumarins. Combination of the IMA and MgI(2)-assisted demethylation of the 5-methoxy group along with isomerization of the formed chromanone systems as key steps successfully led to the concise synthesis of (+)-inophyllum B and (+)-calanolide A, possible candidates for AIDS drugs. Further examination of the asymmetric IMA with cinchona alkaloids lacking a methoxy group on the quinoline skeleton suggested the influence of the methoxy substituent on stereoselectivity at the stereogenic centers of the chromanone systems.     

Enantioselective alkynylation of carbonyl compounds with trimethoxysilylalkynes catalyzed by lithium binaphtholate

Enantioselective alkynylation of aldehydes and ketones was accomplished using trimethoxysilylalkynes as alkynylating reagents and lithium 3,3′-diphenylbinaphtholate as a catalyst. Optically active propargylic alcohols were obtained in good to high chemical yields and enantioselectivities. Alkynylation of acetylpyridines afforded biologically active pyridyl propargylic alcohols in good enantioselectivities.     

An effective synthesis of N,N-dimethylamides from carboxylic acids and a new route from N,N-dimethylamides to 1,2-diaryl-1,2-diketones

Carboxylic acids were heated at 150 °C in DMF in the presence of 1.25 equiv of thionyl chloride to give corresponding N,N-dimethylamides in good yields. Tandem chlorination and amidation reactions occurred in the one-pot procedure. Dicarboxylic acids needed prolonged reaction time to produce bisamides in good yields. Some benzamides were efficiently converted into corresponding 1,2-diaryl-1,2-diketones (benzils) under acyloin condensation conditions in the presence of 4,4′-di-tert-butylbiphenyl (DBB) in THF. Ultrasonic irradiation effectively accelerates the reaction, but it is not critical. However, the presence of DBB is fatal to the reaction. Although a few synthetic methods for benzils from benzoic acids have been reported so far, this method is one of the most convenient and highly reproducible procedures.     

Enantioselective visualization of <Emphasis Type="SmallCaps">D</Emphasis>-alanine in rat anterior pituitary gland: localization to ACTH-secreting cells

The cellular localization of D-alanine (D-Ala) in the rat pituitary gland, the tissue containing the highest amount of D-Ala, has been clarified for the first time by enantioselective visualization of D-Ala using our own established mouse monoclonal antibody against D-Ala. D-Ala immunopositive cells were present predominantly in the anterior lobe, while no intense staining was observed in the intermediate and posterior lobes. The anterior pituitary gland contains five types of cells secreting specific hormones (growth hormone, adrenocorticotropic hormone (ACTH), gonadotropic hormone, prolactin, and thyroid-stimulating hormone), and the double staining results indicated that D-Ala is localized to the ACTH-secreting cells. The localization of D-Ala is clearly different from that of D-aspartic acid (D-Asp), which is observed in the prolactin cells. Considered together with our previous findings that D-Ala is localized to the insulin-secreting beta-cells in the pancreas, and both ACTH and insulin are typical regulatory hormones of blood glucose, D-Ala is suggested to have some functional relationships to blood glucose level regulation in mammals.