Excess Volumes of Water + Acetonitrile and Water + Dimethylsulfoxide at 30°C and the Effect of the Excess Thermal Expansivity Coefficients on Derived Thermodynamic Properties

Excess molar volumes of water + acetonitrile, and water + dimethylsulfoxide mixtures were measured at 30°C. Excess thermal expansivity coefficients ^E were calculated from values of at 30° and 25°C previously reported.^(1,2) The ^E of polar mixtures are relatively large, several times 10^-5 K^-1 and as much 10^-4 K^-1, while those of nonpolar mixtures are at most several times 10^-6 K^-1. These values are several percent of the total expansivity coefficient of the mixture and significantly affect thermodynamic calculation of the estimation of isothermal compressibilities and isochoric heat capacities from isentropic compressibilities and isobaric heat capacities.     

Control of stepwise radial complexation in dendritic polyphenylazomethines

The fourth generation of a dendritic polyphenylazomethine (DPA G4) has 2, 4, 8, and 16 imine groups in the first, second, third, and fourth shells, respectively (total, 30 imine groups). DPA G4 can trap 30 equiv of SnCl(2) molecules, because the imine group is complexed with SnCl(2) at a ratio of 1:1. During addition of 30 equiv of SnCl(2) to DPA G4, four shifts in the isosbestic point were observed in the UV-vis spectra, and the amount of SnCl(2) added in each step is in agreement with the number of imine groups in each shell of DPA G4. This result shows that the complexation of the imine groups in DPA G4 with SnCl(2) occurs stepwise in the order of the first, second, third, and fourth shells. The unique stepwise complexation was also observed in DPA G2 and G3 as two and three shifts of the isosbestic point, respectively. The stepwise complexation was supported by TEM, NMR, and a novel shell-selective reduction (SSR) method for imines. An expansion in the molecular size of DPA G4 by the complexation was revealed by molecular modeling and TEM measurements. The stepwise complexation is caused by the different basicity of the imine groups between the shells, which was supported by the chemical shifts of the peaks attributed to the imine carbons in the (13)C NMR spectra. The gradients in the basicity were controlled by the introduction of electron-withdrawing or -releasing groups to the core of the dendrimers; the core imines were complexed last in DPAs having a 2,3,5,6-tetrafluoro or 2,5-dichlorophenyl core due to the low basicity of the core imines. The different complexation pattern was also clearly confirmed by the SSR method.     

Facile synthesis of 6a-carbaprostaglandin i2

The optically active 6a-carbaprostaglandin I₂ (2), a stable mimic of natural prostacylin (1), was synthesized from the lactone 4 or the hydroxy acid 5, which were general synthetic intermediates for natural prostaglandins.     

Bis[3-(triethoxysilyl)propyl]tetrasulfide: the first liquid sulfur-transferring agent useful for conversion of nucleoside phosphites to the phosphorothioates

This paper describes bis[3-(triethoxysilyl)propyl]tetrasulfide, which is the first liquid sulfur-transferring agent useful for the conversion of nucleoside phosphite intermediates in the synthesis of the phosphorothioates using a phosphoramidite strategy. This liquid reagent is preferable to existing solid sulfur-transferring agents, because it enables solid-phase synthesis with an automated DNA/RNA synthesizer, while avoiding the risk of accumulation of reagent deposits in the delivery tubes and valves of the synthesizer during sulfurization.     

Analysis of exponent values in Gaussian‐type functions for development of protonic and deuteronic basis functions

We analyzed the exponent (α) values in Gaussian‐type functions (GTF) for protons and deuterons in BH₃, CH₄, NH₃, H₂O, HF, and their deuterated molecules for the development of nuclear basis functions, which are used for molecular orbital (MO) calculations that directly include nuclear quantum effects. The optimized α (α_opt) value in the single s‐type ([1s]) GTF for protons is changed due to the difference in flexibility of the electronic basis sets. The difference between the energy obtained by using the α_opt value for each molecule and that obtained by using the average α (α_ave) value for these exponents with the 6‐31G(d,p) electronic basis function is only 2 × 10^?5 a.u. The α_ave values of protonic and deuteronic [1s] GTFs by the present calculation are 24.1825 and 35.6214, respectively. We found that the α_ave values enable the evaluation of the total energy and the geometrical changes in hydrogen bonding, such as O…H? O, O…H? N, and O…H? C, while the α_opt value became small by forming a hydrogen bond. The result using only the [1s] GTF for the protonic and deuteronic basis functions is sufficient to explain the differences of energy and geometry induced by the H/D isotope effect, although the total energy of ～5 × 10^?4 a.u. was improved by using the s‐, p‐, and d‐type ([1s1p1d]) GTFs for protons and deuterons. We clearly demonstrate that the protonic and deuteronic basis functions based on the α_ave value enable us to apply the method to other sample molecules (glycine, malonaldehyde, and formic acid dimer). The protonic and deuteronic basis functions we developed treat the quantum effects of protons and deuterons effectively and extend the application range of the MO calculation to include nuclear quantum effects. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2006     

Stereocontrolled synthesis of 8,11-dideoxytetrodotoxin, an unnatural analogue of puffer fish toxin

8,11-Dideoxytetrodotoxin, an unnatural tetrodotoxin analogue, was synthesized in a highly stereoselective manner from a common intermediate from our synthetic studies on tetrodotoxin. The key features in the synthesis were as follows: neighboring group participation of a trichloroacetamide to allow regioselective and stereoselective hydroxylation, protection of a delta-hydroxylactone as an ortho ester, and guanidine installation through the use of Boc-protected isothiourea. Global deprotection of the fully protected intermediate under acidic conditions gave 8,11-dideoxytetrodotoxin, which exhibited very weak biological activities.     

Lithium intercalation in layer structured compound β-ZrNCl

A layer structured crystal -ZrNCl forms a lithium intercalation compound Li_xZrNCl. The upper limit for x determined on the compound prepared by the n-butyl lithium technique is 0.29. In the electrochemical process, a pressed -ZrNCl cathode is further reduced up to x=11.25 at potentials as low as 0.80.6 V relative to Li/Li⁺. The lithium intercalate swells in various polar solvents, increasing the basal spacing. However, in contrast to the salt-like intercalates of transition metal chalcogenides and FeOCl, the lithium intercalated -ZrNCl does not form hydration phases, but reacts with water, evolving hydrogen. These results can be interpreted in terms of the formation of an alloy-like intercalate like the alkali intercalates of graphite. On intercalation, -ZrNCl is changed from pale yellow-green to black in color, and the electrical conductivity increases by a factor of 10⁶.     

Orally active CCR5 antagonists as anti-HIV-1 agents: synthesis and biological activity of 1-benzothiepine 1,1-dioxide and 1-benzazepine derivatives containing a tertiary amine moiety

The search for orally active CCR5 antagonists was performed by chemical modification of the 1-benzothiepine 1,1-dioxide 3 and 1-benzazepine 4 lead compounds containing a tertiary amine moiety. Replacement of methyl group with a 2-(C(2-4) alkoxy)ethoxy group at the 4-position on the 7-phenyl group of the 1-benzothiepine ring resulted in both enhanced activity and significant improvement in the pharmacokinetic properties upon oral administration in rats. Introduction of C(2-4) alkyl, phenyl or (hetero)arylmethyl groups as the 1-substituent on the 1-benzazepine ring together with the 2-(butoxy)ethoxy group led to further increase of activity. Among the 1-benzazepine derivatives, the isobutyl (6i), benzyl (6o) or 1-methylpyrazol-4-ylmethyl (6s) compounds were found to exhibit highly potent inhibitory effects, equivalent to the injectable CCR5 antagonist 1, in the HIV-1 envelope-mediated membrane fusion assay. In particular, compound 6s showed the most potent CCR5 antagonistic activity (IC(50)=2.7 nM) and inhibitory effect (IC(50)=1.2 nM) on membrane fusion, together with good pharmacokinetic properties in rats. The synthesis of 1-benzothiepine 1,1-dioxide and 1-benzazepine derivatives and their biological activity are described.     

Model experiments on surugatoxin synthesis. an approach in the construction of the pentacyclic ring system

Synthesis of the ethyl ester 2a of the debromo-aglycone of surugatoxin 1 has been achieved in 10 steps starting from readily available ethyl 2-(2-oxo-3-indolenyl)-3-oxo-4-phthalimidobutyrate 3.