Stereocontrolled synthesis of the IJK ring segment of yessotoxin

A stereocontrolled synthesis of the IJK ring segment of yessotoxin is described. Cyclization of 11 mediated by SmI₂ gave the IJ ring system 12 as the sole product. Construction of the K ring moiety was performed by the acid catalyzed cyclization of epoxy alcohol 20 to afford the IJK ring segment in a highly stereocontrolled manner.     

Flavour issues for string-motivated heavy scalar spectra with a low gluino mass: the G 2-MSSM case

In recent years it has been learned that scalar superpartner masses and trilinear couplings should both generically be larger than about 20?TeV at the short-distance string scale if our world is described by a compactified string or M-theory with supersymmetry breaking and stabilized moduli (Acharya et?al. in arXiv:1006.3272 [hep-ph], 2010). Here we study implications of this, somewhat generally and also in detail for a particular realization (compactification of M-theory on a G ₂ manifold) where there is significant knowledge of the superpotential and gauge kinetic function, and a light gluino. In a certain sense this yields an ultraviolet completion of minimal flavour violation. Flavour violation stems from off-diagonal and non-universal diagonal elements of scalar mass matrices and trilinear couplings, and from renormalization group running. We also examine stability bounds on the scalar potential. While heavy scalars alone do not guarantee the absence of flavour problems, our studies show that models with heavy scalars and light gluinos can be free from such problems.     

Chemical constituents of Blumea balsamifera of Indonesia and their protein tyrosine phosphatase 1B inhibitory activity

A methanol extract of the leaves of Blumea balsamifera (L.) DC. (Asteraceae) afforded a new guaian-type sesquiterpene, epiblumeaene K (1), together with four known guaian-type sesquiterpenes (2-5), three known sesquiterpenes (6-8), and nine known flavonoids (9-17) by a combination of chromatography and preparative TLC techniques. Their structures were elucidated by extensive spectroscopic methods and comparison with the literature data. Among the isolated compounds, a known sesquiterpene, beta-caryophyllene 8R,9R-oxide (6), exhibited a significant PTP1B inhibitory activity in a dose-dependent manner, with an IC50 value of 25.8 microM (5.62 microg/mL).     

Curvature-dependent excitation propagation in cultured cardiac tissue

The geometry of excitation wave front may play an important role on the propagation block and spiral wave formation. The wave front which is bent over the critical value due to interaction with the obstacles may partially cease to propagate and appearing wave breaks evolve into rotating waves or reentry. This scenario may explain how reentry spontaneously originates in a heart. We studied highly curved excitation wave fronts in the cardiac tissue culture and found that in the conditions of normal, non-inhibited excitability the curvature effects do not play essential role in the propagation. Neither narrow isthmuses nor sharp corners of the obstacles, being classical objects for production of extremely curved wave front, affect non-inhibited wave propagation. The curvature-related phenomena of the propagation block and wave detachment from the obstacle boundary were observed only after partial suppression of the sodium channels with Lidocaine. Computer simulations confirmed the experimental observations. The explanation of the observed phenomena refers to the fact that the heart tissue is made of finite size cells so that curvature radii smaller than the cardiomyocyte size loses sense, and in non-inhibited tissue the single cell is capable to transmit excitation to its neighbors.     

An Expansion of Crystalline Sponge X-ray Analysis to Elucidate the Molecular Structure of Reactive Compounds via Ion Pair Formation

The crystalline sponge (CS) method allows structural elucidation of a target compound (guest) in solution by single crystal X-ray diffraction through trapping the guest into the CS framework. In principle, the CS method is inapplicable to reactive compounds that break the CS framework, such as acidic, basic, or nucleophilic ones. Here, a solution to this problem is disclosed wherein an ion pair of the guest compound is formed during the guest-soaking step by adding a suitable reagent. The ion pair can be observed and does not damage the CS framework. Using the developed method, amino, guanidino, and amidino compounds have been successfully analyzed as ion pairs with sulfonic acids. Practical utility has been shown because the absolute configurations of optically resolved amine derivatives were revealed with only a few micrograms. This demonstrates that the ion-pair-soaking method is simple and expands the range of compounds applicable to the CS method.     

Constituents of Zingiber aromaticum and their CYP3A4 and CYP2D6 inhibitory activity

A new sesquiterpene 2,9-humuladien-6-ol-8-one (1) was isolated from methanol extract of Zingiber aromaticum, along with 15 known compounds. The structures of the isolated compounds were elucidated on the basis of spectroscopic analyses. The isolated compounds were tested for their inhibitory activity on the metabolism mediated by cytochrome P450 3A4 (CYP3A4) and CYP2D6.     

Photocontrolled microphase separation of block copolymers in two dimensions

A novel ABA-type triblock copolymer, where A and B correspond to azobenzene (Az) containing polymethacrylate and poly(ethylene oxide) (PEO), respectively, was synthesized by atom transfer radical polymerization. Langmuir-Blodgett monolayers showed characteristic microphase separation structures depending on the isomerization state of the Az unit. The trans-to-cis isomerization induced an anisotropic elongation of the domain of the Az polymer parallel to the rod maintaining the width. Thus, successful photocontrol of nanostructures formed by the block copolymer in the two dimensions was performed. A plausible model for the Az packing and PEO conformation is proposed.     

Convergent total syntheses of gambierol and 16-epi-gambierol and their biological activities

The convergent total syntheses of gambierol (1) and 16-epi-gambierol (2) have been achieved. The ABC and FGH ring segments 4 and 5 were prepared from known compounds 6 and 13, respectively, by linear manners. The fragments prepared were connected by our own synthetic strategy including the intramolecular allylation of alpha-acetoxy ether followed by ring-closing metathesis to furnish the octacyclic ether 3. The diiodoalkene 45, prepared from 3, was converted to the Z-iodoalkene 50 via a novel and stereoselective hydrogenolysis followed by deprotection. Construction of the triene side chain was performed by the modified Stille coupling of 50 with the Z-vinylic stannane 41 to afford 1. The similar transformations were carried out on the epimeric octacycle 34 to give 2, which showed no toxicity against mice at the concentration of 14 mg/kg.     

Constituents of the roots of Cynanchum bungei Decne. Isolation and structures of four new glucosides, bungeiside-A, -B, -C, and -D.

Four new glucosides, bungeiside-A, -B, -C, and -D, were isolated from the roots of Cynanchum bungei Decne. The structures of the new compounds were determined by chemical and spectroscopic methods, including two-dimensional nuclear magnetic resonance (2D NMR) techniques, especially 1H-detected heteronuclear multiple-bond multiple-quantum coherence.     

(Thio)Amidoindoles and (Thio)Amidobenzimidazoles: An Investigation of Their Hydrogen‐Bonding and Organocatalytic Properties in the Ring‐Opening Polymerization of Lactide

The mechanism of the ring‐opening polymerization (ROP) of lactide catalyzed by two partner hydrogen‐bonding organocatalysts was explored. New amidoindoles 4 a , c , thioamidoindoles 4 b , d , amidobenzimidazoles 5 a , c , and thioamidobenzimidazoles 5 b , c were synthesized and used as activators of the monomer. In the solid state and in solution, compounds 4 and 5 showed a propensity for self‐association, which was evaluated. (Thio)Amides 4 and 5 do catalyze the ROP of lactide in the presence of a cocatalyst, tertiary amine 3 a or 3 b , which activates the growing polymer chain through hydrogen‐bonding. Reactions were conducted in 2–24 h at 20 °C; conversion yields ranged between 22 and 100 %. A detailed study of the intermolecular interactions undertaken between the participating species showed that, as expected, simultaneous weak hydrogen bonds do exist to activate the reagents. Moreover, interactions have been revealed between the partner catalysts 4 / 5 + 3 . ROP catalyzed by these partner activators is thus governed by multiple dynamic equilibria. The latter should be judiciously adjusted to fine‐tune the catalytic properties of (thio)amides and organocatalysts, more generally.