Efficient synthesis of 2-modified 1alpha,25-dihydroxy-19-norvitamin D3 with Julia olefination: high potency in induction of differentiation on HL-60 cells

Six novel 2-substituted analogues of 1alpha,25-dihydroxy-19-norvitamin D(3), 6a,b-8a,b, were efficiently synthesized utilizing (-)-quinic acid as the A-ring precursor. The C2-modified A-rings were prepared as 4-alkylated (3R,5R)-3,5-dihydroxycyclohexanones 12-15 from (-)-quinic acid based on radical allylation at the C4 position of methyl (-)-quinicate. The new type of the CD-ring coupling partner 23 was synthesized from 25-hydroxy Grundmann's ketone 19 to apply to the modified Julia olefination to construct a diene unit between the A-ring and the CD-ring. The coupling yields, including a deprotection step, were 47-62%. After the separation of the diastereomers based on C2 stereochemistry, the structure (2alpha or 2beta) was determined by (1)H NMR experiments and compared to DeLuca's 2-methyl- and 2-ethyl-1alpha,25-dihydroxy-19-norvitamin D(3). Thus, the synthesized 2alpha-(3-hydroxypropyl)-1alpha,25-dihydroxy-19-norvitamin D(3) (8a) showed almost the same potency in binding to the bovine thymus vitamin D receptor (VDR) as the natural hormone 1, while its beta-isomer 8b had only a 3% affinity. Both 2alpha-allyl- and 2alpha-propyl-1alpha,25-dihydroxy-19-norvitamin D(3) (6a and 7a) and their 2beta-analogues (6b and 7b) possessed a weak affinity for the VDR. The strong VDR ligand 8a was ca. 36-fold more potent in induction of HL-60 cell differentiation than 1, and interestingly, even the weaker ligand 8b showed a 6.7-fold higher potency in the cell differentiation activity than that of 1.     

Metallic conductivity and ferromagnetic interaction of iron(III) d spins in the needle crystals of (ethylenedithiotetrathiafulvalenoquinone-1,3-dithiolemethide)(2).FeBr(4) salt

The 2:1 charge-transfer (CT) salts (1(2).FeBr(4) and 1(2).GaBr(4)) of ethylenedithiotetrathiafulvalenoquinone-1,3-dithiolemethide (1) with FeBr(4)(-) and GaBr(4)(-) counteranions were obtained as needle crystals, whose structures are almost the same as each other. The 1 molecules form a one dimensionally stacked column with alternation of their molecular axis direction, while the counteranions are aligned in parallel with the 1-stacked columns with the direction of their distorted-tetrahedral geometry maintained. The room-temperature electrical conductivities measured on the single crystals of 1(2).FeBr(4) and 1(2).GaBr(4) were 4.6 and 2.1 S cm(-1), respectively. From the temperature dependences of their electrical conductivities in both cases the electrical conducting properties were metallic between ca. 170 and 300 K, but below ca. 170 K converted to be semiconducting and continued till 5 K, although the activation energies are very small (4-10 meV). For 1(2).FeBr(4) very weak and antiferromagnetic interaction occurred between the d spins of FeBr(4)(-) ions in the temperature range of ca. 1-300 K. However, below ca. 15 K the ferromagnetic interaction was reversely preferential possibly by participation of the pi spin of 1.     

Convenient synthesis of 3,3,3-trifluoropropenyl compounds from aromatic aldehydes by means of the TBAF-mediated Horner reaction

A simple synthesis of 3,3,3-trifluoropropenyl compounds by means of the TBAF-mediated Horner reaction is described. The reagent, 2,2,2-trifluoroethyldiphenylphosphine oxide, was readily prepared either by Arbuzov reaction of ethyl diphenylphosphinite with 2,2,2-trifluoroethyl iodide or by treating chlorodiphenylphosphine with trifluoroacetic acid and water. Treatment of the phosphine oxide with aromatic aldehydes in the presence of TBAF at room temperature afforded the corresponding 3,3,3-trifluoropropenyl compounds in good yields. The present method is very convenient for preparing 3,3,3-trifluoropropenyl compounds from aromatic aldehydes in terms of availability of the reagent, operational simplicity, and good yields of the products.     

Dioxopyrrolines. LXII. Diels-Alder reaction of 1-Aryl-4- and 5-methoxycarbonyl-1H-pyrrole-2,3-diones with various 1,3-dienes

Two new dioxopyrrolines (1-aryl-4-methoxycarbonyl-1H-pyrrole-2,3-dione 6 and the 5-methoxycarbonyl isomer 8) behaved as good dienophiles to some kind of 1,3-dienes examined. In most cases, the products were explained by the reaction where the largest lobe of HOMO of dienes reacted to the larger LUMO of dienophiles in an expected cis-endo manner. However, in the reactions of 8 with alkylbutadienes, piperylene and isoprene, abnormality in the reaction was observed, which was well explained by taking account of steric factors.     

Miscibility evaluation of SPS/APS blend investigated from crystallization dynamics

The miscibility of crystalline syndiotactic polystyrene (SPS)/non-crystalline atactic polystyrene (APS) blend was estimated by the crystallization dynamics method, which evaluated the nucleation rate, the crystal growth rate and the surface free energy parameter. The melting temperature depression suggested that SPS/APS blends were the miscible system but not in molecular level. The relationship between the blend content and the chemical potential difference evaluated at a constant crystal growth rate showed a good linear relationship. These facts suggested that SPS/APS blends contained the concentration fluctuation with the size between few nm to less than 80 nm. This revised version was published online in July 2006 with corrections to the Cover Date.     

Hydrogel Microchambers Integrated with Organic Electrodes for Efficient Electrical Stimulation of Human iPSC‐Derived Cardiomyocytes

A hydrogel‐based microchamber with organic electrodes for efficient electrical stimulations of human induced pluripotent stem cell‐derived cardiomyocytes (hiPSC‐CMs) is described. The microchamber is made from molecularly permeable, optically transparent, and electrically conductive polyvinyl alcohol (PVA) hydrogel and highly capacitive carbon electrode modified with poly(3,4‐ethylenedioxythiophene) (PEDOT). Spheroids of hiPSC‐CMs are cultured in microchambers, and electrically stimulated by the electrode for maturation. The large interfacial capacitance of the electrodes enables several days of electrical stimulation without generation of cytotoxic bubbles even when the electrodes are placed near the spheroids. The spheroids can be cultivated in the closed microchambers because of the permeated nutrients through the hydrogel, thus the spheroids are stably addressable and the culture medium around the sealed microchambers can be simply exchanged. Synchronized beating of the spheroids can be optically analyzed in situ, which makes it possible to selectively collect electrically responsive cells for further use. As the hydrogel is electrically conductive, the amount of electrical charge needed for maturing the spheroids can be reduced by configuring electrodes on the top and the bottom of the microchamber. The bioreactor will be useful for efficient production of matured hiPSC‐CMs for regenerative medicine and drug screening.     

Conformational Changes and Redox Properties of Bimetallic Single Helicates of Hexapyrrole-α,ω-dicarbaldehydes

The hexapyrrole-α,ω-dicarbaldehydes 1 a and 1 b were metallated with Cu^II, Ni^II, and Pd^II to give bimetallic complexes where a pair of 3 N+O four-coordinate metal planes are helically distorted and the central 2,2′-bipyrrole subunit adopts a cis or trans conformation. X-ray crystallographic analysis of the bisCu complex revealed a closed form with a cis-2,2′-bipyrrole subunit and an open form with a trans-2,2′-bipyrrole subunit. The bisPd complexes took a closed form both in the solid state and in solution. They are regarded as single helicates of two turns and the energy barrier for the interchange between an M helix and a P helix was remarkably influenced by the bulky 3,3′-substituent of the central 2,2′-bipyrrole subunit. Although the bisNi complexes adopt a closed form in the solid state, they exist as a homohelical open C₂-symmetric form or a heterohelical open C_i-symmetric form in solution. A theoretical study suggested that the closed form of 1 a Pd was stabilized by the Pd–Pd interaction. Compound 1 a Pd was reversibly oxidized by one electron at 0.14 V versus ferrocene/ferrocenium (Fc/Fc⁺) and this oxidized species showed Vis/NIR absorption bands at λ=767 and 1408 nm.     

Asymmetric Aza-Diels–Alder Reaction with Ion-Paired—Iron Lewis Acid—Brønsted Acid Catalyst

The development and use of a multiple-activation catalyst with ion-paired Lewis acid and Brønsted acid in an asymmetric aza-Diels–Alder reaction of simple dienes (non-Danishefsky-type electron-rich dienes) was achieved by utilizing the [FeBr₂]⁺[FeBr₄]⁻ combination prepared in situ from FeBr₃ and chiral phosphoric acid. Synergistic effects of the highly active ion-paired Lewis acid [FeBr₂]⁺[FeBr₄]⁻ and a chiral Brønsted acid are important for promoting the reaction with high turnover frequency and high enantioselectivity. The multiple-activation catalyst system was confirmed using synchrotron-based X-ray absorption fine structure measurements, and theoretical studies. This study reveals that the developed catalyst promoted the reaction not only by the interaction offered by the ion-paired Lewis acid and the Brønsted acid but also noncovalent interactions.     

Self-ordering process of phenanthrene polyesters observed by the simultaneous DSC-XRD method

Phase transition behavior of polyesters derived from 2,7-phenanthrene dicarbonic acid diethylester and alkanediols with even methylene carbon number was investigated by the simultaneous DSC-XRD method. The smectic A phase was observed on cooling from the molten state. The transition entropy from the isotropic state to the smectic A phase was about 9.0 J mol^-1 K^-1, which depended on the methylene carbon number. The linear expansion coefficients, based on the (001) spacing of the crystalline phase at room temperature, were 1.3·10^-4 K^-1 (crystalline phase), 5.7·10^-4 K^-1 (crystallization region), 1.7·10^-3 K^-1 (smectic A phase) during cooling, and 1.5·10^-4 K^-1 (crystalline phase), and 1.0·10^-3K^-1(melting region) on heating. This revised version was published online in July 2006 with corrections to the Cover Date.