We isolated five different phage clones containing histone gene clusters with up to five H1 genes per phage clone from a Mytilus edulis genomic library. Among these H1 genes, nine gene types coding for five different H1 proteins have been identified. All H1 histone genes were located on repetitive restriction fragments with only slightly different sizes. The H1 coding regions show highly related sequences, suggesting that the multitude of H1 genes has evolved by gene duplication events. Core histone genes could not be found on these five Mytilus edulis genome fragments.

A series of picolinamide- and pyrimidine-4-carboxamide-based inhibitors of 11β-hydroxysteroid dehydrogenase type 1 was synthesized and evaluated to optimize the lead compound 9. The combination of the replacement of a pyridine ring of 9 with a pyrimidine ring and the introduction of an additional fluorine substituent at the 2-position of the phenyl ring resulted in the discovery of a potent, selective, and orally bioavailable inhibitor, 18a (SKI2852), which demonstrated no CYP and PXR liabilities, excellent PK profiles across species, and highly potent and sustainable PD activity. Repeated oral administration of 18a significantly reduced blood glucose and HbA1c levels and improved the lipid profiles in ob/ob mice. Moreover, the HbA1c-lowering effect of metformin was synergistically enhanced in combination with 18a.

A ternary coupling of norbornadiene and iodonium salts or diazonium salts with organostannanes, alkynes, or sodium tetraphenylborate catalyzed by ligand-free palladium was accomplished at ambient temperature under mild conditions. Combination of the Heck-type arylation of olefins with palladium-catalyzed cross-coupling reactions (the so called three-component coupling reaction or ternary coupling reaction) is an important methodology to construct complex molecules directly, 1 especially to construct the prostaglandin analogues. However, there was a restriction in the applicable olefins which have high insertion and no effect in β -elimination. Previously the palladium-catalyzed three-component coupling of organic halides and organostannanes, alkynes, or tetraphenylborate ion was restricted to norbornene. Kosugi et al. 2 reported the coupling of norbornadiene in the ternary coupling with organostannanes. Recently, Kosugi et al. 3 reported that 1,3-dioxole was utilized as the olefin in this coupling. In connection with our programs to utilize iodonium salts and diazonium salts in palladium-catalyzed cross-coupling, 4 we have investigated the ternary coupling of iodonium salts 5 and diazonium salts 6 with norbornadiene in the presence of organostannanes, alkynes, and sodium tetraphenylborate. Here, we wish to report the mild ternary coupling and carbonylative coupling of norbornadiene and iodonium or diazonium salt with organostannanes, alkynes, and sodium tetraphenylborate (Scheme).The results of the ternary coupling of norbornadiene and diphenyliodonium tetrafluoroborate with organostannanes, phenylacetylene, sodium tetraphenylborate, and phenylboronic acid catalyzed by palladium acetate are summarized in Table 1. When norbornadiene ( 1 ) (2 equiv) was reacted with diphenyliodonium tetrafluoroborate (1 equiv) in anhydrous DMF in the presence of Pd(OAc) 2 (5 mol %) at room temperature followed by addition of tributylphenylstannane (1 equiv) in DMF slowly via a syringe pump for 1 h and then stirred for 1 hour at room temperature, the coupled product 8a was obtained in 84% yield (entry 1 in Table 1). By the same method, alkynyltributylstannane 4b was also coupled to give compound 9 (entry 2). Alternatively, norbornadiene ( 1 ) was also coupled with phenylacetylene ( 5 ) to afford 9 in 76% yield (entry 3). This is the combination of Heck and Sonogashira reactions. Heck addition followed by coupling with a nucleophile was accomplished with sodium tetraphenylborate (entry 4). Sodium tetraphenylborate ( 6 ) was coupled to norbornadiene ( 1 ) with diphenyliodonium tetrafluoroborate ( 2 ) to afford 8a in 72% yield. However, Heck addition of 2 to norbornadiene ( 1 ) followed by Suzuki-type addition gave the coupled product 8a in a low yield (38%) (entry 5). It is notable that biscarbonylative ternary coupling was carried out at atmospheric pressure of CO with NaBPh 4 ( 6 ) to afford diketone 10 7 in 73% yield (entry 6). The use of PhB(OH) 2 ( 1 ) instead of NaBPh 4 ( 6 ) afforded diketone 10 in 32% yield (entry 7).This ter...

High dielectric constant (Ba0.65Sr0.35)(Ti0.41Zr0.59)O3 (BSTZ) thin films were prepared on Pt/Ti/SiO2/Si substrates at 500 °C from the target composition of (Ba0.65Sr0.35)(Ti0.65Zr0.35)O3 by the rf magnetron sputtering technique and evaluated as a function of annealing temperature. The 95-nm-thick BSTZ films showed a dense morphology with a small grain size and an increase of the dielectric constant with increasing annealing temperature. The dielectric constant and dissipation factor of BSTZ films annealed at 750 °C were 610 and 0.025 at an applied frequency of 100 kHz, respectively. The leakage current density of films increased with increasing annealing temperature, and the value for films annealed at 750 °C was about 9.0×10−9 A/cm2 at 400 kV/cm. The dominant transport mechanism of BSTZ films was interface-limited Schottky emission. The BSTZ films formed by rf sputtering are attractive for Gbit-scale dynamic random access memory applications.

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