2,2′-Isopropylidenebis[(4S,5R)-4,5-di(2-naphthyl)-2-oxazoline] ligand for asymmetric cyclization-carbonylation of meso-2-alkyl-2-propargylcyclohexane-1,3-diols

The oxidative cyclization-carbonylation of meso-2-alkyl-2-propargylcyclohexane-1,3-diols mediated by Pd(II) with chiral bisoxazoline (box ligand) afforded bicyclic-β-alkoxyacrylates. Based on a ligand screening, 2,2′-isopropylidenebis[(4S,5R)-4,5-di(2-naphthyl)-2-oxazoline] ligand has been developed. The products with a chiral quaternary carbon were obtained in 71-100% yields with 85-95% ee.     

Novel rearrangement of twisted 2,4-di-alkyl 2-trans-4-trans pentadienals: An approach to cyclopentenones based on molecular mechanical consideration

Rearrangement of 2,4-di-$\text{trans}$-pentadienals $\text{IVa-d}$ was described as a consequence of the successive alkyl substitutions on the C-2 and C-4 positions. ¹H-FT nmr spectroscopy suggested that the reaction involves ketene $\text{VIII}$ as an intermediate.     

Magnetic microcapsules for targeted delivery of anticancer drugs

To achieve targeted distribution of anticancer drugs with sustained activity, ferromagnetic ethylcellulose microcapsules containing an anticancer drug, mitomycin C (FM-MMC-mc), were prepared by a method based on phase separation principles. Two prototypes of FM-MMC-mc were made: one with the drug as the core and zinc ferrite on its capsular surface (outer type); the other with both the drug and zinc ferrite as the core (inner type). Both preparations provided a sustained-release property and a sensitive response to conventional magnetic force, although certain differences in the release rate of drug, magnetic responsiveness, and particle size were found between the two dosage forms. Animal studies showed that the magnetic microcapsules could be magnetically controlled in the artery and urinary bladder. VX2 tumors in the rabbit hind limb and urinary bladder were successfully treated with magnetic control of FM-MMC-mc. Pharmacokinetic study revealed that the targeting of the microcapsules markedly enhanced the drug absorption into the surrounding tissues for a prolonged period of time. The results indicate the feasibility and effectiveness of the magnetic microcapsules as a targeted drug delivery system.     

Alcohol‐Vapor Inclusion in Single‐Crystal Adsorbents [MII2(bza)4(pyz)]n (M=Rh,Cu): Structural Study and Application to Separation Membranes

The vapor absorbency of the series of alcohols methanol, ethanol, 1‐propanol, 1‐butanol, and 1‐pentanol was characterized on the single‐crystal adsorbents [M^II₂(bza)₄(pyz)]_n (bza=benzoate, pyz=pyrazine, M=Rh ( 1 ), Cu ( 2 )). The crystal structures of all the alcohol inclusions were determined by single‐crystal X‐ray crystallography at 90 K. The crystal‐phase transition induced by guest adsorption occurred in the inclusion crystals except for 1‐propanol. A hydrogen‐bonded dimer of adsorbed alcohol was found in the methanol‐ and ethanol‐inclusion crystals, which is similar to a previous observation in 2 ?2EtOH (S. Takamizawa, T. Saito, T. Akatsuka, E. Nakata, Inorg. Chem. 2005 , 44, 1421–1424). In contrast, an isolated monomer was present in the channel for 1‐propanol, 1‐butanol, and 1‐pentanol inclusions. All adsorbed alcohols were stabilized by hydrophilic and/or hydrophobic interactions between host and guest. From the combined results of microscopic determination (crystal structure) and macroscopic observation (gas‐adsorption property), the observed transition induced by gas adsorption is explained by stepwise inclusion into the individual cavities, which is called the “step‐loading effect.” Alcohol/water separation was attempted by a pervaporation technique with microcrystals of 2 dispersed in a poly(dimethylsiloxane) membrane. In the alcohol/water separation, the membrane showed effective separation ability and gave separation factors (alcohol/water) of 5.6 and 4.7 for methanol and ethanol at room temperature, respectively.     

1-D cobalt(II) spin transition compound with strong interchain interaction: [Co(pyterpy)Cl(2)].X

Cobalt(II) compounds [Co(pyterpy)Cl(2)].MeOH (1.(MeOH)) and [Co(pyterpy)Cl(2)].2H(2)O (1.(2H(2)O)) were synthesized. The compound 1.(MeOH) forms the quasi 3-D networks by making pi-pi stacking between the 1-D chains. The methanol molecules from 1.(MeOH) can be removed by heating, and substituted by absorption of water molecules. The MeOH molecules in 1.(MeOH) are removed by heating at 410 K, and they are substituted by water molecules to form 1.(2H(2)O). 1.(2H(2)O) exhibits a S = (3)/(2) (HS) left arrow over right arrow S = (1)/(2) (LS) spin transition with a thermal hysteresis. We have succeeded in constructing a guest dependent 1-D spin-crossover cobalt(II) compound.     

Synthesis of (±)‐Kempa‐6,8‐dien‐3‐ol (=(2aRS,3SR,4aSR,7RS,7aSR,10bSR,10cSR)‐2,2a,3,4,4a,5,6,7,7a,8,10b,10c‐Dodecahydro‐2a,7,10,10c‐tetramethylnaphth[2,18‐cde]azulen‐3‐ol)

The synthesis of kempa‐6,8‐dien‐3β‐ol ( 4a ), as a synthetic leading model of the natural product 4b , was carried out starting from intermediate 12 , the synthetic route of which has been developed previously (Scheme 1). The conversion of 12 to the model compound 4a involved the elaboration of three structure modifications by three processes, Tasks A, B, and C (see Scheme 2). Task A was achieved by epoxy‐ring opening of 41 with Me₃SiCl (Scheme 9), and Task B being performed by oxidation at the 13‐position, followed by hydrogenation, and then epimerization (Schemes 4 and 5). The removal of the 2‐OH group from 12 (Task C) was achieved via 30b according to Scheme 6, whereby 30b was formed exclusively from 30a / 31a 1 : 1 (Scheme 7). In addition, some useful reactions from the synthetic viewpoint were developed during the course of the present experiments.     

Dynamics and thermodynamics of dimerization of parallel G-quadruplexed DNA formed from d(TTAGn) (n=3-5)

Parallel G-quadruplexes formed from oligonucleotide sequences, d(TTAGn), where n = 3-5, have been shown to form a dimer through end-to-end stacking of 3'-terminal G-tetrads. The monomers and dimers of the G-quadruplexes are in dynamic equilibrium with an exchange rate of approximately 1 s-1. A thermodynamic study demonstrated that the dimerization of the G-quadruplexes is largely enthalpic in origin.     

Endo- and aminopeptidase activities of rat cathepsin H.

Employing soluble denatured protein substrates and their derivatives, the proteolytic activity of rat cathepsin H was investigated. The enzyme showed aminopeptidase activity which sequentially released amino acid from the N-terminal of the substrate. The aminopeptidase activity did not act on N alpha-acetylated peptides and showed moderate ionic-strength dependence when methionyl-methylcoumarylamide was employed as a substrate. These results indicate that the activity essentially requires an N-terminal free amino group of the substrate and recognizes it electrostatically to some extent. On the other hand, the enzyme was also indicated to exhibit endopeptidase activity by employing appropriate N alpha-acetylated peptide substrates. In contrast to the aminopeptidase activity, the endopeptidase activity showed rather strict specificity, preferring hydrophobic residues at P2 and P3 sites. Because of the broad specificity and high efficiency of the aminopeptidase activity, it was difficult to directly observe endopeptidase activity in the digestion of large peptide substrates with a free alpha-amino terminal. Thus, this is the first experimental evidence that indicates endopeptidase activity by assigning internal peptide bonds cleaved by this activity. From this data, we proposed a model of the binding site of this enzyme.     

Site-selective photocycloadditions of 2-pyrones with electron-poor olefins and the derivation from the cycloadducts

Photosensitized cycloaddition of 4,6-dimethyl-2-pyrone ( 1 ) with methacrylonitrile ( 3b ) afforded two types of [2 + 2]cycloadducts, 4b and 6b , across the C₅-C₆ and C₃-C₄ double bonds in 1 , respectively. Photosensitized reactions of 1 with dimethyl maleate and dimethyl cyclobutene-1,2-dicarboxylate gave [2 + 2]cycload-ducts 4d, 4e across the C₅-C₆ double bond, in addition to [4 + 2]cycloadduct 9d or bicyclo[4.2.0]octadiene 10e . The photoreactions of methyl 2-pyrone-5-carboxylate ( 2 ) with 3b and 2-chloroacrylonitrile ( 3c ) gave [4 + 2]cycloadducts 5b, 5c in addition to [2 + 2]cycloadducts 11b and 11c across the C₅-C₆ double bond in 2 . The photocycloaddition mechanism was explained from results calculated by means of PM3-CI method. Namely, the site- and/or regio-selective products, 4, 5, 8, 9 and 10 were thought to come from the same site-selective radical intermediates in the case of electron-poor olefins. Pyrolysis and/or hydrolysis of the cycload-ducts 4e, 5b, 5c gave 5,6-dihydro-2-pyrone 12 or benzene derivatives.