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.     

Reaction paths of some open-shell reactive intermediates

The intermolecular interaction energy for reacting systems in singlet, triplet and doublet states was partitioned by the perturbation expansion method into the chemically meaningful five interaction terms: the Coulomb, exchange-repulsion, induction, dispersion, and charge-transfer energies. In the local ZDO approximation, these energy terms were evaluated for the dimerization of methylenes (^1,3CH₂), the additions of carbenes (^1,3CH₂ and^1,3CF₂) as well as amino radicals (²NH₂ and²NF₂) toward ethylene, and the hydrogen abstractions by methylenes (^1,3CH₂), nitrene (³NH), and hydroxyl radical (²OH) from methane. It has been found that the reaction path is much influenced by the spinmultiplicity, and that the charge-transfer and exchange-repulsion terms play a dominant role in determining the course of reactions.     

Preparation of Sr2CeO4:Eu3+,Dy3+ white luminescence phosphor particles and thin films by using an emulsion liquid membrane system

Sr(2)CeO(4) and Sr(2)CeO(4):Eu(3+),Dy(3+) phosphor particles and thin films were prepared by using an emulsion liquid membrane (ELM, water-in-oil-in-water (W/O/W) emulsion) system, containing VA-10 (2-methyl-2-ethylheptanoic acid) as extractant (cation carrier). A two-step extraction enabled efficient extraction for Sr(3+) and rare earth ions, and the resulting precursor metal oxalate particles produced in the internal water phase of the ELM system were about 60 nm in diameter. Calcination of the oxalate particles in air gave submicrometer-sized Sr(2)CeO(4) and Sr(2)CeO(4):Eu(3+),Dy(3+) particles, which showed blue and white luminescence, respectively, by UV excitation. Blue and white luminescence phosphor thin films were also prepared by soaking alumina substrates into the W/O emulsion containing precursor oxalate particles, followed by calcination in air.     

Preparation and reaction of cyclopropyltriphenylphosphonium salt

Cyclopropyltriphenylphosphonium bromide (2a) was conveniently prepared from 3-bromopropyltriphenylphosphonium bromide (1a). The Wittig reaction of cyclopropyltriphenylphosphonium bromide (2a) with carbonyl compounds gave alkylidenecyclopropanes (4, 6 and 7). Successive treatment of 1a with two equivalents of base and carbonyl compounds gave alkylidenecyclopropanes (4 and 5) without isolation of intermediary 2a. 2-Methylcyclopropyltriphenylphosphonium bromide (2b) was prepared and allowed to react with carbonyl compounds.     

Gas chromatography of bile acids as their hexafluoroisopropyl ester-trifluoroacetyl derivatives.

Bile acids, such as cholic, chenodeoxycholic, deoxycholic, lithocholic and ursodeoxycholic acids, were allowed to react with hexafluoroisopropanol and tri-fluoracetic anhydride at 37 for 30 min. The resulting derivatives were gas chromatographed on QF-1, with flame ionization detection, and were identified by gas chromatography-mass spectrometry. Separation was good. By using this method, these acids were detected in samples of human duodenal fluid; the ratios of each were 24.4, 41.5, 24.9, 2.3 and 6.9%, respectively.     

Optical rotation inversion of porphyrin-DNA complexes

A porphyrin-DNA complex in which helical porphyrin assemblies were stacked as π-stacked aggregates on a DNA scaffold was found. The complex indicates the inversions of optical rotation by only the control of ionic equilibrium without any structural changes of DNA scaffold.     

Rhodium-catalyzed synthesis of a C(3) disubstituted oxindole: an approach to diazonamide A

A two step synthesis of a C(3) disubstituted oxindoles via the rhodium(II)-catalyzed coupling of diazoketone (6) and 3-methyloxindole (9) is reported.     

A new synthetic method: Direct replacement of the nitro group by hydrogen or deuterium

The nitro group in tertiary or secondary aliphatic nitro compounds is replaced by hydrogen or deuterium on treatment with tributyltin hydride or tributyltin deuteride, respectively.     

Metal-containing initiator systems. IV. Polymerization of methyl methacrylate by systems of some activated metals and organic halides

A study of the polymerization of methyl methacrylate initiated by the binary systems of some activated metals and organic halides has been made. It was found that the initiator activities of these systems were greatly dependent on the kind and the preparation or activation method of the metals (i.e., oxidation potential, surface area, and purity), and also on the kind of organic halides (i.e., bond-dissociation energy of their carbon–halogen bonds). From the kinetic studies of the polymerization at 60°C with the system reduced nickel–carbon tetrachloride, the rate of polymerization was found to be proportional to the monomer concentration and to the square root of concentration of both nickel and carbon tetrachloride at the lower concentration range of carbon tetrachloride, indicating that the system induced the radical polymerization. A similar conclusion was also obtained from the copolymerization with styrene with this system at 60°C, i.e., the resulting copolymer composition curve was in agreement with that obtained with azobisisobutyronitrile (AIBN). The apparent overall activation energy for the methyl methacrylate polymerization with this system was estimated to be 7.5 kcal/mole, which was considerably lower than that with AIBN. On the basis of the results obtained, an initiation mechanism for the polymerization with these initiator systems is presented and discussed.     

Synthesis of substituted polymethylenes by radical polymerization of alkyl N,N-dialkylfumaramates and maleamates: Relative reactivity of the isomers

Bulk polymerization of alkyl N,N-dialkylfumaramates (FAE) and maleamates (MAE) was performed in the presence of a radical initiator. It has been found that FAE is more reactive than MAE when the reactivity of the two geometrical isomers was compared for their homo- and copolymerizations. From investigation on the effect of ester and N-substituents of these monomers, it has been found that the isopropyl ester shows a higher reactivity than the methyl ester and that N-ethyl and n-butyl substitution gives polymers with high molecular weight of more than several thousands. The resulting substituted polymethylenes from FAE and MAE were characterized and compared with each other. The isomerization of MAE to FAE with morpholine as an isomerization catalyst and monomer-isomerization radical polymerization were also investigated.