Synthesis of 4-[(1,3-diaminopyrrolo[3′,4′:4,5]pyrido[2,3-d]-pyrimidin-8-yl)benzoyl]-L-glutamic acid as a potential antifolate

This paper is dedicated to the memory of Professor Roland K. Robins The synthesis of 4-[(1,3-diaminopyrrolo[3′,4′:4,5]pyrido[2,3-d]pyrimidin-8-yl)benzoyl]-L-glutamic acid ( 18 ), a potential antifolate and anticancer agent, has been achieved starting from 1,4-dibromobutan-2-ol with alkyl p-aminobenzoic acids. Condensation of these two agents gave 1-(4-alkoxycarbonylphenyl)pyrrolidin-3-ols 7a,b , which were oxidized to the corresponding pyrrolidin-3-one derivatives 8a,b . Compounds 8a,b were converted into 1,3-diamino-8-(4-alkoxycarbonylphenyl)-7,8-dihydro-9H-pyrrolo[3′,4′:4,5]pyrido[2,3-d]pyrimidines 12a,b in 4 steps. Saponification of 12b the benzoate ester and coupling with di-tert-butyl glutamate afforded a mixture of 7,8-dihydro product 16 and its aromatized derivative 17 . Finally hydrolysis of esters 16 or 17 gave only the title compound 18 . The 7,8-dihydro tricyclic derivatives were easily air-oxidized to form their fully aromatized compounds. The title compound 18 was one tenth less active than MTX against HL-60 cells in culture.     

Emulsifier-free emulsion polymerization of tetrafluoroethylene by radiation. I. Effects of reaction conditions on the polymerization rate and polymer molecular weight

The radiation-induced emulsifier-free emulsion polymerization of tetrafluoroethylene was carried out at an initial pressure of 2–25 kg/cm², temperature of 30–110°C, and under a dose rate of 0.57 × 10⁴?3.0 × 10⁴ rad/hr. The rate of polymerization was shown to be proportional to 1.0 and 1.3 powers of the dose rate and initial pressure, respectively, and is maximal at about 70°C. The molecular weight of polytetrafluoroethylene (PTFE) lies in the range of 10⁵?10⁶, increases with reaction time in the early stage of polymerization, and is maximal at 70°C but is almost independent of the dose rate. An interesting discovery is that PTFE, a hydrophobic polymer, forms as a stable latex in the absence of emulsifier. When PTFE latex coagulates during polymerization under certain conditions, the polymerization rate decreases, probably because polymerization proceeds mainly on the polymer particle surface. The observed rate acceleration and successive increase in polymer molecular weight may be due to slow termination of propagating radicals in the rigid PTFE particles.     

Surface treatment of silicon carbide using TiO2(IV) photocatalyst

Silicon carbide (SiC) and diamond were decomposed to CO(2)(g) by the photocatalysis with TiO(2) at room temperature, although the decomposition rate of diamond was very slow. According to the XPS spectra of Si2p on the SiC surface, SiO(2) was simultaneously formed on the surface by the TiO(2) photocatalysis. The thickness of the SiO(2) formed on the SiC surface during the photocatalytic oxidation for 1 h was estimated to be about 40 A from the depth profile of the XPS spectra using Ar etching. The SiC surface was oxidized by the TiO(2) photocatalysis even under the condition without a direct contact with the TiO(2). This indicates that the photocatalytic oxidation of the SiC occurs due to active oxygen species photogenerated on the TiO(2) surface, but not by hole produced in the valence band of the TiO(2). Moreover, a remote surface treatment system using the quartz beads coated with TiO(2) was developed for the SiC surface oxidation. Consequently, the TiO(2) photocatalysis will be very useful for the surface treatment of SiC such as photopatterning without defects and damage to the substrate because the photocatalytic reaction is carried out under mild conditions.     

Synthesis of N3-substituted uridine and related pyrimidine nucleosides and their antinociceptive effects in mice

Seventy eight N(3)-substituted derivatives of uridine (1), thymidine (2), 2'-deoxyuridine (3), 6-azauridine (4), 2',3'-O-isopropylideneuridine (5), and arabinofuranosyluracil (6) were synthesized and their antinociceptive effects were evaluated. N(3)-(2',4'-Dimethoxyphenacyl)uridine (1l), N(3)-(2',4'-dimethoxyphenacyl)2'-deoxyuridine (3l), and N(3)-(2',5'-dimethoxyphenacyl)arabinofuranosyluracil (6m) possessed 93, 86, and 82% of the antinociceptive effects tested by hot plate, respectively. The antinociceptive effects of three derivatives were 5.8, 5.4, and 5.1-folds of the effect of N(3)-phenacyluridine (1h) (16%), respectively. The structure-activity relationship of N(3)-substituted pyrimidine nucleosides was also discussed.     

X-ray gated Mössbauer spectroscopic studies on57Co-labelled cobalt/II/ fluoride

KX-ray-gated emission Mössbauer spectra of⁵⁷Co-labelled CoF₂ and CoF₂.2H₂O were measured at room temperature, using the coincidence technique. A difference was found in the relative intensity of⁵⁷Fe(II)/⁵⁷Fe(III) between the X-ray-gated and non-gated emission spectra. The results are explained in terms of local radiolytic effects of water of crystallization and the chemical effects associated with the de-excitation processes caused by EC-decay.     

Preparation of immunoaffinity mini-columns for the analysis of platelet activating factor (PAF) in biological samples.

Using an antibody to BN 52719, an analogue of platelet activating factor (PAF), immunoaffinity mini-columns for the separation of PAF from biological samples were prepared. Rabbits were immunized with BN 52719 and immunoglobulin G (IgG) from the antiserum was coupled with Sepharose 4B. The resulting suspension of the IgG-coated Sepharose 4B in 25 mM phosphate buffer (pH 6.9) was poured into a plastic mini-column (bed volume 2.0 x 0.8 cm). Stepwise elution of the column with methanol revealed that lyso-PAF is eluted with 20-30% methanol in water whereas PAF is eluted with 50-80% methanol. For the determination of PAF in biological samples, it is recommended that lipids are extracted from the samples and the extract, reconstituted in 20% methanol, is loaded on the column. The column is then washed with 50% methanol followed by elution of PAF with 80% methanol. A small amount of [3H]PAF is added to the samples for measurement of the recoveries of PAF during the procedures of extraction and elution. The PAF is then quantified by radioimmunoassay or bioassay. Employing the immunoaffinity mini-column and radioimmunoassay, the contents of PAF in macrophages and conditioned medium after stimulation with calcium ionophore A23187, or tumor promoters such as TPA and thapsigargin, were measured.     

Novel chiral porphyrins with C2 symmetry

Described is the preparation of chiral octaethylporphyrin derivatives having two 2-substituted naphthyl groups in a trans orientation at the 5- and 15-meso positions and formyl or hydroxymethyl or alkoxymethyl group derived therefrom at the 10-meso position. One of the derivatives has been successfully resolved into enantiomers by means of HPLC.     

A study of electronic structures of Pt3M (M=Ti,V,Cr,Fe,Co,Ni) polycrystalline alloys with valence-band photoemission spectroscopy

The surface valence-band densities of states (DOS) of Pt(3)M (M=Ti,V,Cr,Fe,Co,Ni) polycrystalline alloys were investigated with ultraviolet photoemission spectroscopy. Upon annealing the ion-sputter-cleaned alloys at high temperatures, the observed valence-band DOS spectra clearly show the modified electronic structures on the surfaces suggesting the surface segregation of Pt as predicted in thermodynamic models. The measured d-band centers and widths for the annealed alloy surfaces show qualitatively the same trend as predicted by density-functional-theory calculations based on the model of a Pt "skin" on the topmost surface layer and a subsurface layer enriched in the 3d transition metal.     

NMR and quantum chemical study on the OH...pi and CH...O interactions between trehalose and unsaturated fatty acids: implication for the mechanism of antioxidant function of trehalose

Trehalose is a disaccharide that attracts much attention as a stress protectant. In this study, we investigated the mechanism of the antioxidant function of trehalose. The spin-lattice relaxation times (T(1)) of (1)H and (13)C NMR spectra were measured to investigate the interaction between trehalose and unsaturated fatty acid (UFA). We selected several kinds of UFA that differ in the number of double bonds and in their configurations (cis or trans). Several other disaccharides (sucrose, maltose, neotrehalose, maltitol, and sorbitol) were also analyzed by NMR. The T(1) values for the (1)H and (13)C signals assigned to the olefin double bonds in UFA decrease with increasing concentration of trehalose and the changes reaches plateaus at integer ratios of trehalose to UFA. The characteristic T(1) change is observed only for the combination of trehalose and UFA with cis double bond(s). On the other hand, from the (13)C-T(1) measurements for trehalose, the T(1) values of the C-3 (C-3') and C-6' (C-6) are found to change remarkably by addition of UFA. (1)H[bond](1)H NOESY measurements provide direct evidence for complexation of trehalose with linoleic acid. These results indicate that one trehalose molecule stoichiometrically interacts with one cis-olefin double bond of UFA. Computer modeling study indicates that trehalose forms a stable complex with an olefin double bond through OH...pi and CH...O types of hydrogen bonding. Furthermore, a significant increase in the activation energy is found for hydrogen abstraction reaction from the methylene group located between the double bonds that are both interacting with the trehalose molecules. Therefore, trehalose has a significant depression effect on the oxidation of UFA through the weak interaction with the double bond(s). This is the first study to elucidate the antioxidant function of trehalose.