The crystal structure and absolute configuration of the antitumor platinum complex trans(OH)-Pt(OH)2(malonato)(1R,2R-cyclohexanediamine).

The absolute configuration of the anti-tumor complex trans(OH)-Pt(OH)2(malonato)(1R,2R-cyclohexanediamine) was determined by X-ray anomalous scattering technique. The final unit cell was monoclinic, space group P2(1) with a = 9.142 A, b = 7.788 A, c = 11.946 A, beta = 96.48 degrees, Z = 2. The crystal structure was determined by direct method and difference Fourier synthesis, and refined to R = 0.025 and Rw = 0.033 based on 2768 independent reflections. The platinum atom has roughly octahedral coordination. The cyclohexane ring has the expected chair configuration, with two amino groups in equatorial positions while the malonato ligand, in contrast, shows a boat conformation for six membered Pt O-C-C-C-O ring.     

Synthesis and anti-HIV-1 activity of novel 10-thiaisoalloxazines,a structural analog of C-5 and/or C-6 substituted pyrimidine acyclonucleoside

A series of novel 10-thiaisoalloxazine derivatives bearing an alkoxymethyl or benzyloxymethyl moiety at the N-1 position has been synthesized through the bromination of 1-substituted-5-hydroxyuracils and subsequent condensation with aminobenzenethiol in a one-pot reaction. Contrary to the previous report, the formation of intermediary 5,6-diethoxy-5-hydroxy-5,6-dihydrouracil seems to be not the necessary factor for the formation of the thiaisoalloxazines, since the reaction proceeds in tetrahydrofuran (THF) or acetonitrile far more smoothly than in ethanol. The anti-human immunodeficiency virus (HIV)-1 activity of the resulted thiaisoalloxazine derivatives was evaluated in lymphocyte cells based on the inhibitory activity against the viral-induced cytopathic activity. Among the derivatives, compounds 6, 7, and 8 bearing an alkoxymethyl moiety at the N-1 position exhibited modest inhibitory activity towards the cytotopathic effect of HIV-1.     

Chemical conversion of various celluloses to glucose and its derivatives in supercritical water

The supercritical water biomass conversion system was designed and developed in our laboratory. The reaction vessel with cellulose sample was treated with this system at supercritical state of water for a designated period (3–105s) under the conditions of a tin bath temperature of 500°C and pressure of 35MPa. The recovered products of hydrolysates were then analyzed by high performance liquid chromatography. The obtained results indicated that a high amount of glucose and levoglucosan can be achieved from both celluloses I and II for 5–10s supercritical treatment, while that from starch for 3–5s treatment. Although this difference could be due to a difference in the molecular structure between cellulose and starch, a difference between celluloses I and II was not significant. Instead, an accessibility of the water towards cellulose molecules seemed to be significant for their chemical conversion. With the longer treatment, amounts of these compounds observed were decreased due to decomposition. Therefore, it may be concluded that, compared with acid hydrolysis or enzymatic saccharification, cellulose may be hydrolyzed to glucose and its derivatives more or less to the same degree as in corn starch under supercritical state. This finding suggests that the supercritical treatment can overcome the difficulties in hydrolyzing cellulose to glucose, found in the acid hydrolysis or enzymatic saccharification techniques.     

Effects of poly(ethylene glycol) (PEG) concentration on the permeability of PEG-grafted liposomes

Poly(ethylene glycol)-grafted liposomes (PEG-liposomes) were prepared from dipalmitoylphosphatidylcholine (DPPC) with various amounts of distearoyl-N-monomethoxy poly(ethylene glycol)-succinyl-phosphatidylethanolamines (DSPE-PEG) with PEG molecular weights of 1000, 2000, 3000 and 5000. The effects of DSPE-PEG concentration on the permeability of PEG-liposomes were investigated using carboxyfluorescein (CF). In the gel state, the CF leakage from PEG-liposomes was decreased with increasing mole fractions of DSPE-PEG for all PEG molecular weights. In the liquid-crystalline state, the CF leakage from PEG-liposomes containing DSPE-PEG1000 gradually increased with increasing mole fractions of DSPE-PEG, while that of PEG-liposomes whose molecular weight in PEG units was above 2000 rapidly decreased by the addition of DSPE-PEG. Furthermore, no effect of PEG molecular weight on CF leakage was observed. The relationship between the fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene (DPH) (or 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH)) and the mole fraction of DSPE-PEG for PEG-liposomes was also investigated. No significant changes in fluorescence polarization of DPH for liposomal bilayer membranes was observed in the gel and liquid-crystalline states due to the addition of DSPE-PEG, while that of TMA-DPH was decreased compared with that of liposomes without DSPE-PEG in both states.     

A new oligosaccharide synthesis using special hydroxy protecting group

A new hydroxy protecting group for convenient preparation of oligosaccharide was developed using uni-chemo protection (UCP) concept. The UCP group was comprised of polymerized amino acid derivatives and protecting each hydroxyl groups by ester linkage. Depending on the polymerization degree, the hydroxyl groups were characterized and controlled. Using this protecting group, two kinds of sialyl-T analogues were successfully synthesized from same sugar parts merely by repeating Edman degradation and coupling.     

Simultaneous discrimination of diastereotopic groups and faces: the first example in intramolecular [3+2] and [2+2+1] cycloaddition reactions

To explore a novel concept for controlling diastereoselectivity, systematic studies on the sense and degree of diastereotopic groups and face selections in intramolecular [3 + 2] (nitrile oxide and nitrone) and [2 + 2 + 1] (Pauson-Khand) cycloadditions have been conducted. Optically pure methyl (S)-3,4-O-isopropylidene-3,4-dihydroxybutanoate (5) and methyl (S)-2,3-O-isopropylidene-2,3-dihydroxypropanoate (6) were converted to substrate aldehydes (1-4) that bear geminal allyl groups and four types of controllers with the intention of imparting a stereochemical bias to the allylic groups and their faces. The controllers involve 1,2-bis(tert-butyldimethylsiloxy), 1,3-bis(tert-butyldimethylsiloxy), 1,2-acetonide, and 1,3-acetonide groups, which are referred to as 1,2-(TBDMSO)(2), 1,3-(TBDMSO)(2), 1,3-dioxolane, and 1,3-dioxane, respectively. Twelve runs of cycloaddition reactions as combinations between the three types of reactions and the four types of substrates were performed to provide bicyclo[4.3.0] or -[3.3.0] adducts of synthetic importance in which isoxazolidine, isoxazoline, or cyclopentenone segments were fused. For every case, high levels of diastereoselectivity have been achieved: >99% (in eight cases), 82%, and 76% for the discrimination of diastereotopic groups and 68-->99% for the discrimination of diastereotopic faces. On the basis of the absolute structures of the cycloadducts, plausible stereochemical models are proposed.     

Direct coupling of microcolumn liquid chromatography with in-tube solid-phase microextraction for the analysis of antidepressant drugs

The direct coupling of in-tube solid-phase microextraction (in-tube SPME) with microcolumn liquid chromatography (micro-LC) has been investigated for the analysis of antidepressants in human urine. The use of in-tube SPME has been clearly shown to be advantageous for the on-line coupling of the SPME method, as the sample pretreatment technique, with micro-LC as the separation technique. This is because much smaller amounts of the sample solutions, desorption solvents and the mobile phase are required compared with conventional SPME-LC systems. The parameters for preconcentration have been investigated for the extraction capillary with the newly developed 'wire-in-tube' configuration.     

DNA cleavage reaction of antitumour antibiotic, kapurimycin A3, with deoxytetranucleotide d(CGCG)2

Kapurimycin A3 (kap A3, 1 ), an antitumour antibiotic, alkylates N7 of guanine₂ (G₂) and G₄ of d(C₁G₂C₃G₄)₂ to produce their covalent adducts 2 (64 %) and 3 (7.0 %), respectively. Heating at 90 °C for 5 min degraded both adducts to kap A3 - G adduct (5) with the concurrent release of their respective abasic-site containing oligomers 4 and 6.     

SYNTHESIS OF ORGANOGERMANE OLIGOMERS VIA LIGAND SUBSTITUTION POLYMERIZATION FROM 1, 4-DIOXANE COMPLEX OF GERMANIUM DICHLORIDE

Some organogermanium oligomers with different side groups were synthesized via li-gand substitution polymerization from 1, 4-dioxane complex of germanium dichloride withdifferent organolithitum compounds. The oligomers were isolated through either precipi-tation from methanol or extraction using toluene with a yield of no less than 50%. Theweiglit average molecular weight (M_w) of the oligomers is ranging from 1.4×10~3 to 5.9×10~3depending on the type and alkyl length of the organolithium compounds used.