Chiral Atropisomeric 8,8'-Diiodobinaphthalene for Asymmetric Dearomatizing Spirolactonizations in Hypervalent Iodine Oxidations.

A new type of binaphthyl-based chiral iodide functionalized at positions 8 and 8' of the naphthalene rings has been found as a promising structural motif for the asymmetric hypervalent iodine(III) oxidations, specifically, for the dearomatizing spirocyclization of naphthol carboxylic acids showing expectedly better enantioselectivities versus other atropisomeric biaryls, i.e., a conventionally used binaphthalene having the diiodides in the minor groove.

[Mass spectrometric determination of polyfunctionalized nucleoside phosphoramidites using LSI/FAB].

Nucleoside phosphoramidites (PAs) are the most widely used building blocks in the contemporary solid-phase synthesis of oligonucleotides. Accurate molecular weight measurements of such acid-labile compounds may be easily determined in a matrix system comprising triethanolamine (TEOA)-NaCl by liquid secondary ionization mass spectrometry (LSIMS) or fast atom bombardment mass spectrometry (FABMS), using a double-focusing mass spectrometer. The present method rapidly and easily measures the accurate MWs of various PAs as adduct ions [M+Na]⁺, affording molecular formulas in place of elemental analysis. Further, the intensities by LSIMS of [M+Na]⁺ were found to be enhanced to the highest degree by adjustment of the mole ratio of PA and NaCl, fixing the amount of TEOA. In addition, the effects of the metal ion in the matrix were investigated. The present method is a powerful tool for the mass spectral identification of polyfunctionalized nucleoside PAs.

Antitumor Agents. 282. 2'-(R)-O-acetylglaucarubinone, a quassinoid from Odyendyea gabonensis as a potential anti-breast and anti-ovarian cancer agent.

A new quassinoid, designated 2'-(R)-O-acetylglaucarubinone (1), and seven known quassinoids (2-8) were isolated, using bioactivity-guided separation, from the bark of Odyendyea gabonensis (Pierre) Engler [syn. Quassia gabonensis Pierre]. The structure of 1 was determined by spectroscopic analysis and by semisynthesis from glaucarubolone. Complete (1)H and (13)C NMR assignments of compounds 1-8 were also established from detailed analysis of two-dimensional NMR spectra, and the reported configurations in odyendene (7) and odyendane (8) were corrected. Compound 1 showed potent cytotoxicity against multiple cancer cell lines. Further investigation using various types of breast and ovarian cancer cell lines suggested that 1 does not target the estrogen receptor or progesterone receptor. When tested against mammary epithelial proliferation in vivo using a Brca1/p53-deficient mice model, 1 also caused significant reduction in mammary duct branching.

Bisphenol A 3,4-quinone induces the conversion of xanthine dehydrogenase into oxidase in vitro.

In the present study, we assessed the influence of bisphenol A (BPA) and bisphenol A 3,4-quinone (BPAQ) on the conversion of xanthine dehydrogenase (XD) into xanthine oxidase (XO) in the rat liver in vitro. BPA up to 100 micromol/L did not affect the XO and XD activities in the partially purified cytosolic fraction from rat liver, whereas BPAQ (2-10 micromol/L) dose-dependently enhanced the XO activity concomitant with a decrease in the XD activity, implying that BPAQ, but not BPA, can convert XD into the reactive oxygen species (ROS) producing the form XO. Furthermore, it was found that BPAQ could increase the generation of ROS and oxidize the guanine moiety of deoxyguanosine in the DNA of primary rat hepatocyte cultures. These results suggest that BPAQ has the potential to convert XD into XO in the liver, which in turn may lead to ROS generation and oxidative DNA damage in this region.

Dysfunctional very-low-density lipoprotein synthesis and release is a key factor in nonalcoholic steatohepatitis pathogenesis.

UNLABELLED: The specific mechanisms of nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH) pathogenesis remain unknown. In the present study we investigated the differences between NAFL and NASH in terms of liver lipid metabolites and serum lipoprotein. In all, 104 Japanese subjects (50 men and 54 postmenopausal women) with histologically verified NAFL disease (NAFLD) (51 with NAFL, 53 with NASH) were evaluated; all diagnoses were based on liver biopsy findings and the proposed diagnostic criteria. To investigate the differences between NAFL and NASH in humans, we carefully examined (1) lipid inflow in the liver, (2) lipid outflow from the liver, (3) very-low-density lipoprotein (VLDL) synthesis in the liver, (4) triglyceride (TG) metabolites in the liver, and (5) lipid changes and oxidative DNA damage. Most of the hepatic lipid metabolite profiles were similar in the NAFL and NASH groups. However, VLDL synthesis and lipid outflow from the liver were impaired, and surplus TGs might have been produced as a result of lipid oxidation and oxidative DNA damage in the NASH group. CONCLUSION: A growing body of literature suggests that a deterioration in fatty acid oxidation and VLDL secretion from the liver, caused by the impediment of VLDL synthesis, might induce serious lipid oxidation and DNA oxidative damage, impacting the degree of liver injury and thereby contributing to the progression of NASH. Therefore, dysfunctional VLDL synthesis and release may be a key factor in progression to NASH.

Mass determination of phosphoramidites.

Nucleoside phosphoramidites are the most widely used building blocks in contemporary solid-phase synthesis of oligonucleotides. The accurate molecular weight measurements of such molecules, which are acid-labile compounds, may be easily determined by mass spectrometry using a matrix system, triethanolamine/NaCl, on a liquid secondary ion mass spectrometer (LSIMS) or fast-atom bombardment (FAB) MS equipped with a double-focusing mass spectrometer. The present method rapidly and easily measures the accurate molecular weights of various phosphoramidites as adduct ions [M+Na]+ with an average mass error smaller than 0.4 ppm, allowing determination of the formulas of the phosphoramidites in place of elemental analysis. Further, it was found that intensities of molecular-related ions could be enhanced to the highest degree by adjustment of the molar ratio of phosphoramidite and NaCl, fixing the amount of triethanolamine on LSIMS, making the present method a powerful tool for identification of phosphoramidites by mass spectrometry.