5 research outputs found

    Asymmetric synthesis using sulfimides

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    Asymmetric synthesis, the synthesis of chiral molecules, has developed into one of the most important areas of chemistry. Numerous methods are used to prepare chiral compounds, one of which involves using chiral acyl anion equivalents. The potential of imides of cyclic sulfimides 148 as chiral acyl anion equivalents was found to be limited to simple alkylations using sodium hydride and an alkyl iodide in DMF. Alkylated adducts 154,158 and 159 were prepared with good diastereoselectivity, with the anti and anti-anti geometries being preferred for 154 and 158, and 159, respectively. The conformations of the parent sulfimides 148 were investigated. We found that cyclic sulfimides (1,3,4-oxathiazines) 132 were inaccessible, which precluded our investigation into the potential of this new class of compound as chiral acyl anion equivalents. In the course of this work, the BPTM group was developed as a replacement for the troublesome PTM group as a protecting group for primary, secondary and benzylic alcohols. Vinyl sulfimides 186 were prepared using a modified Wadsworth-Emmons reaction, with good E selectivity. Additions of alcohols to give adducts 185 proceeded with good diastereoselectivity. The attempted deprotection of adduct 185b using hydrogenolysis resulted in reduction of the sulfimide group to yield protected ß-hydroxy sulfide 192. Radical additions to vinyl sulfimides 186 resulted in 2-vinyl oxa-heterocycles 202 and 210, with THE and THP as solvent, respectively. A radical addition mechanism has been proposed, but uncertainty still exists as this mechanism can not explain both triethylborane and benzoyl peroxide mediated reactions as the E/Z selectivities are different. At this stage, an ionic mechanism can not be ruled out. 2-Vinyl oxa-heterocycles 202 and 210 have been converted, using Taylor's variant of the Malherbe-Bellus reaction, into 9- and 10-membered lactones 220 and 221, respectively, which are closely related to a number of important natural products. Considerable progress has been made in developing a new asymmetric sulfimidation procedure. Promising enantioselectivites have been observed using a copper-catalysed decompsition of tosyl azide or PhI=NTs 224 into nitrenes. Interception of the nitrenes by sulfide within the chiral influence of C-2 symmetric chiral ligands 225 or 231 yielded sulfimide 65. A discrete copper-nitrene species is thought to be an intermediate in the catalytic cycle

    Roles of cell fusion, hybridization and polyploid cell formation in cancer metastasis

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    Cell-cell fusion is a normal biological process playing essential roles in organ formation and tissue differentiation, repair and regeneration. Through cell fusion somatic cells undergo rapid nuclear reprogramming and epigenetic modifications to form hybrid cells with new genetic and phenotypic properties at a rate exceeding that achievable by random mutations. Factors that stimulate cell fusion are inflammation and hypoxia. Fusion of cancer cells with non-neoplastic cells facilitates several malignancy-related cell phenotypes, e.g., reprogramming of somatic cell into induced pluripotent stem cells and epithelial to mesenchymal transition. There is now considerable in vitro, in vivo and clinical evidence that fusion of cancer cells with motile leucocytes such as macrophages plays a major role in cancer metastasis. Of the many changes in cancer cells after hybridizing with leucocytes, it is notable that hybrids acquire resistance to chemo- and radiation therapy. One phenomenon that has been largely overlooked yet plays a role in these processes is polyploidization. Regardless of the mechanism of polyploid cell formation, it happens in response to genotoxic stresses and enhances a cancer cells ability to survive. Here we summarize the recent progress in research of cell fusion and with a focus on an important role for polyploid cells in cancer metastasis. In addition, we discuss the clinical evidence and the importance of cell fusion and polyploidization in solid tumors

    Learning from each other

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