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Application of Hexamethyldisilathiane as a Counterattack Reagent in Chemical Transformations and Development of Lignans and Novel Platinum Complexes as New Anticancer Agents
Dissertation

Application of Hexamethyldisilathiane as a Counterattack Reagent in Chemical Transformations and Development of Lignans and Novel Platinum Complexes as New Anticancer Agents

林明濬
Doctor of Philosophy (PHD), 國立清華大學, 化學系
2006

Abstract

反撲試劑 六甲基二矽硫醚 木酚素 新穎鉑類化合物 抗癌 counterattack reagent Hexamethyldisilathiane Lignan Novel Platinum Complexes anticancer
In this thesis, I report the application of “counterattack reagent” hexamethyldisilathiane on the accomplish of a series of novel double functional group transformations. Furthermore, I synthesize the derivatives of nordihydroguaiaretic acid (NDGA) and novel platinum complexes as a new anticancer agents. In Part 1 of this thesis, a series of novel double functional group transformations were established. These transformations convert nitrocycloalkenes to □-substituted ketoximes in “one flask” procedure. Sophisticated mechanisms are involved in these reactions. In those efficient tandem processes, hexamethyldisilathiane acts as a counterattack reagent. In Part 2 of this thesis, water soluble derivatives of nordihydroguaiaretic acid (NDGA), Malotse-M3N, was synthesized by coupling tri-O-methyl-NDGA (M3N) with maltose in the presence of boron trifluoride-diethyl etherate in CH2Cl2 and deprotection by use of sodium methoxide. Maltose-M3N inhibits the growth of the five human cancer cell lines in vitro with IC50 values of 20 □M to 40 □M. Nevertheless, inhibition of CDC2 and survivin expression is observed. Four daily intratumoral injections of Malotse-M3N into C3 tumors also effectively suppresses CDC2 and survivin expression and induces apoptosis throughout the whole tumor tissues without toxicities. In Part 3 of this thesis, A series of novel organoplatinum complexes were synthesized by adding sodium 2-mercaptopyridine N-oxide and a series of sulfoxides to K2PtCl4 in DMF and H2O (1 : 5) condition. In vitro growth inhibitory effect of those organoplatinum complexes were evaluated in human cancer cell lines Cal27. We found five of those organoplatinum complexes exhibited noteworthy anticancer activity.

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