Studies On The Utilization Of 1-Dehydroxybaccatin VI Resources From Taxus Chinensis,Rehd.Var. Mairei

A naturally occurring diterpenoid Paclitaxel (Taxol?, known also in the literature as taxol). isolated from the bark of the Pacific yew (Taxus brevifolia), has proved to be one of the most important new anticancer drug introduced in the last decades, owing to its great potential in the successful treatment of wide types of cancer, a unique antitumor mechanism of action, and complex molecular architecture. However, this source is neither abundant nor rapidly renewable, and it has been in short supply. Huge research efforts have been devoted to the search for sustainable alternatives. The most promising approach in terms of ecology and economy is at present the semi-synthesis of Paclitaxel. We report here studies on the exploitation of 1-dehydroxybaccatin VI resources.In the first section, 1-dehydroxybaccatin VI, corresponding to the diterpenoid core of Paclitaxel and available in relatively high yield (up to 0.08%), was isolated from roots of Taxus chinensis, Rehd. var. mairei. C18-silica gel reversed phase chromatography, column chromatography on silica gel and recrystallization were used to purify 1-dehydroxybaccatin VI. The operation conditions of chromatography were optimized. The structural assignments of the compound were based on their spectral data, including 2D NMR experiments and chemical correlation. The X-ray crystallographic analysis of 1-deoxy-baccatin VI provided unambiguous characterization for the structures. The solid-state conformation of 1-dehydroxybaccatin VI showed that both esterification of the 7-hydroxyl, 9-hydroxyl, 10-hydroxyl and removal of oxygen functionality at 1-position had little effect on the conformation of tetracyclic system.The second part of this thesis is study on synthesis of novel 1-dehydroxybaccatin VI derivatives. The use of potassium carbonate, hydrazine monohydrate and magnesium in methanol for the selective deacylation on 1-deoxybaccatinVI was described, and Montmorillonite K10 provided a method suitable for effective, selective ketalization occurring predominantly at C 9 and C 10 hydroxyl group of its derivatives. These protocols should prove to be of utility to more efficient semisyntheses of taxol analogs. Their structures were elucidated using extensive spectroscopic techniques (IR, 1HNMR, DEPT, COSY and MS). In addition, the conformations for these compounds were obtained by X-ray diffraction methods.In the final section, The crystal structures of 7 1-dehydroxybaccatin VI derivatives were analyzed. The effects of the induction by different substitution on the...