| Paclitaxel (taxol) is currently regarded as one of the most promising new drugs in cancer chemotherapy. Because of its novel configuration, special anti-cancer mechanism, strong tumor-inhibiting activity and wide spectrum antileukemic, taxol has been approved to be used in clinical treatment of ovarian and breast cancer by Food and Drug Administration of America (FDA) since 1992. In recent years, other studies have revealed its effect against other cancers. However, owing to serious lack of natural source of taxol, its application in clinical treatment is greatly limited. At present, taxol was obtained mostly from the extraction of the stem bark of the yew trees. The loss of stem bark will lead to the death of yew trees, which grow very slowly. In addition, the output of taxol is quite low due to the low content of taxol in stem bark of yew trees(40~ 165mg/kg of bark). It means if we want to get lkg taxol, we will have to gain 10000kg stem bark, which will eventually destroy plant resources and natural envi -ronment in the world. Therefore,the supply problem of taxol can not be solved by natural source in the long term.Although the total synthesis of taxol has been achieved, the complicated synthetic steps, too low total yields and high costs make it impossible to produce the taxol in a large scale at the moment. Fortunately, the problem has been partially circumvented by semi-synthesis methods in which people utilize similar compounds to taxol, such as 10-deacety -1baccatin III. This kind of compound (10-deacetylbaccatin III) could be easily extracted from the leaves of taxus baccata (European yew) with a high yield and can be supplied continuously without threatening the survival of the yew species, but its anti-cancer activity is not as effective as pacilitaxel (Taxol). If 10-deacetylbaccatin III is coupled to the C13 sidechain(N-benzoyl-(2R,3S)-3-phenylisoserine), the taxol can be obtained. So the development of short and practical synthetic routes to the taxol side chain, which are adaptable for industrial-scale production, has become very important.There are numerous papers devoted to the preparation of the taxol C13 side chain. The project reported in this paper aims at developing easily manipulated, lowly costed ways to obtain the C13 side chain with high yields. We accomplished the following work on the basis of the Sharpless Asymmetric Dihydroxylation (AD) of olefins.1. Synthesis of two free chiral ligands 1,2 for AD and AA reactions1.4-bis(9-O-quininyl) phthalazine (A) was synthesized by the improved method according to the reported papers. Then A was transformed into 1,2 by the oxidation of OsO4 in acetone-H2O system.2. Synthesis of two free chiral ligands 3,4 for AD and AA reactionsLigands 3,4 could be got from A through a three-step route. Firstly, A was heated with 2-mercaptoethanol in the presence of azo-bis -isobutyronitrile (AIBN) in CHCl3 to a mixture of intermidate. Then the intermediate was directly oxidized in THF-BuOH at room temperature to produce 3,4.3. Evaluation of chiral ligands 1~4 in the AD reaction(1) Ligands 1~4 were applied to AD reaction of olefins respectively in two standard AD systems. Good yields and excellent enantioseletivity were obtained, especially for the trans-cinnamate.(2) For AD reaction of olfins, the free ligand 1 were recovered and reused for five runs in both systems, so did 3, 4 or 3+4(1:1). No significicant decrease in activity and enantioseletivity were observed within their recycling use. However, the first recovery rate of ligand 2 in 'BuOH-H2O system was only 51%, which was much lower than that of ligands 1,3 or 4 in the same process. Fortunately, ligand 2 was succeeded in acetone-H2O system.4. Application of chiral Ligands 1-4 to the AA reactions of four olefinsThe homogeneous AA reaction of olefins catalyzed by ligands 1~4 respectively afforded good yields and excellent enantioseletivity,While ligand 3 and 4 catalyze AA reaction of styrene, each of them can be recovered and reused for 3 runs with the yields and ees...
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