| The extraction and purification of 10-DeacetylbaccatinⅢ, which was the precursor of Taxotere, from the branchs and leaves of Taxus cuspidata was studied. And Taxotere which was an anti-cancer drug was synthesized by connecting pure 10-DABⅢand synthetical precursor of side chain. Some conclusions were obtained.1. The conditions of HPLC for the qualitative and quantitative analysis of 10-DABⅢwere established: the chromatographic column was Curosil-PFP 5μ(4.6 mm×250 mm); detecting wavelength was 232.1 nm, flowing rate was 1 mL/min, injected volume was 10μL, mobile phase was CH3CN/H2O (25/75,V/V) between 1-25 min, and CH3CN/H2O (37/63,V/V) between 25-60 min. The results showed the examination of 10-DABⅢwas precise, steady and exact under the HPLC conditions, which were applicable for the analysis of 10-DABⅢin Taxus plants and other preparation.2. The better process conditions of 10-DABⅢextraction from the branchs and leaves of Taxus cuspidata were obtained: extraction method was ultrasonic extraction; extraction solvent was 80% EtOH; ratio of liquid to solid was 1:15; extraction time was 30 min; extration degree was 3 times. 10-DABⅢcould be extracted rapidly and effectively under the above-mentioned conditions. And the extraction yield of 10-DABⅢwas 0.052%.3. The better purification path of 10-DABⅢextracted from the branchs and leaves of Taxus cuspidata were established: firstly, added 3 times water into the crude ethanol extraction by which many thin polarity compounds could be removed with the deposition, while 10-DABⅢwas holded in the water phase; then, extracted the water phase with chloroform for 3 times; disposed the organic phase by silica gel chromatography with 60% ethyl acetate in petroleum benzine, after which the content of 10-DABⅢwas 63%; finally, white powder of 10-DABⅢwith 90% purity could be got by crystallizing and recrystallizing. The yield of 10-DABⅢof the whole process was 59%.4. Taxotere was synthesized with the pure 10-DABⅢby the improved route. Firstly, theβ-lactam was synthesized with the material ofα-methylbenzylamine,benzaldehyde,glycollic acid and acetyl chloride. Then, ring opening product with two chiral centre was obtained by the reaction of deacetylation and ring cleavage reaction under acid catalysis. The ring opening product was debenzylated by H2 under catalyzation with Pd-C. Then the amino-group and hydroxide radical were protected with Di-tert-butyl dicarbonate and p-anisaldehyde dimethyl acetal. Finally, the precursor was accomplished by the hydrolyze reaction in the presence of KOH. It's purity was 98%, and the yield was 22.6%.Secondly, C7 and C10 hydroxide radical of 10-DABⅢwas protected with 2,2,2- trichloroethyl chloroformate．Then,the precursor was connected with prOtected 10-DABⅢin the presence of DIC and DMAP．The aim compound-Taxotere was obtained after eliminating the protect groups in two steps．It's purity was 97%,and the yield of three steps was 62%．... |
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