- Docetaxel side chain 2'-derived novel taxanes antitumor compound as well as synthesis method and application thereof
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The invention discloses a docetaxel side chain 2'-derived novel taxanes antitumor compound shown as the general structure formula (I) as well as a synthesis method and application thereof. In the formula, X is N or O, R is H or acetyl, and R' is H, nitryl, cyano, methoxyl or a halogen group. The synthesis method takes 10-deacetylbaccatin is used as a raw material; after 7-OH and 10-OH are protected, condensation with phenylisoserine (side chain) protecting 3'-NHBoc and 2'-OH in the presence of condensation agents DCC (Dicyclohexylcarbodiimide) and DMAP (Dimethylaminopyridine) is performed; esterification with substituted phenyl isoxazole carboxylic acid or substituted phenyl oxadiazole methyl carboxylic acid in the presence of the DCC and the DMAP is performed; finally, a protecting group is removed to obtain the compound. The compound disclosed by the invention has relatively high activity on tumor cells.
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- NOVEL AMINO ACID MOLECULE AND USES THEREOF
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There is provided novel amino acid molecules and processes for their preparation. There is also provided novel amino acid molecules and their use in processes for preparing the compounds that are useful for the synthesis of paclitaxel, and docetaxel, the anticancer drug.
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Page/Page column 30
(2011/11/12)
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- A novel method to synthesize docetaxel and its isomer with high yields
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Side chains of docetaxel and its isomer were obtained through Staudinger cycloaddition and catalytic hydrogenation of chlorophenyl intermediates, using chlorobenzaldehyde as starting material. Syntheses of three novel chiral azetidinone derivatives through the Staudinger cycloaddition reaction of chlorophenyl chiral amine Schiff base with different substituted positions were described and their ring-opening reaction under the catalysis of Pd/MgCO 3 or Pd/C to afford side chains of docetaxel and its isomer in high yields was investigated. Finally, docetaxel and its isomer were obtained. Single crystal of (3S,4R)-3-hydroxy-N-[(S)(1-phenyl)ethyl]-4 -(2′-chlorophenyl) -2-azetidinone (4c) was obtained, the configuration of which was determined by X-ray diffraction. Because of the mild cyclization reaction condition and convenient asymmetric resolution operation when p-chlorobenzaldehyde was employed instead of benzaldehyde, the yield of cyclization and hydrogenation increased dramatically and the total yield of docetaxel was higher than the result in literature. When o-chlorobenzaldehyde was employed instead of benzaldehyde an isomer of docetaxel was obtained by the same way.
- Qi, Chuan-Min,Wang, Yun-Feng,Yang, Ling-Chun
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p. 679 - 684
(2007/10/03)
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