A novel method to synthesize docetaxel and its isomer with high yields

✍ Scribed by Chuan-Min Qi; Yun-Feng Wang; Ling-Chun Yang

• Publisher: Journal of Heterocyclic Chemistry
• Year: 2005
• Tongue: English
• Weight: 108 KB
• Volume: 42
• Category: Article
• ISSN: 0022-152X
• DOI: 10.1002/jhet.5570420430

✦ Synopsis

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.