Paclitaxel Prodrug Synthesis and Purification

Example 4

Paclitaxel prodrug was synthesized following a five-step synthesis process and purified by column chromatography (FIG. 8). Briefly, commercially available paclitaxel (Avachem Scientific, Inc.) was treated with succinic anhydride in the presence of pyridine to give 2′-succinyl paclitaxel. NHS ester (6) of this intermediate may be obtained by reaction with N-succinimidyl diphenylphosphate (SDPP). The ester was treated with an excess of mono-Boc-ethylene diamine at low temperature followed by deprotection of the tert-Boc. A flexible, linear diamine (1,3-diamino propane) was chosen to reduce the steric hindrance. Finally, the paclitaxel amine was subjected to reductive amination with ALDO PC (or PE) to produce paclitaxel prodrugs (7).