Water soluble derivatives of taxol

摘要

Sulfonated 2'-acryloyltaxol and sulfonated 2'-O-acyl acid taxol derivatives are synthesized which have improved water solubility and stability while maintaining bioactivity. In particular, 2'-((3-sulfo-1-oxopropyl)oxy)taxol sodium salt is synthesized by reacting taxol with acrylic acid, and subsequently reacting the 2'-acryloyltaxol with bisulfite in a Michael reaction. 2'-((4-((2-sulfoethyl)amino)-1,4-dioxobutyl)oxy)taxol sodium salt and 2'-((4-((3-sulfopropyl)amino)-1,4-dioxobutyl)oxy)taxol sodium salt are synthesized by reacting 2'-succinyltaxol with the tetrabutylammonium salts of taurine and 3-aminopropyl sulfonic acid, respectively, and subsequently exchanging the ammonium with sodium. Glycol derivatives of 2'-O-acyl acid taxols with improved water solubility are synthesized by reaction of a glycol with 2'-O-acyl acid taxol.