Synthesis of a paclitaxel isomer: C-2-acetoxy-C-4-benzoate paclitaxel.
A synthesis of the C-2-acetoxy-C-4-benzoate paclitaxel 2 is described. This analog has the substituents at C-2 and C-4 transposed. The key steps in the synthesis include the sequential use of Red-Al as reducing agent for the regioselective reduction of the C-2 benzoate and the C-4 acetoxy within the baccatin core. Iso-paclitaxel 2 was considerably less potent than paclitaxel in tubulin polymerization and in vitro cytotoxicity assays.
Chen
S H
SH
Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, CT 06492-7660, USA.
Farina
V
V
Vyas
D M
DM
Doyle
T W
TW
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D015195:Drug Design; D007202:Indicators and Reagents; D008968:Molecular Conformation; D015394:Molecular Structure; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000737:chemistry; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; D007202:Indicators and Reagents; D014404:Tubulin; D017239:Paclitaxel