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...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 1998-08, Vol.8 (16), p.2227-2230
Main Authors: Chen, Shu-Hui, Farina, Vittorio, Vyas, Dolatrai M., Doyle, Terrence W.
Format: Article
Language:English
Subjects:
Animals
Antineoplastic agents
Antineoplastic Agents, Phytogenic - chemical synthesis
Antineoplastic Agents, Phytogenic - chemistry
Antineoplastic Agents, Phytogenic - toxicity
Biological and medical sciences
Cell Survival - drug effects
Drug Design
General aspects
Indicators and Reagents
Medical sciences
Molecular Conformation
Molecular Structure
Paclitaxel - analogs & derivatives
Paclitaxel - chemistry
Pharmacology. Drug treatments
Structure-Activity Relationship
Tubulin - chemistry
Tubulin - drug effects
Tubulin - metabolism
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Summary: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. The synthesis and preliminary biological evaluation of iso-paclitaxel ( 2) is described.
ISSN:0960-894X
1464-3405
DOI:10.1016/S0960-894X(98)00383-7