A novel D-ring modified taxoid: synthesis and biological evaluation of a γ-lactone analogue of docetaxel

The synthesis of a novel D-ring modified docetaxel analogue, in which the oxetane ring is replaced with a γ-lactone, was achieved from 10-deacetylbaccatin III. The key steps of the synthesis include the direct acetylation of the secondary hydroxyl group at C-5 and D-ring opening and intramolecular a...

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Bibliographic Details
Published in:Organic & biomolecular chemistry 2012-01, Vol.10 (2), p.361-366
Main Authors: Gao, Feng, Yang, Zhan-Kun, Chen, Qiao-Hong, Chen, Xiao-Guang, Wang, Feng-Peng
Format: Article
Language:English
Subjects:
Antineoplastic Agents - chemical synthesis
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Cell Line, Tumor
Cell Proliferation - drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Humans
Lactones - chemistry
Molecular Conformation
Stereoisomerism
Structure-Activity Relationship
Taxoids - chemical synthesis
Taxoids - chemistry
Taxoids - pharmacology
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Summary:The synthesis of a novel D-ring modified docetaxel analogue, in which the oxetane ring is replaced with a γ-lactone, was achieved from 10-deacetylbaccatin III. The key steps of the synthesis include the direct acetylation of the secondary hydroxyl group at C-5 and D-ring opening and intramolecular aldol reaction to form the γ-lactone. In MTT assays, this analogue proved to have equipotent cytotoxicity relative to paclitaxel towards HCT8, HePG2 and BGC23 cancer cell lines, and be more potent than paclitaxel against A549 and A375. It represents the first example of D-ring modified taxoids with significant cytotoxicity.
ISSN:1477-0520
1477-0539
DOI:10.1039/c1ob06535a