Total Syntheses of Parthenolide and Its Analogues with Macrocyclic Stereocontrol

The first total synthesis of parthenolide (1) is described. The key feature of this synthesis is the formation of a 10-membered carbocylic ring by a macrocyclic stereocontrolled Barbier reaction, followed by a photoinduced Z/E isomerization. The biological evaluation of a small library of parthenoli...

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Bibliographic Details
Published in:Journal of medicinal chemistry 2014-08, Vol.57 (16), p.7098-7112
Main Authors: Long, Jing, Zhang, Shan-Feng, Wang, Pan-Pan, Zhang, Xue-Mei, Yang, Zhong-Jin, Zhang, Quan, Chen, Yue
Format: Article
Language:English
Subjects:
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Cell Line, Tumor - drug effects
Cell Proliferation - drug effects
Chemistry Techniques, Synthetic
Drug Screening Assays, Antitumor
Humans
MCF-7 Cells - drug effects
Neoplasms
Sesquiterpenes - chemical synthesis
Sesquiterpenes - chemistry
Structure-Activity Relationship
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Summary:The first total synthesis of parthenolide (1) is described. The key feature of this synthesis is the formation of a 10-membered carbocylic ring by a macrocyclic stereocontrolled Barbier reaction, followed by a photoinduced Z/E isomerization. The biological evaluation of a small library of parthenolide analogues (19, 33, and 34) disclosed a preliminary structure–activity relationship (SAR). The results revealed that the C1, C10 double bond configuration of parthenolide has little or no effect on the activity, and the C6 and C7 configurations of the lactone ring have a moderate impact on the activities against some cancer cell lines.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm5009456