Structure-Activity Studies of Antitumor Taxanes: Synthesis of Novel C-13 Side Chain Homologated Taxol and Taxotere Analogs

Taxol and taxotere analogs with one carbon homologated side chains were synthesized from 10-deacetylbaccatin III and a key oxazolidineacetic acid intermediate, which was synthesized in four steps from (S)-(+)-2-phenylglycine. 10-Deacetyl-1a'-homotaxol and 1a'-homotaxotere were at least 27...

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Bibliographic Details
Published in:Journal of medicinal chemistry 1994-09, Vol.37 (18), p.2981-2984
Main Authors: Jayasinghe, Lalith R, Datta, Apurba, Ali, Syed M, Zygmunt, Jan, Vander Velde, David G, Georg, Gunda I
Format: Article
Language:English
Subjects:
Alicyclic compounds, terpenoids, prostaglandins, steroids
Chemistry
Docetaxel
Exact sciences and technology
In Vitro Techniques
Molecular Conformation
Organic chemistry
Paclitaxel - analogs & derivatives
Paclitaxel - chemical synthesis
Paclitaxel - pharmacology
Preparations and properties
Structure-Activity Relationship
Taxoids
Terpenoids
Tubulin - drug effects
Tubulin - metabolism
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Description
Summary:Taxol and taxotere analogs with one carbon homologated side chains were synthesized from 10-deacetylbaccatin III and a key oxazolidineacetic acid intermediate, which was synthesized in four steps from (S)-(+)-2-phenylglycine. 10-Deacetyl-1a'-homotaxol and 1a'-homotaxotere were at least 27 times less active than taxol in the microtubule assembly assay. The inability of these homologs to induce microtubule formation may be due to unfavorable solution conformations, preventing productive interactions with the taxol binding site on microtubules.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm00044a020