Antineoplastic agents. 565. Synthesis of combretastatin D-2 phosphate and dihydro-combretastatin D-2.

Abstract

A modified synthetic route to combretastatin D-2 (5) was devised in order to further evaluate its biological activity, for its conversion to phosphate prodrugs (25-28), and as a route to obtaining dihydro-combretastatin D-2 (42). A parallel first total synthesis of dihydro-combretastatin D-2 was completed, proceeding from a saturated 3-phenylpropionic ester intermediate via the Ullmann biaryl ether reaction (39-41). In contrast to the cancer cell growth inhibitory activity exhibited by combretastatin D-2, relatively minor structural modifications (41, 42) caused elimination of those properties.

• Authors: George R Pettit, Peter D Quistorf, Jeremy A Fry, Delbert L Herald, Ernest Hamel, Jean-Charles Chapuis
• Journal: Journal of natural products (J Nat Prod) Vol. 72 Issue 5 Pg. 876-83 (May 22 2009) ISSN: 1520-6025 [Electronic] United States
• PMID: 20161135 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Phytogenic
• Bibenzyls
• Lactones
• Phenyl Ethers
• Prodrugs
• combretastatin D2
• combretastatin

Topics

• Antineoplastic Agents, Phytogenic (chemical synthesis, chemistry, pharmacology)
• Bibenzyls (chemical synthesis, chemistry, pharmacology)
• Crystallography, X-Ray
• Drug Design
• Drug Screening Assays, Antitumor
• Lactones (chemical synthesis, chemistry, pharmacology)
• Molecular Structure
• Phenyl Ethers (chemical synthesis, chemistry, pharmacology)
• Prodrugs (chemical synthesis, chemistry, pharmacology)
• Structure-Activity Relationship