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A Concise Synthesis of Fumagillol
David A Vosburg1, Sven Weiler1, Erik J Sorensen1
1The Skaggs Institute for Chemical Biology, and Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037 (USA), Fax: (+1) 619-784-2798.
Abstract:
A 13-step synthesis of (±)-fumagillol (1), the direct precursor of the potent angiogenesis inhibitors TNP-470 and fumagillin, from crotonaldehyde, diethylamine, and acrolein (see the scheme) has been achieved. The synthesis features a remarkable hetero-Claisen rearrangement. Small-molecule inhibitors of angiogenesis are promising chemotherapeutic agents for the treatment of cancer and inflammatory diseases.
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