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Synfacts 2007(2): 0117-0117  
DOI: 10.1055/s-2006-955759
Synthesis of Natural Products and Potential Drugs
© Georg Thieme Verlag Stuttgart · New York

Formal Synthesis of Diflomotecan

Contributor(s): Philip Kocienski
R. Peters*, M. Althaus, C. Diolez, A. Rolland, E. Manginot, M. Veyrat
F. Hoffmann-La Roche, Basel, Switzerland; Ipsen, Les Ulis and Expansia, Aramon, France
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Publication History

Publication Date:
23 January 2007 (online)

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Significance

Camptothecin is an alkaloid from the Chinese tree Camptotheca accuminata with potent topisomerase I activity. The lactone ring easily hydrolyses in neutral media to a nearly inactive carboxylate. Diflomotecan has greater hydrolytic stability. Two asymmetric syntheses of diflomotecan are reported, both based on an Evans acetate aldol reaction. The more efficient second route to the fragment I (9 steps, 11.1% overall) involving a single chromatography is shown here. The good dr in the acetate aldol reactions using lithium enolates is noteworthy.