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Synfacts 2006(9): 0872-0872  
DOI: 10.1055/s-2006-942049
Synthesis of Natural Products and Potential Drugs
© Georg Thieme Verlag Stuttgart · New York

Synthesis of IC86518

Contributor(s): Philip Kocienski
P. J. Nichols*, J. A. DeMattei, B. R. Barnett, N. A. LeFur, T.-H. Chuang, A. D. Piscopio, K. Koch
Array BioPharma, Boulder, USA
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Publication History

Publication Date:
23 August 2006 (online)

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Significance

IC86518 is an inhibitor of phospho­diesterase type 4 (PDE4) (IC50 = 14 nm) and a lead for the treatment of inflammation. The key step in the synthesis is an efficient asymmetric conjugate addition (4-kg-scale) of a malonate to a nitroalkene catalyzed by the bis(oxazoline) ligand C (J. Ji et al. J. Am. Chem. Soc. 1999, 121, 10215-10216). Over 1 kg of the final product was produced by the route depicted.