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Synfacts 2010(10): 1109-1109  
DOI: 10.1055/s-0030-1258076
Synthesis of Natural Products and Potential Drugs
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis of a Phosphodiesterase-4 Inhibitor

Contributor(s): Philip Kocienski
X. Jiang*, G. T. Lee, E. B. Villhauer, K. Prasad*, M. Prashad
Novartis Pharmaceuticals Corporation, East Hanover, USA
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Publication History

Publication Date:
22 September 2010 (online)

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Significance

The target phosphodiesterase-4 (PDE-4) inhibitor H is a potential candidate for the treatment of chronic obstructive pulmonary disease and asthma. A six-step scalable synthesis (27% overall yield) of H features an efficient and mild construction of the 1,7-naphthyridine ring system in E. A fortuitous epimerization that generated D primarily as the trans isomer (trans/cis = 95:5) was compromised in the subsequent conversion of E into F (trans/cis = 4:1).