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Synfacts 2010(9): 0984-0984  
DOI: 10.1055/s-0030-1257877
Synthesis of Natural Products and Potential Drugs
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis of a Histamine H3 Receptor Antagonist

Contributor(s): Philip Kocienski
D. J. Pippel*, L. K. Young, M. A. Letavic, K. S. Ly, B. Naderi, A. Soyode-Johnson, E. M. Stocking, N. I. Carruthers, N. S. Mani
Johnson & Johnson Pharmaceutical Research and Development, San Diego, USA
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Publication History

Publication Date:
23 August 2010 (online)

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Significance

The target molecule is a histamine H3 receptor antagonist under investigation for various CNS disorders. The synthesis depicted was designed to access the (2R,4S)-4-hydroxyproline core from cheap (2S,4R)-4-hydroxyproline (<$2/g) via a double inversion sequence. The first inversion of the C2 stereocenter was accomplished by formation of La Rosa’s bicyclic lactone D (P. Dalla Croce, C. La Rosa Tetrahedron: Asymmetry 2002, 13, 197).