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DOI: 10.1021/jo1019688

Asymmetric Synthesis Of All The Known Phlegmarine Alkaloids.

Bradley H Wolfe, A. Libby, R. Al-awar, C. J. Foti, D. Comins
Published 2010 · Chemistry, Medicine

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The asymmetric synthesis of all four of the known natural phlegmarines and one synthetic derivative has been accomplished in 19-22 steps from 4-methoxy-3-(triisopropylsilyl)pyridine. Chiral N-acylpyridinium salt chemistry was used twice to set the stereocenters at the C-9 and C-2' positions of the phlegmarine skeleton. Key reactions include the use of a mixed Grignard reagent for the second N-acylpyridinium salt addition, zinc/acetic acid reduction of a complex dihydropyridone, and a von Braun cyanogen bromide N-demethylation of a late intermediate. These syntheses confirmed the absolute stereochemistry of all of the known phlegmarines.
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