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Synfacts 2011(5): 0463-0463  
DOI: 10.1055/s-0030-1259793
Synthesis of Natural Products and Potential Drugs
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis of Strychnine

Contributor(s):Steven V. Ley, Philippa B. Cranwell
D. B. C. Martin, C. D. Vanderwal*
University of California, Irvine, USA
A Synthesis of Strychnine by a Longest Linear Sequence of Six Steps
Chem. Sci.  2011,  2:  649-651  
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Publication History

Publication Date:
15 April 2011 (online)

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Key words

Wieland-Gumlich intermediates - Brook rearrangement - intramolecular conjugate addition - Zincke aldehydes

Significance

Strychnine is a highly toxic alkaloid isolated from seeds of the Strychnos nux vomica tree. It was first synthesized by Woodward and co-workers in 1954, and has since proved a popular target within the synthetic community. This approach is highly efficient and only requires six steps in the longest ­linear sequence.

Comment

The conversion of Zincke aldehyde C into tetracycle D via base-mediated cyclization proceeded efficiently and in good yield (D. B. Martin, C. Vanderwal J. Am. Chem. Soc. 2009, 131, 3472). Alkylation of bromide G (three steps from 1,4-butynediol) with amine F provided alcohol H. This underwent a 1,4-Brook rearrangement in situ, which upon treatment with a copper(I) source provided the core of strychnine. Unfortunately, after extensive optimization, the yield remained low and the major byproduct was due to protodesilylation.

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