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Synfacts 2014; 10(1): 0009
DOI: 10.1055/s-0033-1340354
Synthesis of Natural Products and Potential Drugs
© Georg Thieme Verlag Stuttgart · New York

Synthesis of Jerantinine E

Rezensent(en):
Erick M. Carreira
,
Mathias J. Jacobsen
Frei R, Staedler D, Raja A, Franke R, Sasse F, Gerber-Lemaire S, Waser J * Ecole Polytechnique Fédérale de Lausanne, Switzerland and Helmholtz Centre for Infection Research, Braunschweig, Germany
Total Synthesis and Biological Evaluation of Jerantinine E.

Angew. Chem. Int. Ed. 2013;
52: 13373-13376
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Publikationsverlauf

Publikationsdatum:
13. Dezember 2013 (online)

 
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Key words

jerantinine E - aspidosperma alkaloids - formal homo-Nazarov cyclization

Significance

Jerantinine E was isolated in 2008 from Tabernaemontana corymbosa. This Aspidosperma alkaloid shows potent cytotoxic activity against human KB cells. The authors report the first synthesis of racemic jerantinine E. Separation of (+)- and (–)-jerantinine E allowed for further biological evaluation. Additionally, investigations into the mode of action revealed potent inhibition of tubulin polymerization.


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Comment

The synthesis commenced with an organo-lithium addition to Weinreb amide B. Treatment of the resulting ketone D with copper (II) triflate resulted in a formal homo-Nazarov cyclization, which gave tetracyclic intermediate E as a single diastereomer. A double-alkylation sequence of F followed by selective demethylation of G afforded jerantinine E in 17 steps from A and 16% overall yield.


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