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Synfacts 2020; 16(09): 1026
DOI: 10.1055/s-0040-1705835
Synthesis of Natural Products and Potential Drugs

The First Total Synthesis of (+)-Resiniferatoxin

Contributor(s):
Erick M. Carreira
,
Patrick Pfaff
Wender PA, *, Jesudason CD, Nakahira H, Tamura N, Tebbe AL, Ueno Y. Stanford University, USA
The First Synthesis of a Daphnane Diterpene:  The Enantiocontrolled Total Synthesis of (+)-Resiniferatoxin.

J. Am. Chem. Soc. 1997;
119: 12976-12977
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Key words

(+)-resiniferatoxin - daphnane diterpenoid - [5+2]-oxidopyrylium cycloaddition - zirconocene-mediated cyclization - Achmatowicz reaction - orthoester formation

Significance

In 1997, Wender and co-workers reported the first total synthesis of (+)-resiniferatoxin, a daphnane diterpenoid isolated from spurge Euphorbia resinifera. Mediated by TRPV1, it exhibits analgesic potencies 103 to 105greater than capsaicin. It also has a score of 16 billion on the Scoville scale.


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Comment

In their seminal work, the authors employed a [5+2]-oxidopyrylium cycloaddition to generate a [6,7]-scaffold. C was further elaborated by Cp2ZrBu2-mediated cyclization and reductive iodoether fragmentation en route to the target, which was completed in a total of 45 steps.


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Publication History

Article published online:
18 August 2020

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