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Synfacts 2020; 16(12): 1395
DOI: 10.1055/s-0040-1719538
Synthesis of Natural Products and Potential Drugs

Formal Synthesis of (–)-Quinine

Contributor(s):
Erick M. Carreira
,
Fabian Glatz
Woodward RB, Doering WE. Havard University, Cambridge, USA
The Total Synthesis of Quinine.

J. Am. Chem. Soc. 1945;
67: 860-874
DOI: 10.1021/ja01221a051.
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Key words

(–)-quinine - chinchona alkaloid - Hofmann elimination - Claisen condensation - malaria

Significance

Quinine, a natural product isolated from the chinchona tree, displays anti malaria properties. The alkaloid has been used in medicine for centuries. Since the seminal report by Woodward, several groups achieved the total synthesis of quinine, among them Uskoković (1970), Stork (2001), and Jacobsen (2004).


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Comment

Isoquinoline A was converted into ketone D, which fragmented to oxime E upon treatment with EtONO. Reduction and Hofmann elimination led to acid G. Protection of the acid and the amine gave rise to H that underwent Claisen condensation. Deprotection and resolution gave (+)-quinotoxine, which Rabe and Kindler (1918) and later Williams (2008) have transformed to (–)-quinine.


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Publication History

Article published online:
17 November 2020

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