Synfacts 2021; 17(12): 1299
DOI: 10.1055/s-0041-1737082
Synthesis of Natural Products and Potential Drugs

Total Synthesis of (+)-Heilonine

Contributor(s):
Erick M. Carreira
,
Lukas Lüthy
Cassaidy KJ, Rawal VH. * The University of Chicago, USA
Enantioselective Total Synthesis of (+)-Heilonine.

J. Am. Chem. Soc. 2021;
142: 16394-16400
DOI: 10.1021/jacs.1c08756.
 

Significance

(+)-Heilonine is a steroidal alkaloid that was isolated in 1989 from Fritillaria ussuriensisMaxim. It is a member of the cevanine alkaloids, of which only one has been synthesized prior to this work. (+)-Heilonine consists of a hexacyclic framework, including a quinolizidine.


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Comment

Ester D is accessed in enantiomerically enriched form via an asymmetric Diels–Alder reaction, and rapidly elaborated into ketone G. Ketone G was subjected to a Robinson annulation, yielding enone H. Lactam L, accessible via an Evans-aldol stratey, was alkylated with propargyl bromide K, giving triyne M. The key rhodium-catalyzed cyclotrimerization of M yielded arene N with the scaffold of the natural product. Few steps remained to access the natural product (+)-heilonine.


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Publication History

Publication Date:
17 November 2021 (online)

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