Synfacts 2021; 17(05): 0488
DOI: 10.1055/s-0040-1719775
Synthesis of Natural Products and Potential Drugs

Total Synthesis of (±)-Luciduline

Contributor(s):
Erick M. Carreira
,
Patrick Pfaff
Oppolzer W, *, Petrzilka M. University of Geneva, Switzerland
A Total Synthesis of d,l-Luciduline by a Regioselective Intramolecular Addition of an N-Alkenylnitrone.

J. Am. Chem. Soc. 1976;
98: 6722-6723
DOI: 10.1021/ja00437a062.
 

Significance

In 1976, Oppolzer and Petrzilka reported the total synthesis of luciduline, an alkaloid isolated from Lycopodium lucidulum. The route featured a highly regioselective [3+2]-nitrone cycloaddition, which in this strategic setting can be interpreted as an equivalent of a Mannich reaction. In addition, the authors reported a highly concise route consisting of only seven linear steps. Of note, no protecting groups were required to furnish the natural product in 27% overall yield.


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Comment

Ketone B is generated by a Diels–Alder reaction between cyclohexenone A and butadiene. B is converted to oxime C at which stage the diastereomers are separated by crystallization. After reduction, nitrone E is generated in situ from hydroxylamine D by condensation with formaldehyde. The nitrone undergoes an intramolecular [3+2] cyclo­addition to furnish isoxazolidine F. Methylation, reduction of the N–O bond, and subsequent Jones oxidation finish the total synthesis of (±)-luciduline hydrochloride.


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Publication History

Publication Date:
20 April 2021 (online)

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