Total Synthesis of (±)-Luciduline

Key words

(±)-luciduline - alkaloids - nitrones - [3+2] cycloaddition - Diels–Alder reaction

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.

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.

Publication History

Article published online:
20 April 2021