Synthesis of (+)-Kuraramine

Abstract

The first synthesis of (+)-kuraramine via oxidative cleavage of (-)-N-methylcytisine is reported. An alternative but unsuccessful approach to (+)-kuraramine is also described based on extending an intramolecular enolate addition protocol that had previously been applied successfully to cytisine.

Key words

cytisine - kuraramine - alkaloids

References and Notes

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9

For silane 4, the key NMR signals [^¹H NMR (500 MHz, CDCl₃): δ = 4.34 (1 H, d, J = 1.0 Hz, H10) and ^¹³C NMR (126 MHz, CDCl₃): δ = 54.2 (C10)] showed the presence of a single diastereomer. The small coupling constant (J = 1.0 Hz) suggested an equatorial-equatorial coupling between H9 and H10. The equatorial assignment of H10 was further supported by NOE data: irradiation of H10 showed enhancements of H9, H11 and SiCH₃, while irradiation of H8_ax and H8_eq showed no enhancement associated with H10.

11

For carbinol 5, the key NMR signal [^¹H NMR (400 MHz, CDCl₃): δ = 5.80 (1 H, s, H10)] showed the presence of a single diastereomer and suggested the same (likely thermodynamic) stereochemical preference as silane 4.

13

Key NMR signals for aldehyde 9: ^¹H NMR (400 MHz, CDCl₃): δ = 9.63 (1 H, s, H10). ^¹³C NMR (101 MHz, CDCl₃): δ = 200.3 (C10).

15

Supporting Information (as a pdf) is available with this paper and contains full experimental details of all compounds reported and copies of spectra, including NOE experiments.