Total Synthesis of Ajmaline

Key words

ajmaline - reductive amination - glycol cleavage/Pictet–Spengler reaction - decarboxylation/ Mannich reaction - chiral resolution - epimerization - reductive cyclization

Significance

In 1970, van Tamelen and co-workers reported the total synthesis of ajmaline. The alkaloid, which was first isolated in 1931 from the roots of Rauvolfia serpentine, is utilized as an antiarrhythmic agent. The synthetic strategy features a glycol cleavage/Pictet–Spengler sequence. This transformation had been previously employed by van Tamelen and co-workers in their synthesis of yohimbine.

Comment

Diol E, assembled by reductive amination between aldehyde C and amine D, is the precursor for the glycol cleavage/Pictet–Spengler sequence, furnishing aldehyde F. Decarboxylation of F initiates a Mannich reaction, giving rise to aldehyde G. After chiral resolution, epimerization, and reductive cyclization, the obtained deoxyajmaline was converted to ajmaline through dealkylation and oxidative ring closure.

Publication History

Article published online:
14 May 2024