van Tamelen EE,
*,
Oliver LK.
Stanford University, USA
The Biogenetic-Type Total Synthesis of Ajmaline.
J. Am. Chem. Soc. 1970;
92: 2136-2137
DOI:
10.1021/ja00710a059
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.
