Krüger S, Gaich T * Leibniz University of Hannover, Germany
Enantioselective, Protecting-Group-Free Total Synthesis of Sarpagine Alkaloids – A
Generalized Approach.
Angew. Chem. Int. Ed. 2014;
DOI:
10.1002/anie.201407280
Key words
alkaloids - cycloaddition - Fischer indole synthesis - ring expansion
Significance
The authors report the enantioselective total synthesis of three sarpagine indole
alkaloids which were isolated from the plant family Apocynaceae. The route relies on a common intermediate G, which is impressively accessed using key features such as a [5+2] oxidopyridinium
cycloaddition and a ring expansion. The three natural products were synthesized in
only eight steps starting from known materials (12 steps from commercially available
compounds).
Comment
The synthesis commenced with a [5+2] cycloaddition between oxidopyridinium salt A and Aggarwal’s chiral ketene equivalent B, thus yielding the desired regioisomer C in a 2:1 ratio. Next, ketone G was accessed through an intramolecular palladium-catalyzed enolate coupling of D, followed by Wittig reaction, deprotection of the dithiolane, and ring expansion.
The indole was introduced in the last step by a Fischer indole synthesis using phenylhydrazines
with different substitution patterns to afford the three targets.
