Fei Y,
Fan B,
Liu Z,
Ba M,
Cui Z,
Yang P *,
Li A *.
Zhengzhou University and Shanghai Institute of Organic Chemistry, P. R. China
Concise Total Synthesis of Ambiguine P.
J. Am. Chem. Soc. 2025;
147: 18391-18396
DOI:
10.1021/jacs.5c00395
Keywords
(±)-ambiguine P - hapalindole-type alkaloids - Fischer indole synthesis - Cope rearrangement
- Prins-type cyclization - Friedel–Crafts alkylation
Significance
Yang and Li report the total synthesis of hapalindole-type alkaloid (±)-ambiguine
P.
Characterized by their 6–5–6–7–6-pentacyclic
scaffold, ambiguines are the most structurally
complex members of this family. (–)-Ambiguine P
has been isolated from the cyanobacterium
Fischerella ambigua and members of the
ambiguine family have exhibited antimicrobial
activity.
Comment
The indole of (±)-ambiguine P was assembled via Fischer indole synthesis, followed
by
C3-geranylation. Construction of the carbon scaffold of the natural product was
completed via a Cope/Prins/Friedel–Crafts cascade reaction, yielding the pentacyclic
intermediate G. Subsequent desaturation and oxidation reactions completed the
synthesis of (±)-ambiguine P in six steps from ketone A.
