Guo X.-F,
Shao H,
Ma Z.-H,
Sun J,
Zhou Q,
Zhao Y.-M.
*
Shaanxi Normal University, Xi’an, P. R. of China
Bioinspired Collective Total Synthesis of (±)-Rhynchines A–E.
Org. Lett. 2024;
26: 3135-3139
DOI:
10.1021/acs.orglett.4c00727
Key words
(±)-rhynchine E - Pictet–Spengler reaction - 1,2-migration - aldol addition - C–H
oxidation - Krapcho decarboxylation
Significance
In 2021, a new class of structurally unique monoterpene indole alkaloids was isolated
from Uncaria rhynchophylla, rhynchines A–E. Zhao and co-workers now report the first racemic total synthesis
of rhynchine E as well as rhynchine A–D. A biosynthetic relationship of the rhynchines
natural products to hirsuteine, which is also commonly found in the isolation plant,
was proposed.
Comment
The synthesis commenced with the formation of tetracyclic triester E from pyridinium salt C, through a Pictet–Spengler reaction. Subsequent treatment with NaBH3CN in AcOH, triggered conjugated reduction and a 1,2-migration, forming the core tetrahydroazepine
G. The tetrahydrofuran ring of (±)-rhynchine E was formed via C–H oxidation using K3[Fe(CN)6].
