A flexible approach to both type II and III lepadin alkaloids is developed for the
first time. A key Diels–Alder reaction based on a novel chiral ketolactone dienophile
is employed to obtain the desirable all-cis-trisubstituted cyclohexene with excellent regio- and stereoselectivity. As the subsequent
closure of the piperidine ring is devised at the N1 and C2 position via an intramolecular
nucleophilic amination, the two stereochemical types of lepadin frameworks with the
opposite configuration at C2 can be conveniently accessible from a common intermediate.
By the approach, lepadins D, E (type II) and F (type III) are stereoselectively synthesized
from ethyl l-lactate.
Key words
lepadin - alkaloid - total synthesis - stereoselective synthesis - ketolactone dienophile
- Diels–Alder reaction
