Enantioselective synthesis of (+)-anatoxin-a via enyne metathesis

A concise synthesis of the potent nAChR agonist (+)-anatoxin-a () has been completed by a series of nine chemical operations and in 27% overall yield from commercially available d-methyl pyroglutamate (). The strategy featured the application of a new protocol for the diastereoselective synthesis of cis-2,5-disubstituted pyrrolidines bearing unsaturated side chains and an intramolecular enyne metathesis to provide the bridged bicyclic framework of . Thus, d-methyl pyroglutamate () was converted in five steps to , which underwent facile enyne metathesis to deliver the bicyclic diene . Selective oxidative cleavage of the less substituted carbon–carbon double bond in followed by deprotection furnished (+)-anatoxin-a ().