Alkaloids from alkaloids: total synthesis of (±)-7a- epi-hyacinthacine A 1 from Z-protected tropenone via Baeyer–Villiger oxidation

Abstract

Baeyer–Villiger oxidations of several tropane derivatives have been investigated. Whereas tropenones 15a– c underwent exclusive epoxidation to 21a– c, the corresponding 6-oxotropane derivative 28 yielded the desired lactone 29. Baeyer–Villiger oxidation was also possible for the O-isopropylidene-protected diols 32a, b. The resulting lactones 33a, b were employed in the total synthesis of (±)-7a- epi-hyacinthacine A 1 (7a- epi- 7) via an intramolecular nucleophilic alkyllithium addition to a carbamate as the key lactamization step. The target compound was prepared from tropenone 15b in 10 steps and 14% overall yield. Enzymatic resolution of pyrrolidine (±)- 36 provided a formal total synthesis to both enantiomers of 7.