Synthesis of (–)-Calyciphylline N

Key words

(–)-calyciphylline N - alkaloids - Diels–Alder reaction - Nazarov cyclization - hydrogenation

Significance

The authors report the first total synthesis of (–)-calyciphylline N. Although no biodata of this Daphniphyllum alkaloid was published, the complex architecture and potential activity render it an attractive target. Its structure contains six contiguous stereocenters (three of which are quaternary), a dihydropyrrole, and a bicyclo[2.2.2]octane as part of a decahydrocyclopentazulene system.

Comment

An aluminum-catalyzed tethered Diels–Alder reaction of C afforded D as a 9:1 mixture of diastereomers. D was elaborated into J in 22 steps. Treatment with fluoroboric acid effected cyclization, deprotection, and substitution at silicon to give K. Conversion into diene M set the stage for chemo- and diastereoselective iridium-catalyzed hydrogenation to give O, which was carried on to the natural product.