Synfacts 2014; 10(3): 0227
DOI: 10.1055/s-0033-1340708
Synthesis of Natural Products and Potential Drugs
© Georg Thieme Verlag Stuttgart · New York

Synthesis of (–)-Calyciphylline N

Erick M. Carreira
Matthias Westphal
Shvartsbart A, Smith III AB * University of Pennsylvania, Philadelphia, USA
Total Synthesis of (–)-Calyciphylline N.

J. Am. Chem. Soc. 2014;
136: 870-873
Further Information

Publication History

Publication Date:
17 February 2014 (online)



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.



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.