Synfacts 2018; 14(01): 0003
DOI: 10.1055/s-0036-1592042
Synthesis of Natural Products and Potential Drugs
© Georg Thieme Verlag Stuttgart · New York

Synthesis of (–)-Longeracinphyllin A

Erick M. Carreira
Niels Sievertsen
Li J. Zhang W. Zhang F. Chen Y. Li A. * Shanghai Institute of Organic Chemistry, P. R. of China
Total Synthesis of Longeracinphyllin A.

J. Am. Chem. Soc. 2017;
139: 14893-14896
Further Information

Publication History

Publication Date:
15 December 2017 (online)



Alkaloid natural products isolated from leaves and roots of the Daphniphyllum genus of plants are widely used in Chinese herbal medicine. The first and asymmetric total synthesis of (–)-longeracinphyllin A, a member of this structurally complex family of natural products, was accomplished by Li and co-workers. The significance of the approach chosen by the authors lies in the rapid construction of intermediate D and assembly of structurally advanced tetracycle F in large quantities. This enables elegant completion of the highly challenging target by [3+2] cycloaddition in just 21 synthetic steps.



Borrowing from their previously established route for a related natural product (Nat. Chem. 2013, 5, 679), the authors gained expedient entry to the core of the target from abundant precursor C by silver-catalyzed 6-exo-dig cyclization, intramolecular conjugate addition, and asymmetric olefin hydrogenation. Acquisition of enone G proved crucial as this electron-deficient substrate was found to undergo diphosphine-promoted [3+2] cycloaddition with allenoate H, while other olefins would not react. The pentacyclic lactam I was carried on forward to render (–)-longeracinphyllin A.