Synfacts 2016; 12(12): 1225
DOI: 10.1055/s-0036-1589447
Synthesis of Natural Products and Potential Drugs
© Georg Thieme Verlag Stuttgart · New York

Total Synthesis of (+)-Ryanodol

Erick M. Carreira
Nicole Hauser
Chuang KV, Xu C, Reisman SE * California Institute of Technology, Pasadena, USA
A 15-Step Synthesis of (+)-Ryanodol.

Science 2016;
353: 912-915
Further Information

Publication History

Publication Date:
17 November 2016 (online)



(+)-Ryanodol is a highly oxidized complex diterpenoid and the hydrolysis product of ryanodine. It modulates intracellular Ca2+ channels, albeit with lower affinity than the parent natural product. Reisman and co-workers completed the synthesis of (+)-ryanodol in only 15 steps from (S)-pulegone.



Key intermediate G was assembled in seven steps from (S)-pulegone and transformed into enone H by a highly diastereoselective ­Pauson–Khand reaction. Treatment of tetracycle H with SeO2 under strictly anhydrous conditions led to the simultaneous installation of three oxygen functionalities. (+)-Anhydroryanodol was finally converted into (+)-ryanodol by epoxidation and reductive cyclization.