Total Synthesis of (+)-Ryanodol

Key words

(+)-ryanodol - (+)-anhydroryanodol - Pauson–Khand reaction - reductive cyclization - selenium dioxide oxidation

Significance

(+)-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.

Comment

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.