Total synthesis of ryanodol.

Area of Science:

• Organic Chemistry
• Medicinal Chemistry
• Chemical Biology

Background:

• Ryanodol (1) is a natural product derivative, ryanodine, that modulates calcium release channels.
• Ryanodol possesses a complex pentacyclic structure with eight oxygen and three methyl groups, and numerous stereocenters.

Purpose of the Study:

• To achieve the total synthesis of the complex natural product ryanodol.
• To develop a novel and flexible synthetic strategy for generating ryanodine derivatives.

Main Methods:

• Total synthesis of ryanodol (1) in 22 steps from a C2-symmetric tricycle (8).
• Installation of seven stereogenic centers and formation of four C-C bonds within a congested multicyclic framework.

Main Results:

• Successfully synthesized the exceptionally complex ryanodol molecule.
• Developed a flexible strategy applicable to generating diverse chemical derivatives.

Conclusions:

• The total synthesis of ryanodol was accomplished.
• The developed synthetic route provides a platform for creating novel ryanodine analogs for calcium release channel research.