Total synthesis and structural revision of sekothrixide

Area of Science:

• Organic Chemistry
• Natural Product Synthesis

Background:

• Sekothrixide is a 14-membered macrolide natural product.
• The precise stereochemistry of sekothrixide was previously uncertain.

Purpose of the Study:

• To achieve the first total synthesis of sekothrixide.
• To clarify the structural and stereochemical details of natural sekothrixide.

Main Methods:

• Construction of seven contiguous stereocenters in the side chain via epoxide ring-opening reactions.
• Fragment coupling using the ring-closing metathesis (RCM) reaction to form the 14-membered macrolactone ring with an E-trisubstituted olefin.

Main Results:

• Successful total synthesis of sekothrixide.
• The synthesis established the stereochemistry at C4, C6, and C8.
• The results necessitated a revision of the originally proposed structure of natural sekothrixide.

Conclusions:

• The first total synthesis of sekothrixide provides a reliable route to the natural product.
• The synthetic effort corrected the stereochemical assignment at key positions (C4, C6, C8).
• This work clarifies the structure of sekothrixide and contributes to macrolide synthesis strategies.