Abstract
The high reactivity of endoperoxide moieties poses significant challenges for the synthesis of endoperoxide-containing natural products. To overcome this challenge, enzymes from the biosynthetic pathway can be used in vitro to form the endoperoxide moiety in a single step. The enzyme FtmOx1 is known to form the 8-membered endoperoxide ring in vivo for the natural product 13-oxoverruculogen and can be utilized in a synthesis pathway. This study presents the chemoenzymatic synthesis pathway for 13-oxoverruculogen, focusing on the key enzymatic step, subsequent oxidation, and mechanistic studies. This synthetic approach facilitates the production of 13-oxoverruculogen, a potential anti-cancer agent, and enables further mechanistic studies on the enzyme FtmOx1.