Fully Biocatalytic Rearrangement of Furans to Spirolactones.

Area of Science:

• Organic Chemistry
• Biocatalysis
• Natural Product Synthesis

Background:

• Spirolactone motifs are crucial in various bioactive natural products.
• Efficient and stereoselective synthesis of these building blocks remains a challenge.
• Biocatalysis offers a sustainable alternative to traditional chemical synthesis.

Purpose of the Study:

• To develop a streamlined, multienzymatic cascade for preparing optically pure spirolactone building blocks.
• To demonstrate the utility of this biocatalytic method in natural product total synthesis.
• To establish a chemoenzymatic route for synthesizing specific bioactive compounds.

Main Methods:

• A one-pot reaction cascade combining chloroperoxidase, an oxidase, and an alcohol dehydrogenase.
• Biocatalytic conversion of hydroxy-functionalized furans to spirocyclic products.
• Application in the total synthesis of (+)-crassalactone D and lanceolactone A.

Main Results:

• Successful preparation of optically pure spirolactone building blocks.
• Efficient conversion of furan derivatives to spirocyclic structures.
• Demonstrated utility in the total synthesis of (+)-crassalactone D and a chemoenzymatic route to lanceolactone A.

Conclusions:

• A novel and efficient multienzymatic pathway for spirolactone synthesis has been established.
• The developed biocatalytic method is versatile and applicable to complex natural product synthesis.
• This approach offers a sustainable and stereoselective route to valuable chemical scaffolds.