Collective Asymmetric Total Syntheses of Musellarins A-E

Area of Science:

• Organic Chemistry
• Natural Product Synthesis

Background:

• Musellarins are rare cytotoxic diarylheptanoid natural products.
• Musellarins D and E, featuring a cis-fused dihydropyran ring, were synthetically unexplored.

Purpose of the Study:

• To achieve the collective total synthesis of musellarins A-E.
• To establish the first synthetic route to musellarins D and E.
• To correct the stereochemical assignment of musellarins D and E.

Main Methods:

• Development of an Achmatowicz rearrangement-based synthetic strategy.
• Palladium-catalyzed arylation of Achmatowicz rearrangement products with boronic acids.

Main Results:

• Successful total synthesis of musellarins A-E.
• First-time synthesis of musellarins D and E, confirming a cis-fused dihydropyran motif.
• Correction of the C10b configuration for musellarins D and E.
• Access to both trans- and cis-dihydropyran isomers.

Conclusions:

• The developed strategy provides access to both cis- and trans-dihydropyran-containing musellarins.
• This work corrects the stereochemistry of musellarins D and E.
• The synthesis opens avenues for exploring the biological activities of these compounds.