The Discreet Structural Diversity of Briarellins: DU8+ Guided Multiple Structure Revisions Yielded Two Unknown...

Area of Science:

• Natural Product Chemistry
• Computational Chemistry
• Organic Synthesis

Background:

• Briarellins, a class of cyclized cembranoids, were previously proposed to have specific ether or lactone bridges.
• Total synthesis of briarellin J indicated a structural misassignment in the proposed briarellin framework.

Purpose of the Study:

• To computationally re-evaluate the structures of briarellins.
• To correct misassigned structures of briarellin C14-C3 ε-lactones.
• To confirm the structures of briarellin and asbestinin ethers.

Main Methods:

• Utilized a hybrid density functional theory (DFT)/parametric method, DU8+, for computational analysis.
• Revisited and revised proposed structures based on computational data.

Main Results:

• Revised structures of briarellin C14-C3 ε-lactones were identified, featuring novel C14-C11 or C14-C12 lactone bridges.
• The original proposed structures for briarellin and asbestinin ethers were computationally confirmed.

Conclusions:

• The study corrects significant structural misassignments in the briarellin family of natural products.
• New structural types of briarellins with different lactone bridges have been elucidated.
• Computational methods provide a powerful tool for natural product structure elucidation and revision.