Total syntheses of (+)- and (-)-peribysin E

Area of Science:

• Organic Chemistry
• Synthetic Chemistry
• Medicinal Chemistry

Background:

• Cell adhesion inhibitors are crucial in understanding biological processes.
• Peribysin E is a known cell adhesion inhibitor with a complex structure.
• Stereocontrolled synthesis is essential for accessing biologically active molecules.

Purpose of the Study:

• To develop a convergent, stereocontrolled synthetic route to both enantiomers of peribysin E.
• To investigate the mechanism of a key semipinacol-type ring contraction.
• To reassign the absolute configuration of peribysin E.

Main Methods:

• Diels-Alder reaction for cis-decalin framework construction.
• Semipinacol-type ring contraction to establish the C7 quaternary center stereochemistry.
• Deuterium incorporation studies to probe reaction mechanisms.
• Optimized olefin isomerization/Saegusa oxidation for naphthalenedione synthesis.

Main Results:

• Successful stereocontrolled synthesis of peribysin E enantiomers from carvone.
• Identification of potential mechanistic pathways for the ring contraction.
• Development of a novel protocol for synthesizing 1,6(2H,7H)-naphthalenediones.
• Reassignment of the absolute configuration of peribysin E based on enantioselective synthesis.

Conclusions:

• A robust and stereocontrolled synthetic strategy for peribysin E has been established.
• The study provides mechanistic insights into key synthetic transformations.
• The findings contribute to the understanding of peribysin E's structure-activity relationship and stereochemistry.