(±)-Diinsininone: made nature's way

Area of Science:

• Organic Chemistry
• Natural Product Synthesis
• Flavonoid Chemistry

Background:

• Proanthocyanidins (PAs) are a diverse class of natural products with significant biological activities.
• The synthesis of complex PA structures, particularly type-A PAs, remains a synthetic challenge.
• The characteristic [3.3.1]-bicyclic ketal core of certain PAs is crucial for their structure-activity relationship.

Purpose of the Study:

• To report the first synthesis of diinsininone (33), the aglycone of (±)-diinsinin (2).
• To achieve the first construction of a proanthocyanidin (PA) type-A compound featuring a [3.3.1]-bicyclic ketal core.
• To develop a versatile synthetic strategy applicable to other PA type-A compounds.

Main Methods:

• A novel coupling strategy involving a benzopyrilium salt and a flavanone was employed.
• Naringenin was transformed into eriodictyol using 2-iodoxybenzoic acid (IBX) and reductive work-up, mimicking catechol hydroxylase (F3H) activity.
• Flavonoid formation was achieved via an ortho-quinone methide (o-QM) cycloaddition-oxidation sequence.
• Regioselective β-glycosidations of unprotected flavanones were performed.

Main Results:

• Successful synthesis of diinsininone (33), the aglycone of (±)-diinsinin (2).
• Demonstrated the first construction of a proanthocyanidin (PA) type-A compound with a [3.3.1]-bicyclic ketal core.
• Established a coupling strategy between a benzopyrilium salt and a flavanone applicable to other PA type-A compounds.
• Observed reactivity mirroring F3H in the conversion of naringenin to eriodictyol.
• Achieved flavonoid synthesis through o-QM cycloaddition-oxidation and regioselective glycosidations.

Conclusions:

• The reported synthesis of diinsininone (33) and the construction of a PA type-A compound with a [3.3.1]-bicyclic ketal core represent a significant advancement in PA synthesis.
• The developed coupling strategy offers a viable route for accessing other complex PA type-A structures.
• The observed biomimetic transformations provide insights into flavonoid biosynthesis pathways.