A chemo-enzymatic route to differentially protected aryl-naphthalenes

Area of Science:

• Organic Chemistry
• Biocatalysis
• Enzymology

Background:

• Aryl-naphthalene scaffolds are important in medicinal chemistry and materials science.
• Selective functionalization of these scaffolds is crucial for developing new derivatives.
• Enzymatic methods offer green and efficient alternatives for chemical synthesis.

Purpose of the Study:

• To develop a selective enzymatic method for the synthesis of differentially protected aryl-naphthalenes.
• To investigate the regioselectivity of AK lipase in hydrolysis and acetylation reactions on aryl-naphthalene diacetates and diols.
• To provide a facile route to functionalized aryl-naphthalene compounds.

Main Methods:

• Synthesis of aryl-naphthalene diacetates via Garratt-Braverman Cyclization.
• Selective enzymatic hydrolysis of diacetates to monoacetates using AK lipase.
• Enzymatic acetylation of diols to regioisomeric monoacetates using AK lipase.

Main Results:

• High yields of monoacetates (12a-c) were obtained from the selective hydrolysis of diacetates.
• Regioisomeric monoacetates (13a-c) were successfully synthesized by enzymatic acetylation of diols.
• The regioselectivity was attributed to the preferential binding of the more exposed acetoxymethyl or hydroxyl group to the enzyme's active site.

Conclusions:

• AK lipase efficiently catalyzes selective hydrolysis and acetylation reactions on aryl-naphthalene derivatives.
• The developed method provides a straightforward approach to differentially protected aryl-naphthalenes.
• These intermediates are valuable for further synthetic elaborations and the discovery of novel compounds.