Regioselective Oxidation of Tetrahydronaphthalenes to α-Tetralone Derivatives Using DDQ as Oxidizing Agent: Synthesis and Evaluation of Antibacterial and Antifungal Activities

Abstract

An easy and efficient approach for the synthesis of highly regioselective functionalized dihydronaphthalen-1(2H)-one family of α-tetralones from functionalized tetralone precursors which derived from Morita-Baylis-Hillman (MBH) adducts as starting substrates has been developed. The target dihydronaphthalen-1(2H)-ones are obtained through the oxidation of tetrahydronaphthalenes (THN) using DDQ as the oxidizing agent, conducted in aqueous acetic acid at reflux conditions. The yields obtained ranged from 90 to 98%. The resulting dihydronaphthalen-1(2H)-ones were evaluated for their in vitro antibacterial activity against nine Gram-positive and six Gram-negative strains. Additionally, their antifungal properties were assessed against three fungal pathogens by using the microdilution method and Biolog Phenotype Microarrays technology. Remarkably, the synthesized dihydronaphthalen-1(2H)-ones exhibited good antibacterial activity when compared to reference drugs such as vancomycin and ampicillin. Similarly, their antifungal activity is comparable to the effectiveness of the reference drugs cycloheximide and fluconazole.

Scheme 1. Synthesis of Tetrahydronaphthalenes 1a–d

Scheme 2. Protection of Tetrahydronaphthol 1b

Scheme 3. Attempt to Oxidize Acetate 3b Using DDQ

Scheme 4. Attempt to Oxidize Acetate 3b Using CrO₃

Scheme 5. Oxidation of 1b in the Presence of DDQ

Scheme 6. Oxidation of Tetrahydronaphthalenes 1 to α-Tetralones 2 in the Presence of DDQ in CH₃COOH

Figure 1

2D HMBC NMR spectrum of compound 2a.