Synthesis and Evolution of Antioxidant, Anticoagulation, and Antiaggregation Activities of Levoglucosenone Adducts Containing Methyl-Substituted Phenyl Fragments

Adducts of levoglucosenone with p-cresol, 3,4-dimethylphenol, and 2,3,6-trimethylphenol were synthesized in one step. The antioxidant, anticoagulation, and antiaggregation activities of the obtained levoglucosenone derivatives were studied. All adducts exhibited anticoagulation and antiaggregation activities at the level of aspirin. The antioxidant activity of the synthesized compounds was assessed from the rate of their reaction with the peroxyl radical of 1,4-dioxane. As a result, all levoglucosenone derivatives examined in the present study were found to reduce the radical-chain oxidation rate. The highest inhibitory activity was found for (1S,2R,5R)-2-(4-hydroxy-2,3,5-trimethylphenyl)-6,8-dioxabicyclo[3.2.1]octan-4-one. The effective inhibition rate constant of this addition product of 2,3,6-trimethylphenol with levoglucosenone was double that of ionol. The obtained results opened up the prospect of synthesizing optically active phenols for further development of drugs with desired pharmacological properties.