Chemoenzymatic Synthesis of Fragrance Compounds from Stearic Acid.

Abstract

Fatty acids are versatile precursors for fuels, fine chemicals, polymers, perfumes, etc. The properties and applications of fatty acid derivatives depend on chain length and on functional groups and their positions. To tailor fatty acids for desired properties, an engineered P450 monooxygenase has been employed here for enhanced selective hydroxylation of fatty acids. After oxidation of the hydroxy groups to the corresponding ketones, Baeyer-Villiger oxidation could be applied to introduce an oxygen atom into the hydrocarbon chains to form esters, which were finally hydrolyzed to afford either hydroxylated fatty acids or dicarboxylic fatty acids. Using this strategy, we have demonstrated that the high-value-added flavors exaltolide and silvanone supra can be synthesized from stearic acid through a hydroxylation/carbonylation/esterification/hydrolysis/lactonization reaction sequence with isolated yields of about 36 % (for ω-1 hydroxylated stearic acid; 100, 60, 80, 75 % yields for the individual reactions, respectively) or 24 % (for ω-2 hydroxylated stearic acid). Ultimately, we obtained 7.91 mg of exaltolide and 13.71 mg of silvanone supra from 284.48 mg stearic acid.