Chemoenzymatic Synthesis of Musk Flavors from Stearic Acid.

Fatty acids are versatile precursors for fuels, chemicals, polymers, perfumes, etc. The properties and applications of fatty acid derivatives depend on chain-length and functional groups, and their positions. To tailor fatty acids for desired properties, an engineered P450 monooxygenase was here employed for enhanced selective hydroxylation of fatty acids. After oxidation of the hydroxyl group into the corresponding ketone, a Baeyer-Villiger oxidation could be applied to introduce an oxygen atom into the hydrocarbon chain to form esters, which were finally hydrolyzed into a hydroxylated fatty acid or dicarboxylic fatty acid. Based on this strategy, we demonstrate the high-value added flavors, exaltolide and silvanone supra, can be synthesized from stearic acid in a hydroxylation-carbonylation-esterification-hydrolysis-lactonization reaction with the isolated yield of about 36% (for ω-1 hydroxy stearic acid) or 24% (for ω-2 hydroxy stearic acid), 100%, 60%, 80%, 75%, respectively. Finally, we obtained 7.91 mg of exaltolide and 13.71 mg of silvanone supra from 284.48 mg stearic acid.