Regio- and Enantio-selective Chemo-enzymatic C-H-lactonization of Decanoic Acid to (S)-δ-Decalactone.

The conversion of saturated fatty acids to high value chiral hydroxy-acids and lactones poses a number of synthetic challenges: the activation of unreactive C-H bonds and the need for regio- and stereoselectivity. Here we report the first example of a wild type cytochrome P450 monooxygenase (CYP116B46 from Tepidiphilus thermophilus) capable of enantio- and regioselective C5 hydroxylation of decanoic acid 1 to (S)-5- hydroxydecanoic acid 2. Subsequent lactonization yielded (S)-δ- decalactone 3, a high value fragrance compound, with > 90 % ee. Docking studies provide a rationale for the high regio- and enantioselectivity of the reaction.