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

Abstract

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 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 is reported. Subsequent lactonization yields (S)-δ-decalactone 3, a high value fragrance compound, with greater than 90 % ee. Docking studies provide a rationale for the high regio- and enantioselectivity of the reaction.

Keywords: biocatalysis; cytochrome P450; fatty acids; lactones; regioselectivity.