Regiospecific C-H amination of (-)-limonene into (-)-perillamine by multi-enzymatic cascade reactions.

BACKGROUND

(-)-Limonene, one of cyclic monoterpenes, is an important renewable compound used widely as a key building block for the synthesis of new biologically active molecules and fine chemicals. (-)-Perillamine, as derived from (-)-limonene, is a highly useful synthon for constructing more complicated and functionally relevant chemicals.

AIM

We aimed to report a more sustainable and more efficient method for the regiospecific C-H amination of (-)-limonene into (-)-perillamine.

RESULTS

Here, we report an artificial penta-enzymatic cascade system for the transformation of the cheap and easily available (-)-limonene into (-)-perillamine for the first time. This system is composed of cytochrome P450 monooxygenase, alcohol dehydrogenase and w-transaminase for the main reactions, as well as formate dehydrogenase and NADH oxidase for cofactor recycling. After optimization of the multi-enzymatic cascade system, 10 mM (-)-limonene was smoothly converted into 5.4 mM (-)-perillamine in a one-pot two-step biotransformation, indicating the feasibility of multi-enzymatic C7-regiospecific amination of the inert C-H bond of (-)-limonene. This method represents a concise and efficient route for the biocatalytic synthesis of derivatives from similar natural products.