Chemoenzymatic oxygenation method for sesquiterpenoid synthesis based on Fe-chelate and ferric-chelate reductase

Abstract

Sesquiterpenoids are one of the most diverse groups in natural compounds with various chemical structures and bioactivities. In our previous work, we developed the chemoenzymatic oxygenation method based on the combination of Fe(II)-EDTA and ferric-chelate reductase that could synthesize (−)-rotundone, a key aroma sesquiterpenoid of black pepper. Fe(II)-EDTA catalyzed the oxygenation of sesquiterpene to sesquiterpenoid, and ferric-chelate reductase catalyzed the supply and regeneration of Fe(II)-EDTA in this system. We then investigated the effect of various Fe2+-chelates on the catalytic oxygenation of sesquiterpene and applied this system to the synthesis of odor sesquiterpenoids. We determined Fe(II)-NTA to be an efficient oxygenation catalyst by the screening approach focusing on ligand structures and coordination atoms of Fe2+-chelates. Valuable odor sesquiterpenoids such as (+)-nootkatone, (−)-isolongifolenone, and (−)-β-caryophyllene oxide were oxygenatively synthesized from each precursor sesquiterpene by 66%, 82%, and 67% of the molar conversion rate, respectively. Abbreviations: EDTA: ethylenediaminetetraacetate; NTA: nitrilotriacetate; DTPA: diethylenetriaminepentaacetate; phen: o-phenanthroline; cyclam: 1,4,8,11-tetraazacyclotetradecane; TPA: tris(2-pyridylmethyl)amine; GlcDH: glucose dehydrogenase; HP-β-CD: hydroxypropyl-β-cyclodextrin.