Stereospecific Epoxidation of Limonene Catalyzed by Peroxygenase from Oat Seeds

Abstract

Limonene is one of the most abundant naturally occurring cyclic monoterpenes and has recently emerged as a sustainable alternative to petroleum-based solvents as well as a chemical platform for the production of value-added compounds. The biocatalytic epoxidation of both enantiomers of limonene was carried out in the presence of a peroxygenase-containing preparation from oat (Avena sativa) flour. Different reaction profiles were observed depending on the starting enantiomer of limonene, but in both cases the 1,2-monoepoxide was obtained as the main product with excellent diastereoselectivity. Trans-1,2-monoepoxide and cis-1,2-monoepoxide were isolated from the reaction of (R)-limonene and (S)-limonene, respectively, and the reactions were scaled-up to 0.17 M substrate concentration. The process is valuable for operational simplicity, lack of toxic metal catalysts, and cost-effectiveness of the enzymatic source. Pure stereoisomers of 1,2-monoepoxides of limonene constitute a useful starting material for biorenewable polymers, but can be also converted into other chiral derivatives by epoxide ring opening with nucleophiles. As a proof of concept, a tandem protocol for the preparation of enantiopure (1S,2S,4R)-1,2-diol from (R)-limonene and (1R,2R,4S)-1,2-diol from (S)-limonene was developed.

Modelling of green biocatalytic (R)-(+)-limonene oxidation using the mycelium of psychrophilic Cladosporium cladosporioides 01

“…The stereospecificity in the epoxidation of limonene was observed in other systems where a biocatalyst with peroxygenase activity was used in an aqueous environment. 28 Epoxidation of limonene to limonene 1,2-epoxide was also performed by Wiemann et al (2012) who used lipase B from Candida antarctica immobilized on various carriers. Full limonene conversion (>98%) was achieved at 40 °C within less than 24 hours.…”

“…The stereospecificity in the epoxidation of limonene was observed in other systems where a biocatalyst with peroxygenase activity was used in an aqueous environment. 28 Epoxidation of limonene to limonene 1,2-epoxide was also performed by Wiemann et al…”

Expanding the Use of Peroxygenase from Oat Flour in Organic Synthesis: Enantioselective Oxidation of Sulfides

“…At the onset of our work, the standard conditions developed in the peroxygenase-catalyzed epoxidation of different substrates [ 40 , 42 ] were applied for the oxidation of thioanisole 1 ( Scheme 1 ). The peroxygenase biocatalyst was obtained by lyophilization of the aqueous extract of oat flour, as previously described [ 40 ], and the slight excess (1.1 eqv.)…”

“…In our previous work, we have shown that the peroxygenase activity is maintained in a lyophilized raw preparation from oat seeds and applied it in the selective epoxidation of EPA and DHA (and the corresponding ethanolamides), also assigning the absolute configuration and enantiomeric excess of the obtained products [ 40 , 41 ]. The same enzymatic preparation catalyzed the epoxidation of both enantiomers of limonene with excellent regio- and diastereoselectivity [ 42 ]. As a part of a study aimed to better explore the application of oat peroxygenase in asymmetric organic synthesis, the oxidation of thioanisole and some related sulfides was investigated and the obtained results are reported here.…”

Peroxygenase-Catalyzed Selective Synthesis of Calcitriol Starting from Alfacalcidol

“…Thus far, the potential for industrial application of P450s still remains unexplored [ 19 ]. In contrast, unspecific peroxygenases (UPOs) have been considered “ideal” biocatalysts for oxidative functionalization reactions of a variety of activated and nonactivated C-H bonds [ 20 , 21 , 22 , 23 , 24 , 25 , 26 ]. A recent report by Hollmann et al substantially demonstrated the potential of large-scale production of the enzyme yielding practical amounts of these promising catalysts [ 27 ].…”