Stereoselective Biocatalyzed Reductions of Ginger Active Components Recovered from Industrial Wastes

Abstract

Ginger is among the most widespread and widely consumed traditional medicinal plants around the world. Its beneficial effects, which comprise e. g. anticancer and anti‐inflammatory activities as well as gastrointestinal regulatory effects, are generally attributed to a family of non‐volatile compounds characterized by an arylalkyl long‐chained alcohol, diol, or ketone moiety. In this work, ginger active components have been successfully recovered from industrial waste biomass of fermented ginger. Moreover, their recovery has been combined with the first systematic study of the stereoselective reduction of gingerol‐like compounds by isolated alcohol dehydrogenases (ADHs), obtaining the enantioenriched sec‐alcohol derivatives via a sustainable biocatalytic path in up to >99 % conversions and >99 % enantiomeric/diastereomeric excesses.

Functional Characterization and Synthetic Application of Is2-SDR, a Novel Thermostable and Promiscuous Ketoreductase from a Hot Spring Metagenome

“…As mentioned in the introduction, Is2-SDR previously demonstrated interesting reduction activity toward some sterically hindered ketone substrates, e.g., the Wieland–Miescher ketone ( Table 1 , 26 ) [ 22 ] and 6-gingerol ( 28 ) [ 23 ].…”

“…At variance, 6-gingerol ((5 S )-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)decan-3-one, 28 ), was transformed into the 3 R ,5 S diol (gingerdiol) with an excellent e.e. (>99%) and modest conversions (50 %) [ 23 ]. Interestingly, when testing ethyl 2-oxo-4-phenylbutanoate ( 29 ), a bulky–bulky 1,2-ketoester, as a substrate, the R -enantiomer of the corresponding 2-hydroxy ester was obtained with outstanding e.e.…”

“…Is2-SDR reduced 27 with a low conversion and a modest e.e. [ 23 ]. Nevertheless, this enzyme was capable of converting the natural compound 6 S -gingerol ( 28 ), a bulky–bulky substrate, which presents the same “large” group of 27 but is characterized by the presence of 1,3-hydroxyketone installed on the 6 and 8 positions (by traditional nomenclature) of a highly flexible decane chain, resulting in a modest conversion (50%) but in an excellent e.e.…”

“…Nevertheless, this enzyme was capable of converting the natural compound 6 S -gingerol ( 28 ), a bulky–bulky substrate, which presents the same “large” group of 27 but is characterized by the presence of 1,3-hydroxyketone installed on the 6 and 8 positions (by traditional nomenclature) of a highly flexible decane chain, resulting in a modest conversion (50%) but in an excellent e.e. in favor of the 8 R ,6 S diol [ 23 ]. Interestingly, substrate 29 , a 1,2-ketoester (formal) derivative of 27 , was efficiently reduced by Is2-SDR (conversion and e.e.…”

“…Nonetheless, very interesting results were obtained when using Is2-SDR in the biocatalyzed reduction of selected bulky substrates. Specifically, this novel biocatalyst permitted a kinetic resolution of the so-called Wieland–Miescher ketone, a useful intermediate in the synthesis of various complex natural products [ 22 ], as well as the stereoselective reduction of the bulky–bulky ketone 6-gingerol [ 23 ] (see the results and discussion sections for further details).…”