Kinetic resolution of citronellal by chiral aluminum catalysts: <scp>l</scp>-menthol synthesis from citral

Itoh, Hisanori; Maeda, Hironori; Yamada, S.; Hori, Yoji; Mino, Takashi; Sakamoto, Masami

doi:10.1039/c4qo00222a

Cited by 16 publications

(11 citation statements)

References 43 publications

(36 reference statements)

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“…( R )-citronellal is a valuable intermediate for the synthesis of L-menthol through an acidic ene-cyclization and subsequent hydrogenation [1,2,3]. The potential of ( R )-citronellal was also explored for the synthesis of natural vitamin E—a kind of fat-soluble vitamin with relatively high antioxidant ability [4,5].…”

Section: Introductionmentioning

confidence: 99%

Engineering the Enantioselectivity of Yeast Old Yellow Enzyme OYE2y in Asymmetric Reduction of (E/Z)-Citral to (R)-Citronellal

Ying

Huang

et al. 2019

Molecules

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The members of the Old Yellow Enzyme (OYE) family are capable of catalyzing the asymmetric reduction of (E/Z)-citral to (R)-citronellal—a key intermediate in the synthesis of L-menthol. The applications of OYE-mediated biotransformation are usually hampered by its insufficient enantioselectivity and low activity. Here, the (R)-enantioselectivity of Old Yellow Enzyme from Saccharomyces cerevisiae CICC1060 (OYE2y) was enhanced through protein engineering. The single mutations of OYE2y revealed that the sites R330 and P76 could act as the enantioselectivity switch of OYE2y. Site-saturation mutagenesis was conducted to generate all possible replacements for the sites R330 and P76, yielding 17 and five variants with improved (R)-enantioselectivity in the (E/Z)-citral reduction, respectively. Among them, the variants R330H and P76C partly reversed the neral derived enantioselectivity from 32.66% e.e. (S) to 71.92% e.e. (R) and 37.50% e.e. (R), respectively. The docking analysis of OYE2y and its variants revealed that the substitutions R330H and P76C enabled neral to bind with a flipped orientation in the active site and thus reverse the enantioselectivity. Remarkably, the double substitutions of R330H/P76M, P76G/R330H, or P76S/R330H further improved (R)-enantioselectivity to >99% e.e. in the reduction of (E)-citral or (E/Z)-citral. The results demonstrated that it was feasible to alter the enantioselectivity of OYEs through engineering key residue distant from active sites, e.g., R330 in OYE2y.

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Section: Introductionmentioning

confidence: 99%

Engineering the Enantioselectivity of Yeast Old Yellow Enzyme OYE2y in Asymmetric Reduction of (E/Z)-Citral to (R)-Citronellal

Ying

Huang

et al. 2019

Molecules

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“…These complexes have a metal center between two parallel aromatic rings. 14,28 During the transition state of the ringclosing ene reaction, the aromatic rings are in close proximity to 3-vinylcitronellal. This narrow space results in the good diastereoand enantioselectivity seen in the reaction.…”

Section: Cho Chomentioning

confidence: 99%

BINOL-Al catalyzed kinetic resolution of citronellal analogues: synthesis of a variety of fragrances

Itoh¹,

Maeda²,

Yamada³

et al. 2016

Tetrahedron: Asymmetry

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“…( R )-citronellal serves as the key intermediate in the synthesis of L-menthol, which is one of the most popular flavors in the world [ 1 , 2 , 3 , 4 ]. The industrial production of ( R )-citronellal is currently synthesized through chemical approaches starting from myrcene (Takasago company in Japan) or citral (BASF company in Germany).…”

Section: Introductionmentioning

confidence: 99%

Engineering of Yeast Old Yellow Enzyme OYE3 Enables Its Capability Discriminating of (E)-Citral and (Z)-Citral

et al. 2021

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The importance of yeast old yellow enzymes is increasingly recognized for direct asymmetric reduction of (E/Z)-citral to (R)-citronellal. As one of the most performing old yellow enzymes, the enzyme OYE3 from Saccharomyces cerevisiae S288C exhibited complementary enantioselectivity for the reduction of (E)-citral and (Z)-citral, resulting in lower e.e. value of (R)-citronellal in the reduction of (E/Z)-citral. To develop a novel approach for the direct synthesis of enantio-pure (R)-citronellal from the reduction of (E/Z)-citral, the enzyme OYE3 was firstly modified by semi-rational design to improve its (R)-enantioselectivity. The OYE3 variants W116A and S296F showed strict (R)-enantioselectivity in the reduction of (E)-citral, and significantly reversed the (S)-enantioselectivity in the reduction of (Z)-citral. Next, the double substitution of OYE3 led to the unique variant S296F/W116G, which exhibited strict (R)-enantioselectivity in the reduction of (E)-citral and (E/Z)-citral, but was not active on (Z)-citral. Relying on its capability discriminating (E)-citral and (Z)-citral, a new cascade reaction catalyzed by the OYE3 variant S296F/W116G and glucose dehydrogenase was developed, providing the enantio-pure (R)-citronellal and the retained (Z)-citral after complete reduction of (E)-citral.

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Kinetic resolution of citronellal by chiral aluminum catalysts: l-menthol synthesis from citral

Cited by 16 publications

References 43 publications

Engineering the Enantioselectivity of Yeast Old Yellow Enzyme OYE2y in Asymmetric Reduction of (E/Z)-Citral to (R)-Citronellal

Engineering the Enantioselectivity of Yeast Old Yellow Enzyme OYE2y in Asymmetric Reduction of (E/Z)-Citral to (R)-Citronellal

BINOL-Al catalyzed kinetic resolution of citronellal analogues: synthesis of a variety of fragrances

Engineering of Yeast Old Yellow Enzyme OYE3 Enables Its Capability Discriminating of (E)-Citral and (Z)-Citral

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