In contrast to aldehydes, over-reduction is less pronounced on α,β-unsaturated
ketones (Scheme 2.134). Nonracemic levodione, which is a precursor for the
synthesis of carotenoids, such as astaxanthin and zeaxanthin, was obtained in
80% yield and >95% e.e. via yeast-mediated reduction of ketoisophorone. Two
other products arising from reduction of the carbonyl moieties were formed in
minor amounts [1129]. In contrast, no trace of carbonyl reduction was observed
using ene-reductase OPR3 (Scheme 2.134). (3R,3
0 R)-Zeaxanthin is used in human
nutrition and healthcare products and is considered for the treatment of age-related
macula degeneration [1130].
Nitro-olefins are readily reduced by ene-reductases to form chiral nitro-alkanes
(Scheme 2.135) [1131]. Using ene-reductase OPR1 or baker’s yeast, the
corresponding (R)-nitroalkanes were obtained in high e.e. Surprisingly, the
mirror-image product was formed by using isoenzyme OPR2, which is highly
homologous to OPR3 (53%).
Simple monocarboxylic esters require the presence of an additional activating
group, such as a halogen atom or a second ester, to be accepted by OYEs (Scheme
2.136). α-Substituted butenedioic esters were readily reduced by ene-reductases
YqjM and OPR1 with excellent specificities, while the stereochemical outcome
could be controlled by choice of the ene-reductase or by using an (E)- or (Z )configurated substrate: (R)-2-Methylsuccinate was obtained by using OPR1,
regardless of the (E/Z )-configuration of the substrate. In contrast, with YqjM, the
configuration of the product switched when an (E)-fumarate ester was used instead
HO
O
OH
O
O
O
O
O
yield >95%, e.e. 99%
NADPH-recycling
Ene-Reductase OPR3
7%
6%
(fast)
baker´s yeast
baker´s yeast
yield 80%, e.e. >95%
levodione
ketoisophorone
ene-reductase
carbonyl reductases
(slow)
Scheme 2.134 Asymmetric bioreduction of α,β-unsaturated diketone
NO 2
NO 2
NO 2
NAD(P)H-Recycling
NAD(P)H-Recycling
e.e. 93%
98% e.e.
baker's yeast 98% e.e.
OPR3
OPR1
R
S
Scheme 2.135 Stereocomplementary bioreduction of nitro-olefins
2.2 Reduction Reactions
165
ketones (Scheme 2.134). Nonracemic levodione, which is a precursor for the
synthesis of carotenoids, such as astaxanthin and zeaxanthin, was obtained in
80% yield and >95% e.e. via yeast-mediated reduction of ketoisophorone. Two
other products arising from reduction of the carbonyl moieties were formed in
minor amounts [1129]. In contrast, no trace of carbonyl reduction was observed
using ene-reductase OPR3 (Scheme 2.134). (3R,3
0 R)-Zeaxanthin is used in human
nutrition and healthcare products and is considered for the treatment of age-related
macula degeneration [1130].
Nitro-olefins are readily reduced by ene-reductases to form chiral nitro-alkanes
(Scheme 2.135) [1131]. Using ene-reductase OPR1 or baker’s yeast, the
corresponding (R)-nitroalkanes were obtained in high e.e. Surprisingly, the
mirror-image product was formed by using isoenzyme OPR2, which is highly
homologous to OPR3 (53%).
Simple monocarboxylic esters require the presence of an additional activating
group, such as a halogen atom or a second ester, to be accepted by OYEs (Scheme
2.136). α-Substituted butenedioic esters were readily reduced by ene-reductases
YqjM and OPR1 with excellent specificities, while the stereochemical outcome
could be controlled by choice of the ene-reductase or by using an (E)- or (Z )configurated substrate: (R)-2-Methylsuccinate was obtained by using OPR1,
regardless of the (E/Z )-configuration of the substrate. In contrast, with YqjM, the
configuration of the product switched when an (E)-fumarate ester was used instead
HO
O
OH
O
O
O
O
O
yield >95%, e.e. 99%
NADPH-recycling
Ene-Reductase OPR3
7%
6%
(fast)
baker´s yeast
baker´s yeast
yield 80%, e.e. >95%
levodione
ketoisophorone
ene-reductase
carbonyl reductases
(slow)
Scheme 2.134 Asymmetric bioreduction of α,β-unsaturated diketone
NO 2
NO 2
NO 2
NAD(P)H-Recycling
NAD(P)H-Recycling
e.e. 93%
98% e.e.
baker's yeast 98% e.e.
OPR3
OPR1
R
S
Scheme 2.135 Stereocomplementary bioreduction of nitro-olefins
2.2 Reduction Reactions
165