One-Pot Transformation of Ketoximes into Optically Active Alcohols and Amines by Sequential Action of Laccases and Ketoreductases or ω-Transaminases

Article abstract of DOI:10.1002/cctc.201801900

An enzymatic one-pot process for asymmetric transformation of prochiral ketoximes into alcohols or amines was developed by sequential coupling of a laccase-catalyzed deoximation either with a ketone reduction (ketoreductase, KRED) or bioamination (ω-transaminase, ω-TA) in aqueous medium. An accurate selection of biocatalysts provided the corresponding products in excellent enantiomeric excesses and overall conversions ranging from 83 to >99 % for alcohols and 70 to >99 % for amines. Likewise, the employment of exclusively 1 % (w/w) of Cremophor, a polyethoxylated castor oil, as co-solvent enabled to reach concentrations up to 100 mM in the chiral alcohols cascade.

Full text of DOI:10.1002/cctc.201801900

Full Papers
DOI: 10.1002/cctc.201801900
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One-Pot Transformation of Ketoximes into Optically Active
Alcohols and Amines by Sequential Action of Laccases and
Ketoreductases or ω-Transaminases
Raquel S. Correia Cordeiro,[a, b] Nicolás Ríos-Lombardía,[a] Francisco Morís,[a] Robert Kourist,[c]
and Javier González-Sabín*[a]
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An enzymatic one-pot process for asymmetric transformation of
prochiral ketoximes into alcohols or amines was developed by
sequential coupling of a laccase-catalyzed deoximation either
with a ketone reduction (ketoreductase, KRED) or bioamination
(ω-transaminase, ω-TA) in aqueous medium. An accurate
selection of biocatalysts provided the corresponding products
in excellent enantiomeric excesses and overall conversions
ranging from 83 to >99% for alcohols and 70 to >99% for
amines. Likewise, the employment of exclusively 1% (w/w) of
Cremophor®, a polyethoxylated castor oil, as co-solvent enabled
to reach concentrations up to 100 mM in the chiral alcohols
cascade.
Introduction
mediated reduction of oxime ethers and the rhodium-mediated
reduction of oxime ethers led to amines or N-acylamines
respectively, with good yields and high optical purity
(Scheme 1, route a).[7] Similarly, a chemoenzymatic approach
The oxime function is ubiquitous in nature and can be found in
the structure of innumerable natural and synthetic bioactive
compounds as well as in several metabolic pathways, being
modified by the action of enzymes.[1] So for example, from
bacterial origin the group of 2,2’-bipyridyl-containing natural
products includes members bearing oximes such as pyrisulfox-
ins,[2] caerulomycins[3] and collismycins[4] which display antibac-
terial, antifungal and cytotoxic activities, and fungi like
basidiomycete Boreostereum vibrans produce vibralactoximes
with significant cytotoxic activity.[5] On the other hand, oximes
are valuable synthetic precursors of ketones and aldehydes
since those can be prepared from non-carbonyl precursors.
Likewise, they also provide a facile entry to a wide variety of
functionalities such as amines (reduction with metals or
hydrides) and carboxamides (Beckmann rearrangement) which
can be subsequently hydrolyzed into acids, or nitriles (metal- or
enzyme-catalyzed dehydration).[6] However, from the vast
number of synthetic transformations involving oximes, only
very few are asymmetric processes. Particularly, the enantiose-
lective reduction of O-substituted oximes, namely the boron-
Scheme 1. Related catalytic asymmetric transformations on ketoximes.
combining lipase/palladium catalysis provided optically active
amines with very high enantiomeric excess although in their
acetylated form (route b).[8]
[a] R. S. Correia Cordeiro, Dr. N. Ríos-Lombardía, Dr. F. Morís, Dr. J. González-
Sabín
EntreChem SL
Vivero Ciencias de la Salud
33011 Oviedo (Spain)
In recent years considerable progress has been made in
developing multistep one-pot processes since this strategy is
expected to increase sustainability of chemical manufacture
(minimization of waste production, time- and energy-consum-
ing and purification steps).[9] This is particularly appealing when
several biocatalytic reactions are integrated into multi-catalytic
networks emulating Nature, as living organisms use a great
number of enzymatic cascades (in different metabolic path-
ways) employing the same reaction media. Thus, biocatalysts
are intrinsically “green” and aqueous media their natural
environment.[10] Recently, we reported the first biocatalytic
E-mail: jgsabin@entrechem.com
[b] R. S. Correia Cordeiro
Junior Research Group for Microbial Biotechnology
Faculty of Biology and Biotechnology
Ruhr-University Bochum
Bochum 44780 (Germany)
[c] Prof. R. Kourist
Graz University of Technology
Petersgasse 14
Graz 8010 (Austria)
Supporting information for this article is available on the WWW under
https://doi.org/10.1002/cctc.201801900
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deoximation, which enabled to recover ketones from ketoximes
by means of a laccase/TEMPO system.[11] Remarkably, the
reaction took place in aqueous medium under mild reaction
conditions, and the products were isolated in excellent yield
without the need for chromatographic purification. Building on
our interest in multistep enzymatic processes, herein we
present a genuine enzymatic cascade to convert prochiral
ketoximes into optically active alcohols or amines by the one-
pot combination of the above biodeoximation with a subse-
quent stereoselective bioreduction (mediated by KREDs) or
transamination reaction (mediated by ω-TAs) (route c). In fact,
laccases have evolved from mere anti-pollutant reagents to
smart biocatalysts for biooxidation processes,[12] including
examples of catalytic networks in combination with enzymes
such as lipases, oxidoreductases, ω-transaminases or enoate
reductases,[13] although none involving oxime transformations.
Despite the merit of the previous synthetic approaches to
convert oximes into optically active amines (Scheme 1), some
shortcomings remain: route a (metal-catalysed reaction) de-
manded single-isomeric oxime ethers as starting materials since
(Z)-oximes led to (R)-amines and (E)-ketoximes produce the (S)-
counterparts, while for route b (chemoenzymatic route) the
process suffered from long reaction times (5 days) and enabled
exclusively (R)-amines as acetamides, which require very harsh
conditions to be hydrolysed. Conversely, the novel enzymatic
cascade would give facile entry to both enantiomers of chiral
amines from Z/E mixtures of oximes under mild reaction
conditions and in aqueous medium.
binding of hydroxide anion to the copper ion at the active site
and disrupting the internal electron transfer pathway.[12a]
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In order to explore the viability of the coupled process, we
set out to investigate as a bench reaction the biodeoximation
of propiophenone oxime (1a) to propiophenone (1b) using the
reported laccase/TEMPO system. Thus, the released 1b has
proven to be an excellent substrate for both KREDs and ω-TAs.
With the knowledge that Trametes versicolor and TEMPO turned
out to be the most effective pair of laccase and mediator,[11] we
sought to parametrise the biotransformation in terms of
temperature, concentration, and co-solvents with known com-
patibility with KREDs and ω-TAs. Thus, and upon the reported
reaction conditions, the biodeoximation of 1a was completed
in 12 h in a citrate buffer 50 mM (pH 5.0) containing 10% v/v of
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°
acetonitrile (CH3CN, Table 1, entry 1) at 20 C. First, a temper-
Table 1. Parametrisation of the laccase-catalysed biodeoximation of
propiophenone oxime (1a) in the presence of TEMPO and aerial O2.[a]
Entry
Co-solvent
T [ C]
[1a] [mM]
conv. [%][b]
°
1
2
3
4
5
6
7
8
CH3CN
CH3CN
CH3CN
DMSO
1,4-Dioxane
Toluene
t-Amyl alcohol
Cremophor[c]
CH3CN
20
40
50
20
20
20
20
20
20
20
20
20
50
50
50
50
50
50
50
50
100
200
100
200
>99
95
70
95
97
95
97
97
70
30
90
85
9
10
11
12
CH3CN
Cremophor[c]
Cremophor[c]
[a] Reaction conditions for entries 1–8: 1a (50 mM), T. versicolor laccase
(30 U), TEMPO (10% mol), citrate buffer 50 mM pH 5.0 (900 μL) and co-
solvent (90 μL), stirring in an open vessel during 12 h. Experiments were
performed in triplicate; [b] Determined by HPLC; [c] Used exclusively in 1%
w/w.
Results and Discussion
Nature reveals in the living cells how a perfect one-pot system
works. Thus, metabolism is a perfect machinery of enzymatic
networks where multistep reactions are mediated by enzymes
playing in concert in an aqueous environment. Nevertheless,
when mimicking these systems, a number of concerns must be
circumvented to achieve the efficient implementation of such
artificial enzymatic cascades.[14] A first challenge would be
making the target biocatalysts compatible with respect to
preferred pH, T, concentration and co-solvents profiles, but also
specific activities and stability should be balanced, and
inhibition avoided. Particularly, the process envisaged in
Scheme 1 (route c) seems more suitable for a sequential
configuration than for a concurrent one seeing as: i) optimal pH
for laccases and KREDs/ω-TAs are quite distant; more impor-
tantly, ii) if both catalysts are coexisting and functional
simultaneously, the resulting chiral alcohol or amine could be
oxidised by the laccase/TEMPO pair. Accordingly, it was planned
initially a sequential one-pot two-steps process in which once
the oxime cleavage is completed at pH 5.0 by the laccase, the
pH would set to 7.0 and the KRED/ω-TA added to the medium.
Theoretically, the laccase would be deactivated upon these
conditions and the target chiral product prevented from further
oxidation. Actually, it is a known fact that the laccases are
highly influenced by pH, inactivated at basic pH because of
°
ature of 40 C resulted in an acceleration of the process, taking
2 h for the consumption of 90% of 1a (95% conversion after
°
12 h, entry 2). However, an increase to 50 C had a detrimental
effect and enabled a conversion of 70% after 12 h, not evolving
further due to enzyme deactivation (entry 3). Next, four co-
solvents, such as dimethyl sulfoxide (DMSO), 1,4-dioxane,
toluene and tert-amyl alcohol were screened under identical
conditions at 10% v/v. As a result, very high conversions were
reached in all the cases after 12 h (>95%, entries 4–7).
Alternatively, the focus was placed on improving the ecological
footprint of the process. Actually, although the greenness of
biocatalysis is typically assumed, most biotransformations suffer
from issues such as water consumption, wastewater production
or unfavourable metrics, keeping them to reach real industrial
impact.[15] Particularly, the poor solubility of most reagents in
water leads to low substrate loadings and, by extension, poor
economic performances. Likewise, the toxicity of the salts
contained in some aqueous buffers is usually overlooked. Based
on these considerations, the biodeoximation of 1a was ex-
plored at 50 mM in a simplified medium consisting of water
and 1% (w/w) of Cremophor®.[16] The reaction proceeded
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smoothly in such a low percentage of solubiliser and free of
organic co-solvents (entry 8). Finally, the biotransformation was
evaluated at 100 mM and 200 mM using 10% v/v of CH3CN and
1% w/w of Cremophor®. In the first case, reactions rendered
moderate conversion in the presence of CH3CN (70% and 30%
respectively, entries 9–10) meanwhile a high enzymatic per-
formance was achieved owing to the employment of Cremo-
phor® (>85%, entries 11–12).
the released intermediate ketones.[17] Interestingly, the study
included enzymes from a commercial kit (Codexis)[18] and also
two KREDs overexpressed in E. coli with opposite stereo-
selectivity, namely the (R)-selective alcohol dehydrogenase from
Lactobacillus kefir[19] and the (S)-selective from Rhodococcus
ruber.[20] As deduced from Table 2, the synthetic cascade worked
efficiently and enabled to obtain the antipodes of chiral
alcohols in very high ee and overall conversion. Particularly, a
detrimental effect of the laccase/TEMPO system on the overex-
pressed KREDs was observed (see details in the ESI). The only
required setting to solve this drawback was removing the
insoluble portions (e.g., precipitated protein) by centrifugation
after the deoximation step and adding to the supernatant the
reagents for the further reduction. Under these experimental
conditions, most of the selected alcohols were produced with
very high conversions (entries 2,3,10,11,14-19). A further goal of
the project was to enhance the substrate concentration for the
cascade process, which could meet the parameters of a
manufacture setting. Accordingly, the unique properties of
Cremophor® (1% w/w) enabled a conversion of 85–>99% for
some selected deoximations run at 200 mM. Further dilution to
100 mM with the reaction medium required for the bioreduc-
tion provided, alternatively, the (R)-or (S)-enantiomer of alcohols
1c and 4c in 65–97% overall conversion and >99% ee
(entries 4,5,12 and 13). Following an analogous procedure, the
stepwise combination of the laccase-catalysed deoximation of
ketoximes with a further bioamination would produce optically
active amines. From the biocatalytic toolbox there are different
classes of enzymes able to convert prochiral carbonyl com-
pounds into amines: i) ω-TAs transfer a primary amino group
from a donor substrate to an acceptor compound mediated by
pyridoxal-5-phosphate (PLP);[21] ii) amino dehydrogenases
(AmDHs) catalyse the NAD(P)H-dependent reductive amination
of carbonyl compounds with ammonia;[22] iii) IREDs[23] and its
recently discovered subclass reductive aminases (RedAms)[24]
accept secondary linear and cyclic amino donors and give entry
to secondary and tertiary amines. Among, these, we focused on
the first group and unlike KREDs, preliminary feasibility tests
unveiled the inactivation of ω-TAs by Cremophor®. Accordingly,
the deoximation for this enzymatic cascade should be set up in
the presence of acetonitrile as co-solvent. Likewise, ω-TAs
generally require lower substrate concentration than KREDs for
an optimal enzymatic performance. With this premises, 1a
(50 mM) was subjected to deoximation by means of the
treatment with the laccase/TEMPO system in citrate buffer
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8
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Next, the substrate scope of the biotransformation was
investigated. Thus, a series of ketoximes was selected (Figure 1),
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Figure 1. Enzymatic deoximation of ketoximes (conversion values in paren-
thesis).
including those derived from propiophenone (1a–4a), aceto-
phenone (5a–12a), non-benzylic (13a–15a), aliphatic (16a)
and cyclic ketones (17a). Following the reaction conditions
depicted in Table 1 (entry 1), ketoximes were in most cases
quantitatively converted into the corresponding ketones after
20 h. Likewise, the products were isolated in high yields (>
90%) by simple extraction without need for further purification.
Conversely, 17a led to very low conversion meanwhile the
reaction did not work with 16a, the only aliphatic substrate.
Once assessed the viability of the biodeoximation with a
variety of ketoximes, we focused on the first of the devised
enzymatic cascades, namely that aimed at chiral alcohols. Thus,
the initial deoximation of 1a (50 mM) was performed in citrate
°
buffer 50 mM pH 5.0 (containing 10% CH3CN) and 20 C by the
combined action of the laccase and TEMPO, the substrate being
totally converted into ketone 1b after 12 h. Then, the reaction
mixture was diluted with a phosphate buffer 125 mM pH 7.0
(1 mM NADP+) for a final substrate concentration of 25 mM,
and the ketoreductase P1-A04 and i-PrOH for cofactor recycling
and equilibrium shift, were subsequently added.
Pleasantly, HPLC-monitoring showed quantitative reduction
of the transiently formed ketone in 8 h, the resulting chiral
alcohol (R)-1c displaying >99% ee (Table 1, entry 1). Seeing as
the feasibility of the catalytic system, it looks clear that both
laccase and TEMPO do not inhibit the KRED, which preserves
the activity in terms of reaction rate and selectivity. Particularly,
the complete conversion discarded a hypothetical oxidation of
the target 1c by the laccase, which was inactivated by the basic
conditions of the second step. Next, and on the basis of the
established reaction conditions, some ketoximes depicted in
Figure 1 were subjected to this enzymatic one-pot two-step
sequence. Moreover, a careful selection of the KRED attending
to previous reports ensured a high enantioselectivity towards
°
50 mM pH 5.0 (containing 10% CH3CN) at 20 C following the
previous procedure (Table 1, entry 1). After 12 h, the reaction
mixture was submitted to pH adjustment with a phosphate
buffer 100 mM pH 8.5 for a final substrate concentration of
17 mM and pH 7.5. Likewise, the resulting reaction medium
contained i-PrNH2 (1 M) and PLP (1 mM). Then, ω-transaminase
ATA-025 and DMSO (2.5% v/v) were added, and after 24 h of
°
shaking at 50 C the amine (R)-1d was obtained in enantiopure
form and 85% of overall conversion (Table 3, entry 1). Identi-
cally, the employment of the stereocomplementary biocatalyst
ATA-026 provided the enantiomer (S)-1d with high conversion
(c=88%) and >99% ee (entry 2). Likewise, the absence of by-
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Table 2. One-pot sequential enzymatic transformation of ketoximes into optically active alcohols.[a]
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2
3
4
5
6
7
8
Entry
Substrate
Substrate conc. [mM]
KRED
Co-solvent
[% v/v]
Product distribution[b,c] [%]
ee alcohol[d]
[%]
Ketoxime
Ketone
(b)
Alcohol
(c)
(a)
9
1
2
3
4
5
50
50
50
200
P1-A04
L. kefir
R. ruber
L. kefir
R. ruber
CH3CN (10%)
CH3CN (10%)
CH3CN (10%)
Cremophor® (1%)
<1
<1
<1
15
<1
<1
<1
20
>99
>99
>99
65
>99 (R)
>99 (R)
>99 (S)
>99 (R)
>99 (S)
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
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200
Cremophor® (1%)
15
5
80
6
7
8
50
50
200
P1-A04
P3-H12
L. kefir
CH3CN (10%)
CH3CN (10%)
Cremophor® (1%)
<1
<1
<1
15
17
94
85
83
6
>99 (R)
>99 (S)
-
9
200
R. ruber
Cremophor® (1%)
<1
50
45
>99 (S)
10
11
12
50
50
200
L. kefir
R. ruber
P1-A04
CH3CN (10%)
CH3CN (10%)
Cremophor® (1%)
<1
<1
<1
<1
<1
4
>99
>99
96
98 (R)
>99 (S)
>99 (R)
13
200
R. ruber
Cremophor® (1%)
<1
3
97
>99 (S)
14
15
50
50
L. kefir
CH3CN (10%)
CH3CN (10%)
<1
<1
85
15
-
R. ruber
<1
>99
>99 (S)
16
17
50
50
L. kefir
CH3CN (10%)
CH3CN (10%)
<1
<1
5
5
95
95
>99 (R)
>99 (S)
R. ruber
18
19
50
50
L. kefir
CH3CN (10%)
CH3CN (10%)
<1
<1
6
9
94
92
>99 (R)
>99 (S)
R. ruber
[a] Reaction conditions detailed in the ESI. The substrate concentration was diluted in half after the first step. Experiments were performed in triplicate; [b]
Consumption of the ketoxime in the first step was checked by HPLC analysis; [c] The ratio of ketoxime (a), ketone (b), and alcohol (c) was measured by HPLC
analysis; [d] Enantiomeric excess determined by chiral HPLC.
products from an over-oxidation of the amine suggested the
laccase-inactivation in the basic conditions of the second step.
Encouraged by the success of this enzymatic catalytic system,
we extended the methodology to some ketoximes from
Figure 1. For this, the ω-TA was chosen for each particular
ketone according to previous reports,[9c,25] from both a commer-
cial kit (Codexis)[26] and three ω-TAs overexpressed in E. coli: the
S-selective ω-TAs from Chromobacterium violaceum (Cv)27 and
(S)-Arthrobacter (ArS)28 and the R-selective TAs from (R)-
Arthrobacter (ArR)29 (entries 3–15). Gratefully, the overall con-
version was very high in most cases (c=from 70 to >99%),
without traces of the starting ketoxime. With regards to the
selectivity, the ω-TAs displayed perfect asymmetry towards
most of the intermediate ketones (>99% ee), with identical
values to those reported in the single bioamination. Again, the
laccase/TEMPO system exerted some kind of inhibition on the
overexpressed enzymes, which could be bypassed by avoiding
the insoluble portions (see the ESI) and adding to the super-
natant the reagents for the enzymatic amination. Under these
experimental conditions all the selected amines were produced
in quantitative conversion (entries 9, 11–15).
The effective validation of both synthetic sequences high-
lights the suitability of multi-step enzymatic approaches run in
one-pot fashion as a valuable alternative to existing methods.
Importantly, the bioconversion of ketoximes into chiral amines
does not require isomerically pure oximes and provides free
amines as products. On the other hand, the enzymatic cascade
aimed at chiral alcohols underlines the advantages of Cremo-
phor® in the fields of chemocatalysis and biocatalysis and will
open up new perspectives for further exploration of one-pot
processes in aqueous media. Finally, the synthetic utility of this
catalytic platform was showcased by performing a selected
example, namely the conversion of ketoxime 4a into alcohol 4c
on preparative scale (100 mg). As detailed in Table 2 (entry 13),
4a underwent effective deoximation at 200 mM by the
assistance of 1% (w/w) of Cremophor®. Once the oxime was
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Table 3. One-pot sequential enzymatic transformation of ketoximes into optically active amines.[a]
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2
3
4
5
6
7
8
9
Entry
Substrate[b]
ω-TA
Product distribution[c,d] [%]
ee amine[e] [%]
°
T [ C]
Ketoxime
(a)
Ketone
(b)
Amine
(d)
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11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
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56
57
1
2
ATA-025
ATA-026
50
50
<1
<1
15
12
85
88
>99 (R)
>99 (S)
3
4
ATA-025
ATA-251
50
50
<1
<1
30
20
70
80
>99 (R)
>99 (S)
5
6
ATA-024
ATA-251
50
50
<1
<1
15
25
85
75
>99 (R)
>99 (S)
7
8
ATA-024
ATA-237
50
50
<1
<1
9
91
89
>99 (R)
>99 (S)
11
9
ATA-033
ATA-256
50
50
<1
<1
<1
>99
96 (R)
10
8
92
>99 (S)
11
ATA-254
50
<1
<1
>99
>99 (S)
12
13
ArR
Cv
30
30
<1
<1
<1
<1
>99
>99
>99 (R)
>99 (S)
14
15
ArR
ArS
30
30
<1
<1
<1
<1
>99
>99
>99 (R)
>99 (S)
[a] Reaction conditions detailed in the ESI. Experiments were performed in triplicate; [b] Substrate concentration was fixed at 50 mM for the biodeoximation
and 17 mM for the subsequent bioamination; [c] Consumption of the ketoxime in the first step was checked by HPLC analysis; [c] The ratio of ketoxime (a),
ketone (b), and amine (d) was measured by HPLC analysis; [d] Enantiomeric excess determined by chiral HPLC.
completely consumed (HPLC analysis), the reaction mixture was Conclusions
diluted to 100 mM with the aqueous buffer for the bioreduction
(containing NAD+) and fed with the ADH from R. ruber and i-
PrOH. Thus, the bioreduction of the formed ketone intermedi-
ate 4b took place smoothly, (S)-4c being obtained with very
high conversion (>95% overall conversion). Further filtration
on silica gel rendered pure (S)-4c in 85% yield and >99% ee.
We disclose an expedient, stereoselective and operationally
simple protocol for the synthesis of either optically active
amines or alcohols from ketoximes, through the sequential one-
pot combination of: i) an enzymatic deoximation mediated by a
laccase/TEMPO catalytic system; ii) subsequent enantioselective
bioamination or bioreduction of the transiently formed ketones.
ChemCatChem 2019, 11, 1–7
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© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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2018, 118, 270–348. d) S. Gandomkar, A. Zadlo, W. Kroutil, ChemCat
Chem 2019, 11, DOI: 10.1002/cctc.201801063.
In both cases, the desired final products were obtained in high
yields and excellent enantiomeric excesses. Likewise, it is worth
noting the use of a one-pot methodology, in which the
aqueous reaction medium from the deoximation step feeds the
enzymatic amination/reduction.
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Acknowledgements
Authors acknowledge funding from the European Union’s Horizon
2020 MSCA ITN-EID program (grant agreement No 634200). The
authors also thank Dr. Martin Schürmann (InnoSyn) and Prof.
Harald Gröger (Bielefeld University) for the generous gift of the
KRED of Rhodococcus ruber and Lactobacillus kefir, respectively,
as well as Dr. Wolfgang Kroutil for the ω-TAs Cv, ArS and ArR.
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Keywords: one-pot reaction · oxime · alcohol dehydrogenase ·
transaminase · enzymatic cascade
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Manuscript received: November 20, 2018
Revised manuscript received: December 17, 2018
Version of record online: ■■■, ■■■■
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FULL PAPERS
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Choose your path: A sequential com-
bination of laccases and either ketor-
eductases or ω-transaminases proved
to be an optimal method for convert-
ing ketoximes into enantiopure
R. S. Correia Cordeiro, Dr. N. Ríos-
Lombardía, Dr. F. Morís, Prof. R.
Kourist, Dr. J. González-Sabín*
1 – 7
One-Pot Transformation of
alcohols or amines, respectively.
Ketoximes into Optically Active
Alcohols and Amines by Sequential
Action of Laccases and Ketoreduc-
tases or ω-Transaminases
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