Efficient Biocatalytic Reductive Aminations by Extending the Imine Reductase Toolbox

Article abstract of DOI:10.1002/cctc.201701379

Chiral secondary and tertiary amines are ubiquitous in pharmaceutical, fine, and specialty chemicals, but their synthesis typically suffers from significant sustainability and selectivity challenges. Biocatalytic alternatives, such as enzyme-catalyzed reductive amination, offer several advantages over traditional chemistry, but industrial applicability has not yet been demonstrated. Herein, we report the use of cell lysates expressing imine reductases operating at 1:1 stoichiometry for a variety of amines and carbonyls. A collection of biocatalysts with diversity in coverage of small molecules and direct industrial applicability is presented.

Full text of DOI:10.1002/cctc.201701379

Accepted Article
Title: Efficient biocatalytic reductive aminations by extending the imine
reductase toolbox
Authors: Gheorghe-Doru Roiban, Marcelo Kern, Zhi Liu, Julia Hyslop,
Pei Lyn Tey, Matthew S. Levine, Lydia S. Jordan, Kristin
Brown, Timin Hadi, Leigh Anne F Ihnken, and Murray J.B.
Brown
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: ChemCatChem 10.1002/cctc.201701379
Link to VoR: http://dx.doi.org/10.1002/cctc.201701379
A Journal of
www.chemcatchem.org

10.1002/cctc.201701379
ChemCatChem
COMMUNICATION
Efficient biocatalytic reductive aminations by extending the imine
reductase toolbox
Gheorghe-Doru Roiban,*,[a] Marcelo Kern,[a] Zhi Liu,[b] Julia Hyslop,[a] Pei Lyn Tey,[a] Matthew S.
Levine,[b] Lydia S. Jordan,[b] Kristin K. Brown,[c] Timin Hadi,[b] Leigh Anne F. Ihnken,[b] and Murray J.B.
Brown[a]
Abstract: Chiral secondary and tertiary amines are ubiquitous in
pharmaceutical, fine, and specialty chemicals, but their synthesis
typically suffers from significant sustainability and selectivity
challenges. Biocatalytic alternatives, such as enzyme catalyzed
reductive amination, offer several advantages over traditional
chemistry, but industrial applicability has not yet been demonstrated.
Herein, we report the use of cell lysates expressing imine reductases
operating at 1:1 stoichiometry for a variety of amines and carbonyls.
A collection of biocatalysts with diversity in coverage of small
molecules and direct industrial applicability is presented.
minimal hazardous waste. Biocatalysis also offers more flexibility
since the adoption of directed evolution allows for rapid
optimization of an enzyme to meet the requirements of process
chemistry.[4]
Established biocatalytic processes for the preparation of amines
have focused on chiral primary amines, notably hydrolytic
resolution of racemic amides, desymmetrisations with amine
oxidases and chemical reductants, and direct installation via
transaminases.[1] There are also emerging opportunities with
amine dehydrogenases, ammonia lyases, and aminomutases,
with all giving access to primary amines.[5] Direct biocatalytic
routes to secondary and tertiary amines have been reported using
imine reductases (IREDs).[6] Initially, cyclic imine reduction was
reported,[7] followed by subsequent formal intermolecular
reductive amination.[8] These activities were restricted to small
primary aliphatic amines, required a large excess of amine
nucleophile and high biocatalyst loading, making them less
attractive for industrial applications. Recently, Aleku et al.
reported an IRED homolog from Aspergillus oryzae (AspRedAm)
capable of reductive amination at 1:1 stoichiometry for a subset
of amines and carbonyls, using purified protein preparations.[9]
The purified protein approach allows for activity enrichment and
reduction in background carbonyl reduction from endogenous
host enzymes, but is an undesirable manufacturing strategy due
to the extra cost and complexity associated with the purification
process. Maugeri and Rother reported successful reductive
The majority of marketed drugs either contain amine functional
groups or are derived from amine intermediates, with up to 40%
of active pharmaceutical ingredients (APIs) containing a chiral
amine moiety.[1] Hence, the large-scale production of secondary
and tertiary amines as structural motifs commonly found in APIs
is of great interest to the pharmaceutical industry.[2] There are
many established chemical methods for the preparation of amines,
including nucleophilic alkylation, hydrogenation of imines,
enamines, and enamides, enantioselective hydroamination,
nucleophilic carbanion or radical addition to imino compounds, as
well as classical Mannich and Strecker reactions. These methods
tend to use precious or heavy metal catalysts, high pressures
and/or temperatures, organic solvents, stoichiometric hydride
reductants, or potentially genotoxic alkyl halides.[2-3] Recently,
biocatalytic approaches have emerged as an attractive alternative,
offering more sustainable processes under ambient aqueous
conditions with high chemo-, regio-, and stereoselectivity with
amination with lyophilized whole cells expressing IREDs,[10]
a
good first step toward industrial application, but with limited
demonstrated substrate scope. Herein, we report a collection of
enzymes catalyzing reductive amination at 1:1 stoichiometry, as
cell lysates, with diverse coverage of small molecule space. We
view the members of this IRED panel as potential evolution
starting points on the path of delivering manufacturing-relevant
enzymes for industrial biocatalytic reductive amination. The panel
of 85 enzymes we tested includes AspRedAm,[9] several other
known IRED sequences from the literature[7c, 7e, 9, 11] and IRED
database,[12] and novel putative IREDs chosen based on
homology to known, active sequences (see the Supporting
Information, Table S1, Figures S1-2). The proteins were
expressed in 96-well plate format (see the Supporting Information,
Table S2, Figure S3) and used in screening reactions as clarified
cell lysate. Initial screening with selected IREDs with arylamines
indicated a pH optimum of 6-7 and a slight preference for
potassium phosphate buffer (see the Supporting Information,
Figure S3), in contrast to previously reported pH optima of 9-9.5
for enzymatic reductive amination with aliphatic amines.[8b-d]
Subsequent reactions were all performed in 100 mM potassium
phosphate pH 7 except where indicated.
[a]
Dr. G.-D. Roiban, Dr. M. Kern, J. Hyslop, P. Lyn Tey, Dr. M. J. B.
Brown
Advanced Manufacturing Technologies
GlaxoSmithKline
Medicines Research Centre, Gunnels Wood Road, Stevenage SG1
2NY, United Kingdom
E-mail: gheorghe.d.roiban@gsk.com
Z. Liu, M. S. Levine, L. S. Jordan, Dr. T. Hadi, Dr. L. A. F. Ihnken
Advanced Manufacturing Technologies
GlaxoSmithKline
709 Swedeland Road, King of Prussia, Pennsylvania 19406, United
States
[b]
[b]
Dr. K. K. Brown
Molecular Design, Computational and Modeling Sciences
GlaxoSmithKline
1250 S. Collegeville Road, Collegeville, Pennsylvania 19426, United
States
Supporting information for this article is given via a link at the end of
the document.
This article is protected by copyright. All rights reserved.

10.1002/cctc.201701379
ChemCatChem
COMMUNICATION
The reductive amination activity of each enzyme was tested
across a number of carbonyl and amine pairs at 1:1 stoichiometry
(Scheme 1). Results for selected enzymes are shown in Table 1
(see Supporting Information for full data set, Table S3). High
conversions (>60%) were seen for several enzymes for
arylamines 1 and 3 with cyclohexanone a and for aniline 1 plus
phenylacetaldehyde c or benzaldehyde d. This represents an
important extension of the substrate scope of IREDs as
arylamines have not previously been reported as good enzymatic
reductive amination substrates. The compounds in Scheme 1
were chosen as model substrates as they are representative of
pharmacologically active moieties. N-Benzylaniline is used in the
manufacture of Antazolin, Bepridil, and Efonidipine[13] and
substituted N-phenethylanilines have been reported as potent
thrombin inhibitors.[14]
of cyclohexanone a with equimolar amounts of isopropylamine,
cyclohexylamine, n-propylamine, or N-methyl propan-1-amine.
Moderate (10-60%) to high conversions were also observed with
aliphatic amines, including formation of N-(thiophen-3-
ylmethyl)cyclohexanamine 4a, the core of a potent melanin-
concentrating hormone receptor antagonist[15] whose chemical
synthesis is reported as tedious and low yielding.[16] Moderate
conversions to amphetamine analogues 6b, and 7b were
observed after reductive amination of p-fluorophenylacetone b
with methylamine 6, and propargylamine 7. Both IR-01 and IR-13
showed moderate conversion with N-methylpropargylamine 8
with cyclohexanone a, the first report of IRED-catalyzed tertiary
amine formation using equimolar reactants. No conversion was
observed from any of the top seven enzymes tested for reaction
Scheme 1. Biocatalytic reductive amination.
Table 1. Conversion and selectivity for chosen enzymatic reductive amination reactions.
1a[a]
conv
93
99
96
56
78
64
0
1c[a]
conv
>99
99
>99
95
91
94
6
1d[a], [d]
conv
99
96
99
89
81
88
3
1e[a]
ee[e]
2a[a]
conv
19
3a[b]
conv
62
53
61
60
48
36
3
4a[a]
conv
97
5a[a]
conv
74
20
59
12
54
<2
-
6b[c]
ee[f]
7a[a]
conv
68
28
55
63
15
39
-
7b[c]
8a[a]
conv
17
4
IRED
IR-01
IR-10
IR-13
IR-22
IR-24
IR-49
IR-59
IR-69
IR-72
IR-75
conv
54
32
46
30
18
3
conv
26
4
conv
60
15
27
0
ee
26 (-)
62 (+)
41 (-)
56 (-)
90 (+)
37 (+)
61 (+)
(nd)[g]
(nd)[g]
83 (+)
91 (+)
(nd)[g]
(nd)[g]
83 (-)
83 (R)
12
19
22 (R)
34 (S)
(nd)[g]
(nd)[g]
97 (R)
98 (R)
95 (R)
99 (R)
99 (S)
10
85
14
0
14
7
1
43
>99 (-) 11
81
0
0
<2
<2
-
(nd)[g]
(nd)[g]
(nd)[g]
(nd)[g]
(nd)[g]
0
0
0
0
0
15
12
12
0
9
0
11
62
47
40
15
0
0
2
7
13
6
30
-
-
-
0
0
2
0
13
-
0
-
-
3
0
2
0
15
82
-
4
-
-
% Conversions at [a]4h, or [b]1h in 100 mM potassium phosphate pH 7 or [c]24h in 100 mM Tris pH 9; Reaction conditions: a-d (32 mM), 1-8 (35 mM, 1.1 equiv),
GDH (0.31 mg/mL), glucose (63 mM), NADP+ (1.5 mM), 30 °C, final volume 0.4 mL. [d]Approximately 2% conversion seen in background reaction. [e]Enantiomeric
excess (%ee) of first eluting enantiomer by chiral HPLC. [f]%ee reported with optical rotation sign. [g]Not determined (nd) due to low or no conversion. Dash “-
“ indicates not tested.
This article is protected by copyright. All rights reserved.

10.1002/cctc.201701379
ChemCatChem
COMMUNICATION
Such levels of reductive amination using aqueous cell lysate, at
neutral pH, and with low amine equivalents are unprecedented.
Furthermore, there was <2% background carbonyl reduction to
the corresponding alcohol, indicating relatively high IRED activity
compared to endogenous host cell ketoreductase activity, in
contrast to previous reports.[8b,10,17] Given the challenges of
performing reductive aminations without large amine excess,[8] we
were pleased to find a high number of active enzymes (69 out of
86, 80%) giving at least 5% conversion for at least one carbonyl
plus amine combination using stoichiometric reactants with
unoptimized conditions (see the Supporting Information, Table
S3). Further, in most cases, at least one enzyme gave >50%
conversion, often with several >90% conversion. This indicates
the high quality of this panel of enzymes in comparison with other
reported IRED collections.[18] For the reactions presented here,
IR-01 proved to be the most active enzyme in many cases.
However, other screening efforts have found IR-01 to be inactive
while other IREDs show excellent activity, demonstrating that a
diverse collection of biocatalysts is beneficial. Furthermore,
excellent and complementary enantiospecificity is demonstrated
for 6b and 7b providing access to both enantiomers. Reported
chemical approaches to these compounds have been limited to
wasteful resolutions[35-36] and recently reported IRED catalysed
conversions have required large amine excesses and only
provide a single enantiomer with good[9] or moderate[8d] ee.
Additionally this panel demonstrates resolution of prochiral e with
access to both enantiomers with moderate to excellent ee.
The substrate scope of the seven best-performing enzymes
producing 1a was further investigated at lower biocatalyst loading
with a series of substituted anilines and cyclohexanone a (Table
2). Both steric and electronic effects seemed to play a role in
enzyme activity. Generally, the tested IREDs were more active
with m- and p-subsituted anilines than o-substitued, with bulky o-
substituents like ethyl and isopropyl not tolerated at all. Anilines
with electron-donating substituents were preferred over those
with electron-withdrawing groups. Though the mechanism was
not explicitly investigated here, this suggests amine
nucleophilicity and therefore imine formation at least partially
contributes to the rate-determining step of the overall
transformation.
1a
9a
10a
11a
12a
13a
14a
15a
16a
IR-01
IR-10
IR-13
IR-22
IR-24
IR-49
36
20
25
4
9
4
60
49
46
3
65
53
52
4
52
59
57
16
71
39
70
16
68
6
42
<2
32
<2
34
<2
<2
<2
<2
<2
<2
<2
<2
8
<2
<2
<2
9
18
<2
<2
12
3
53
4
55
<2
69
13
<2
Percent conversions under same reaction conditions as for Table 1[a], 4h.
The synthetic utility of these IREDs was further demonstrated
by exploration of their regioselectivity. Selective monoalkylation of
a
symmetric diamine is chemically challenging, frequently
requires the use of route extending protecting groups, and
employs catalytic nitro reduction in the case of aromatic
amines.[20] We incubated the top seven IREDs with benzene-1,4-
diamine 17 with either 1 or 2 equiv of cyclohexanone a and
determined the mono:di alkylated product ratio (Table 3).
Remarkably, IR-01and IR-10 provided almost complete selectivity
for mono-alkylated product 17a even in the presence of 2 equiv
of cyclohexanone a. Complementary preference for the
disubstituted product 18 was observed for IR-13 and IR-24, even
in the presence of 1 equiv of cyclohexanone a.
Table 3. Regioselective reductive amination.[a]
IRED
% conversion of a[b]
Product ratio 17a:18
Table 2. Aryl amine substrate scope for enzymatic reductive amination.[a]
IR-01
IR-10
IR-13
IR-22
IR-24
IR-49
88 (97)
78 (88)
81 (98)
32 (43)
76 (89)
71 (96)
100:0 (99:1)
99:1 (97:3)
27:73 (6:94)
88:12 (84:16)
21:79 (10:90)
94:6 (69:31)
[a]Reaction conditions same as for Table 1[a]
.
[b]Values shown in parentheses
are for reactions run at 2 equiv of cyclohexanone a.
This article is protected by copyright. All rights reserved.

10.1002/cctc.201701379
ChemCatChem
COMMUNICATION
appreciable ketone reduction was observed.[10] Finally, we
demonstrated that this panel of enzymes can perform regio- and
stereoselective transformations in an efficient manner, even at
low amine stoichiometry. With selectivity, high activity, crude
preparation, low loadings, and low substrate stoichiometry
demonstrated, members of this collection of enzymes exhibit all
the characteristics of a potential industrial biocatalyst. These
enzymes are actively being used at GSK for project-direct
applications.
Industrial applicability was examined with a subset of
enzymes in 400 mg preparative reactions with cyclohexanone a
plus a selection of amines (Table 4 and Chart S1). Reaction at
neutral pH with 1 equiv of amine gave isolated yields in the range
of 20-50% from unoptimized reaction and isolation conditions,
with automated purification emphasizing purity over yield. We
also demonstrated successful preparative scale reactions using
stoichiometric reactants for several other carbonyl and amine
combinations (Chart S1).
Acknowledgements
These results demonstrate that IRED catalyzed reductive
amination at low stoichiometric excess is far more common than
previously reported. Aleku et al.[9] described six key residues
related to reductive aminase activity, which are fully conserved in
only three of the 85 IREDs reported in this work. This includes the
previously reported fungal enzymes AspRedAm[9] (IR-72) and
AdRedAm[9] (IR-59), and bacterially derived IR-69 from
Streptomyces sp. PRh5. None of these were in the top seven
performing enzymes, but did give activity for at least one carbonyl-
amine combination.
This research was supported by the Innovative Medicines
Initiative (IMI) joint undertaking project CHEM21 under grant
agreement no. 115360, resources of which are composed of
financial contribution from the European Union’s Seventh
Framework Programme (FP7/2007-2013) and EFPIA companies
in kind contribution.
Keywords: Imine reductases • reductive amination • chiral
amines • biocatalysis • chiral synthesis
Table 4. Regioselective reductive amination.[a]
[1]
[2]
D. Ghislieri, N. J. Turner, Top. Catal. 2013, 57, 284-300.
Chiral Amine Synthesis: Methods, Developments and Applications, (Ed
T.C. Nugent), Wiley-VCH, Weinheim, 2010.
[3]
a) S. A. Lawrence, Amines: synthesis, properties and applications,
Cambridge University Press, 2004; b) Stereoselective Formation of
Amines, Vol. 343, (Eds.: W. Li, X. Zhang) Springer, Berlin, Heidelberg,
2014.
R
IRED
Product
Isolated yield
[b] (%)
[4]
a) J.-M. Choi, S.-S. Han, H.-S. Kim, Biotechnol. Adv. 2015, 33, 1443-
1454; b) G. W. Huisman, S. J. Collier, Curr. Opin. Chem. Biol. 2013, 17,
284-292; c) R. Martínez, U. Schwaneberg, Biological research 2013, 46,
395-405; d) N. J. Turner, Catalysis Science & Technology 2012, 2, 1523-
1523.
IR-49
IR-22
IR-10
1a
37
23
46
[5]
a) M. J. Abrahamson, E. Vázquez‐Figueroa, N. B. Woodall, J. C. Moore,
A. S. Bommarius, Angew. Chem. Int. Ed. 2012, 51, 3969-3972; b) M. M.
Heberling, B. Wu, S. Bartsch, D. B. Janssen, Curr. Opin. Chem. Biol.
2013, 17, 250-260.
7a
[6]
[7]
a) J. H. Schrittwieser, S. Velikogne, W. Kroutil, Adv. Synth. Catal. 2015,
357, 1655-1685; b) G. Grogan, N. J. Turner, Chem. Eur. J. 2016, 22,
1900-1907.
11a
a) K. Mitsukura, M. Suzuki, K. Tada, T. Yoshida, T. Nagasawa, Org
Biomol Chem 2010, 8, 4533-4535; b) K. Mitsukura, M. Suzuki, S.
Shinoda, T. Kuramoto, T. Yoshida, T. Nagasawa, Biosci. Biotechnol.
Biochem. 2011, 75, 1778-1782; c) M. Rodriguez-Mata, A. Frank, E. Wells,
F. Leipold, N. J. Turner, S. Hart, J. P. Turkenburg, G. Grogan,
ChemBioChem 2013, 14, 1372-1379; d) M. Gand, H. Müller, R.
Wardenga, M. Höhne, J. Mol. Catal. B: Enzym. 2014, 110, 126-132; e)
P. N. Scheller, S. Fademrecht, S. Hofelzer, J. Pleiss, F. Leipold, N. J.
Turner, B. M. Nestl, B. Hauer, ChemBioChem 2014, 15, 2201-2204.
a) T. Huber, L. Schneider, A. Präg, S. Gerhardt, O. Einsle, M. Müller,
ChemCatChem 2014, 6, 2248-2252; b) P. N. Scheller, M. Lenz, S. C.
Hammer, B. Hauer, B. M. Nestl, ChemCatChem 2015, 7, 3239-3242; c)
D. Wetzl, M. Gand, A. Ross, H. Müller, P. Matzel, S. P. Hanlon, M. Müller,
B. Wirz, M. Höhne, H. Iding, ChemCatChem 2016, 8, 2023-2026; d) P.
Matzel, M. Gand, M. Höhne, Green Chem. 2017, 19, 385-389.
G. A. Aleku, S. P. France, H. Man, J. Mangas-Sanchez, S. L.
Montgomery, M. Sharma, F. Leipold, S. Hussain, G. Grogan, N. J. Turner,
Nat Chem 2017, doi:10.1038/nchem.2782.
IR-13
12a
51
[a]Reaction conditions: ketone/aldehyde (11 mM), amine (11 mM), GDH
(0.08 mg/mL w/w), glucose (22 mM), NADP+ (0.5 mM), 100 mM potassium
phosphate buffer pH 7, 30 °C, final volume 400 mL, 4h. [b]Isolated yields after
mass directed auto purification (MDAP).
[8]
[9]
We have shown extended IRED amine substrate scope to
include a range of anilines and heteroaromatic amines, which
were previously reported as incompatible with biocatalytic
reductive amination.[9] Importantly, these results were obtained
with cell lysates without significant side reactions, allowing for
economical scale up. The recently reported work with whole cells
expressing IREDs also has large scale potential, but the
biocatalyst loading was ~10-30x higher than in this study and
[10] Z.
Maugeri,
D.
Rother,
J.
Biotechnol.
2017.
doi.org/10.1016/j.jbiotec.2017.05.015.
This article is protected by copyright. All rights reserved.

10.1002/cctc.201701379
ChemCatChem
COMMUNICATION
[11] a) S. Hussain, F. Leipold, H. Man, E. Wells, S. P. France, K. R.
Mulholland, G. Grogan, N. J. Turner, ChemCatChem 2015, 7, 579-583;
b) G. A. Aleku, H. Man, S. P. France, F. Leipold, S. Hussain, L. Toca-
Gonzalez, R. Marchington, S. Hart, J. P. Turkenburg, G. Grogan, N. J.
Turner, ACS Catalysis 2016, 6, 3880-3889.
[16] N. Fleury‐Brégeot, J. Raushel, D. L. Sandrock, S. D. Dreher, G. A.
Molander, Chem. Eur. J. 2012, 18, 9564-9570.
[17] P. N. Scheller, B. M. Nestl, Appl. Microbiol. Biotechnol. 2016, 100,
10509-10520.
[18] a) D. Wetzl, M. Berrera, N. Sandon, D. Fishlock, M. Ebeling, M. Muller,
S. Hanlon, B. Wirz, H. Iding, Chembiochem 2015, 16, 1749-1756; b) H.
Li, Z.-J. Luan, G.-W. Zheng, J.-H. Xu, Adv. Synth. Catal. 2015, 357,
1692-1696.
[12] S. Fademrecht, P. N. Scheller, B. M. Nestl, B. Hauer, J. Pleiss, Proteins
2016, 84, 600-610.
[13] a) M. Sittig, Pharmaceutical Manufacturing Encyclopedia, William
Andrew Pub., 2015; b) I. Agranat, Synthesis 2009, 2009, 2116-2116.
[14] K. D. Kreutter, T. Lu, L. Lee, E. C. Giardino, S. Patel, H. Huang, G. Xu,
M. Fitzgerald, B. J. Haertlein, V. Mohan, Bioorg. Med. Chem. Lett. 2008,
18, 2865-2870.
[19] a) Z. Nad, T. Kallay, M. Sziladi, T. Montay, Process for the preparation
of propargyl ammonium-chloride. US Patent 5449828A, Sep 12, 1995.;
b) A. Plenevaux, S. L. Dewey, J. S. Fowler, M. Guillaume, A. P. Wolf, J.
Med. Chem. 1990, 33, 2015-2019.
[15] F. Giordanetto, O. Karlsson, J. Lindberg, L.-O. Larsson, A. Linusson, E.
Evertsson, D. G. Morgan, T. Inghardt, Bioorg. Med. Chem. Lett. 2007,
17, 4232-4241.
[20] P. G. Wuts, T. W. Greene, Greene's protective groups in organic
synthesis, John Wiley & Sons, 2006.
This article is protected by copyright. All rights reserved.

10.1002/cctc.201701379
ChemCatChem
COMMUNICATION
COMMUNICATION
Gheorghe-Doru Roiban,*,[a] Marcelo
Kern,[a] Zhi Liu,[b] Julia Hyslop,[a] Pei Lyn
Tey,[a] Matthew S. Levine,[b] Lydia S.
Jordan,[b] Kristin K. Brown,[c] Timin
Hadi,[b] Leigh Anne F. Ihnken,[b] and
Murray J.B. Brown[a]
Page No. – Page No.
Biocatalytical reductive amination made easy: A panel of IREDs give broad
substrate coverage using stoichiometric reactants with excellent selectivity.
Efficient biocatalytic reductive
aminations by extending the imine
reductase toolbox
This article is protected by copyright. All rights reserved.