Redox self-sufficient biocatalyst network for the amination of primary alcohols

Article abstract of DOI:10.1002/anie.201204683

Driving the machinery: A biocatalytic redox-neutral cascade for the preparation of terminal primary amines from primary alcohols at the expense of ammonia has been established in a one-pot one-step method (see picture). Applying this artificial biocatalyst network, long-chain 1,ω-alkanediols were converted into diamines, which are building blocks for polymers, in up to 99 % conversion. Copyright

Full text of DOI:10.1002/anie.201204683

Angewandte
Chemie
DOI: 10.1002/anie.201204683
Biocatalysis
Redox Self-Sufficient Biocatalyst Network for the Amination of
Primary Alcohols**
Johann H. Sattler, Michael Fuchs, Katharina Tauber, Francesco G. Mutti, Kurt Faber, Jan Pfeffer,
Thomas Haas, and Wolfgang Kroutil*
Amines are essential building blocks in the chemical industry,
for instance in the large-scale production of polymers and
dyes. Furthermore, amines are key intermediates for the
synthesis of a plethora of bioactive compounds for the
pharmaceutical, agrochemical, and chemical industry.[1] For
their preparation carbonyl compounds are frequently reduc-
tively aminated.[2] Instead of using carbonyl compounds
(aldehydes or ketones) as substrate it was recently shown
that also alcohols can serve as alternative starting material
employing metal catalysts[3,4] or in the established Mitsunobu
reaction.[5] Alcohols are transformed to the corresponding
Scheme 1. Artificial redox-neutral multi-enzyme network for the bioami-
nation of primary alcohols. ADH: alcohol dehydrogenase, w-TA: w-
transaminase, AlaDH: l-alanine dehydrogenase, and PLP: 5’-pyridoxal
phosphate.
amines by various metal catalysts through 1) an initial
catalytic dehydrogenation of the alcohol to give the corre-
sponding carbonyl compound and hydrogen, 2) subsequent
formation of the imine, and 3) final hydrogenation leads to
the desired amination product. Since the hydrogen required
for the final hydrogenation step is generated by dehydrogen-
ation of the alcohol in the first step, this approach was named
“borrowing-hydrogen” methodology[6] also known as “hydro-
gen auto-transfer” reaction.[7] Hence, there is no need for
additional hydrogen gas.
Although the transformation of alcohols to amines is
vividly investigated employing metal catalysts, no comparable
process has been reported for (primary) alcohols employing
biocatalytic methods.[8] One reason being that no single
enzyme is known for the interconversion of alcohols to
amines.
Our aim was to construct an artificial multi-enzyme
cascade for the transformation of primary alcohols to the
corresponding amines: Similar to the metal-catalyzed reac-
tion sequence for alcohols, the first step was designed as an
oxidation step catalyzed by an alcohol dehydrogenase
(ADH)[9] consuming NAD+ leading to the formation of the
aldehyde and NADH (Scheme 1). In the second sequential
step, an w-transaminase (w-TA)[10,11] should aminate the
intermediate aldehyde requiring an amine donor. l-Alanine
was chosen as amine donor, since it can be recycled in situ
from pyruvate, the co-product of the transamination. Other
commonly employed amine donors such as 2-propylamine,
benzylamine, 1-phenylethylamine cannot be recycled simul-
taneously by enzymes. For the regeneration of l-alanine from
pyruvate an l-alanine dehydogenase (AlaDH)[12] was chosen,
which consumes ammonia and NADH. The latter was
provided from the oxidation step where NADH was liber-
ated. Thus, the AlaDH connected the oxidation step with the
reductive amination step by transferring the hydride from
NADH—the by-product of the oxidation—to the amination
step by regenerating the amine donor alanine from pyruvate.
Consequently, only an ADH can be used in the oxidation step
and not an alcohol oxidase, which consumes molecular O2
leading to hydrogen peroxide as a side product.
Overall, this designed artificial pathway to transform
primary alcohols to amines represents a redox-neutral
cascade[13,14] thus no external oxidation or reduction equiv-
alents are consumed.
[*] J. H. Sattler, M. Fuchs, K. Tauber, Dr. F. G. Mutti, Prof. Dr. K. Faber,
Prof. Dr. W. Kroutil
In an initial study suitable NAD+-dependent ADHs for
the oxidation of primary alcohols were selected whereby the
ADH from horse liver[15] (HL-ADH, E-isoenzyme;
NP_001075997.1) and the thermostable ADH from Bacillus
stearothermophilus (ADH-hT; P42328.1)[16] turned out to be
best. ADH-hT was used for further studies because of its
simpler overexpression in E. coli. For the amination two w-
TAs were identified as suitable, namely one from Chromo-
bacterium violaceum[17] (CV-wTA) and a variant of an (S)-
selective w-TA from Arthrobacter citreus (ArS-wTA).[18] The
AlaDH originated from Bacillus subtilis.[19]
Department of Chemistry, Organic and Bioorganic Chemistry
University of Graz, Heinrichstrasse 28, 8010 Graz (Austria)
E-mail: wolfgang.kroutil@uni-graz.at
Dr. J. Pfeffer, Dr. T. Haas
Evonik Degussa GmbH, CREAVIS Technologies & Innovation
Paul-Baumann-Strasse 1, 45772 Marl (Germany)
[**] This work has been supported by Evonik. Financial support by the
European Commission (project: AmBioCas, grant agreement
number: 245144, THEME KBBE-2009-3-3-02,), as well as the COST
Action CM0701 “Cascade Chemoenzymatic Processes—New Syn-
ergies Between Chemistry and Biochemistry” is acknowledged.
Testing 1-hexanol as substrate at a concentration of 50 mm
in the presence of all three enzymes (ADH, w-TA, and
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201204683.
Angew. Chem. Int. Ed. 2012, 51, 1 – 5
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1
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Communications
AlaDH) led to full conversion to 1-hexylamine in the cascade
demonstrating that the transformation of a primary alcohol to
the corresponding amine is feasible (Table 1, entry 1). Elon-
gating the chain length led to lower conversion (entries 2, 4),
which could be partly improved by the addition of a cosolvent
Testing first 1,8-octanediol 4a as substrate led to high
amounts of amino alcohol formation 6a and low amounts of
the diamine 8a (Table 2, entry 1) employing ArS-wTA and
methyl tert-butyl ether (MTBE) as cosolvent. Switching to the
transaminase CV-wTA boosted the conversion to 98% with
Table 1: Amination of primary alcohols through a redox-neutral cascade
Table 2: Biocatalytic diamination of 1,w-diols (Scheme 2).[a]
(Scheme 1).[a]
No. Sub. Solv. (v%) T [8C] Conversion Amount
Amount
No. Substrate 1
Conversion Aldehyde 2 Amine 3
[%]
of 6 [%]
of 8 [%]
[%]
[%]
[%]
1
2
3
4
5
6
7
8
9
10
4a
4a
4a
4a
4a
4a
4a
4b
4b
4b
MTBE (30) 35[b]
MTBE (30) 25
52
98
95
>99
99
99
>99
99
>99
>99
49
52
80
18
16
1
<1
6
2
3
46
15
82
83
98
>99
93
98
99
1
2
3
4
5
6
7
8
9
1-hexanol 1a
1-octanol 1b
1-octanol 1b
1-decanol 1c
>99
<1
<1
<1
<1
<1
<1
13
>99
50
57
2
25
10
87
70
>99
50
DME (40)
DME (30)
DME (20)
DME (10)
DME (10)
DME (20)
DME (20)
DME (10)
25
25
25
25
20
25
20
20
57[b]
2
1-decanol 1c
25[b]
1-dodecanol 1d
benzyl alcohol 1e
cinnamyl alcohol 1 f
3-phenyl-1-propanol 1g
10[b]
>99
>99
>99
30
<1
1
[a] Reaction conditions: substrate (50 mm), CV-wTA (1 mg, 0.2 U) and
ADH-hT (1 mg, 0.25 U), AlaDH (0.04 mg, 0.25 U), PLP (0.35 mm),
NAD+ (0.75 mm), ammonium chloride (275 mm), l-alanine (250 mm),
pH 8.5, 24 h, 208C. [b] 1,2-Dimethoxyethane (10v%) was added as
cosolvent.
[a] General reaction conditions: Substrate (50 mm; Sub.), CV-wTA
(1 mg, 0.25 U) and ADH-hT (1 mg, 0.2 U), AlaDH (0.1 mg, 0.7 U), PLP
(0.35 mm), NAD+ (0.75 mm), ammonium chloride (275 mm), l-alanine
(250 mm), pH 8.5, 20 h. [b] ArS-wTA used instead of CV-wTA.
(entries 3, 5). From various organic solvents tested,[20] 1,2-
dimethoxyethane turned out to be best suitable. Alcohols
bearing an aromatic moiety like benzyl alcohol, cinnamyl
alcohol, or 3-phenyl-1-propanol were rather well converted to
the corresponding amine with conversions from 70% up to
> 99% (entries 7–9).
46% diamine 8a formation and 52% of amino alcohol 6a
(entry 2). To increase the availability of the barely soluble diol
4a, the water miscible solvent 1,2-dimethoxyethane was
tested. Careful optimization of temperature and amount of
cosolvent 1,2-dimethoxyethane allowed finally to achieve
99% formation of the diamines 8a and 8b (entries 9 and 10).
Aldehyde-functionalized intermediates 5 and 7 were never
detected in significant amounts in any experiment nor any
traces of the corresponding acids.
The diamination of 1,10-decanediol was finally also
performed on a preparative scale (174 mg of substrate) with
the optimized conditions leading to 94% conversion and 70%
isolated yield.
The advantage of this artificial metabolism results from its
self-sufficiency concerning redox equivalents, thus no exter-
nal hydride source such as glucose or formate was required,
thus, the overall process was redox neutral. The only
stoichiometric reagent required is ammonium as the amine
source. To minimize waste of salt, no common buffer salts like
Tris (Tris = tris(hydroxymethyl)aminomethane) or phosphate
were used. Therefore this process represents an environ-
mentally benign concept yielding valuable
Aromatic[21] and aliphatic diamines, especially hexame-
thylenediamine, are common building blocks for polyamides
(e.g. nylon).[22] In a current effort to identify novel bifunc-
tional building blocks for amide polymers possessing new
properties and originating from renewable resources,[3a,23]
fatty acids represent a promising source for buildings
blocks, which can be converted to w-hydroxy acids.[24]
Unfortunately nature furnishes mainly access to hydroxy-
functionalized compounds.[25] Therefore, amination of the
corresponding reduced 1,w-diols would be an interesting
option to access novel 1,w-diamine building blocks for
polymers. Obviously in this case two redox-neutral oxida-
tion–amination sequences had to take place in tandem, thus
overall four sequential simultaneous steps were required to
get to the diamine (Scheme 2).
building blocks for the polymer industry,
otherwise only accessible through routes
demanding harsh conditions.[26]
Summarizing, we have presented the
first bioamination of primary alcohols
employing a synthetic redox-self-sufficient
cascade. By setting up this “artificial meta-
bolic” pathway, a green method for the
selective amination of alcohols by a highly
atom-efficient one-pot transformation is
available, thereby expanding the toolbox
Scheme 2. Double bioamination of long-chain n-alkane-1,w-diols.
for biocatalytic transformations.[27]
2
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Chemie
J. M. J. Williams, Dalton Trans. 2009, 753 – 762; c) G. W. Lamb,
Experimental Section
J. M. J. Williams, Chim. Oggi 2008, 26, 17 – 19; d) M. H. S. A.
Hamid, P. A. Slatford, J. M. J. Williams, Adv. Synth. Catal. 2007,
349, 1555 – 1575.
Representative procedure exemplified for the diamination of 1,10-
decanediol 4b: Substrate 4b (174.2 mg, 1 mmol) was dissolved in
DME (2 mL, 10v%; DME = 1,2-dimethoxyethane) in
a round
[7] a) G. Guillena, D. J. Ramꢂn, M. Yus, Chem. Rev. 2010, 110,
1611 – 1641; b) G. Guillena, D. J. Ramon, M. Yus, Angew. Chem.
2007, 119, 2410 – 2416; Angew. Chem. Int. Ed. 2007, 46, 2358 –
2364.
[8] Biocatalytic transformations of alcohols to amines have only
been reported for a-hydroxy acids to the corresponding a-amino
acids involving amino acid dehydrogenases and alcohol dehy-
drogenases: a) transformation of mandelic acid to l-phenyl-
glycine: V. Resch, W. M. F. Fabian, W. Kroutil, Adv. Synth. Catal.
2010, 352, 993 – 997; b) transformation of lactate to alanine: C.
Wandrey, E. Fiolitakis, U. Wichmann, Ann. N. Y. Acad. Sci. 1984,
434, 91 – 94.
bottom flask (50 mL) and l-alanine (445 mg, 5 mmol) dissolved in
4 mL H2O was added as well as NH4Cl (320 mg, 6 mmol in 1.5 mL
H2O). The pH was adjusted to pH 8.5 by addition of 80 mL of a 6m
NaOH solution. NAD+ (10 mg, 12 mmol) and PLP (2 mg, 8 mmol;
PLP = pyridoxal 5’-phosphate), each dissolved in 500 mL of H2O, were
added as well as additional 3.12 mL of H2O, the ADH (4 mL, 5 U),
the w-transaminase (4 mL, 4 U) and the alanine dehydrogenase
(300 mL, 5 U). After shaking at 208C, 120 rpm (orbital shaker, Infors
Unitron) for 22 h the product was separated from the reaction
mixture and purified through a weak acid cation exchanger. Finally,
173 mg (0.70 mmol, 70% yield) of the product 8b were obtained. For
details see the Supporting Information.
[9] a) F. Hollmann, I. W. C. E. Arends, K. Buehler, A. Schallmey, B.
Bꢁhler, Green Chem. 2011, 13, 226 – 265; b) T. Matsuda, R.
Yamanaka, K. Nakamura, Tetrahedron: Asymmetry 2009, 20,
513 – 557; c) K. Goldberg, K. Schroer, S. Lꢁtz, A. Liese, Appl.
Microbiol. Biotechnol. 2007, 76, 237 – 248; d) K. Edegger, H.
Mang, K. Faber, J. Gross, W. Kroutil, J. Mol. Catal. A 2006, 251,
66 – 70.
Received: June 15, 2012
Published online: && &&, &&&&
Keywords: alcohols · amination · biocatalysis · polymers
.
[10] For recent reviews on w-transaminases see: a) S. Mathew, H.
Yun, ACS Catal. 2012, 2, 993 – 1001; b) P. Tufvesson, J. Lima-
Ramos, J. S. Jensen, N. Al-Haque, W. Neto, J. M. Woodley,
Biotechnol. Bioeng. 2011, 108, 1479 – 1493; c) D. Koszelewski, K.
Tauber, K. Faber, W. Kroutil, Trends Biotechnol. 2010, 28, 324 –
332; d) N. J. Turner, M. Truppo in Chiral Amine Synthesis:
Methods, Developments and Applications (Ed.: T. C. Nugent),
Wiley-VCH, Weinheim, 2010, pp. 431 – 459; e) H. C. Hailes,
P. A. Dalby, G. J. Lye, F. Baganz, M. Micheletti, N. Szita, J. M.
Ward, Curr. Org. Chem. 2010, 14, 1883 – 1893; f) J. Ward, R.
Wohlgemuth, Curr. Org. Chem. 2010, 14, 1914 – 1927; g) M.
Hçhne, U. T. Bornscheuer, ChemCatChem 2009, 1, 42 – 51.
[11] Selected recent studies involving w-transaminases (2011): a) J.-
H. Seo, D. Kyung, K. Joo, J. Lee, B.-G. Kim, Biotechnol. Bioeng.
2011, 108, 253 – 263; b) K. E. Cassimjee, M. S. Humble, V. Miceli,
C. G. Colomina, P. Berglund, ACS Catal. 2011, 1, 1051 – 1055;
c) F. G. Mutti, J. Sattler, K. Tauber, W. Kroutil, ChemCatChem
2011, 3, 109 – 111; d) H.-S. Bea, H.-J. Park, S.-H. Lee, H. Yun,
Chem. Commun. 2011, 47, 5894 – 5896.
[12] a) M. D. Truppo, J. D. Rozzell, J. C. Moore, N. J. Turner, Org.
Biomol. Chem. 2009, 7, 395 – 398; b) D. Koszelewski, I. Lav-
andera, D. Clay, G. M. Guebitz, D. Rozzell, W. Kroutil, Angew.
Chem. 2008, 120, 9477 – 9480; Angew. Chem. Int. Ed. 2008, 47,
9337 – 9340; c) F. G. Mutti, C. S. Fuchs, D. Pressnitz, N. G.
Turrini, J. H. Sattler, A. Lerchner, A. Skerra, W. Kroutil, Eur.
J. Org. Chem. 2012, 1003 – 1007.
[13] Redox-neutral sequential cascades involving exclusively
enzymes have been reported in Ref. [7] and for: a) the combi-
nation of an alcohol dehydrogenase and an enoate reductases: B.
Boonstra, D. A. Rathbone, C. E. French, E. H. Walker, N. C.
Bruce, Appl. Environ. Microbiol. 2000, 66, 5161 – 5166; b) the
combination of an alcohol dehydrogenase and a Baeyer– Vil-
liger mono-oxygenase: R. Gagnon, G. Grogan, S. M. Roberts, R.
Villa, A. J. Willetts, J. Chem. Soc. Perkin Trans. 1 1995, 1505 –
1511; A. J. Willetts, C. J. Knowles, M. S. Levitt, S. M. Roberts, H.
Sandey, N. F. Shipston, J. Chem. Soc. Perkin Trans. 1 1991, 1608 –
1610; c) the combination of two alcohol dehydrogenases to
achieve racemization: C. C. Gruber, B. M. Nestl, J. Gross, P.
Hildebrandt, U. T. Bornscheuer, K. Faber, W. Kroutil, Chem.
Eur. J. 2007, 13, 8271 – 8276.
[1] a) Chiral amine synthesis (Ed.: T. C. Nugent), Wiley-VCH,
Weinheim, 2010; b) H. A. Wittcoff, B. G. Reuben, J. S. Plotkin,
Industrial Organic Chemicals, 2nd ed., Wiley-Interscience, New
York, 2004.
[2] a) A. Pagnoux-Ozherelyeva, N. Pannetier, M. D. Mbaye, S.
Gaillard, J.-L. Renaud, Angew. Chem. 2012, 124, 5060 – 5064;
Angew. Chem. Int. Ed. 2012, 51, 4976 – 4980; b) J. L. Klinken-
berg, J. F. Hartwig, Angew. Chem. 2011, 123, 88 – 98; Angew.
Chem. Int. Ed. 2011, 50, 86 – 95; c) A. Henseler, M. Kato, K.
Mori, T. Akijama, Angew. Chem. 2011, 123, 8330 – 8330; Angew.
Chem. Int. Ed. 2011, 50, 8180 – 8183; d) T. C. Nugent, M. El-
Shazly, Adv. Synth. Catal. 2010, 352, 753 – 819; e) C. K. Savile,
J. M. Janey, E. C. Mundorff, J. C. Moore, S. Tam, W. R. Jarvis,
J. C. Colbeck, A. Krebber, F. J. Fleitz, J. Brands, P. N. Devine,
G. W. Huisman, G. J. Hughes, Science 2010, 329, 305 – 309.
[3] Selected recent examples: a) M. Lafrance, M. Roggen, E. M.
Carreira, Angew. Chem. 2012, 124, 3527 – 3530; Angew. Chem.
Int. Ed. 2012, 51, 3470 – 3473; b) S. Imm, S. Bꢀhn, M. Zhang, L.
Neubert, H. Neumann, F. Klasovsky, J. Pfeffer, T. Haas, M.
Beller, Angew. Chem. 2011, 123, 7741 – 7745; Angew. Chem. Int.
Ed. 2011, 50, 7599 – 7603; c) D. Pingen, C. Mꢁller, D. Vogt,
Angew. Chem. 2010, 122, 8307 – 8310; Angew. Chem. Int. Ed.
2010, 49, 8130 – 8133; d) S. Imm, S. Bꢀhn, L. Neubert, H.
Neumann, M. Beller, Angew. Chem. 2010, 122, 8303 – 8306;
Angew. Chem. Int. Ed. 2010, 49, 8126 – 8129; e) R. Kawahara, K.-
i. Fujita, R. Yamaguchi, J. Am. Chem. Soc. 2010, 132, 15108 –
15111; f) O. Saidi, A. J. Blacker, M. M. Farah, S. P. Marsden,
J. M. J. Williams, Angew. Chem. 2009, 121, 7511 – 7514; Angew.
Chem. Int. Ed. 2009, 48, 7375 – 7378; g) M. H. S. A. Hamid, C. L.
Allen, G. W. Lamb, A. C. Maxwell, H. C. Maytum, A. J. A.
Watson, J. M. J. Williams, J. Am. Chem. Soc. 2009, 131, 1766 –
1774; h) B. Blank, S. Michlik, R. Kempe, Chem. Eur. J. 2009, 15,
3790 – 3799; i) C. Gunanathan, D. Milstein, Angew. Chem. 2008,
120, 8789 – 8792; Angew. Chem. Int. Ed. 2008, 47, 8661 – 8664.
[4] First reports on amination of alcohols: a) R. Grigg, T. R. B.
Mitchell, S. Sutthivaiyakit, N. Tongpenyai, J. Chem. Soc. Chem.
Commun. 1981, 611 – 612; b) Y. Watanabe, Y. Tsuji, Y. Ohsugi,
Tetrahedron Lett. 1981, 22, 2667 – 2670.
[5] a) K. C. K. Swamy, N. N. B. Kumar, E. Balaraman, K. V. P. P.
Kumar, Chem. Rev. 2009, 109, 2551 – 2651; b) O. Mitsunobu, M.
Yamada, Bull. Chem. Soc. Jpn. 1967, 40, 2380 – 2382.
[6] For reviews see: a) G. E. Dobereiner, R. H. Crabtree, Chem.
Rev. 2010, 110, 681 – 703; b) T. D. Nixon, M. K. Whittlesey,
[14] For a recent review on cascades involving redox steps see:
a) J. H. Schrittwieser, J. Sattler, V. Resch, F. G. Mutti, W. Kroutil,
Curr. Opin. Chem. Biol. 2011, 15, 249 – 256; Review on multi-
Angew. Chem. Int. Ed. 2012, 51, 1 – 5
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
3
These are not the final page numbers!

.
Angewandte
Communications
enzymatic synthesis: b) F. Lopez-Gallego, C. Schmidt-Dannert,
Curr. Opin. Chem. Biol. 2010, 14, 174 – 183.
[22] S. M. Aharoni, n-Nylons: Their Synthesis Structure and Proper-
ties, Wiley, New York, 1997.
[15] a) D. H. Park, B. V. Plapp, J. Biol. Chem. 1991, 266, 13296 –
13302; b) S. Al-Karadaghi, E. S. Cedergren-Zeppezauer, S.
Hovmoller, K. Petratos, H. Terry, K. S. Wilson, Acta Crystallogr.
Sect. D 1994, 50, 793 – 807.
[16] a) R. Cannio, M. Rossi, S. Bartolucci, Eur. J. Biochem. 1994, 222,
345 – 352; b) X. Zhang, T. C. Bruice, Biochemistry 2007, 46, 837 –
843.
[17] a) U. Kaulmann, K. Smithies, M. E. B. Smith, H. C. Hailes, J. M.
Ward, Enzyme Microb. Technol. 2007, 41, 628 – 637; b) M. S.
Humble, K. E. Cassimjee, M. Hꢃkansson, Y. R. Kimbung, B.
Walse, V. Abedi, H.-J. Federsel, P. Berglund, D. T. Logan, FEBS
J. 2012, 279, 779 – 792; c) D. Koszelewski, M. Gçritzer, D. Clay,
B. Seisser, W. Kroutil, ChemCatChem 2010, 2, 73 – 77.
[18] A. R. Martin, R. DiSanto, I. Plotnikov, S. Kamat, D. Shonnard, S.
Pannuri, Biochem. Eng. J. 2007, 37, 246 – 255.
[23] G.-Q. Chen, M. K. Patel, Chem. Rev. 2012, 112, 2082 – 2099.
[24] a) S. Honda Malca, D. Scheps, L. Kꢁhnel, E. Venegas-Venegas,
A. Seifert, B. M. Nestl, B. Hauer, Chem. Commun. 2012, 48,
5115 – 5117; b) M. Schrewe, A. Magnusson, C. Willrodt, B.
Bꢁhler, A. Schmid, Adv. Synth. Catal. 2011, 353, 3485 – 3495;
c) D. Scheps, S. Honda Malca, H. Hoffmann, B. M. Nestl, B.
Hauer, Org. Biomol. Chem. 2011, 9, 6727 – 6733; d) W. H. Lu,
J. E. Ness, W. C. Xie, X. Y. Zhang, J. Minshull, R. A. Gross, J.
Am. Chem. Soc. 2010, 132, 15451 – 15455; e) J. C. Lewis, F. H.
Arnold, Chimia 2009, 63, 309 – 312; f) P. Meinhold, M. W. Peters,
A. Hartwick, A. R. Hernandez, F. H. Arnold, Adv. Synth. Catal.
2006, 348, 763 – 772.
[25] A. M. Ruppert, K. Weinberg, R. Palkovits, Angew. Chem. 2012,
124, 2614 – 2654; Angew. Chem. Int. Ed. 2012, 51, 2564 – 2601.
[26] G. Bellussi, C. Perego, Cattech 2001, 4, 4 – 16.
[19] F. G. Mutti, C. S. Fuchs, D. Pressnitz, J. H. Sattler, W. Kroutil,
Adv. Synth. Catal. 2011, 353, 3227 – 3233.
[27] a) U. T. Bornscheuer, G. W. Huisman, R. J. Kazlauskas, S. Lutz,
J. C. Moore, K. Robins, Nature 2012, 485, 185 – 194; b) J. M.
Woodley, Trends Biotechnol. 2008, 26, 321 – 327; c) D. J. Pollard,
J. M. Woodley, Trends Biotechnol. 2007, 25, 66 – 73; d) H. E.
Schoemaker, D. Mink, M. G. Wubbolts, Science 2003, 299, 1694 –
1697.
[20] Solvents tested: Diethyl ether, diiospropyl ether, methyl-tert-
butyl ether, acetonitril, toluene, dichloromethane, chloroform,
tert-butanol, formamide, dimethylformamide, and ethyl acetate.
[21] X.-G. Li, M.-R. Huang, W. Duan, Y.-L. Yang, Chem. Rev. 2002,
102, 2925 – 3030.
4
www.angewandte.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2012, 51, 1 – 5
These are not the final page numbers!

Angewandte
Chemie
Communications
Biocatalysis
J. H. Sattler, M. Fuchs, K. Tauber,
F. G. Mutti, K. Faber, J. Pfeffer, T. Haas,
W. Kroutil*
&&&& — &&&&
Redox Self-Sufficient Biocatalyst Network
for the Amination of Primary Alcohols
Driving the machinery: A biocatalytic
redox-neutral cascade for the preparation
of terminal primary amines from primary
alcohols at the expense of ammonia has
been established in a one-pot one-step
method (see picture). Applying this arti-
ficial biocatalyst network, long-chain 1,w-
alkanediols were converted to diamines,
which are building blocks for polymers, in
up to 99% conversion.
Angew. Chem. Int. Ed. 2012, 51, 1 – 5
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
5
These are not the final page numbers!