Thioesters as Acyl Donors in Biocatalytic Friedel-Crafts-type Acylation Catalyzed by Acyltransferase from Pseudomonas Protegens

Article abstract of DOI:10.1002/cctc.201801856

Functionalization of aromatic compounds by acylation has considerable significance in synthetic organic chemistry. As an alternative to chemical Friedel-Crafts acylation, the C-acyltransferase from Pseudomonas protegens has been found to catalyze C?C bond formation with non-natural resorcinol substrates. Extending the scope of acyl donors, it is now shown that the enzyme is also able to catalyze C?S bond cleavage prior to C?C bond formation, thus aliphatic and aromatic thioesters can be used as acyl donors. It is worth to mention that this reaction can be performed in aqueous buffer. Identifying ethyl thioacetate as the most suitable acetyl donor, the products were obtained with up to >99 % conversion and up to 88 % isolated yield without using additional base additives; this represents a significant advancement to prior protocols.

Full text of DOI:10.1002/cctc.201801856

Full Papers
DOI: 10.1002/cctc.201801856
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Thioesters as Acyl Donors in Biocatalytic Friedel-Crafts-type
Acylation Catalyzed by Acyltransferase from Pseudomonas
Protegens
Anna Żądło-Dobrowolska,[a] Nina G. Schmidt,[a, b] and Wolfgang Kroutil*[a, b]
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Functionalization of aromatic compounds by acylation has
considerable significance in synthetic organic chemistry. As an
alternative to chemical Friedel-Crafts acylation, the C-acyltrans-
ferase from Pseudomonas protegens has been found to catalyze
CÀ C bond formation with non-natural resorcinol substrates.
Extending the scope of acyl donors, it is now shown that the
enzyme is also able to catalyze CÀ S bond cleavage prior to CÀ C
bond formation, thus aliphatic and aromatic thioesters can be
used as acyl donors. It is worth to mention that this reaction
can be performed in aqueous buffer. Identifying ethyl thioace-
tate as the most suitable acetyl donor, the products were
obtained with up to >99% conversion and up to 88% isolated
yield without using additional base additives; this represents a
significant advancement to prior protocols.
Introduction
to the electron-rich nature of the compound causing multiple
C-acylations as well as O-acylations.[8] The acylations are mostly
performed in organic solvents (e.g., nitrobenzene or nitro-
The design and development of catalytic and regioselective
strategies for the C-acylation of aromatic compounds is of
significant importance for organic synthesis.[1] The resulting
aromatic ketones are important building blocks that are widely
used for manufacturing products such as pharmaceuticals,
agrochemicals, flavors and fragrances.[2] Functionalization of
aromatic compounds via Friedel-Crafts reaction is traditionally
achieved by treating the starting material at high temperatures
with stoichiometric amounts of Lewis acids (e.g., AlCl3, BF3,
GaCl3, BeCl2) or Brønsted acids (e.g., HF, H2SO4, CF3COOH, HCl,
phosphoric acids).[3] Either the corresponding acid chloride,
anhydride or a carboxylic acid serves as an acyl donor.[4] In
recent years, several improved protocols have been reported
for the direct acylation, and most of them employ heteroge-
neous supports and catalysts (e.g., zeolites, clays, metal oxides,
acids, nafion, and graphene),[5] alternative solvents (e.g., super-
critical CO2, ionic liquids, hexafluoro-2-propanol, deep eutectic
solvents)[6] or activated carboxylic acid equivalents (e.g. twisted
amides).[7]
methane) or at elevated temperatures of up to 300 C.[9] Besides
°
the insufficient reaction control which often leads to product
mixtures, another drawback of most chemical methods is the
need for hazardous reagents. As an alternative, a biocatalytic
approach running the reaction in aqueous media was recently
published: originally an acyltransferase from Pseudomonas
fluorescens was found to be involved in CÀ C bond formation in
the biosynthesis of 2,4-diacetylphloroglucinol (DAPG).[10] Sub-
sequently, it was shown that a homologue acyltransferase from
Pseudomonas protegens (PpATaseCH) exhibits promiscuous
activity, accepting also non-natural, activated esters, like
isopropenyl acetate, phenyl acetate and N-acetyl imidazole for
the biocatalytic Friedel-Crafts acylation of resorcinol derivatives
leading to C4-acylated products.[11] Thus, the enzyme cleaves a
CÀ O or CÀ N bond in the acetyl donor and enables subsequently
a CÀ C bond formation to give the final C-acetylated product.
Moreover, PpATaseCH was identified to catalyze CÀ N bond
formation using aniline derivatives as substrates in aqueous
media.[12]
In particular, regioselective C-acylation of (poly)phenolic
substrate remains a challenging task, which is mostly attributed
Since thioesters have been reported as outstanding surro-
gates for carboxylic acid derivatives in a vast number of
biotransformations,[13] we investigated their application in a
Friedel-Crafts-type bioacylation. According to the best of our
knowledge, this class of compounds has never been employed
before as acyl donors in the Friedel-Crafts-type acylation of
aromatic compounds. As an alternative to the commonly
employed acyl chlorides and anhydrides in chemical Friedel-
Crafts reactions, a thioester is easy to handle since this class of
compound is tolerant to column purification and air stable
compared to the corresponding acyl chlorides.[14]
[a] Dr. A. Żądło-Dobrowolska, Dr. N. G. Schmidt, Prof. W. Kroutil
Institute of Chemistry
University of Graz
NAWI Graz, BioTechMed Graz,
Graz 8010 (Austria)
E-mail: wolfgang.kroutil@uni-graz.at
[b] Dr. N. G. Schmidt, Prof. W. Kroutil
ACIB GmbH
Graz 8010 (Austria)
Supporting information for this article is available on the WWW under
https://doi.org/10.1002/cctc.201801856
© 2018 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.
This is an open access article under the terms of the Creative Commons
Attribution Non-Commercial License, which permits use, distribution and
reproduction in any medium, provided the original work is properly cited
and is not used for commercial purposes.
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Results and Discussion
complete consumption of substrate (up to >99%, Table 1). It is
worth to mention, that performing the reaction with the natural
acetyl thioester acetyl-CoA as possible donor did not lead to
any detectable conversion.
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The reactivity of thioesters in comparison to the reactivity of
carboxylic acid esters has been of longstanding interest, mainly
due to their importance in living organisms.[15] Whereas in
organic synthetic chemistry, thioester formation is a common
strategy to activate carboxylic acid building blocks leading to
activated acyl units, which are fused with other chemical
building blocks, mostly by CÀ C, CÀ O or CÀ N bond formation.[16]
Now, aliphatic and aromatic thioesters 2a–d were investigated
as acyl donors in the Friedel-Crafts-type biocatalytic reaction.
For this purpose, the substrate resorcinol (1a, 10 mM) was
suspended in KPi-buffer adjusted to pH 7.5, and cell-free extract
containing recombinant PpATaseCH was subsequently added,
followed by addition of the acetyl donor (100 mM, 2a–d).
Transformations were studied in the presence and absence of
imidazole as an additive, since imidazole was previously
identified to promote the bioacylation using either IPEA or vinyl
acetate.[11]
All tested thioesters afforded the product 2,4-dihydroxyace-
tophenone (3a) in good to excellent yields (58–>99%, Table 1).
Thus, in the observed reaction the enzyme breaks a CÀ S bond
in the acetyl donor and enables subsequently CÀ C bond
formation. Acetylation was observed exclusively at C4 position
of 3a, thus neither multiple substitution nor O-acylation was
detectable after 18 h of reaction. C-acylation in the absence of
imidazole using aliphatic thioesters, such as ethyl thioacetate
(2a) or 2-acetylthioacetophenone (2d) led to very high
conversions, 81% and 93% respectively. Moderate conversion
was observed using S-4-nitrobenzyl thioacetate (2c, 58%). S-
Phenyl thioacetate (2b) turned out to be a very suitable donor
substrate leading to product 3a with 95% yield. In all cases,
imidazole as an additive improved the reaction leading to
Comparing the pH of the reaction mixture before and after
imidazole addition revealed a shift from 7.5 to 8.3. For
comparison, a reaction performed in buffer adjusted to pH 8.3
in the absence of imidazole led to lower conversion compared
to reaction performed in the presence of imidazole (Table 2). To
gain an insight into the imidazole effect, the time course of the
reaction was monitored (Figure 1). Although imidazole pro-
motes the reaction reaching completion within 24 h, the
reaction in the absence of imidazole was slightly slower
requiring approximately 30 h for completion. Importantly, O-
acetylated product formation (4a) was observed only at the
initial stage of the reaction and its formation was much more
pronounced in the presence of imidazole.
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Since various organic amines have been reported to
enhance the Friedel-Craft-like biotransformation,[17] the influ-
Table 2. Influence of amine additives on the CÀ C bioacylation of 1a.
Entry Donor Additive
Additive concentration
[mM]
pH Yield
[%]
1
2
3
4
5
6
7
8
2a
2a
2a
2a
2b
2b
2b
2b
2a
2a
2a
2b
2b
2b
2a
none
0
7.5 81
7.6 79
Imidazole 10
Imidazole 50
Imidazole 100
8
89
8.3 >99
7.5 95
7.6 93
none
0
Imidazole 10
Imidazole 50
Imidazole 100
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
none
8
93
8.3 96
8.4 89
9.6 95
10 99
8.4 91
9.6 91
10 91
8.3 74
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10
50
100
10
50
100
0
10
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12
13
14
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Table 1. PpAtaseCH catalyzed bioacylation of resorcinol (1) employing
aromatic and aliphatic thioesters as acyl donors in the absence and
presence of imidazole.
Reaction conditions: cell-free E. coli extract containing PpATaseCH (0.066 U)
in KPi-buffer (100 mM, pH 7.5, total volume 1 mL), resorcinol (1,
0.01 mmol), donor 2a or 2b (0.01 mmol–0.1 mmol) with or without
imidazole or DABCO (100 mM added from a 1 M stock solution prepared in
°
the reaction buffer), 35 C, 18 h.
Entry
Donor
HPLC conversion
with Im
HPLC conversion
without Im
[%]
[%]
1
2
2
3
2a
2b
2c
2d
>99
>99
>99
>99
81
95
58
93
Reaction conditions: cell-free E.coli extract containing PpATaseCH (0.066 U)
in KPi-buffer (100 mM, pH 7.5, total volume 1 mL), resorcinol (1a,
0.01 mmol), donor 2a–2d (0.1 mmol) with or without imidazole (100 mM
added from a 1 M stock solution prepared in the reaction buffer), 35 C,
18 h. Experiments were performed in duplicate.
Figure 1. Time course for the PpATaseCH-catalyzed acetylation of 1a
(10 mM) with ethyl thioacetate (2a, 100 mm) leading to 3a in the presence
(*) or absence (*) of imidazole and O-acetylated co-product 4a, in the
presence (~) or absence (Δ) of imidazole.
°
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Table 3. Monitoring the progress of the bioacetylation of resorcinol (1a) with ethyl thioacetate (2a) as acyl donor.
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2
3
Entry
Reaction Time
[h]
Enzyme [U]
Donor conc.
[mM]
Substrate conc.
[mM]
HPLC yield 3
[%]
Space time
yield 3
[gLÀ 1 hÀ 1
]
4
5
6
7
8
1
2
3
4
5
6
18
18
18
18
18
18
0.066
0.066
0.066
0.066
0.066
0.132
15
50
100
100
200
200
10
10
10
20
20
20
22
60
81
46
51
62
19
51
68
78
86
105
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Reaction conditions: cell-free E. coli extract containing PpATaseCH (0.066–0.132 U) in KPi-buffer (100 mM, pH 7.5) with the acceptor 1 (10–20 mM) and the
°
donor 2a (15–200 mM) as indicated below, 35 C, 18 h, 750 rpm.
ence of DABCO additionally to imidazole was examined. The
acetylation was performed at varied DABCO or imidazole
concentrations (Table 2). A 10-fold decrease of imidazole or
DABCO concentration from 100 mM to 10 mM using 2a led
only to a slightly lower conversion, 79% and 89% respectively
(entries 2 and 9). In contrast, no effect was observed for 2b
(entries 5–8 and 12–14), which seemed to be insensitive for
imidazole or DABCO addition. This is an important observation,
since in comparison to carboxylic acid esters as donors,[11]
thioesters work without amine additives. Therefore, the environ-
mental footprint is reduced since no amine additive is required.
Consequently, ethyl thioacetate was chosen as acyl donor for
further experiments. According to the best of our knowledge it
is the first report employing thioesters as alternative acyl donors
in Friedel-Crafts-type acylation.
Subsequently, process intensification was investigated.
Table 3 summarizes key optimization results employing ethyl
thioacetate as an acyl donor. First, the concentration of
thioester was decreased from 100 mM to 50 mM at constant
enzyme (0.066 U) and substrate concentration (10 mM) leading
to a conversion of 60% and a space time yield of 51 g LÀ 1 hÀ 1
(Entry 2). At lower acetyl donor concentration (15 mM) the
conversion dropped to just 22% (Entry 1). Increasing the
concentration of the acetyl acceptor (resorcinol) from 10 mM to
20 mM and keeping the enzyme and donor concentrations
constant, led to lower conversion (46%) however accompanied
by higher space-time yield (78 gLÀ 1 hÀ 1). To increase further the
space time yield, a 2-fold concentrated bioconversion was run
at 20 mM substrate 1a with 200 mM donor 2a. After 18 h space
time yield reached 86 gLÀ 1 hÀ 1 compared to 68 in the control
(Table 3, entry 5 vs. 3). Increasing the enzyme amount up to
0.132 U improved space time yield to 105 gLÀ 1 hÀ 1 despite the
moderate conversion (62%, entry 6). Because of the sensitivity
of this enzyme towards high substrate loadings, 10 mM
substrate with 100 mM donor was chosen as the conditions for
the transformation of further substrate and scale up.
Table 4. Acetylation of various substrates using ethyl thioacetate and
semi-preparative experiments.
Using ethyl thioacetate as acetyl donor, a broad set of acyl
acceptors 1a–j were tested. Since the reaction rates in the
absence of imidazole were slower, reaction times were
elongated up to 24 h, so that the bioacylation of 1a reached
96% conversion (Table 4). Resorcinols bearing chloro-substitu-
ent (3f) or different lengths of alkyl chains at position C6 (3b–
3e) were accepted providing products with conversions up to
40%. Compound with a methyl group at C6 underwent lower
conversion (3b, 7%) than either ethyl (3c, 32%), n-butyl (3d,
30%) or n-hexyl group (3e, 25%). In all cases, imidazole
addition improved conversions significantly, for instance for 3d
the conversion was improved from 30% to 90%. Resorcinol
derivatives possessing methoxy (3g) or chloro group (3h) at
position C5 were not accepted as substrates. Furthermore,
aniline (1i) and 3-hydroxyaniline (1j) were examined as acyl
acceptors. In this case a CÀ N instead of a CÀ C bond was formed,
thus leading to the corresponding acetanilides with up to
>99% conversion. In the presence of imidazole as an additive,
Entry
Product
w/o Im [%]
Im [%]
1
2
3
4
5
6
8
9
3a
3b
3c
3d
3e
3f
3g
3h
3i
96 (88)
7
32
30
25
40
<1
<1
79 (37)
>99 (58)
>99
16
50 (49)
90 (70)
34 (37)
51 (45)
<1
<1
>99
>99
10
11
3j
Reaction conditions: cell-free E. coli extract containing PpATaseCH (0.066 U)
in KPi-buffer (100 mM, pH 7.5) with the acceptor 1 (10 mM) and the donor
2a (100 mM) with or without imidazole (100 mM added from a 1 M stock
solution prepared in the reaction buffer), 35 C, 24 h, 750 rpm; conversions
were determined by HPLC, values within parentheses refer to yields of
isolated products.
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donor 2a–2d (0.1 mmol, 100 mM final concentration) and amine
additive (imidazole or DABCO, 100 mM final concentration, added
from 1 M stock solution prepared in the reaction buffer). The
reaction reached also completion, however background reac-
tion was observed.
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2
3
4
5
6
7
8
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Finally, reaction scale-up was performed in 25 mL volume
using 10 mM substrate (values in brackets, Table 4) to avoid
potential enzyme inhibition. In the case of substrate 1a, 2,4-
dihydroxyacetophenone (3a) was isolated with 88% yield
(33.6 mg), highlighting excellent acyl transfer efficiency.
Acetanilide 3i and 3j were isolated with up to 58% (12.4 mg,
22 mg, respectively). Since for C6-substituted compounds
moderate conversions were observed on analytical scale, scale-
up was run in 100 mM imidazole solution. The isolated product
yields from preparative scale experiments were comparable to
those determined on analytical scale. In case of products 3e
and 3f an additional hydrolysis step was necessary since after
biotransformation a mixture of C-acylated and O-acylated
products was obtained.
°
reaction mixture was shaken for 18–24 h at 35 C and 750 rpm in an
orbital shaker. Reaction was quenched by addition of acetonitrile
(1 mL). The precipitated protein was removed by centrifugation
(30 min, 14,000 rpm) and the supernatant was subjected to HPLC
for determination of conversions. As a negative control, reactions
without enzyme were performed. All experiments were performed
in duplicate (Table 1) or as a single study (Tables 2–4).
Semi-preparative Scale Friedel-Crafts Bioacylation. Resorcinol
derivative 1a–1f or aniline derivative 1i–1j (0.25 mmol, 10 mM
final concentration) was dissolved in potassium phosphate buffer
(100 mM, pH 7.5) in a shaking flask. Cell-free extract containing the
PpATaseCH (2.5 mL, 1.65 U) was added to the reaction mixture
followed by ethyl thioacetate (266 μL, 2.5 mmol, 100 mM final
concentration) addition. For substrates 1c–1f, imidazole (2.5 mmol,
100 mM final concentration, added from a 1 M stock solution
prepared in the reaction buffer) was added. The bioacetylation
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(25 mL total volume) was run at 35 C and 120 rpm for 24 h. The
resulting suspension was extracted with ethyl acetate (2×20 mL),
centrifuged (5 min, 4,000 rpm). Then organic layers were separated,
combined and dried over anhydrous MgSO4. Solvent was removed
under reduced pressure and crude product was purified by column
chromatography using silica gel, DCM/MeOH or cyclohexane/EtOAc
Conclusions
A range of commercially available thioesters were evaluated as
acyl donors for the biocatalytic Friedel-Crafts-type acetylation of
resorcinol derivatives. Ethyl thioester was identified as a very
suitable acyl donor, which allowed the synthesis of valuable
aromatic ketones with moderate to high isolated yields (up to
>99% conv. and 88% isolated yield). The method presented is
broadly applicable to resorcinol and its derivatives, tolerating a
wide range of functional groups at position C6, while
substitution at C5 is not tolerated. Bioconversions may be run
at 20 mM or higher providing satisfactory space time yields.
Importantly, in contrast to previous protocols no imidazole as
additive is required, which makes this method a feasible new
tool for the toolbox of biocatalytic CÀ C bond formation.[18,19]
1
as an eluent. Compounds were characterized by H NMR and 13C
NMR and GC-MS and the chemical identity was confirmed by
comparison to literature. For compounds 3e and 3f a mixture of C-
acylated and O-acylated products was observed. To remove O-
acylated products, mixture was submitted to hydrolysis with 1 N
NaOH for 1 h at rt, then acidified with 1 N HCl, extracted with EtOAc
and purified by column chromatography.
1-(2,4-dihydroxyphenyl)ethan-1-one (3a)
1H NMR (300 MHz, DMSO-d6): δ [ppm]=12.61 (s, 1H), 10.63 (s, 1H),
7.75 (d, J=8.8 Hz, 1H), 6.38 (dd, J=8.8, 2.4 Hz, 1H), 6.24 (d, J=
2.3 Hz, 1H), 2.52 (s, 3H); 13C NMR (75 MHz, DMSO-d6): δ [ppm]=
203.17, 165.34, 164.66, 134.18, 113.31, 108.57, 102.74, 26.82; GC-MS
(EI+, 70 eV): m/z (%)=152.1 [M+] (47), 137.0 [C7H5O3+] (100), 109
[C6H5O2+] (3).
Experimental Section
General Methods. 1H- and 13C-NMR spectra were recorded in CDCl3,
DMSO-d6 or acetone-d6 solution. Chemical shifts are expressed in
parts per million using TMS as an internal standard. TLC was done
on Kieselgel 60 F254 aluminum sheets. Reference compounds: 3b,
3c, 3d, 3e, 3f were synthesized according to the general
procedure, reference compounds 3a, 3i, 3j were commercial
products of analytical grade.
1-(5-ethyl-2,4-dihydroxyphenyl)ethan-1-one (3c)
1H NMR (300 MHz, CDCl3): δC [ppm]=12.62 (s, 1H), 7.47 (s, 1H), 6.35
(s, 1H), 2.65–2.54 (m, 5H), 1.24 (t, J=7.5 Hz, 3H); 13C NMR (75 MHz,
CDCl3): δC [ppm]=202.91, 163.10, 161.25, 131.58, 122.64, 113.88,
103.10, 77.44, 77.02, 76.59, 26.18, 22.47, 14.07. GC-MS (EI+, 70 eV):
m/z (%)=180.1 [M+] (36), 165.0 [C9H9O3+] (100).
General Procedure for Chemical Friedel-Crafts Acylation. The
corresponding resorcinol derivative 1a–1f (1 equiv.) was dissolved
by dropwise adding BF3·2CH3COOH (2.5 mL, 18.0 mmol). The
resulting solution was stirred and refluxed for 3 to 4 h. After cooling
the reaction mixture to room temperature 0.5 M aqueous KOAc
(50 mL) was added dropwise and stirring was continued for further
30 minutes. The crude precipitate was filtered and recrystallized
from MeOH/H2O (1:1, 60 mL) affording the 2,4-dihydroxyacetophe-
none analogs 3b–3f. Selected compounds were additionally
purified by column chromatography.
1-(5-butyl-2,4-dihydroxyphenyl)ethan-1-one (3d)
1H NMR (300 MHz, Acetone-d6): δC [ppm]=12.61 (s, 1H), 9.37 (s,
1H), 7.65 (s, 1H), 6.35 (s, 1H), 2.64–2.52 (m, 5H), 1.67–1.48 (m, 2H),
1.38 (dq, J=14.4, 7.2 Hz, 2H), 0.94 (t, J=7.3 Hz, 3H); 13C NMR
(75 MHz, Acetone-d6): δC [ppm]=202.71, 163.35, 162.56, 132.67,
121.33, 113.13, 102.26, 32.05, 28.96, 25.36, 22.26, 13.34; GC-MS (EI+,
70 eV): m/z (%)=208.1 [M+] (25), 193.1 [C11H13O3+] (13), 165.0
[C9H9O3+] (100).
Screening Procedure. Resorcinol derivative 1a–1h or aniline
derivative 1i–1j (0.01 mmol, 10 mM final concentration) was
suspended in potassium phosphate buffer (100 mM, pH 7.5). Then,
cell-free extract of recombinant ATase (0.066 U) was added to the
reaction mixture. The bioacylation was started by addition of the
1-(5-hexyl-2,4-dihydroxyphenyl) ethan-1-one (3e)
1H NMR (300 MHz, Acetone-d6) δ 12.61 (s, 1H), 9.40 (s, 1H), 7.65 (s,
1H), 6.35 (s, 1H), 2.66–2.50 (m, 5H), 1.70–1.49 (m, 2H), 1.42–1.25 (m,
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6H), 0.89 (dd, J=8.8, 5.2 Hz, 3H); 13C NMR (75 MHz, Acetone-d6): δ
[ppm]=202.69, 163.36, 162.59, 132.66, 121.38, 113.12, 102.26,
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31.57, 29.80, 29.69, 29.26, 25.37, 22.40, 13.44; GC-MS (EI+, 70 eV):
+
m/z (%)=236.1 [M+] (15), 221.1 [C13H17O3+] (7), 165.0 [C9H9O3
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1-(5-chloro-2,4-dihydroxyphenyl)ethan-1-one (3f)
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7.91 (s, 1H), 6.51 (s, 1H), 2.62 (s, 3H); 13C NMR (75 MHz, Acetone-d6):
δ [ppm]=202.72, 163.37, 159.70, 132.54, 113.94, 111.52, 103.85,
25.55; GC-MS (EI+, 70 eV): m/z (%)=186.0 [M+] (41), 171.0
[C7H4ClO3+] (100).
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1H NMR (300 MHz, CDCl3): δ [ppm]=7.52 (d, J=7.9 Hz, 2H), 7.34 (t,
J=7.9 Hz, 2H), 7.12 (t, J=7.4 Hz, 1H), 2.19 (s, 3H); 13C NMR (75 MHz,
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1H NMR (300 MHz, DMSO-d6): δ [ppm] 9.77 (s, 1H), 9.31 (s, 1H), 7.18
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28
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39
40
41
42
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44
45
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(EI+, 70 eV): m/z (%)=151.1 [M+] (44), 109.1 [C6H7NO+] (100).
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This study was financed by the Austrian Science Fund (FWF) Lise
Meitner Fellowship grant M 2172-B21. NGS was financed by the
Austrian FFG, BMWFJ, BMVIT, SFG, Standortagentur Tirol and ZIT
through the Austrian FFG-COMET-Funding Program.
Conflict of Interest
The authors declare no conflict of interest.
Keywords: Friedel-Crafts reaction · thioesters · acyltransferase ·
acylation · CÀ C bond formation
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Manuscript received: November 14, 2018
Revised manuscript received: December 5, 2018
Version of record online: ■■■, ■■■■
ChemCatChem 2019, 11, 1–6
www.chemcatchem.org
5
© 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA

Full Papers
FULL PAPERS
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New tool available: As an alternative
to chemical Friedel-Crafts acylation,
the C-acyltransferase from Pseudomo-
nas protegens catalyzes CÀ C bond
Dr. A. Żądło-Dobrowolska, Dr. N. G.
Schmidt, Prof. W. Kroutil*
1 – 6
Thioesters as Acyl Donors in Bioca-
talytic Friedel-Crafts-type Acylation
Catalyzed by Acyltransferase from
Pseudomonas Protegens
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