Enzymatic Cleavage of Aryl Acetates

Article abstract of DOI:10.1002/cctc.201600678

Seven enzymes have been screened for the cleavage of aryl acetates. Phenyl and naphthyl acetates react with lipases and esterases, whereas the sterically demanding anthracene acetate gave a conversion only with porcine liver esterase and esterase 2 from Bacillus subtilis (BS2). These two enzymes have been employed on a preparative (0.5 mmol) scale and afforded cleavage products in 91 and 94 % yields, even for anthracene acetate. Thus, this method is superior to chemical cleavage with catalytic amounts of sodium methoxide (Zemplén conditions), which gave only low conversions. Finally, regioselectivity has been achieved with an anthracene bisacetate, in which an ethyl group controls the cleavage of the first acetate. This indicates that steric interactions play a crucial role in the enzymatic cleavage of aryl acetates, which might be interesting for future applications or the development of enzyme inhibitors.

Full text of DOI:10.1002/cctc.201600678

DOI: 10.1002/cctc.201600678
Full Papers
Enzymatic Cleavage of Aryl Acetates
Marcel Bauch, Dominique Bçttcher, Uwe T. Bornscheuer, and Torsten Linker*
[a]
[b]
[b]
[a]
Seven enzymes have been screened for the cleavage of aryl
acetates. Phenyl and naphthyl acetates react with lipases and
esterases, whereas the sterically demanding anthracene ace-
tate gave a conversion only with porcine liver esterase and es-
terase 2 from Bacillus subtilis (BS2) . These two enzymes have
been employed on a preparative (0.5 mmol) scale and afforded
cleavage products in 91 and 94% yields, even for anthracene
acetate. Thus, this method is superior to chemical cleavage
with catalytic amounts of sodium methoxide (Zemplꢀn condi-
tions), which gave only low conversions. Finally, regioselectivity
has been achieved with an anthracene bisacetate, in which an
ethyl group controls the cleavage of the first acetate. This indi-
cates that steric interactions play a crucial role in the enzymat-
ic cleavage of aryl acetates, which might be interesting for
future applications or the development of enzyme inhibitors.
Introduction
In recent years, enzyme catalysis has attracted much attention,
and numerous examples have been reported, which include
the development of tailor-designed enzymes by protein engi-
During the course of our investigations on the addition of
1
[6]
singlet oxygen ( O ) to arenes, we have investigated esters of
2
anthracene and naphthalene and reactions of the correspond-
[
1]
[7]
neering and industrialized processes.
Esterases and lipases are especially suitable biocatalysts for
ing endoperoxides. Therefore, we became interested in the
enzymatic cleavage of simple naphthyl and anthryl acetates
(1b and 1c, respectively) as model systems. In particular, 1c
should react very slowly because of steric hindrance. Herein,
we describe the cleavage of aryl acetates with various enzymes
and we could convert anthracene esters for the first time, for
which the esterase 2 from Bacillus subtilis (BS2) was suitable.
These results should also be of considerable interest for the
development of new enzyme inhibitors.
[
2]
the cleavage of acetate groups, and many applications have
[
3]
been found in protecting group chemistry. However, sterically
demanding substrates react quite slowly with such wild-type
enzymes. Recently, we have demonstrated that esterase 2 from
Bacillus subtilis (BS2) and its double mutant overcome this
problem to cleave even tert-butyl esters and provide high ste-
[
4]
reoselectivities. However, the catalytic chemical (Zemplꢀn
[
5]
conditions) or enzymatic cleavage of aryl acetates 1 is still
challenging (Scheme 1).
Results and Discussion
The released phenolates 2 are stable and not basic enough
to deprotonate methanol to afford products 3. Thus, the reac-
tions stop at low conversions.
To compare the enzymatic and chemical cleavages of aryl
acetates, we investigated their reaction with NaOMe (Zemplꢀn
[5]
conditions) first. We selected p-nitro-substituted arenes 1d–f
as substrates as this group stabilizes the negative charge of
the formed phenolate well. Furthermore, the p-nitro phenoxy
group is often used as a standard in enzymatic cleavages by
[8]
[9]
glycosidases or lipases because of its stability and ease of
[10]
detection by UV spectroscopy.
However, the reaction of
p-nitrophenyl acetate (1d) with 0.1 equivalents of NaOMe in
methanol for 1 h gave only 37% conversion (Scheme 2), al-
though catalytic amounts of NaOMe (Zemplꢀn conditions) are
sufficient to cleave all acetyl protecting groups from
Scheme 1. Cleavage of aryl acetates 1a–c under Zemplꢀn conditions.
[5a]
carbohydrates.
[a] M. Bauch, Prof. Dr. T. Linker
The corresponding naphthyl (1e) and anthryl (1 f) deriva-
tives gave even lower conversions, which is in accordance to
the mechanism presented in Scheme 1. As a result of the
higher stability of alcoholates 2e and 2 f than 2d, the deproto-
nation of the solvent is less favored. Therefore, a complex
barium salt has been developed for the cleavage of aryl ace-
Department of Chemistry
University of Potsdam
Karl-Liebknecht-Str. 24-25, 14476 Potsdam (Germany)
E-mail: linker@uni-potsdam.de
[
b] Dr. D. Bçttcher, Prof. Dr. U. T. Bornscheuer
Department of Biotechnology & Enzyme Catalysis
University of Greifswald
[11]
tates under only slightly basic conditions, which indicates
the importance of the pH dependence. However, a complete
conversion with simple NaOMe as the catalyst is not possible.
Felix-Hausdorff-Str. 4, 17487 Greifswald (Germany)
Supporting information for this article can be found under http://
dx.doi.org/10.1002/cctc.201600678.
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Figure 1. Screening of seven enzymes for the cleavage of aryl acetates 1d
(
blue), 1e (red), and 1 f (green). a) PPL, b) CAL-A, c) CAL-B, d) CRL), e) PFEI,
Scheme 2. Cleavage of aryl acetates 1d–f with NaOMe.
f) PLE, g) BS2. For more details see Supporting Information.
To further prove this hypothesis, we cleaved aryl acetates
2e compared to the phenolate 2d. However, 1 f does not give
any conversion with lipases PPL, CAL-A, or CRL at all and reacts
with CAL-B only very slowly (Figure 1a–d). Clearly, 1 f is steri-
cally too hindered for such enzymes. This is a clear drawback
of lipases, especially as we are mainly interested in the reac-
tions of anthryl acetates for applications in singlet oxygen
1
d–f with 1 equivalent of NaOMe. Now the complete conver-
sion could be achieved after 1 h, and the phenols 3d–f were
isolated in high yields (Scheme 2, Experimental Section).
In summary, the chemical cleavage of aryl acetates is chal-
lenging and requires stoichiometric amounts of NaOMe. We
explain this behavior by the stability of the phenolates 2,
which are not basic enough to deprotonate the solvent for
complete conversion. Therefore, the enzymatic cleavage of aryl
acetates seems to be an attractive alternative to establish a cat-
alytic process.
[7]
chemistry.
Therefore, we turned our attention to the esterase I from
Pseudomonas fluorescens (PFEI), porcine liver esterase (PLE),
and BS2 (Figure 1e–g). BS2 is very attractive for the cleavage
[4]
of sterically hindered esters. Again, the naphthyl acetate 1e
reacted faster than 1d in accordance with our mechanistic ex-
planations for the lipases. Importantly, although PFEI gave no
conversion, PLE and BS2 reacted substantially faster with 1 f,
even in a comparable rate to 1d. A possible explanation for
this could be that both PLE and BS2 can act on bulky esters of
tertiary alcohols because of the presence of a GGG(A)X-
To find appropriate conditions and suitable enzymes for the
cleavage of aryl acetates, we screened seven different lipases
and esterases with our model compounds 1d–f on an analyti-
cal scale (Figure 1). Therefore, we prepared a system using
phosphate buffer (50 mm, pH 7.5) and 10% DMSO at 378C to
determine the rate of conversion of each enzyme–substrate
pair. The high extinction coefficients of the hydrolysis products
and their distinct wavelengths compared to the acetates
[13]
motif, and hence these esterases provide more space to ac-
commodate the substrates in the binding pocket. This is the
first example of the enzymatic cleavage of a sterically hindered
anthracene acetate, which might be interesting for future
preparative applications or the investigation of enzyme–ligand
interactions.
(
l=403.5, 460.0, and 456.5 nm for 3d, 3e, and 3 f, respective-
ly) allowed easy monitoring by using UV/Vis spectroscopy at
À5
À1
very low concentrations (3ꢂ10 molL ). All values were di-
vided by the lowest value to obtain a relative overview of the
conversion rate (for more details see Supporting Information).
We started our screening with four lipases, porcine pancreas
lipase type II (PPL), Candida antarctica lipase A (CAL-A), Candi-
da antarctica lipase B (CAL-B), and Candida rugosa lipase (CRL;
Figure 1a–d), which are commercially available and often used
After the successful screening of various enzymes on an ana-
lytical scale, we became interested in the preparative cleavages
of aryl acetates for synthetic applications. We focused on PLE
and BS2, which gave the best results in our analytical studies
(Figure 1). Now, we used the aforementioned buffer system
but on a 0.5 mmol scale. The reactions were performed for 1 h,
and the products were isolated by column chromatography
after the determination of the conversion by using NMR spec-
troscopy (Supporting Information).
[
2,12]
for enzymatic ester cleavages.
However, the reactions with
p-nitrophenyl acetate (1d) proceeded only slowly, presumably
because acetates are not the most suitable substrates for
these lipases, which are known to prefer medium-to-long-
[
2]
chain fatty acids.
Initially, we investigated the p-nitro-substituted arenes 1d–f
under preparative conditions (Scheme 3). Indeed, 1d and 1e
gave full conversions on a 0.5 mmol scale after 60 min, and the
Interestingly, 1e reacted faster with all lipases, which might
be because of the higher stability of the cleaved naphtholate
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of the starting material (Scheme 4). The cleaved diol is again
oxidized very quickly in air to the corresponding anthraqui-
[9c]
none 6h, which was isolated as the main product. Addition-
ally, we found the mono cleavage products 7a and 7b in their
tautomeric keto forms as byproducts (Scheme 4, Supporting
Information). Interestingly, the ratio of these two products is
not 50:50 but approximately 60:40. Thus, the sterically less hin-
dered acetate is cleaved faster than the ester close to the ethyl
group. This indicates again that steric interactions play a crucial
role in the enzymatic cleavage of aryl acetates, which might be
interesting for future applications or the development of
enzyme inhibitors.
Scheme 4. Cleavage of two aryl acetate groups within one substrate.
Conclusions
Scheme 3. Preparative cleavages of aryl acetates with PLE and BS2.
We describe new enzymatic cleavages of aryl acetates. Their
chemical hydrolysis with catalytic amounts of sodium methox-
ide in methanol (Zemplꢀn conditions) gives only low conver-
sions. We explain this behavior by the stability of the released
phenolate, which is not basic enough to deprotonate the sol-
vent and cannot initiate a catalytic cycle.
products 3d and 3e were isolated by column chromatography
in 96–99% yield (Scheme 3, Supporting Information).
As expected, 1 f reacts more slowly and gives incomplete
conversion with both enzymes. A problem is the fast oxidation
of anthrol 3 f and its tautomeric keto form to anthraquinone
Therefore, we turned our attention to enzymatic reactions,
and screened four lipases and three esterases in the cleavage
of aryl acetates with different steric demands on an analytical
scale. Interestingly, for all enzymes, the naphthyl acetate reacts
faster than the phenyl acetate, which can be explained by the
higher stability of the released naphthoate compared to the
phenolate. However, the anthryl acetate reacts with lipases not
at all or very slowly because of its high steric demand. Thus, it
turns out that only esterases that bear the GGG(A)-X-motif are
able to act on sterically demanding substrates such as tertiary
alcohols or arenes. Indeed, porcine liver esterase and BS2
cleaved the acetate group of anthracene at a similar rate as for
the phenyl system.
(
6 f) by air under the preparative conditions, in accordance
[
7c]
with our previous studies on anthracenes. Thus, 6 f was iso-
lated and characterized as a byproduct in ꢀ35% yield
(Scheme 3, Supporting Information).
To overcome this problem and to demonstrate the enzymat-
ic cleavage with a synthetically more interesting arene without
nitro group, we selected 9-acetoxy anthracene (1g) as the next
substrate, and anthrone (3g), which is the tautomeric form of
the cleavage product, could be isolated in 91–94% yield
(Scheme 3, Supporting Information).
Finally, we wished to cleave two aryl acetate groups within
the same substrate (Scheme 4). As a result of solubility prob-
lems, we introduced an additional ethyl group into our starting
material, but bisacetate 1h can be synthesized easily in only
To demonstrate the synthetic usefulness of these two en-
zymes, we investigated aryl acetate cleavages on a preparative
(0.5 mmol) scale as well. Indeed, with porcine liver esterase
and esterase 2 from Bacillus subtilis (BS2), not only do p-nitro-
substituted arenes react but also simple 9-acetoxy anthracene
[
14]
one step (Supporting Information).
Indeed, both ester
groups can be cleaved at the same time with full conversion
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gave a full conversion and high yields. Finally, we found a re-
markable influence of a remote ethyl group on the selectivities,
which can be explained by steric interactions.
After column chromatography (PE/EtOAc 3:1), the reaction of p-ni-
trophenyl acetate (1d, 91 mg, 0.50 mmol) afforded 68 mg (98%) of
p-nitrophenol (3d) with PLE and 67 mg (96%) with BS2.
[
17]
p-Nitrophenol (3d): Pale yellow solid. M.p. 1138C (Lit.
112–
1
1
13 8C); R =0.36 (PE/EtOAc 2:1); H NMR (600 MHz, CDCl ): d=6.01
f
3
Experimental Section
(
s, 1H; OH), 6.93 (d, J=9.2 Hz, 2H; 2-H, 6-H), 8.18 ppm (d,
13
J=9.2 Hz, 2H; 3-H, 5-H); C NMR (125 MHz, CDCl ): d=115.8 (d,
C-2, C-6), 126.4 (d, C-3, C-5), 141.8 (s, C-4), 161.4 ppm (s, C-1);
HRMS (GC–TOF): m/z calcd for C H NO : 139.0269 [M ]; found:
1
Melting points were determined by using a Mel-Temp from Electro-
thermal. TLC was performed using TLC Silica gel 60 F254 aluminum
3
+
1
13
sheets from Merck. H NMR and C NMR spectra were measured
by using Bruker Avance 300 (300 MHz, 75 MHz) and Bruker Avance
8
7
4
39.0274.
6
00 (600 MHz, 125 MHz) NMR spectrometers and TMS was used as
After column chromatography (PE/EtOAc 3:1), the reaction of
internal reference (0 ppm). The IR spectra were recorded of neat
samples by using a Nicolet 6700 FRIR spectrometer from Thermo
Electron Corporation. The UV/Vis spectra were measured by using
an ATI Unicam UV/Vis UV3 spectrometer or a Shimadzu UV-160A
with a solvent-filled reference cuvette. HRMS were recorded by
using a GC–MS Trace DSQ II mass spectrometer. Elemental analysis
was performed by using a Vario EL III elemental analyzer.
p-nitronaphthyl acetate (1e, 116 mg, 0.50 mmol) afforded 92 mg
(97%) of p-nitronaphthol (3e) with PLE and 93 mg (99%) with BS2.
[18]
p-Nitronaphthol (3e): Bright yellow solid. M.p. 165–1668C (Lit.
1
1
66–168); R =0.29 (PE/EtOAc 3:1); H NMR (300 MHz, CD OD):
f
3
d=4.91 (s, 1H; OH), 6.84 (d, J=8.6 Hz, 1H; 2-H), 7.52–7.57 (m, 1H;
-H), 7.61–7.72 (m, 1H; 6-H), 8.30–8.36 (m, 2H; 3-H, 8-H), 8.68–
7
13
CAL-A and CAL-B were obtained from c-Lecta (Leipzig, Germany).
PLE, PPL, and CRL were purchased from Sigma Aldrich (St. Louis,
USA). The recombinant enzymes were produced as described earli-
8.71 ppm (m, 1H; 5-H); C NMR (75 MHz, CD OD): d=107.0 (d,
3
C-2), 124.2 (d, C-8), 124.3 (d, C-5), 126.1 (s, C-9), 126.9 (d, C-7),
128.7 (s, C-10), 128.9 (d, C-3), 131.0 (d, C-6), 138.9 (s, C-4), 161.6 (s,
[15]
[16]
er: PFEI and BS2.
C-1), 182.8 ppm (s, OAc); IR (film): n˜ =3322 (br), 1574 (w), 1493 (w),
À1
1
1
315 (w), 1277 cm (m); HRMS (GC–TOF): m/z calcd for C H NO :
1
0
7
3
+
89.0426 [M ]; found: 189.0427; elemental analysis calcd (%) for
C H NO (189.17): C 63.49, H 3.73, N 7.40; found: C 63.53, H 3.76,
N 7.28.
10
7
3
General procedure for reactions under Zemplꢀn conditions
The acetate (0.25 mmol) was dissolved in dry methanol (80 mL)
and freshly prepared sodium methoxide (0.1 or 1 equiv. per acetyl
group, 125 mm in dry methanol) was added at RT. The solution
was stirred for 1 h, neutralized with cationic ion-exchange resin
and filtered. The solvent was removed in vacuo, and the crude
product was purified by column chromatography. Yields and ana-
lytical data are given in the Supporting Information.
After column chromatography (CHCl /PE 1:1), the reaction of
p-nitro-9-acetoxyanthracene (1 f, 141 mg, 0.50 mmol) afforded
3
6
0 mg (50%) of anthrol 3 f in its tautomeric keto form with PLE
and 36 mg (35%) of anthraquinone (6 f), whereas BS2 afforded
4 mg (45%) of 3 f and 32 mg (31%) of 6 f.
5
[19]
p-Nitroanthrone (3 f): Pale yellow solid. M.p. 1378C (Lit. 136–
1
1
388C); R =0.33 (CHCl /PE 2:1); H NMR (600 MHz, CD Cl ): d=6.92
f
3
2
2
(
s, 1H; 10-H), 7.69–7.76 (m, 6H; 2-H, 3-H, 4-H, 5-H, 6-H, 7-H), 8.32–
13
General procedure for the enzymatic cleavage of aryl ace-
tates on an analytical scale
8.34 ppm (m, 2H; 1-H, 8-H); C NMR (125 MHz, CD Cl ): d=86.7 (d,
2 2
C-10), 128.3 (d, C-1, C-8), 129.2 (d, C-4, C-5), 131.4 (d, C-2, C-7),
1
1
32.6 (s, C-8a, C-9a), 133.0 (s, C-4a, C-10a), 134.2 (d, C-3, C-6),
To a gently stirred solution of the substrate (0.03 mm) in phosphate
buffer (50 mm, pH 7.5) and DMSO (10% v/v) at 378C, the appropri-
ate amount of esterase solution was added to a total volume of
83.0 ppm (s, C-9); IR (film): n˜ =2977 (w), 2362 (w), 1666 (s), 1595
À1
(m), 1551 (s), 1357 (m), 1303 (m), 1220 cm (m); HRMS (GC–TOF):
+
m/z calcd for C H NO : 239.0582 [M ]; found: 239.0587; elemental
analysis calcd (%) for C H NO (239.23): C 70.29, H 3.79, N 5.86;
14
9
3
2
5 mL. The mixture was distributed into 1 mL vials and stirred by
14
9
3
using a thermoshaker (Eppendorf, Hamburg, Germany) at 378C.
Every 75 s one sample was analyzed by using UV/Vis spectroscopy
to determine the absorbance of the hydrolysis product. At least
four measurements were taken per substrate–enzyme pair. The ab-
sorbances were normalized and plotted against the time to obtain
the conversion rate. This rate was divided by the quotient of de-
ployed enzyme units and the amount of substrate to obtain a di-
mensionless value (for details see Supporting Information).
found: C 70.33, H 3.78, N 5.65.
[20]
Anthraquinone (6 f): Pale yellow solid. M.p. 2828C (Lit.
282–
1
2
848C); Rf =0.27 (CHCl /PE 1:1); H NMR (300 MHz, CDCl3):
3
d=7.51–7.54 (m, 4H; 2-H, 3-H, 6-H, 7-H), 7.93–7.96 ppm (m, 4H;
13
1
-H, 4-H, 5-H, 8-H); C NMR (75 MHz, CDCl ): 121.7 (d, C-1, C-4, C-5,
3
C-8), 124.1 (s, C-4a, C-8a, C-9a, C-10a), 126.4 (d, C-2, C-3, C-6, C-7),
1
2
50.0 ppm (s, C-9, C-10); HRMS (GC–TOF): m/z calcd for C H O :
14 8 2
08.0524 [M ]; found: 208.0528.
+
After column chromatography (CHCl /PE 1:1), the reaction of 9-ace-
toxyanthracene (1g, 118 mg, 0.50 mmol) afforded 91 mg (94%) of
anthrone (3g) with PLE and 88 mg (91%) with BS2.
3
General procedure for the enzymatic cleavage of aryl ace-
tates on a preparative scale
To a stirred solution of the substrate (0.50 mmol) in DMSO (20 mL),
a solution of the enzyme (20 mg) in phosphate buffer (50 mm,
pH 7.5, 180 mL) was added and stirred at 378C for 1 h. The product
was extracted into dichloromethane (5ꢂ25 mL). The combined or-
ganic layers were washed with water (50 mL) and brine (50 mL).
[
21]
Anthrone (3g): Pale yellow solid. M.p. 154–1558C (Lit. 1548C);
1
R =0.26 (CHCl /PE 1:1); H NMR (600 MHz, CD Cl ): d=4.38 (s, 2H;
f
3
2
2
10-H), 7.46–7.49 (ddd, J=7.9, 7.2, 1.3 Hz, 2H; 2-H, 7-H), 7.50–7.52
(ddd, J=7.7, 1.3, 0.5 Hz, 2H; 4-H, 5-H), 7.61–7.63 (ddd, J=7.7, 7.2,
1.5 Hz, 2H; 3-H, 6-H), 8.30–8.31 ppm (ddd, J=7.9, 1.5, 0.5 Hz, 2H;
After drying over MgSO , the solvent was removed in vacuo, and
4
13
the crude product was purified by column chromatography.
1-H, 8-H); C NMR (125 MHz, CD Cl ): d=32.7 (t, C-10), 127.3 (d,
2 2
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C-2, C-7), 127.6 (d, C-1, C-8), 129.0 (d, C-4, C-5), 132.4 (s, C-8a, C-9a),
33.1 (d, C-3, C-6), 141.1 (s, C-4a, C-10a), 184.3 ppm (s, C-9); IR
Keywords: arenes · enzyme catalysis · regioselectivity · steric
hindrance · substituent effects
1
(
(
film): n˜ =3062 (w), 3031 (w), 2875 (w), 1657 (m), 1602 (m), 1465
À1
w), 1401 (w), 1311 (s), 1173 (m), 1154 cm (w); HRMS (GC–TOF):
+
m/z calcd for C H O [M ]: 194.0732; found: 194.0740.
1
4
10
[
1] a) Enzyme Catalysis in Organic Synthesis, Vol. 1–3 (Eds.: O. May, H.
Grçger, K. Drauz), Wiley-VCH, Weinheim, 2012; b) U. T. Bornscheuer, G.
Huisman, R. J. Kazlauskas, S. Lutz, J. Moore, K. Robins, Nature 2012, 485,
After column chromatography (PE/CHCl3 1:1), the reaction of
9
2
,10-diacetoxy-2-ethylanthracene (1h, 161 mg, 0.50 mmol) afforded
-ethylanthraquinone (6h, 77 mg, 65%), 9-acetoxy-2-ethylanthrone
185–194.
(
1
7a, 25 mg, 18%), and 10-acetoxy-2-ethylanthrone (7b, 20 mg,
4%) with PLE, whereas the reaction with BS2 afforded 2-ethylan-
thraquinone (6h, 65 mg, 55%), 9-acetoxy-2-ethylanthrone (7a,
2 mg, 23%), and 10-acetoxy-2-ethylanthrone (7b, 23 mg, 16%).
[
2] U. T. Bornscheuer, R. J. Kazlauskas, Hydrolases in Organic Synthesis,
2nd ed., Wiley-VCH, Weinheim, 2005.
[3] Review: A. Reidel, H. Waldmann, J. Prakt. Chem. 1993, 335, 109–127.
[4] a) E. Barbayianni, C. G. Kokotos, S. Bartsch, C. Drakou, U. T. Bornscheuer,
G. Kokotos, Adv. Synth. Catal. 2009, 351, 2325–2332; b) M. Schmidt, E.
Barbayianni, I. Fotakopoulou, M. Hçhne, V. Constantinou-Kokotou, U. T.
Bornscheuer, G. Kokotos, J. Org. Chem. 2005, 70, 3737–3740.
3
2
(
-Ethylanthraquinone (6h): Pale yellow solid. M.p. 109–1108C
[22] 1
Lit. 1088C); R =0.32 (CHCl /PE 1:1); H NMR (600 MHz, CDCl3):
f
3
[
5] a) G. Zemplꢀn, E. Pascu, Ber. Dtsch. Chem. Ges. 1929, 62, 1613–1614;
b) Z. Wang, Comprehensive Organic Name Reactions and Reagents, Wiley,
Hoboken, NJ, 2009; c) B. Ren, M. Wang, J. Liu, J. Ge, X. Zhang, H. Dong,
Green Chem. 2015, 17, 1390–1394.
d=1.33 (t, J=7.7 Hz, 3H; CH ), 2.82 (q, J=7.7 Hz, 2H; CH ), 7.61
(
J=1.7, 0.6 Hz, 1H; 1-H), 8.21 (dd, J=7.9, 0.6 Hz, 1H; 4-H), 8.28–
8
CH ), 29.3 (t, CH ), 126.5 (d, C-1), 127.2 (d, C-8), 127.3 (d, C-5), 127.6
(
C-8a), 133.9 (d, C-6), 134.0 (d, C-7), 134.1 (d, C-3), 151.5 (s, C-2),
1
2
3
2
dd, J=7.9, 1.7 Hz, 1H; 3-H), 7.77–7.80 (m, 2H; 6-H, 7-H), 8.11 (dd,
13
.31 ppm (m, 2H; 5-H, 8-H); C NMR (125 MHz, CDCl ): d=15.1 (q,
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3
3
2
d, C-4); 131.6 (s, C-4a), 133.6 (s, C-9a), 133.7 (s, C-10a), 133.7 (s,
12112–12115.
83.1 (s, C-9), 183.5 ppm (s, C-10); IR (film): n˜ =3322 (w), 3025 (w),
[
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966 (m), 2874 (w), 1673 (s), 1590 (s), 1456 (m), 1325 (s), 1287 (s),
À1
+
1
2
175 cm (m); HRMS (GC–TOF): m/z calcd for C H O [M ]:
16
12
2
36.0837; found: 236.0828.
[
9
1
-Acetoxy-2-ethylanthrone (7a): Yellow oil. R =0.27 (CHCl /PE
f 3
1
:1); H NMR (600 MHz, CDCl ): d=1.33 (t, J=7.6 Hz, 3H; CH ), 2.18
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3
(
(
7
8
0
s, 3H; OAc), 2.74 (q, J=7.6 Hz, 2H; CH ), 7.18 (s, 1H; 9-H), 7.34
2
[
[
[
[
dd, J=1.7, 0.6 Hz, 1H; 1-H), 7.37 (dd, J=8.0, 1.7 Hz, 1H; 3-H),
.51–7.54 (m, 2H; 6-H, 8-H), 7.62 (ddd, J=8.1, 7.9, 1.5 Hz, 1H; 7-H),
1
980, 26, 724–729.
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.21 (dd, J=8,0, 0.6 Hz, 1H; 4-H), 8.28 ppm (ddd, J=8.2, 1.5,
1
3
.5 Hz; 1H; 5-H); C NMR (125 MHz, CDCl ): d=15.2 (q, CH ), 21.4
3
3
(
q, OAc), 29.2 (t, CH ), 66.8 (d, C-9), 127.5 (d, C-5), 127.8 (d, C-4),
2
1
27.8 (d, C-1), 128.6 (d, C-6), 129.1 (d, C-3), 129.2 (d, C-8), 129.7 (s,
C-4a), 131.9 (s, C-10a), 138.9 (s, C-8a), 139.0 (s, C-9a), 150.8 (s, C-2),
71.1 (s, OAc), 183.1 ppm (s, C-10).
1
[
5
27–532.
1
0-Acetoxy-2-ethylanthrone (7b): Yellow oil. R =0.28 (CHCl /PE
f 3
1
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1
:1); H NMR (600 MHz, CDCl ): d=1.30 (t, J=7.6 Hz, 3H; CH ), 2.16
3 3
(
s, 3H; OAc), 2.76 (q, J=7.6 Hz, 2H; CH ), 7.20 (s, 1H; 10-H), 7.46–
2
[
7
.50 (m, 2H; 3-H; 4-H), 7.53–7.56 (m, 2H; 5-H, 7-H), 7.64 (ddd,
J=7.9, 7.2, 1.4 Hz, 1H; 6-H), 8.13 (dd, J=1.6, 0.6 Hz, 1H; 1-H),
[
[
13
8
.30 ppm (ddd, J=8.1, 1.4, 0.5 Hz; 1H; 8-H); C NMR (125 MHz,
CDCl ): d=15.4 (q, CH ), 21.4 (q, OAc), 28.8 (t, CH ), 66.8 (d, C-10),
3
3
2
1
26.7 (d, C-1), 127.6 (d, C-8), 128.7 (d, C-7), 128.8 (d, C-4), 129.3 (d,
[19] Y. M. Atroshchenko, S. S. Gitis, A. Y. Kaminskii, Zh. Org. Khim. 1988, 24,
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C-4a), 139.1 (s, C-10a), 145.7 (s, C-2), 171.2 (s, OAc), 183.7 ppm
639–644.
[
[
[
20] T. B. Patrick, E. C. Hayward, J. Org. Chem. 1974, 39, 2120–2121.
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(
s, C-9).
710.
Acknowledgements
Received: June 6, 2016
Published online on && &&, 0000
We thank the Universities of Potsdam and Greifswald for gener-
ous financial support. We thank Stefan Saß for introducing M.B.
to the potential of enzymatic reactions.
ChemCatChem 2016, 8, 1 – 6
www.chemcatchem.org
5
ꢁ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
&
These are not the final page numbers! ÞÞ

FULL PAPERS
M. Bauch, D. Bçttcher, U. T. Bornscheuer,
T. Linker*
&& – &&
Enzymatic Cleavage of Aryl Acetates
Size matters: Although phenyl and
naphthyl esters react smoothly with
lipases and esterases, sterically demand-
ing anthracene acetate was hitherto
inert towards enzymatic cleavage.
Herein we describe esterase 2 from
Bacillus subtilis (BS2) as a suitable cata-
lyst for such substrates on an analytical
and preparative scale. In contrast, the
use of sodium methoxide (Zemplꢀn
conditions) as the catalyst gives only in-
complete conversions.
&
ChemCatChem 2016, 8, 1 – 6
www.chemcatchem.org
6
ꢁ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÝÝ These are not the final page numbers!