Synthetic Versatility of Lipases: Application for Si-O Bond Formation and Cleavage

Article abstract of DOI:10.1055/s-0037-1610281

Several commercially available lipases were examined in a study on O-Si bond formation and cleavage applying silicon-based protecting groups and alcohols or the corresponding silyl ethers. With regard to deprotection, from silyl ether to the corresponding alcohol, only the solvent and the lipase were necessary. The influence of the protecting group, the lipase source, and the substituent was investigated to optimize the results. The TMS moiety could be removed in 24 hours of reaction at room temperature in aqueous systems (conv. up to 99%, depending on the substrate and lipase). The reverse reactions, that is, with the protection of the alcohols, were carried out in hexane using different silyl chlorides. The TMS, TES, and TBS moieties were successfully inserted in the primary and secondary alcohols without the need for dry conditions or an inert atmosphere, presenting conversions of up to 99%, depending on the substrate.

Full text of DOI:10.1055/s-0037-1610281

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
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P. B. Brondani et al.
Paper
Synthesis
Synthetic Versatility of Lipases: Application for Si–O Bond
Formation and Cleavage
Patrícia Bulegon Brondani*a
Mateus Mittersteinerb
Morgana Aline Voigta
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Bruna Heloisa Klinkowskib
Dilamara Riva Scharfb
Paulo Cesar de Jesusb
a Departamento de Ciências Exatas e Educação,
Universidade Federal de Santa Catarina,
Blumenau, SC, 89036-256, Brazil
patyqmc@gmail.com
b Departamento de Química, Universidade Regional
de Blumenau, Blumenau, SC, 89019-917, Brazil
Received: 30.07.2018
Accepted after revision: 22.08.2018
Published online: 21.09.2018
agents. In some of the reactions, fluoride salts such as TBAF,
KF, or NaF can be applied in combination with a catalyst in
order to help the O–Si bond cleavage, through the formation
of the new strong Si–F bond. Some of the conditions re-
quired in deprotection processes can cause side reactions
involving other functional groups present in the sub-
strates.8–10
DOI: 10.1055/s-0037-1610281; Art ID: ss-2018-m0512-op
Abstract Several commercially available lipases were examined in a
study on O–Si bond formation and cleavage applying silicon-based pro-
tecting groups and alcohols or the corresponding silyl ethers. With re-
gard to deprotection, from silyl ether to the corresponding alcohol,
only the solvent and the lipase were necessary. The influence of the
protecting group, the lipase source, and the substituent was investigat-
ed to optimize the results. The TMS moiety could be removed in 24
hours of reaction at room temperature in aqueous systems (conv. up to
99%, depending on the substrate and lipase). The reverse reactions,
that is, with the protection of the alcohols, were carried out in hexane
using different silyl chlorides. The TMS, TES, and TBS moieties were suc-
cessfully inserted in the primary and secondary alcohols without the
need for dry conditions or an inert atmosphere, presenting conversions
of up to 99%, depending on the substrate.
The conditions for protecting alcohols with silicon-
based protecting groups generally involve an excess of an
organic base (imidazole or triethylamine) and aggressive
and strictly dried solvents (THF, DMF, or MeCN) under inert
atmosphere.11 Only a few methodologies involving alterna-
tive techniques, for instance, the application of NaOH as the
catalyst rather than amines12 or PdCl2,7 could be found in
the literature. The results for both systems were promising,
but a strictly inert atmosphere is still required. Other au-
thors have reported the use of complex catalysts in a sol-
vent-free system, avoiding anhydrous conditions. These
catalysts, however, require previous preparation.13–15
Since the protection and deprotection of alcohols play a
key role in the organic synthesis of polyfunctional organic
molecules, mild and selective methods are required.3,16 En-
zymes can be used in reactions under mild conditions, most
of the time with high selectivity.17 Nevertheless, only a few
authors have presented protocols where enzymes, of any
kind, were used successfully to perform such reactions.
In one of these studies, enzymes from marine sponges
(silicateins) were applied for this purpose. The authors
were able to produce two recombinant silicateins (Silα and
TF-Siα), which were used to perform the hydrolysis and the
condensation of the Si–O bond in organic substrates. The
hydrolysis was tested only for 4-nitrophenyl silyl ether de-
rivatives in an effort to develop a colorimetric assay. The
cleavage of the Si–O bond occurred but at a relatively slow
Key words biocatalysis, lipases, silyl ethers, alcohol protection, alco-
hol deprotection
Organosilanes are widely used in organic synthesis in
applications such as the formation of new carbon–carbon
bonds,1,2 the transformation to other functional groups and,
more commonly, as protecting groups for the hydroxyl moi-
ety. In spite of the development of synthetic models with
the absence of protecting groups, those containing silicon
are still broadly applied because they are efficiently in-
stalled and are stable toward a useful variety of reagents
and reaction conditions.3–6 Thus, new methodologies for
protection/deprotection are constantly being developed.3,4
A large number of protocols for silyl ether removal have
been reported.3 Unfortunately, many of these methodolo-
gies involve severe conditions such as acidic (e.g., Cl3CCO2H
or TsOH), basic (e.g., NaOH or KOH), oxidizing (e.g., NaIO4 or
PCC, for example), or reducing (e.g., DIBAL-H or LiAlH4)3,5–8
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–I

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P. B. Brondani et al.
Paper
Synthesis
rate. The authors also investigated the condensation reac-
tion, by generating the silyl ethers from their corresponding
silanols and alcohols, but the degree of conversion was very
low for most substrates (up to 41.2% at 75 °C). In addition,
the silicateins were able to catalyze the transetherification
reaction successfully, where the silyl group from one silyl
ether could be transferred to a recipient alcohol with con-
versions up to 99% in a 72 hour reaction at 75 °C.18
In addition to this study, for the construction of the O–Si
bond some authors have used alkoxysilanes as electrophiles
for transetherification and condensation reactions mediat-
ed by enzymes.19,20 In one of these studies, several en-
zymes, including bovine pancreatic trypsin, Rhizopus ory-
zae lipase (ROL), and chicken egg white lysozyme, were in-
vestigated in the transetherification reaction applying
trimethylethoxysilane or phenyldimethylethoxysilane with
1-octanol or tert-butyl alcohol. The best results were ob-
served using 1-octanol, ROL, and trimethylethoxysilane
(34.9% of Me3SiOn-Oct) or 1-octanol, chicken egg white ly-
sozyme and phenyldimethylethoxysilane (41.8% of PhMe2-
SiOt-Bu), both results obtained with 24 hours of reaction at
room temperature.20
Although it is known that organosilanes can be used as
substrates for isolated enzymes or microorganisms,21–24 no
extensive studies applying commonly used commercially
available enzymes, under mild conditions, to perform the
cleavage of the O–Si bond leading to the corresponding al-
cohol, could be found in the literature.24 In addition, al-
though some authors have investigated the formation and
cleavage of O–Si bonds using enzymes, in a survey of the lit-
erature no studies applying chlorosilanes for the construc-
tions of O–Si bond mediated by enzymes could be found.
Herein, we report a study on the use of commercially
available lipases to perform the silyl ether removal and in-
sertion while protecting groups in alcohols.
Lipases were selected based on the type of reactions
they are able to catalyze and because they are commercially
available, easy to handle, and are the most common class of
enzymes applied in organic synthesis.25 The proposed
mechanism for the cleavage of the O–Si bond in silyl ethers
applying lipases has already been published and it involves
the serine attack at silicon and the cleavage of the Si–LG
bond, forming the new Ser–SiR3 bond.24 Concerning the
construction of the O–Si bond, a possible mechanism is also
published. The proposal includes the reaction of Ser-OH
portion with the silane forming the reactive species.19,20 It
seems that, in order to form or to cleave the O–Si bond, an
intermediate Ser–SiR3 is formed and it is involved in both
mechanisms. The reactions are carried out by the well-
known serine-histidine-aspartic acid triad involvement.
We started our investigation by attempting to remove
the silyl protecting groups from the silyl ether generating
the corresponding alcohols, using as the substrate 1-pheny-
lethanol protected with TMS [Si(Me)3] (1), TES [Si(Et)3] (2),
TBS [Si(Me)2t-Bu] (3), or TBDPS [Si(Ph)2t-Bu] (4) (Scheme
1). Compounds 1–4 were chosen as substrates because the
corresponding alcohol [1-phenylethanol (5)] is a well-
known substrate for lipases.13
OH
OR
OR
lipase, solvent
r.t., 200 rpm
1 R = TMS
1-phenylethanol
silyl ether derivative
2 R = TES
3 R = TBS
4 R = TBDPS
5
1–4
Scheme 1 Lipase-mediated deprotection reaction of 1–4 generating
the corresponding alcohol 5
In this study, several commercially available lipases
were applied with different solvents and reaction times
(16, 24, or 48 h) at room temperature. The selected lipases
are: lipases from Candida antarctica B (Cal-B and Lip. 435,
technical grade and food grade, respectively), Aspergillus
oryzae lipase (AOL), Pseudomonas fluorescens lipase (PFL),
Porcine pancreas lipase (PPL), Candida rugosa lipase (CRL),
Rhizomucor miehei lipase (RML), Pseudomonas cepacia
lipase type II (PSC-II), and lipase from Thermomyces lanugi-
nosus (TLL).
Some of the test conditions led to TMS removal, as can
be seen in Table 1. When an immobilized lipase (Cal-B, Lip.
435, PFL, or PSC-II) was applied as the catalyst, the reac-
tions were carried out in three different solvent systems
(Tris-HCl pH 7, hexane, or a mixture of the two). Since low
stability of non-immobilized enzymes in organic solvent is
generally observed, only immobilized enzymes were tested,
using hexane as the solvent.26 In the reactions applying
AOL, PPL, CRL, RML, or TLL an aqueous buffered system
(Tris-HCl pH 7) was the only solvent used. Despite the fact
that the immobilized enzymes are known to show good re-
sults in organic solvents, especially in hexane, in all cases
better results were achieved when Tris-HCl pH 7 buffer was
used as the solvent (Table 1, entries 2, 5, 9, and 15). Of the
lipases tested, Cal-B (entry 2) presented the best conversion
rate (c = 47%, ee = 0%) and AOL (entry 7) showed the best
enantioselectivity (c = 28%, ee = 43%). It is important to note
that control reactions in the absence of enzyme were con-
ducted under the same experimental conditions and no
conversion was detected. In an attempt to improve the con-
version and enantioselectivity, Tris-HCl pH 9 was also test-
ed as the solvent, but the results were the same as those ob-
tained using Tris-HCl pH 7.
Unfortunately, no conversion was observed for the reac-
tions using substrates containing TES (2), TBS (3), or TBDPS
(4) as protecting groups and the listed lipases, even in 72
hours reaction time using Tris-HCl pH 7 or 9 and hexane or
biphasic systems. It is known from the literature that the
fluoride ion can aid the O–Si cleavage and several method-
ologies make use of this additive.9 Thus, for the substrates 2,
3, and 4, the addition of a salt containing fluoride in the re-
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P. B. Brondani et al.
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actions was tested. Three different salts were applied (NaF,
KF, and TBAF) in reactions using a Tris-HCl buffer (50
mmolL–1, pH 7 or 9), the mixture of hexane and a Tris-HCl
buffer (1:1 v/v), MeOH or 1,4-dioxane. The choice of the
solvents was based on the solubility of the salts. Once again,
even after 72 hours of reaction, no conversion was ob-
served.
Given that Cal-B and AOL presented the best results for
the TMS removal from compound 1 (Table 1, entries 2 and
7), further studies were carried out only with these two li-
pases. In this context, the amount of enzyme in the reaction
medium was investigated. As Table 1 shows the results for
the reaction applying 10 mg of Cal-B or AOL, the new tests
were conducted with 15, 20, and 25 mg. When Cal-B was
used as the biocatalyst, full (or almost full) conversion was
observed (c = 90% using 15 mg, and c = >99% using 20 or 25
mg, in all cases ee = 0%). In the reaction applying AOL we
observed a slight increase in the conversion as the amount
of the enzyme was increased and a diminishment of the en-
antioselectivity (conv. = 36–40%, ee = 9–15%). This behavior
is also observed for some other lipases.27 In these cases a
possible kinetic competition between the isomers is hap-
pening and the selectivity of the reaction is governed only
by the ratio of the constants leading to the isomers. Thus,
the optical purity of the product is not dependent on the
extent of the conversion.28
The effect of the temperature of the reaction medium
was also evaluated, considering reactions using substrate 1,
10 mg of Cal-B or AOL, 24 hours of reaction and 50 mmol L–1
Tris-HCl buffer pH 7 as the solvent. The new tests were car-
ried out applying the following temperatures: 35, 40, and
50 °C (Table 2). The conversion was clearly increased at
50 °C when AOL was used as the catalyst (Table 2, entry 6),
but the enantioselectivity decreased in all cases with this
enzyme. When Cal-B was the catalyst, the optimum ob-
served conversion was achieved at 25 °C (Table 1). This spe-
cific reaction (the cleavage of the O–Si bond using lipases)
was not extensively studied in the literature, but in this
case the optimum temperature was room temperature
rather than the usual 37–40 °C.29
In order to investigate the enantiomeric excess of the si-
lyl ether 1, the best conditions from Table 1 (entries 2 and
7) was applied in a larger scale reaction (3 mmol). In this
Table 1 Lipase-Mediated Deprotection Reactions of 1a
Entry
Lipaseb
Time (h)
Solvent
Conv. (%)c
ee 5 (%)d
e
1
2
Cal-B
Cal-B
Cal-B
Lip. 435
Lip. 435
Lip. 435
AOL
24
24
24
24
24
24
24
48
48
48
24
24
24
48
24
48
24
hexane
23 ± 0.5
47 ± 0.4
26 ± 1
–
e
Tris-HCl pH 7
Tris-HCl pH 7/hexane
hexane
–
e
3
–
4
23 ± 1
8 ± 1
5
Tris-HCl pH 7
Tris-HCl pH 7/hexane
Tris-HCl pH 7
hexane
45 ± 0.5
28 ± 0.5
28 ± 1
32 ± 2
6
1 ± 0.1
43 ± 1
7
8
PFL
10 ± 0.5
33 ± 2
32 ± 1.5
33 ± 0.6
14 ± 0.4
36 ± 1
9
PFL
Tris-HCl pH 7
Tris-HCl pH 7/hexane
Tris-HCl pH 7
Tris-HCl pH 7
Tris-HCl pH 7
hexane
10
11
12
13
14
15
16
17
PFL
31 ± 1.5
43 ± 0.6
40 ± 1
PPL
CRL
36 ± 0.5
30 ± 0.3
RML
29 ± 0.8
f
f
PSC-II
PSC- II
PSC-II
TLL
–
–
Tris-HCl pH 7
Tris-HCl pH 7/hexane
Tris-HCl pH 7
36 ± 1
28 ± 1.3
f
f
–
–
46 ± 1.2
24 ± 1.1
a The reaction mixture contained 10 mg of lipase, 0.06 mmol of substrate 1, and the solvent (final volume 500 μL), and was shaken at r.t. For entries 3, 6, 10, and
16, the reactions were carried out in a 1:1 v/v mixture of Tris-HCl pH 7 and hexane. In all cases when Tris-buffer was the solvent, 50 mmol L–1 of buffer was
applied.
b Cal-B and Lip. 435: Lipases from Candida antarctica B, technical grade and food grade, respectively; AOL: Aspergillus oryzae lipase; PFL: Pseudomonas fluorescens
lipase; PPL: Porcine pancreas lipase; CRL: Candida rugosa lipase; RML: Rhizomucor miehei lipase; PSC-II: Pseudomonas cepacia lipase type II; TLL: lipase from Thermo-
myces lanuginosa.
c Conversion was determined by GC using a calibration curve based on both areas (reactant and product).
d The enantiomeric excess presented is for (S)-1-phenylethanol (5). The absolute configuration was determined by comparison with data from the literature.29
The enantiomers of the silyl ethers could not be separated in the available GC column.
e No enantiomeric excess was observed. All reactions were carried out in duplicate.
f No reaction was observed.
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P. B. Brondani et al.
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Synthesis
Table 2 Temperature Variation in the Lipase-Mediated Deprotection of 1a
While chemically performing the deprotection of 1
(with HCl/THF, 40 °C in 12 h reaction, 75% yield) the result
was compared to that obtained, for example, in the meth-
odology presented herein, using 20 mg of Cal-B for 0.06
mmol of substrate in Tris-HCl pH 7, for 24 hours at room
temperature. A larger scale reaction was performed under
these conditions (applying 3 mmol of substrate) and an iso-
lated yield of 97% was observed for the corresponding alco-
hol (further details, see: SI). The methodology with Cal-B is
milder (pH 7 and r.t.), the enzyme can be reused (in this
case the enzyme was used 3 times)31 and it is easy to apply
in daily laboratory experiments.
To continue the study of deprotection using secondary
TMS derivatives as substrates, the influence of different
substituents was investigated. New reactions were per-
formed with a few different substrates applying the opti-
mized conditions described above (Table 1, entries 2 and 7).
The results for these reactions can be seen in Scheme 2.
As shown in Scheme 2, the lipase Cal-B could be used to
perform the desired reaction with the majority of the sub-
strates, while AOL meditated the transformation only with
substrates 6, 8, and 11. None of the lipases tested removed
TMS from substrate 7 (p-NH2 derivative). The other sub-
strates could be deprotected to some extent for at least one
of the enzymes applied, for example, the full conversion of
substrate 11 (p-NO2 derivative) was observed in the pres-
ence of Cal-B or AOL. As a strong electron-withdrawing
group, the NO2 group can aid the O–Si cleavage, stabilizing
any negative partial charge of the oxygen during the course
Entry
Lipaseb
Temp (°C)
Conv. (%)c
1
2
3
4
5
6
Cal-B
Cal-B
Cal-B
AOL
35
40
50
35
40
50
35 ± 1.6
44 ± 0.3
53 ± 0.1
27 ± 0.2
33 ± 0.7
62 ± 1
AOL
AOL
a The reaction mixture contained 10 mg of lipase, 0.06 mmol of substrate
1, and 50 mmol L–1 Tris-HCl pH 7 (final volume 500 μL).
b Cal-B: Lipase from Candida antarctica B, technical grade; AOL: Aspergillus
oryzae lipase.
c Conversion was determined by GC using a calibration curve based on both
areas (reactant and product). All reactions were carried out in duplicate.
way, we were able to separate the alcohol 5 from the silyl
ether 1, using column chromatography, and 1 was chemi-
cally transformed into the corresponding alcohol. In this
procedure, a mixture of HCl (2 mol L–1)/THF (1:10) was ap-
plied in a 12-hour reaction at 40 °C. This methodology
yielded the corresponding alcohol 5 in 75% yield [for fur-
ther details, see the Supporting Information (SI)].30 The re-
sults in terms of conversion and ee of the alcohol 5 were the
same as those reported in Table 1. After isolating the prod-
ucts, we observed that the enantiomeric excess of the si-
lylated fraction 1 was 0% for the Cal-B mediated reaction
and 17% for reaction catalyzed by AOL.
6 R = 4-MeC6H4
7 R = 4-NH2C6H4
8 R = 4-BrC6H4
9 R = 4-FC6H4
11 R = 4-NO2C6H5
12 R = naphthyl
13 R = furanoyl
14 R = propyl
Cal-B or AOL
Tris-HCl pH 7
r.t., 200 rpm, 24 h
OTMS
OH
R
R
6–14
15–23
10 R = 2,4-Cl2C6H3
OH
OH
OH
H2N
Br
15
16
17
Cal-B: conv. 24% 0.3
AOL: conv. 24%
Cal-B: conv. 90% 1.3
AOL: conv. 26% 0.4
Cal-B: no reaction observed
AOL: no reaction observed
1
OH
Cl
OH
OH
F
Cl
O2N
18
19
20
Cal-B: conv. 65 0.7
AOL: no reaction observed
Cal-B: conv. 85 0.3
AOL: no reaction observed
Cal-B: conv. > 99%
AOL: conv. > 99%
0
0
OH
OH
O
OH
21
22
23
Cal-B: conv. 95% 0.1
AOL: conv.no reaction observed
Cal-B: conv. 65% 0.4
AOL: no reaction observed
Cal-B: conv. 15% 0.3
AOL: no reaction observed
Scheme 2 Lipase-mediated deprotection reactions using the substrates 6–14 in order to obtain the alcohols 15–23
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–I

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P. B. Brondani et al.
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of the reaction. This effect can explain the greater degree of
conversion observed. On the other hand, the NH2 group can
hinder the reaction, being a strongly electron-donating
group. For the substrates 6, 8, 9, and 10 the electronic effect
is milder. The differences observed in terms of degree of
conversion may be related to the accommodation of the
substrates in the active site of each enzyme. The enzyme
Cal-B showed a good degree of deprotection of the naphthyl
(12, c = 95%) and furyl (13, c = 65%) derivatives, leading to
the corresponding alcohols 21 and 22, respectively. Howev-
er, when the enzyme AOL was used, no conversion was ob-
served. The reactions using 2-pentanol TMS-derivative 14
as the substrate showed low conversion to the correspond-
ing alcohol 23 with Cal-B (15%) and, once again, no reaction
was observed when applying AOL. No enantiomeric excess
was observed in the alcohol fraction when the substrates
9–14 were used as the starting material (chiral substrates)
for the enzymes investigated. However, when the substrates
6 or 8 were used as starting materials an enantiomeric ex-
cess of the S-derivative in the product (12% for 15 and 26%
for 17) was observed when applying AOL. On the other
hand, Cal-B did not show any enantioselectivity.
Having established the best conditions for the deprotec-
tion of secondary alcohols, we expanded the scope by ap-
plying the optimal experimental conditions to deprotect a
less hindered alcohol [1-pentanol (28), a primary alcohol]
protected with the aforementioned protecting groups, TMS
(24), TES (25), TBS (26), or TBDPS (27) (Scheme 3). Once
again, we observed only the deprotection of the TMS deriv-
ative 24. The enzyme Cal-B led to the product in 95% (± 0.3)
of conversion and AOL led to 91% (± 0.5) of conversion to 1-
pentanol. These results suggest that the lack of conversion
observed for the TES, TBS, and TBDPS derivatives is not due
to steric effects of the alcohol moiety itself. This is probably
attributable to the presence of bulkier protecting groups in
the substrate hindering the accommodation in the active
site of the lipases. In addition, reports in the literature indi-
cate that silicon-containing molecules can be more chal-
lenging as a substrate when compared to organic esters.32
presents two TMS moieties, one protecting the phenolic
portion and the other the primary alcohol, was also applied
as the substrate. Once again, deprotection was observed
only in the reaction with Cal-B, cleaving regioselectively the
O–Si bond leading to the primary alcohol, the intact silyl
ether remaining attached to the aromatic ring (32, conv. =
45%) (Scheme 4). It is expected that the primary OTMS moi-
ety will react more easily, but in this case an interesting
product was produced. During the synthesis of the starting
materials it was possible to chemically protect only the pri-
mary alcohol (producing 29) or both hydroxyl groups (pro-
ducing 31) (for further details, see the SI), but the product
containing only the phenolic part protected 32 was not pre-
viously observed. Another interesting observation relates to
the conversion rates, with the conversion of 29 to the corre-
sponding alcohol 30 being low for a primary alcohol (41%).
This is probably due to the presence of the hydroxyl moiety
attached to the aromatic ring (an electron-donating group),
in agreement with the results in Scheme 2. In the case of
compound 31, since the phenolic hydroxyl group is protect-
ed, the electronic effect is milder. However, the presence of
two protected sites generates a bulkier compound, lower-
ing the conversion to the alcohol 32 (45%). Considering that
compound 32 has an interesting chemical structure, a new
test was performed using 31 as the starting material and 20
mg of Cal-B, in 24 hours of reaction at room temperature. In
this case, full conversion was achieved with the regioselec-
tive deprotection of the primary alcohol. On applying the
chemical deprotection using HCl/THF, both hydroxyl groups
were deprotected leading to 30.
Cal-B or AOL
HO
HO
Tris-HCl pH 7
OTMS
OH
r.t., 200 rpm, 24 h
29
30
Cal-B: conv. 41% 0.1
AOL: no reaction observed
Cal-B or AOL
Tris-HCl pH 7
TMSO
OH
TMSO
OTMS
r.t., 200 rpm, 24 h
Cal-B or AOL
Tris-HCl pH 7
r.t., 200 rpm, 24 h
31
32
OR
OH
Cal-B: conv. 45% 0.3 (10 mg)
conv. > 99% 0.5 (20 mg)
AOL: no reaction observed
24 R = TMS
25 R = TES
26 R = TBS
28
27 R = TBDPS
Scheme 4 Lipase-mediated deprotection reaction of 29 or 31 generat-
ing the corresponding alcohol 30 or 32, respectively
Scheme 3 Lipase-mediated deprotection reaction of 24–27 generat-
ing the corresponding alcohol 28
Based on the promising results obtained in the previous
experiments, we investigated the reverse reactions: protec-
tion of alcohols with the aforementioned protecting groups
catalyzed by lipases. Since Cal-B and AOL presented the best
results for the previously studied system, further tests were
performed with these two lipases. First, 1-phenylethanol
Continuing with the application of Cal-B and AOL in the
deprotection reactions, further tests were performed using
compound 29, bearing a free phenolic moiety and a prima-
ry OTMS moiety, as the starting material. The reaction led
to the deprotection of the primary alcohol (30, conv = 41%)
only in the case of Cal-B (Scheme 3). Compound 31, which
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P. B. Brondani et al.
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Synthesis
(5) was reacted with TMSCl, TESCl, TBSCl, and TBDPSCl us-
ing a buffered system (Tris-HCl pH 7 or 9) or hexane as the
solvent.
On protecting 1-phenylethanol (5) and 1-pentanol (28),
moderate to excellent conversions were observed with TMS
(1 and 24), TES (2 and 25) and TBS (3 and 26). The com-
pounds 1-(naphthalen-2-yl)ethanol (21), 1-(furan-2-yl)eth-
anol (22), and 2-pentanol (23) were expected to behave
similarly to 1-phenylethanol (5), but the silyl ether deriva-
tive was obtained only when TMS was the protecting
group. These results may be related to the accommodation
of the starting materials in the active site of the enzyme.
When the starting material was the diol 30, the protection
of both hydroxyl groups was observed with TMS, TES, or
TBS. No reaction occurred using TBDPS, which was expect-
ed given the size of this group and considering previously
reported results.32 No significant enantiomeric excess was
observed in the protection of compounds 5 with TMSCl or
TESCl and in the protection of 21 or 22 with TMSCl (chiral
compounds). However, in the protection of 5 with TBSCl the
alcohol fraction presented 41% of ee for the S-derivative,
which could be due to the substituent in the silicon moiety
(tert-butyl and dimethyl rather than trimethyl or triethyl).
The reactions in Scheme 5 were performed using 1.5
equivalents of Si(R3)3Cl. In all cases, a larger excess of the si-
lyl protecting group was also evaluated (2 equiv), but simi-
lar results were observed. For reactions applying 1 equiva-
lent of the protecting group, lower conversions were ob-
tained. Control experiments in the absence of the enzyme
were performed and no conversion was observed.
With the buffered (aqueous) systems, none of the test
conditions led to conversion, not even with an excess of
SiR3Cl (1, 1.5, and 2 equiv were tested). These results were
expected and are in agreement with the fact that the major-
ity of the protocols are performed in anhydrous conditions,
because of the instability of SiR3Cl in water. It is reasonable
to assume that, for the protection, the equilibrium should
be shifted to favor the formation of silyl ether, applying an
excess of the protecting group and low concentration of
water. On this basis, the reactions were repeated using hex-
ane as the solvent because lipase-catalyzed reactions occur
smoothly in nonpolar solvents, since they can trap water
around the enzyme, creating a micro-aqueous layer and
maintaining its conformation and catalytic activity.33 Since
AOL is not an immobilized lipase, only Cal-B was applied as
the catalyst. In this case, it was possible to perform some of
the protection reactions and the observed products and
conversion rates can be seen in Scheme 5.
OSi(R3)3
R2
Cal-B, hexane
OH
R2
r.t, 200 rpm, 24 h
+
HCl
R1
(R3)3SiCl
R1
R1 = alkyl, aryl
R2 = Me, H
5, 21–23, 28 or 29
R3 = TMS, TES, TBS or TBDPS
OTMS
OTES
OTBS
During this study, the protection reactions to obtain
compounds 1–3, 12–14, 24–26, 31, 33, and 34 were per-
formed applying traditional methodologies.34 The reactions
were carried out in an inert atmosphere with anhydrous
THF and a basic medium (excess of imidazole was applied),
or in solvent-free conditions but also applying an excess of
imidazole. When the protecting source was TMSCl or TESCl
the reactions could be performed at room temperature, but
when the source was TBSCl or TBDPSCl reflux conditions
had to be applied in the case of reactions in THF and for the
solvent-free procedure the reactions were carried out at 55
°C. The yields of the reactions were 85–96% for the above-
mentioned compounds (for further details, see the SI). On
comparing the lipase-mediated methodology with the tra-
ditional procedure, the enzymatic reactions were milder
and the results for the production of 1, 12, 24, 25, and 26
were comparable.
1
2
3
conv. 95% 0.1
conv. 43% 0.3
conv. 50%
1
OTMS
OTMS
OTMS
O
12
13
conv. 13% 0.3
14
conv. 99% 0.2
conv. 63% 1.1
OTMS
OTES
OTBS
24
25
26
conv. 78% 0.4
conv. 81% 0.3
conv. 83% 0.5
TMSO
TESO
OTMS
OTES
Besides a comparison with the traditional methodolo-
gies, the results reported herein can be compared with
those of the studies applying enzymes cited in the intro-
duction. Bassindale et al. applied alkoxysilanes as the sili-
con source and primary alcohols in transetherification re-
actions using Rhizopus oryzae lipase (ROL) and chicken egg
white lysozyme and conversion rates of up to 41.8% were
observed.24 Applying the methodology presented herein,
conversion rates of up to 99% were obtained using primary
and secondary alcohols and chlorosilanes as protecting
sources.
31
33
conv. 34% 0.4
conv. 31% 0.8
TBSO
OTBS
34
conv. 25% 0.9
Scheme 5 Results for the reactions to perform the protection of 5,
21–23, 28, or 29 with silicon protecting groups (TMSCl, TESCl, TBSCl, or
TBDPSCl) catalyzed by Cal-B. Reagents and conditions: Cal-B (10 mg), 5
(0.06 mmol), protecting group reagent (0.08 mmol), hexane (500 μL).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–I

G
P. B. Brondani et al.
Paper
Synthesis
The results presented herein are promising since, for the
first time, the cleavage of O–Si bond leading to the corre-
sponding alcohols was successfully performed using a
lipase (a commercially available enzyme). TMS removal was
achieved to some extent with the majority of enzymes
tested. The lipases Cal-B (conv. = 47%) and AOL (conv. =
28%, ee = 43%) presented the best results in terms of con-
version and enantioselectivity in the removal of the silyl
moiety from substrate 1 and, when applying a higher
amount of catalyst, full conversion was achieved. In addi-
tion, the new deprotection methodology could be applied
to the majority of the TMS-containing substrates tested. In
terms of the construction of a new O–Si bond, for the first
time this study showed that enzymes can be used to per-
form the reaction with chlorosilanes as a silicon source. The
methodology was successfully applied to protect the major-
ity of the tested alcohols with silyl chlorides, using only
lipase and the desired silicon-based protecting group. The
reactions proceeded smoothly, without the need for an
inert atmosphere and/or anhydrous conditions, furnishing
the protected alcohols with conversion up to 99%.
the GC chromatograms with those obtained in a previous study.29 The
conversion rates were established by GC using a calibration curve
based on both areas (reactant and product). Control experiments
were performed in the absence of enzyme for all conditions tested
and no reaction was observed. All reactions were carried out in dupli-
cate.
Protection Reactions Catalyzed by Lipases; General Procedure
The lipase (10 mg) was placed in a 3 mL Eppendorf® flask containing
hexane, the corresponding alcohol (0.06 mmol), and the R3SiCl (0.08
mmol). The mixture was placed in an orbital shaker (200 rpm). The
reactions were carried out for 24 h. After the established time, the re-
actions were stopped and the mixture was filtered and analyzed by
GC. The absolute configurations were established by comparison of
the GC chromatograms with those described in a previous study.29
The conversion rates were established by GC using a calibration curve
based on both areas (reactant and product). Control experiments
were performed in the absence of an enzyme for all conditions tested,
and no reaction was observed. All reactions were carried out in dupli-
cate. All compounds obtained from this section were analyzed by GC
using the corresponding silyl ethers (prepared using traditional
methodologies) and the alcohols as standards (NMR data available in
the SI).
Protection Reactions Using Traditional Methodologies; General
Procedure
Reagents were purchased from commercial vendors and used with-
out further purification. The compounds were purified by flash chro-
matography using silica gel (230–400 mesh) as the stationary phase.
TLC was performed using silica gel plates F-254 (0.25 mm thickness).
For visualization, the TLC plates were either placed under ultraviolet
light or stained with I2 vapor. Most reactions were monitored by TLC
for the disappearance of the starting material. NMR spectra were re-
corded on a Bruker Ultrashield spectrometer operating at the fre-
quency of 300 MHz (1H NMR) and 75 MHz (13C NMR) or a Bruker DPX-
400 operating at the frequency of 400 MHz (1H NMR) and 100 MHz
To a stirred solution of the corresponding alcohol (10 mmol) in anhyd
THF (20 mL) was added dropwise imidazole (15 mmol) dissolved in
THF (30 mL). The mixture was stirred for 30 min and then TBSCl, TBD-
PSCl, TESCl, or TMSCl (12 mmol) was added dropwise during 15 min.
The reactions with TBSCl or TBDPSCl were hetead to reflux for 4 h and
the reactions involving TESCl or TMSCl were stirred for 4 h at r.t. The
whole procedure was carried out under N2 atmosphere. After that, the
mixture was quenched by H2O (50 mL) at 0 °C and extracted with
EtOAc (3 × 30 mL). The combined organic layers were dried (MgSO4),
filtered, and the solvent was removed under vacuum. The products
were purified by column chromatography over silica gel using hexane
and EtOAc (90:10) as eluent. The products were obtained as oils and
were characterized by 1H, 13C NMR, and LRMS and the data are listed
below. All the NMR spectra and more details about the procedure are
available in the SI.
(
13C NMR). CDCl3 was used as a deuterated solvent and TMS as an ex-
ternal standard. Data are reported as follows: chemical shift (δ), mul-
tiplicity (standard abbreviations), coupling constants (J) in hertz, and
integrated intensity. Low-resolution mass spectra were obtained on a
Shimadzu GCMS-QP 2010 Plus with an RTX-5MS column (30 m × 0.25
mm × 0.25 mm). GC analysis for the determination of the enantio-
meric excesses was carried out using a GC Agilent 7890 B (FID detec-
tor), with a β-DEX 120 column (30 m × 0.25 mm × 0.25 μm) (Supelco).
Further information can be found in the Supporting Information.
Trimethyl(1-phenylethoxy)silane (1)
Colorless oil; yield: 1.81 g (93%).
1H NMR (300 MHz, CDCl3): δ = 7.37 (m, 5 H), 4.93 (q, J = 6.00 Hz, 1 H),
1.49 (d, J = 6.00 Hz, 3 H), 0.12 (s, 9 H).
13C NMR (75 MHz, CDCl3): δ = 146.4, 128.1, 126.8, 125.3, 70.6, 26.8,
0.1.
Deprotection Reactions Catalyzed by Lipases; General Procedure
The lipase (10 mg) was placed in a 3 mL Eppendorf® flask containing
hexane, 50 mmol·L–1 Tris-HCl buffer at pH 7 or 9, or a biphasic system
of hexane/Tris buffer (1:1 v/v) (final volume 500 μL). The correspond-
ing silyl ether was added (0.06 mmol) and the mixture was placed in
an orbital shaker (200 rpm). The reactions were carried out for 16–72
h and after the established time, the reactions were stopped. The re-
actions performed in an aqueous or biphasic solvent system were ex-
tracted with EtOAc (2 × 500 μL), dried (Na2SO4) and analyzed by GC. In
the case of the reactions using hexane alone, only filtration was car-
ried out prior to analysis by GC. All alcohols obtained as the products
were commercially available or prepared by reduction of the corre-
sponding ketones (commercially available) and were used as stan-
dards for the GC analysis. The reactants were prepared using tradi-
tional methodologies (as can be seen below and in more details in the
SI). The absolute configurations were established by comparison of
GC-MS (EI, 70 eV): m/z (%) = 194 (25), 179 (100), 105 (35), 77 (30), 75
(60).
Triethyl(1-phenylethoxy)silane (2)
Colorless oil; yield: 2.27 g (96%).
1H NMR (300 MHz, CDCl3): δ = 7.30 (m, 5 H), 4.86 (q, J = 6.00 Hz, 1 H),
1.43 (d, J = 6.00 Hz, 3 H), 0.94 (m, 9 H), 0.54 (m, 6 H).
13C NMR (75 MHz, CDCl3): δ = 147.2, 128.4, 127.1, 125.6, 70.9, 27.3,
7.1, 5.2.
GC-MS (EI, 70 eV): m/z (%) = 207 (40), 103 (100), 75 (50), 47 (30).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–I

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P. B. Brondani et al.
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Synthesis
tert-Butyldimethyl(1-phenylethoxy)silane (3)
[1-(2,4-Dichlorophenyl)ethoxy]trimethylsilane (10)
Colorless oil; yield: 2.24 g (95%).
Yellow oil; yield: 2.41 g (92%).
1H NMR (300 MHz, CDCl3): δ = 7.36 (m, 5 H), 4.93 (q, J = 6.20 Hz, 1 H),
1.45 (d, J = 6.40 Hz, 3 H), 0.94 (s, 9 H), 0.08 (s, 3 H), 0.01 (s, 3 H).
13C NMR (75 MHz, CDCl3): δ = 146.9, 128.0, 126.6, 125.1, 70.8, 27.7,
1H NMR (300 MHz, CDCl3): δ = 7.53 (d, J = 8.40 Hz, 1 H), 7.24 (dd, J =
9.00, 2.70 Hz, 2 H), 7.22 (d, J = 2.10 Hz, 1 H), 5.15 (q, J = 6.30 Hz, 1 H),
1.36 (d, J = 6.30 Hz, 3 H), 0.07 (s, 9 H).
25.8, 18.2, –4.8, –4.7.
13C NMR (75 MHz, CDCl3): δ = 142.78, 132.84, 131.31, 128.67, 128.17,
127.33, 66.83, 25.26, 0.09.
GC-MS (EI, 70 eV): m/z (%) = 221 (20), 193 (30), 91 (25), 75 (100), 41
(20).
GC-MS (EI, 70 eV): m/z (%) = 262 (20), 248 (70), 174 (100), 75 (50).
tert-Butyldiphenyl(1-phenylethoxy)silane (4)
[1-(4-Nitrophenyl)ethoxy]trimethylsilane (11)
Light yellow oil; yield: 3.20 g (89%).
Yellow oil; yield: 2.10 g (87%).
1H NMR (300 MHz, CDCl3): δ = 7.77 (m, 15 H), 4.88 (q, J = 6.20 Hz, 1
H), 3.05 (d, J = 6.20 Hz, 3 H), 1.10 (s, 9 H).
13C NMR (75 MHz, CDCl3): δ = 146.5, 135.8, 134.5, 133.7, 129.5, 129.4,
1H NMR (300 MHz, CDCl3): δ = 8.16 (d, J = 8.10 Hz, 2 H), 7.48 (d, J =
8.10 Hz, 2 H), 4.93 (q, J = 6.60 Hz, 1 H), 1.42 (d, J = 6.60 Hz, 3 H), 0.09
(s, 9 H).
128.0, 127.5, 127.4, 126.7, 125.4, 71.8, 27.1, 26.9, 19.3.
13C NMR (75 MHz, CDCl3): δ = 154.1, 147.0, 126.1, 123.6, 69.9, 26.8,
0.08.
GC-MS (EI, 70 eV): m/z (%) = 256 (20), 199 (100), 181 (25), 105 (20),
77 (30), 45 (30).
GC-MS (EI, 70 eV): m/z (%) = 238 (25), 224 (45), 107 (30), 91 (30), 75
(100), 73 (50), 45 (30).
[1-(4-Methylphenyl)ethoxy]trimethylsilane (6)
Trimethyl[1-(naphthalen-2-yl)ethoxy]silane (12)
Colorless oil; yield: 1.87 g (90%).
Yellow oil; yield: 2.37 g (97%).
1H NMR (300 MHz, CDCl3): δ = 7.57–7.64 (m, 4 H), 7.21–7.31 (m, 3 H),
4.83 (q, J = 6.60 Hz, 1 H), 1.32 (d, J = 6.60 Hz, 3 H), 0.084 (s, 9 H).
1H NMR (300 MHz, CDCl3): δ = 7.26 (d, J = 8.04 Hz, 2 H), 7.16 (d, J =
8.04 Hz, 2 H), 4.86 (q, J = 6.36 Hz, 1 H), 2.36 (s, 3 H), 1.45 (d, J = 6.39
Hz, 3 H), 0.11 (s, 9 H).
13C NMR (75 MHz, CDCl3): δ = 143.5, 136.4, 128.8, 125.3, 70.4, 26.9,
13C NMR (75 MHz, CDCl3): δ = 144.3, 133.7, 133.1, 128.2, 128.0, 126.2,
21.1, 0.1.
125.8, 124.4, 124.0, 71.2, 23.0, 0.5.
GC-MS (EI, 70 eV): m/z (%) = 193 (100), 119 (30), 91 (35), 75 (70), 73
GC-MS (EI, 70 eV): m/z (%) = 230 (60), 172 (30), 156 (100), 74 (20).
(50), 43 (35).
[1-(Furan-2-yl)ethoxy]trimethylsilane (13)
[1-(4-Aminophenyl)ethoxy]trimethylsilane (7)
Yellow oil; yield: 1.80 g (98%).
Light yellow oil; yield: 0.94 g (45%).
1H NMR (300 MHz, CDCl3): δ = 7.34 (dd, J = 2.10, 0.90 Hz, 1 H), 6.29
(dd, J = 3.30, 1.80 Hz, 1 H), 6.17 (dt, J = 3.30, 0.60 Hz, 1 H), 4.86 (q, J =
6.60 Hz, 1 H), 1.50 (d, J = 6.60 Hz, 3 H), 0.11 (s, 9 H).
13C NMR (75 MHz, CDCl3): δ = 158.1, 141.7, 110.3, 105.4, 64.4, 22.9,
0.3.
1H NMR (300 MHz, CDCl3): δ = 7.09 (d, J = 9.00 Hz, 2 H), 6.63 (d, J =
9.00 Hz, 2 H), 4.70 (q, J = 6.00 Hz, 1 H), 1.42 (d, J = 6.00 Hz, 3 H), 0.03
(s, 9 H).
13C NMR (75 MHz, CDCl3): δ = 144.0, 136.0, 127.0, 116.4, 70.3, 27.2, –
4.8.
GC-MS (EI, 70 eV): m/z (%) = 170 (100), 156 (20), 113 (20), 96 (50), 74
GC-MS (EI, 70 eV): m/z (%) = 210 (30), 209 (60), 137 (40), 119 (40),
(40).
103 (25), 91 (25), 75 (100), 73 (40), 43 (30).
Trimethyl(pentan-2-yloxy)silane (14)
[1-(4-Bromophenyl)ethoxy]trimethylsilane (8)
Colorless liquid; yield: 1.36 g (85%).
Light yellow oil; yield: 2.48 g (91%).
1H NMR (300 MHz, CDCl3): δ = 3.75–3.79 (m, 1 H), 1.27–1.28 (m, 4 H),
1.14 (d, J = 6.00 Hz, 3 H), 0.87–0.92 (m, 3 H), 0.14 (m, 3 H).
13C NMR (75 MHz, CDCl3): δ = 63.0, 32.7, 28.2, 22.7, 14.3, 0.2.
1H NMR (300 MHz, CDCl3): δ = 7.45 (d, J = 9.00 Hz, 2 H), 7.23 (d, J =
9.00 Hz, 2 H), 4.85 (q, J = 6.00 Hz, 1 H), 1.40 (d, J = 6.00 Hz, 3 H), 0.08
(s, 9 H).
13C NMR (75 MHz, CDCl3): δ = 146.0, 131.2, 126.9, 120.4, 70.2, 25.8, –
4.8.
GC-MS (EI, 70 eV): m/z (%) = 160 (5), 145 (30), 117 (100), 75 (70), 73
(90), 45 (25).
GC-MS (EI, 70 eV): m/z (%) = 200 (35), 198 (35), 183 (50), 185 (52),
157 (40), 121 (40), 77 (100), 51 (40), 43 (60).
Trimethyl(pentyloxy)silane (24)
Colorless liquid; yield: 1.39 g (87%).
1H NMR (300 MHz, CDCl3): δ = 3.79 (t, J = 6.90 Hz, 2 H), 1.39–1.72 (m,
6 H), 1.01–1.06 (m, 3 H), 0.14 (m, 3 H).
13C NMR (75 MHz, CDCl3): δ = 63.0, 32.7, 28.2, 22.7, 14.3, 0.2
[1-(4-Fluorophenyl)ethoxy]trimethylsilane (9)
Yellow oil; yield: 1.89 g (89%).
1H NMR (300 MHz, CDCl3): δ = 7.50–7.53 (m, 2 H), 7.20–7.24 (m, 2 H),
5.14 (q, J = 6.00 Hz, 1 H), 1.35 (d, J = 6.30 Hz, 3 H), 0.051 (s, 9 H).
13C NMR (75 MHz, CDCl3): δ = 162.1 (d, J = 245.47 Hz), 142.6, 127.3 (d,
J = 7.8 Hz), 115.1, 70.4, 23.0, 0.4.
GC-MS (EI, 70 eV): m/z (%) = 145 (95), 103 (35), 75 (100), 73 (50), 45
(25).
Triethyl(pentyloxy)silane (25)
GC-MS (EI, 70 eV): m/z (%) = 212 (30), 198 (100), 124 (70), 74 (30).
Colorless liquid; yield: 1.82 g (90%).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–I

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P. B. Brondani et al.
Paper
Synthesis
1H NMR (300 MHz, CDCl3): δ = 3.63 (t, J = 6.60 Hz, 2 H), 1.58–1.54 (m,
2 H), 1.32–1.36 (m, 4 H), 0.96–0.99 (m, 6 H), 0.54–0.64 (m, 12 H).
References
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13C NMR (75 MHz, CDCl3): δ = 63.6, 33.3, 28.7, 23.2, 14.6, 7.1, 5.1
GC-MS (EI, 70 eV): m/z (%) = 173 (10), 103 (85), 75 (100), 47 (35), 45
(30).
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Colorless liquid; yield: 1.84 g (91%).
1H NMR (300 MHz, CDCl3): δ = 3.84 (t, J = 6.90 Hz, 2 H), 1.73–1.76 (m,
2 H), 1.53–1.56 (m, 4 H), 1.10–1.16 (m, 12 H), 0.29 (s, 6 H).
13C NMR (75 MHz, CDCl3): δ = 63.3, 32.6, 28.0, 25.9, 22.5, 14.1, 5.3
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tert-Butyl(pentyloxy)diphenylsilane (27)
Colorless liquid; yield: 2.97 g (91%).
1H NMR (300 MHz, CDCl3): δ = 7.67–7.70 (m, 4 H), 7.20–7.40 (m, 6 H),
3.67 (t, J = 6.60 Hz, 2 H), 1.56–1.58 (m, 2 H), 1.30–1.35 (m, 4 H) 1.06 (s,
9 H), 0.89 (t, J = 6.90 Hz, 3 H).
13C NMR (75 MHz, CDCl3): δ = 135.9, 134.5, 129.8, 127.9, 64.4, 32.6,
28.3, 27.2, 22.8, 19.4, 14.4
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GC-MS (EI, 70 eV): m/z (%) = 326 (20), 173 (25), 145 (90), 117 (100).
3-{[(Trimethylsilyl)oxy]methyl}phenol (29)
White solid; yield: 1.74 g (89%); mp 230–232 °C.
1H NMR (300 MHz, CDCl3): δ = 7.12–7.17 (m, 1 H), 6.93–6.94 (m, 1 H),
6.80–6.82 (m, 2 H), 4.61 (s, 2 H), 0.029 (s, 9 H).
13C NMR (75 MHz, CDCl3): δ = 157.3, 143.1, 129.9, 118.3, 115.3, 114.7,
65.1, 0.3.
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Yellow liquid; yield: 2.52 g (94%).
1H NMR (300 MHz, CDCl3): δ = 7.14–7.26 (m, 1 H), 6.86–6.95 (m, 2 H),
6.73–6.85 (m, 1 H), 4.65 (s, 2 H), 0.27 (s, 9 H), 0.08 (s, 9 H).
13C NMR (75 MHz, CDCl3): δ = 156.8, 142.9, 129.7, 118.7, 114.7, 114.1,
64.9, 0.65, 0.03.
GC-MS (EI, 70 eV): m/z (%) = 240 (100), 182 (50), 168 (20), 154 (30),
122 (50), 74 (70).
(24) Maraite, A.; Ansorge-Schumacher, M. B.; Ganchegui, B.; Leitner,
W.; Grogan, G. J. Mol. Catal. B: Enzym. 2009, 56, 24.
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Springer: Berlin, 2011, 35–40.
Funding Information
CNPq (447110/2014-4) awarded to P.B.B.
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Acknowledgment
The authors are thankful to the Chemistry Department at FURB and
Prof. Dr. Maria da Graça Nascimento (UFSC – Florianópolis) for donat-
ing some lipases.
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Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0037-1610281.
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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–I