A chemoenzymatic route to chiral siloxanes

Article abstract of DOI:10.1016/j.tet.2016.05.032

An approach employing two enzymes—toluene dioxygenase and immobilized lipase B from Candida antarctica (N435)—was explored as a potential biocatalytic method for the coupling of chiral diols with siloxane species. Analysis of reaction mixtures using¹H NMR spectroscopy suggested that up to 66% consumption of the siloxane starting materials had occurred. Oligomeric species were observed and chiral products from the coupling of a cyclic diol with a siloxane molecule were isolated and characterized by MALDI-ToF MS and GPC. Immobilized lipases from Rhizomucor miehei and Thermomyces lanuginosus were also explored as potential catalysts for the coupling reactions, however, their use only returned starting material.

Full text of DOI:10.1016/j.tet.2016.05.032

Tetrahedron xxx (2016) 1e5
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Tetrahedron
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A chemoenzymatic route to chiral siloxanes
ꢀ
ꢀꢁ
ꢀ
Ravi Naoum, Jacqueline P. Seguin, John F. Trant, Mark B. Frampton, Tomas Hudlicky,
Paul M. Zelisko
*
Department of Chemistry and Centre for Biotechnology, Brock University, 1812 Sir Isaac Brock Way, St. Catharines, Ontario, L2S 3A1, Canada
a r t i c l e i n f o
a b s t r a c t
Article history:
An approach employing two enzymesdtoluene dioxygenase and immobilized lipase B from Candida
antarctica (N435)dwas explored as a potential biocatalytic method for the coupling of chiral diols with
siloxane species. Analysis of reaction mixtures using 1H NMR spectroscopy suggested that up to 66%
consumption of the siloxane starting materials had occurred. Oligomeric species were observed and
chiral products from the coupling of a cyclic diol with a siloxane molecule were isolated and charac-
terized by MALDI-ToF MS and GPC.
Received 22 March 2016
Received in revised form 11 May 2016
Accepted 12 May 2016
Available online xxx
Keywords:
Biotransformations
Chemoenzymatic
Chirality
Transesterification
Siloxane
Immobilized lipases from Rhizomucor miehei and Thermomyces lanuginosus were also explored as
potential catalysts for the coupling reactions, however, their use only returned starting material.
Ó 2016 Elsevier Ltd. All rights reserved.
1. Introduction
hydroxyundecanoic acid.7 1H NMR spectroscopy of the Mosher’s
esters derived from the products showed that the S-monomer was
Biocatalysis is quickly gaining momentum as a technique for
transforming achiral or racemic compounds into optically pure
monomers, and ultimately, polymers.1,2 The use of biocatalysts
permits one potentially to reduce the number of synthetic steps in
a reaction, and to also perform reactions that are more environ-
mentally benign in nature. One notable application of biocatalysis
has been in the use of toluene dioxygenase to synthesize arene cis-
dihydrodiols as chiral building blocks for further chemical elabo-
ration; a transformation that in and of itself is not trivial to achieve
employing traditional chemistry.3 In 2004 Bui and Hudlicky re-
ported the synthesis of some polyhydroxylated chiral polymers
using this strategy.4 The synthesis of these polymers began with the
whole-cell fermentation of bromobenzene with the recombinant
organism E. coli JM109(pDTG601A) that overexpresses toluene
dioxygenase (TDO) and produces cis-dihydrodiols from arenes.5
The diol derived from bromobenzene was further functionalized
and used in acyclic diene metathesis (ADMET) polymerization to
afford chiral materials. Similarly cis-dihydrodiol-derived materials
have also proven amenable monomers for a variety of other poly-
merization techniques including Lewis-acid catalyzed epoxide-ring
opening and head-to-tail DielseAlder polymerizations.6
preferentially incorporated into the polymer over the R-monomer.
Siloxane-based compounds are used in the manufacturing of
a number of products such as semiconductors, glasses, ceramics,
plastics, elastomers, resins, optical fibers, coatings, insulators, and
cosmetics.8 The thermal stability, low glass transition temperatures,
low surface energies, high gas permeability, resistance to oxidation,
and biocompatibility of siloxane-based polymers have in large part
been the impetus for the use of siloxanes in these applications.8
Various reagents, including the use of compounds such as Kar-
stedt’s catalyst, Speier’s catalyst, alkoxytitanium complexes, tin
carboxylates and strong acids and bases are commonly employed in
the synthesis of organosilicon compounds or their modification/
functionalization.8 However, the modification of siloxanes by
strong acids or bases is not always conducive to siloxane bond
stability as redistribution or scission of the siloxane bond may oc-
cur.9 In addition, existing functionality on the groups being used to
modify the siloxane compound may inhibit the effectiveness of
metal-centered catalytic systems. As a result researchers have be-
gun to explore the use of biotechnology as a means of replacing
some of the harsher reagents that are typically employed in the
modification of siloxane systems.10
O’Hagan and Parker reported the use of lipase from Candida
Clarson and Gross reported the synthesis of organo-
siloxaneepolyester copolymers using Candida antarctica lipase B
(CalB) immobilized on acrylic beads (Novozym-435Ò, N435) to
catalyze a polyesterification reaction.11 Poojari et al. investigated
various reaction conditions and their effects on the ultimate
rugosa as
a catalyst in the polymerization of racemic 10-
* Corresponding author. Tel.: þ1 905 688 5550x4389; fax: þ1 905 984 4864;
e-mail address: pzelisko@brocku.ca (P.M. Zelisko).
http://dx.doi.org/10.1016/j.tet.2016.05.032
0040-4020/Ó 2016 Elsevier Ltd. All rights reserved.
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2
R. Naoum et al. / Tetrahedron xxx (2016) 1e5
molecular weights of the polymers.11 Performing reactions at 70 ꢀC
and under vacuum were found to be optimal conditions for
attaining higher molecular weights of the polymers.11
X
O
O
8
O
O
+
O
MeO
Si Si
OMe
8
HO
OH
More recently Zelisko et al. reported the synthesis of disiloxane-
containing polyesters catalyzed by N435.9 These polyesters were
fully characterized and the reusability, as well as the thermal tol-
erance, of N435 was explored. N435 was found to retain at least 90%
of its activity up to 130 ꢀC, after which point catastrophic enzyme
denaturation appeared to occur. Furthermore, N435 could be
reused for at least 10 reactions at 100 ꢀC while maintaining con-
sistent overall monomer conversions; however, the apparent initial
rate constant decreased with each subsequent reaction.9 N435 is an
ideal catalyst system to employ with siloxane systems given its
tolerance of hydrophobic environments such as siloxanes.
Building upon the existing reports in literature, it was of interest
to explore the combination of chiral diol systems with siloxanes
using a principally biotechnological approach. Herein we report the
use of two enzyme systems (toluene dioxygenase (TDO) expressed
in a recombinant E. coli and an immobilized lipase) in the formation
of chiral diolesiloxane conjugates.
1 X = Br, unsaturated
2 X = H, unsaturated
3 X = H, saturated
6
N435
X
X
O
O
O
O
O
HO
O
O
MeO
Si Si
O
8
O
Si Si
OMe
8
O
8
OH
8
O
O
7 = 1 + 6
8 = 1 + 6
9 = 2 + 6
10 = 2 + 6
12 = 3 + 6
11 = 3 + 6
X
X
X
O
O
O
O
O
O
8
O
O
HO
OH
O
O
O
Si Si
O
8
O
Si Si
O
OH
X
OH
O
8
n
8
n
O
O
X
O
O
O
HO
OH
X
O
O
Si Si
O
O
O
O
O
X
O
8
O
8
O
O
n
O
O
O
X
O
O
Si Si
8
8
n
OH
OH
2. Results and discussion
Fig.
2. The
reaction
of
1,3-bis(9-carboxynonylmethylester)-1,1,3,3-
In order to synthesize the chiral components of the siloxane
system, the whole-cell fermentation of bromobenzene using
recombinant E. coli JM109(pDTG601A) that overexpresses toluene
dioxygenase was employed.10,11 The fermentation process effi-
ciently installed a syn vicinal diol onto the ring system. This halo-
genated diol system was subsequently transformed into
brominated, unsaturated, and saturated diol systems (Fig. 1) for use
in the enzyme-mediated transesterification reactions. These func-
tional diols were selected for the transesterification reactions not
only because the free diols possess the stereochemistry preferred
by C. antarctica lipase B but they also possess functionality that can
be accessed following the coupling to siloxane compounds either
directly or through hydrolysis of the acetonide moiety.
tetramethyldisiloxane 6 with chiral diols 1e3 at 100 ꢀC and some representative
structures of compounds in the reaction mixture. Only the numbered compounds were
isolated from the respective reaction systems by column chromatography.
experiments.12 Siloxane polymers of 46ꢁ3 repeat units (w3000 g/
mol) have been modified with chiral branches and used in the
study of liquid crystalline materials.13,14 Previous research has also
demonstrated that larger siloxane systems are tolerated by
N435,15e17 but in an effort to focus on the biocatalysis and trans-
esterification reaction with the chiral substrates, the shorter dis-
iloxane unit was selected as a model system for this work. N435
was selected as the biocatalyst for these reactions because the
enzyme possesses a broad substrate scope, a high degree of effi-
ciency in chemical reactions, and remarkable thermal stability.
Moreover, there is literature precedence concerning the use of
N435 for the synthesis of siloxane-based polyester systems.9e12,15,18
The biocatalytic transesterification reactions were monitored
using 1H NMR spectroscopy and by comparing the integrations of
Br
Br
Br
Br
E. coli
O
i
ii
OH
OH
O
O
JM109(pDTG601A)
O
1
HO
OH
iii
the resonances of the a-protons of the diester carbonyl to those of
the pendent methyl ester functionality. The ratio of these integrals
was used to determine the percent consumption of the starting
diester. As the reaction progressed, the methoxy group of the esters
was liberated and subsequently removed from the reaction as
methanol. The resonance corresponding to the methylene, which is
a triplet, shifts slightly downfield in the 1H spectrum of the product.
Therefore, the ratio of the integration values between the reso-
nance assigned to the methylene in the starting material relative to
the resonance assigned to the methylene in the product was used in
the estimating the extent to which the starting material was con-
verted to the product. The chiral diols for this study were synthe-
sized with R stereochemistry at both diol positions as CalB has
a preference for alcohols with R stereochemistry.19e23
O
O
O
iv
O
HO
HO
OH
OH
3
2
O
O
7
O
O
v
vi
Si
Si
O
O
O
HO
O
7
7
7
4
5
6
Reagents: i. DMP, p-TsOH, acetone; ii. OsO4, H2O, acetone; iii. Bu3SnH, toluene; iv. H2, Pd/C, MeOH;
v. pTsOH, MeOH; vi. hexamethydisiloxane, Karstedt's catalyst, toluene
To further demonstrate the enzymes’ selectivity, identical
transesterification control reactions were performed with siloxane
diester 6 and chiral diols 1, 2, and 3 using lipases from Rhizomucor
miehei and Thermomyces lanuginosus. In all cases, these experi-
ments only returned starting materials.24
Fig. 1. The synthetic scheme for the principle components of the reaction beginning
with the biocatalytic oxidation of bromobenzene using toluene dioxygenase overex-
pressed in E. coli.
1,3-Bis(9-carboxynonylmethylester)-1,1,3,3-tetramethyldisilox-
ane 6 was selected as the model siloxane for the lipase-mediated
reactions with the chiral diol molecules (Fig. 2). Based on pre-
vious research it was known that the distance between the ester
moiety and the siloxane portion of the diester was sufficient to be
tolerated by N435 and would not be a complicating factor in the
2.1. Background hydrolysis
One of the physiological roles of a lipase is to hydrolyze esters to
the corresponding alcohols and acids. In the event that some water
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R. Naoum et al. / Tetrahedron xxx (2016) 1e5
3
Table 2
molecules were trapped within the enzyme active site during the
immobilization process, control experiments were performed in
order to determine the amount of ester hydrolysis that could be
catalyzed by the enzyme under the reaction conditions. This
background hydrolysis, rather than the desired transesterification
of the ester moieties, would also result in a decrease in the in-
tegration of the peak of the protons from the methyl group,
therefore producing a false indication that esterification or poly-
merization had occurred.
Molecular weights of the unfractionated reaction products as determined by MALDI-
ToF MS and GPC after 7 days
Molecular weights (g/mol)
MALDI-ToF MS
Mw
GPC
Reaction products
Mn
Mn
800
Mw
830
820
7,8
9,10
11,12
598ꢁ38
757ꢁ50
850ꢁ51
625ꢁ45
897ꢁ35
940ꢁ72
800
1100
1400
These reactions were carried out by incubating the diester at
100 ꢀC in toluene in the absence of the chiral diols for 24 h, and they
were catalyzed using a 10 wt % of the N435 relative to the diester.
The reactions were terminated after 24 h by cooling the reaction
mixture to room temperature, adding 2.0 mL of diethyl ether, and
this technique may not provide a complete picture of the reaction
products. To corroborate the MALDI-ToF MS data, gel permeation
chromatography (GPC) analysis, relative to polystyrene standards,
of the (Table 2) unfractionated reaction systems was also performed.
GPC analysis revealed that although the reactions did not yield
products that were simply the result of a single transesterification
event, that any higher molecular weight molecules that were syn-
thesized were at best oligomers rather than the possible polymers.
Of the three chiral diols, the fully saturated diol 3 displayed the
greatest potential for forming polymeric species, reaching molec-
ular weight values of Mw¼1400 g/mol and Mn¼1100 g/mol as evi-
denced by GPC; it was not possible to obtain reliable molecular
weight data for these reaction products utilizing MALDI-ToF MS.
Although the GPC data suggested that four units had combined on
average in the reaction mixtures it was unclear whether both hy-
droxyl groups of the chiral diol reacted or if only a single trans-
esterification event was occurring per diol functionality.
€
removing the N435 beads by filtration using a fritted Buchner filter.
Following filtration, the beads were washed with 3ꢂ2.0 mL of
diethyl ether to recover any remaining starting materials or prod-
ucts, and the solvents were removed using a rotary evaporator.
These reactions were carried out in triplicate.
On average, 7% hydrolysis of the diester was observed with N435
at 100 ꢀC. This amount of hydrolysis was considered during analysis
of spectral data for the polymerization reactions and all the data
reported below represents consumption rates above that of this
background.
2.2. Consumption of the siloxane diester
In the absence of the enzyme, transesterification reactions were
not observed between 6 and any of the chiral diols as evidenced by
1H NMR spectroscopy.
2.4. Isolation and identification of individual molecules
In keeping with previous reports,9,10,12,15,18 reactions were car-
ried out at 100 ꢀC over a period of 24 h and 7 days to ascertain the
extent to which the transesterification reactions would occur be-
tween the siloxane diester and the chiral diol molecules. With all
three diol systems the higher temperature resulted in the greatest
consumption of the siloxane diester (Table 1) as determined by 1H
NMR spectroscopy. Chiral diol 3 resulted in the greatest con-
sumption of siloxane diester 6, with the maximum being approx-
imately 60% after 7 days. Of the three chiral diols 3 is fully saturated
and the least sterically hindered. This likely facilitated the in-
corporation of diol 3 into the enzymes’ active site relative to the
other diol species, ultimately resulting in a more efficient trans-
esterification reaction.
Attempts were made to fractionate the reactions in an effort to
isolate and characterize individual molecules and to determine the
substitution pattern with respect to the diol molecules. Although it
was not possible to isolate all of the components of the reactions, as
higher oligomeric species (e.g., tetramers) did not elute from the
column, the species resulting from the transesterification of silox-
ane diester 6 and each of the chiral diol molecules were successfully
isolated. The isolated compounds were fully characterized using 1H
NMR spectroscopy, 13C NMR spectroscopy, 29Si NMR spectroscopy,
FTIR spectroscopy, and MS. Spectral analysis revealed that both of
the hydroxyl moieties at the stereogenic centers in the diol species
were accessible to the N435 and could participate in trans-
esterification reactions (Table 3); regioisomers were distinguished
using NMR spectroscopy. With unsaturated diols 1 and 2 the
transesterification at the hydroxyl group distal to the acetonide
group predominated in the isolated products while the proximal
hydroxyl group relative to the acetonide was the dominant species
isolated from the transesterification reaction with saturated diol 3.
All of the six isolated products 7, 8, 9, 10, 11, 12 from the enzyme-
mediated transesterification reactions were optically active (Table
3). However, given that an accurate concentration of the in-
dividual components from the reaction could not be obtained,
optical activity measurements were not performed on the unfrac-
tionated reaction products, as the results would not be informative.
Table 1
The percent consumption of diester 6 in polymerization reactions with chiral diols 1,
2, and 3 at 100 ꢀC over 24 h and 7 days. All reactions were carried out in 1 mL of
toluene, stirred at 60 rpm, and catalyzed by 10 wt % of N435 (0.8e2 wt % lipase)
relative to the combined mass of the monomers. The remainder of the material was
the starting compound 6
Chiral diol
% Consumption of siloxane diester 6
24 h
7 days
1
2
3
15ꢁ2
12ꢁ2
33ꢁ3
28ꢁ7
23ꢁ1
58ꢁ6
2.5. Competition experiments for hydroxyl selectivity by
N435
2.3. MALDI-ToF and GPC analysis
Matrix-assisted laser desorption ionization time-of-flight
(MALDI-ToF) mass spectroscopy analysis of the unfractionated re-
action systems suggested that the reaction products were simply
the result of a single transesterification event between one of the
chiral diols and the siloxane diester (Table 2). However, not all
analytes respond to MALDI-ToF analysis, raising the possibility that
As part of this work it was of interest to determine if the lipase
had a preference for one of the free hydroxyl groups of the chiral
diol over the other. It was hypothesized that although only slight
electronic differences exist between the two free hydroxyl groups,
that the steric differences may cause the lipase to favor one hy-
droxyl moiety over the other.
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4
R. Naoum et al. / Tetrahedron xxx (2016) 1e5
Table 3
Br
Br
Br
Br
Summary of isolated yields and optical properties of N435-catalyzed trans-
esterification products of siloxane diester 6 and saturated and unsaturated chiral
diols
O
O
O
O
O
O
O
O
i, ii
iii
iv
HO
TIPSO
TIPSO
HO
OH
OH
OMe
OMe
13
14
15
Isolated compound
Isolated Optical rotation
yield (%)
vii
v
Br
Br
O
O
O
O
O
20
viii
4
[
a
]
¼15.1 (c¼0.35, CHCl3)
¼ꢃ9.8 (c¼0.30, CHCl3)
D
HO
O
HO
TIPSO
OMe
16
OMOM
OMOM
18
19
ix
vi
20
D
Br
2
[a
]
O
O
O
HO
O
MeO
OMe
OMOM
17
20
x
Br
O
20
D
8
3
[
a
a
]
¼ꢃ69.1 (c¼0.75, MeOH)
¼ꢃ41.8 (c¼0.15, MeOH)
O
MeO
OH
21
20
D
[
]
xi
O
O
xii
O
OH
O
MeO
MeO
OH
20
D
22
23
16
12
[
a
a
]
¼ꢃ35.3 (c¼0.9, MeOH)
¼ꢃ30.7 (c¼0.7, MeOH)
Reagents: i. triisopropylsilyl trifluoromethanesulfonate, 2,6-lutidine, CH2Cl2; ii. NH4Cl; iii. NaH, CH3I, THF;
iv. TBAF; v. Bu3SnH, AIBN, THF; vi. H2, Pd/C, MeOH; vii, NaH, MOMCl, THF; viii. TBAF, THF; ix. NaH, CH3I;
x. HCl, MeOH; xi. Bu3SnH, AIBN, THF; xii. H2, Pd/C, MeOH
20
D
Fig. 3. Chiral, monoprotected analogues of chiral diols 1, 2, and 3 to probe the sub-
[
]
strate preference of N435.
days. This suggested that the N435 had difficulty processing the
brominated chiral substrate once the steric bulk was increased at
one of the hydroxyl groups. These data would seem to suggest that,
despite the inherent substrate promiscuity exhibited by N435,
there are steric limitations within the active site; CalB has been
shown to process a large variety of artificial substrates that do not
resemble triglycerides. The enzyme active site has been shown to
be tolerant of cyclic molecules,16,27 (aliphatic alcohols/carboxylic
Gotor reported the selective acetylation of the secondary alco-
hols found in shikimic acid using lipases. He noted that C. antarctica
lipase A exhibited greater selectivity for shorter chain acyl donors
while C. antarctica lipase B demonstrated a preference for acyl
donors with longer chains.25 With these results in mind, the sub-
strate preference of N435 for the two hydroxyl moieties in chiral
diols 1, 2, and 3 was examined. Based upon the isolated dimer
species obtained from the transesterification of chiral diols 1, 2, and
3 with 6, the analysis would suggest that, to varying degrees, N435
demonstrates a preference for the secondary alcohol distal to the
acetonide group (Table 4) in each of the three cases. In an effort to
further probe the selectivity of N435 for the two free hydroxyl
groups in the chiral diols, analogues of diols 1, 2, and 3 were syn-
thesized based on a procedure reported by Banwell, where the
hydroxyl groups were selectively protected (Fig. 3).26 This afforded
the opportunity to study the capacity of the lipase to mediate
transesterification reactions when one of the chiral hydroxyl
groups was already blocked and to provide further mechanistic
insights into this reaction.
acids,27 cyclohexanoic acid,
b-, g-, and d
-lactams,28e30 as well as
benzo-fused
b
-lactams31 are also examples of substrates tolerated
by the enzyme) but it would appear that the steric constraints of
reacting both of the free diols in 1 are exacerbated by the presence
of the bromine atom on the ring. The transesterified products were
formed in a 0.9ꢁ0.1:1 ratio indicating that any preference by the
enzyme for either of the hydroxyl groups in the brominated chiral
diol was likely negligible. However, given the reduced reactivity of
these systems by even a slight increase in steric bulk around the
free hydroxyl groups (i.e., methylation) it is unlikely that the bro-
minated diol 1 would be tolerated by N435 for the synthesis of
higher molecular polymeric compounds where transesterification
of both of the free diols would be required; it appears unlikely that
the enzyme active site has adequate space to accommodate both
a bromine atom and another siloxane-ester chain.
Table 4
The apparent selectivity of N435 for the alcohols of the chiral diols in
transesterification reactions with siloxane 6
Chiral substrates 16 and 22 were tested in a similar manner as
the protected brominated substrates. Unsaturated substrates 16
and 22 were reacted in a 1:1:1 ratio with siloxane 6 in toluene at
100 ꢀC with 10 wt % N435 (0.8e2 wt % lipase). In a similar trend to
that observed for the unprotected substrates, N435 processed the
unsaturated substrates more efficiently than the corresponding
brominated species with product formation being observed after 6
days. With substrates 16 and 22 the N435 demonstrated a clear
preference for the hydroxyl moiety distal to the acetonide with the
transesterification product at this location forming in a 0.1ꢁ0.1
Chiral diol
Ratio of distal to proximal ester relative to the position
of the acetonide
1
2
3
1.86ꢁ0.17:1
2.3ꢁ0.3:1
1.28ꢁ0.02:1
When compounds 6, 15, and 21 were reacted in a 1:1:1 ratio in
toluene at 100 ꢀC in the presence of 10 wt % (based on the total mass
of the starting materials, 0.8e2 wt % lipase) of N435, the formation
of products was only observed by 1H NMR spectroscopy after 7
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R. Naoum et al. / Tetrahedron xxx (2016) 1e5
5
(proximal):1 (distal) ratio versus the proximal hydroxyl group. The
data suggest that the in order to accommodate the acetonide
moiety of the chiral diol, the diol is position within the enzyme
active site such that the distal hydroxyl group is more accessible by
both the catalytic triad of the enzyme and the acyl group of the
siloxane species.
Advanced Biomanufacturing Centre for funding this research and
Prof. Alex Adronov (McMaster University) for his assistance with
the acquisition of GPC data.
Supplementary data
Surprisingly, when substrates 17 and 23 were reacted in a 1:1:1
ratio with siloxane 6 at 100 ꢀC in toluene with 10 wt % N435
(0.8e2 wt % lipase), transesterification of the hydroxyl group
proximal to the acetonide was preferred over that of the distal
hydroxyl moiety (1.8ꢁ0.3:1). It is currently unclear why the more
sterically hindered hydroxyl group was favored by the enzyme in
this instance whereas the less sterically hindered hydroxyl group
proximal to the acetonide was favored with the other two chiral
diol systems. The exact reason for this striking inversion of selec-
tivity due to a relatively distal structural change is currently being
explored.
Supplementary data associated with this article can be found in
the online version, at http://dx.doi.org/10.1016/j.tet.2016.05.032.
References and notes
1. Hudlicky, T.; Reed, J. W. Chem. Soc. Rev. 2009, 38, 3117e3132.
2. Clouthier, C. M.; Pelletier, J. N. Chem. Soc. Rev. 2012, 41, 1585e1605.
3. Hudlicky, T.; Reed, J. W. Synlett 2009, 685e703.
4. Bui, V. P.; Hudlicky, T. Tetrahedron 2004, 60, 641e646.
5. Zylstra, G. J.; Gibson, D. T. J. Biol. Chem. 1989, 264, 14940e14946.
6. Trant, J. F.; Ho, H.; Hudlicky, T. Synlett 2014, 2360e2364.
7. O’Hagan, D.; Parker, A. H. Polym. Bull. 1998, 41, 519e524.
8. Brook, M. A. Silicon in Organic, Organometallic and Polymer Chemistry; John
Wiley & Sons: New York, 2000.
3. Experimental
ꢀ
9. Frampton, M. B.; Seguin, J. P.; Marquardt, D.; Harroun, T. A.; Zelisko, P. M. J. Mol.
Catal. B: Enzym. 2013, 85e86, 149e155.
Please refer to the Electronic Supplementary data for full ex-
perimental details.
10. Bio-inspired Silicon-based Materials, Advances in Silicon Science Series (Ed.:
Matisons, J.); Zelisko, P. M., Ed.; Springer: Dordrecht, 2014.
11. Poojari, Y.; Palsule, A. S.; Cai, M.; Clarson, S. J.; Gross, R. A. Eur. Polym. J. 2008, 44,
4139e4145.
4. Conclusions
12. Frampton, M. B.; Zelisko, P. M. Enzyme Microb. Technol. 2014, 58e59, 87e92.
ꢀ
13. Perez-García, L.; Amabilino, D. B. Chem. Soc. Rev. 2007, 36, 941e967.
A chemoenzymatic route employing two enzymes (toluene
dioxygenase and lipase) for the synthesis of siloxane ester oligomers
(w1400 g/mol) has been described. The CalB was challenged with
three chiral diols (two unsaturated 1, 2 and one saturated 3) with the
fully saturated diol species 3 leading to the most efficient trans-
esterification reactions (w60%). Fractionating the reaction products
via column chromatography resulted in the isolation of the species
formed from a single transesterification event between the chiral
diols and siloxane diester. The isolated species revealed that both of
the free alcohols on each chiral diol are enzymatically accessible, al-
though not to the same extent, and the products of the biocatalytic
transesterification reactions retain their optical activity. The N435
demonstrated no selectivity for the diols in the brominated sub-
strates while the hydroxyl group distal to the acetonide was preferred
in the unsaturated substrate and the hydroxyl group proximal to the
acetonide was preferred in the fully saturated chiral substrate.
14. Lewthwaite, R. A.; Gray, G. A.; Toyne, K. J. Mater. Chem. 1992, 2, 119e124.
15. Frampton, M. B.; Zelisko, P. M. Chem. Commun. 2013, 9269e9271.
16. Shaoo, B.; Brandstadt, K. F.; Lane, T. H.; Gross, R. A. Org. Lett. 2005, 7,
3857e3860.
17. Sharma, B.; Azim, A.; Azim, H.; Gross, R. A.; Zini, E.; Focarete, M. L.; Scandola, M.
Macromolecules 2007, 40, 7919e7927.
18. Frampton, M. B.; Subczynska, I.; Zelisko, P. M. Biomacromolecules 2010, 11,
1818e1825.
19. Ottosson, J.; Fransson, L.; Hult, K. Protein Sci. 2002, 11, 1462e1471.
ꢀ ꢀ
€ €
20. Gedey, S.; Liljeblad, A.; Lazar, L.; Fulop, F.; Kanerva, L. T. Can. J. Chem. 2002, 80,
565e570.
21. Yazbeck, D.; Derrick, A.; Panesar, M.; Deese, A.; Gujral, A.; Tao, J. Org. Process Res.
Dev. 2006, 10, 656e660.
22. Yang, B.; Lihammar, R.; Backvall, J.-E. Chem.dEur. J. 2014, 20, 13517e13521.
€
23. Juhl, P. B.; Trodler, P.; Yagi, S.; Pleiss, J. BMC Struct. Biol. 2009, 9, http://dx.doi.
org/10.1186/1472-6807-9-39
ꢀ
24. Seguin, J. P. Enzyme-mediated Synthesis of Disiloxane-containing Chiral Polymers,
Hons (B.Sc. Thesis); Brock University, April 2013.
ꢀ
25. Armesto, N.; Ferrero, M.; Fernandez, S.; Gotor, V. J. Org. Chem. 2002, 67,
4978e4981.
26. Ma, X.; Banwell, M. G.; Willis, A. C. J. Nat. Prod. Res. 2013, 76, 1514e1518.
27. Biomolecular Catalysis; Kim, J., Kim, S. H., Wang, P., Eds.; American Chemical
Society: Washington, DC, 2008.
Acknowledgements
28. Faber, K. Biotransformations in Organic Chemistry, 6th ed.; Springer: Heidelberg.
29. Jones, M.; Page, M. I. J. Chem. Soc., Chem. Commun. 1991, 5, 316e317.
30. Brieva, R.; Crich, J. Z.; Sih, C. J. J. Org. Chem. 1993, 58, 1068e1075.
The authors would like to thank the Natural Sciences and En-
gineering Research Council (NSERC) of Canada and Brock’s
€ €
31. Forro, E.; Fulop, F. Chem.dEur. J. 2006, 12, 2587e2592.
Please cite this article in press as: Naoum, R.; et al., Tetrahedron (2016), http://dx.doi.org/10.1016/j.tet.2016.05.032