Lipases aided esterification of (2,2-dimethyl-1,3-dioxolan-4-yl)methanol

Article abstract of DOI:10.2174/157017861101140113155507

Racemic solketal (2,2-Dimethyl-1,3-dioxolan-4-yl)methanol 1, was treated with carboxylic acids of varying chain length or their vinyl esters in the presence of different lipases. The esterification reaction was carried out in n-hexane or diisopropyl ether as a solvent. The yield of the solketal esters and their enantiopurity were satisfactory, as indicated by gas chromatography using chiral column. Lipases from Rhizopus oryzae and Pseudomonas fluorescence gave the best enantiomeric excess (ee) when the solketal was treated with vinyl butyrate in a solution of diisopropyl ether at room temperature.

Full text of DOI:10.2174/157017861101140113155507

Send Orders for Reprints to reprints@benthamscience.net
6
Letters in Organic Chemistry, 2014, 11, 6-12
Lipases Aided Esterification of (2,2-Dimethyl-1,3-dioxolan-4-yl)methanol
Aurelia Zniszczoꢀ and Krzysztof Z. Walczak*
Department of Organic Chemistry, Bioorganic Chemistry and Biotechnology, Silesian University of Technology,
Krzywoustego 4, 44-100 Gliwice, Poland
Received June 20, 2013: Revised August 08, 2013: Accepted August 14, 2013
Abstract: Racemic solketal (2,2-Dimethyl-1,3-dioxolan-4-yl)methanol 1, was treated with carboxylic acids of varying
chain length or their vinyl esters in the presence of different lipases. The esterification reaction was carried out in
n-hexane or diisopropyl ether as a solvent. The yield of the solketal esters and their enantiopurity were satisfactory, as in-
dicated by gas chromatography using chiral column. Lipases from Rhizopus oryzae and Pseudomonas fluorescence gave
the best enantiomeric excess (ee) when the solketal was treated with vinyl butyrate in a solution of diisopropyl ether at
room temperature.
Keywords: Esterification, solketal, lipases, enantiopurity, biocatalysis.
INTRODUCTION
products formation, especially in chiral environment formed
by enzyme. The enantiomer having a lower activation energy
is formed faster and this is reflected by enantiopurity of
product. If the esterification is performed under conditions
which enable an equilibrium, the more thermodynamically
stable product with higher activation energy is formed [20].
It is typical for esterification of alcohols using acid as an
acyl donor. Under condition of irreversible esterification,
usually kinetically favoured product predominates [21, 22].
The development of biodiesel production (FAME) and
fatty acids demand for the pharmacy and cosmetics industry
resulted in an excess of glycerol, being a second product of
fats processing [1]. The glycerol is partially utilised in the
production of chloromethyloxirane and glycerol acetate
or nitrate [2-4]. The important utilisation of glycerol is its
conversion into solketal, (2,2-Dimethyl-1,3-dioxolan-4-yl)
methanol, valuable product, especially in the form of pure
enantiomers for pharmacy as a chiral, three-carbons building
block [5, 6]. Solketal, is a chiral synthetic precursor of
acylglycerols [7, 8] and glycerophospholipids [9, 10], ꢁ-
blockers [11, 12] and polymers [13, 14]. Enantiomerically
enriched (R)- and (S)- solketal are commercially available
but at a high price since their production according to stan-
dard synthetic protocols is expensive and laborious [15 - 18],
whereas racemic solketal is an inexpensive reagent, obtained
in reaction of glycerol with acetone [19]. Consequently, new
and efficient synthetic routes are required to produce opti-
cally pure solketal as a building block based on glycerol.
Herein, we described an approach for the enantioselective
synthesis of solketal esters using lipases as a biocatalyst.
Lipases (EC3.1.1.3) are a subgroup of carboxylesterases spe-
cifically hydrolyse the triacylglycerols in the presence of
water. Due to the natural activity of lipases the hydrolysis of
the appropriate esters is the most reported attitudes applied
for synthesis of enantiomerically enriched esters or alcohols.
Lipases are also able to form esters in organic solvents in the
presence of traces of water necessary for the formation of
their enzymatically-active shape. When racemic substrate is
used in esterification reaction both enantiomers can be
formed in competitive reactions. Such reaction is kinetically
controlled and depends on the activation energy of both
RESULTS AND DISCUSSION
The racemic solketal 1 was obtained in reaction of
glycerol with anhydrous acetone catalysed by p-TSA in n-
pentane under reflux [19]. The enantiomerically enriched
solketals, namely (S)-(+)-(2,2-dimethyl-1,3-dioxolan-4-
yl)methanol 2a were obtained in three-step synthesis starting
from D-mannitol [16]. The (R)-enantiomer 2b was a com-
mercially available product. The standards of reference, es-
ters of (R)- and (S)-solketal were obtained according to
elaborated procedure in condensation reaction of carboxylic
acids with the appropriate enantiomers in the presence of
N,N’-dicyclohexylcarbodiimide (DCC) in methylene chlo-
ride
solution (Scheme 1).
The esters of racemic solketal 1 were obtained under the
same conditions. In primary trials, 1 was treated with
equimolar amount of carboxylic acids 3a-d in a solution
of an organic solvent (n-hexane or diisopropyl ether) in the
presence of lipases preparations, namely Novozyme 435 and
Lipozyme RMIM (Scheme 2), used in a weight ratio 1:10
with respect to racemic solketal. The reaction was performed
at room temperature. The progress of reaction was monitored
by gas chromatograph system equipped with chiral capillary
column (Table 1 and 2). Tables 1 and 2 also contains E-
values, a measure of the enantioselectivity in kinetic reso-
lution, defined as the ratio of the specificity constants
*Address correspondence to this author at the Department of Organic
Chemistry, Bioorganic Chemistry and Biotechnology, Silesian, University
of Technology, Krzywoustego 4, 44-100 Gliwice, Poland; Tel: +4832 237
1308; Fax: +4832 237 2094; E-mail: krzysztof.walczak@polsl.pl
kcat/K for the two competing enantiomeric substrates [23].
M
Both enzymes to some extent, exhibit activity towards 1.
1875-6255/14 $58.00+.00
© 2014 Bentham Science Publishers

Lipases Aided Esterification of (2,2-Dimethyl-1,3-dioxolan-4-yl)methanol
Letters in Organic Chemistry, 2014, Vol. 11, No. 1
OCOR
R-esters
7
2a
O
O
O
O
4a-d
DCC, DMAP, Et3N
RCOOH
3 - 5 a R = Me
b R = Et
CH2Cl2, r.t.
3a-d
OCOR
c R = n-Pr
d R = n-Bu
2b
S-esters
5a-d
Scheme 1. Synthesis of references compounds.
OCOR
OH
OCOR
Lipase
O
3 - 5 a R = Me
b R = Et
O
RCOOH
3a-d
O
O
O
+
+
O
c R = n-Pr
d R = n-Bu
5a-d
4a-d
1
Scheme 2. Esterification of solketal by carboxylic acids in the presence of lipases.
Table 1. The Primary Trials of Solketal Esterification Using Novozyme 435
n-Hexane
i-Pr O
2
Enzyme
Entry
Acid 3
Time [h]
Yield [%]
ee [%]
S
E
Yield [%]
ee [%]
S
E
1
2
3
4
a
b
c
0.75
0.75
0.75
0.75
6
71
12
10
7
6
9
33
40
25
11
2
2.5
1.8
1
24
39
42
1
11
21
31
Novozyme
435
1.3
1.3
d
In experiments ratio of enzyme : solketal was 1:10 (w/w)
Table 2. The Esterification of Solketal in the Presence of Lipozyme RMIM
Entry
Acid 3
Time [h]
Yield [%]
ee [%]
R
E
1
2
3
4
a
b
c
No reaction
0.75
-
-
-
8
17
19
22
1.4
1.5
1.6
0.75
11
16
d
0.75
In experiments ratio of enzyme : solketal was 1:10 (w/w)
In reactions catalysed by Novozyme 435 5a was ob-
tained after 45 minutes with ee excided 70% (Table 1, entry
1). Extension of alkyl chain in the molecule of acyl donor
3a-d gave the highest conversion of solketal but the enanti-
omeric excess and E-value of formed esters 5a-d decreased
(Table 1, entry 2-4). Acylation in the presence of lipozyme
RMIM gave the appropriate esters 4b-d with (R)-absolute
configuration (Table 2, entry 1-4). The yield of esters 4b-
d is rather low, the best result was obtained for solketal
valerate 4d. When acetic acid 3a was used as an acyl donor
the formation of solketal acetate 4a was not observed. The
observed behaviour remains in an agreement with a recent
work by Machado et al. who found longer acyl chains pref-
erential for kinetic resolution of solketal esters via hy-
drolysis by lipases [24]. These primary tests clearly indi-
cated that the esterification of solketal using our enzyme
preparations is possible. Tests performed using enzymes
such as lipozyme TLIM, lipase from Candida rugosa,
Rhizopus oryzae, Aspergillus niger, spawn from Mucor cir-
cinelloides and Pancreatin, clearly indicated that the in-
vestigated preparations did not show sufficient activity in
this reaction.
To increase the yield of esters another approach was con-
sidered. An alternative reaction pathway for ester synthesis
by using carboxylic acids was irreversible esterification in-
volving vinyl esters. Biotransformations were carried out
using racemic solketal 1 and acyl donor 6b, which gave the
best yield of solketal’s ester. Reactants were used in a ratio
1 : 2 (solketal : acyl donor) in a solution of diisopropyl ether

8
Letters in Organic Chemistry, 2014, Vol. 11, No. 1
OH
Zniszczoꢀ and Walczak
OCOR
OCOR
R'
O
O
Lipase
O
+
O
O
O
+
O
R
O
O
+
R'
6a R = Me, R' = H
b R = n-Pr, R' = H
c R = Me, R ' = Me
5 a,c, d
4a, c, d
1
Scheme 3. Irreversible esterification of solketal.
Table 3. Esterification of Solketal using Vinyl Butyrate 6b in Diisopropyl Ether
Amount of Enzyme
Entry.
Lipase
Time [h]
Yield [%]
ee [%]
E
prep. [mg]
1
2
Lipozyme RMIM
10
2
99
-
0
-
0
-
Immobilised on Sol-gel-AK lipase from
10
2
Candida cylindracea
3
4
Amano lipase A from Aspergillius niger
Lipase from Aspergillus niger
Lipozyme TLIM
10
10
10
10
10
10
20
10
10
10
10
10
10
2
<3
-
7
1.1
-
S
2
-
5
2
92
99
4
1
1.1
0
R
6
Novozyme 435
2
0
7
Lipase from Candida rugosa
Lipase from Rhizopus oryzae
Lipase from Rhizopus oryzae
Pork pancreatin
2
26
-
1.6
-
R
8
2
-
9
120.0
28.5
9
55.3
4.3
2.8
2.9
2.5
10.3
9.5
1.9
R
10
11
12
13
14
15
2
2
2
2
4
2
45
47
R
Lipase from porcine pancreas type II
Spawn from Mucor circinelloides
Amano lipase from Pseudomonas fluorescens
Amano lipase from Pseudomonas fluorescens
Lipase from Candida antarctica CLEA
7
R
43
15
26
41
33
80
76
24
R
R
R
R
**calculated for 100 mg of solketal.
at 25 °C. Several preparations of lipases were applied, the
ratio enzyme : acyl donor was constant, despite enzymes
specific activity (Scheme 3, Table 3).
cation of solketal (entry 19-27), especially when vinyl bu-
tyrate 6b was applied (entry 25-27). The variation of the
proportion solketal 1 to vinyl butyrate 6b does not have a
significant influence on the yield and ee of formed 4c (Table
5, Fig. 1).
The best activity was observed for the lipase from Pseu-
domonas fluorescens. The satisfactory ee was obtained after
2 h without significant decrease of enantiomeric excess when
reaction time was extended to 4 h (Table 3, entry 13, 14).
Lipozyme RMIM and Novozyme 435 gave the high yield of
solketal ester, but unfortunately, ester is produced as a race-
mate (Table 3, entries 1, 6). In the presence of lipase from
Rhizopus oryzae the ester formation took more time and the
yield and ee were moderate. For the further experiments
three lipases were selected, namely spawn from Mucor cir-
cinelloides, Rhizopus oryzae and Pseudomonas fluorescens.
These preparations gave the best result when the yield versus
ee was compared (Table 4). The reaction of esterification
was performed under conditions applied above with usage of
6a-c as an acyl donor.
In conclusion, based on the collection of 13 lipases ap-
plied in the synthesis of solketal esters, the best results were
obtained in irreversible esterification of racemic 1 using the
lipase from Pseudomonas fluorescens. These results will be
used for the optimisation of explored reaction as a starting
point. The immobilisation of lipase on support of different
types is considered at present. The mesoporous silica SBA-
15 modified with octyl groups and oxidised multi-wall car-
bon nanotubes (O-MWCNTs) are chosen for the preliminary
tests. Due to the published reports, immobilisation of an en-
zyme may improve its activity and enantioselectivity. Immo-
bilisation alters physicochemical properties of enzyme
changing its environment (hydrophilicity or hydrophobicity)
or increasing enzyme rigidification. For lipases immobilisa-
tion may become a way to keep “open form” where the
active site is exposed to the medium [25].
Inspection of (Table 4) indicated the high affinity of li-
pase from Pseudomonas fluorescens as a catalyst for esterifi-

Lipases Aided Esterification of (2,2-Dimethyl-1,3-dioxolan-4-yl)methanol
Letters in Organic Chemistry, 2014, Vol. 11, No. 1 9
Table 4. The Influence of Acyl Donor on Esterification Reaction of Solketal
Amount of
Acyl Donor
6
Yield of Ester
Entry
Lipase
Time [h]
ee %
E
Enzyme [mg]
[%]
9.5
21
1
8
24
32
0.5
2
38.5 R
36 R
29 R
42 R
40 R
38.5 R
37 R
31 R
25 R
20
c
2.3
2
3
44.5
6
4
Spawn from Mucor
circinelloides
20
20
40
40
40
20
20
20
1
a
b
c
a
b
c
a
b
2.5
2.5
5
18
6
3
26
7
0.5
1
28
8
47
9
1.5
24
48
72
24
48
72
24
48
72
1
64
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
No reaction
3
57R
57R
Rhizopus oryzae
3.7
4.3
5
7
57R
22
38
52
9
57 R
52 R
46 R
59 R
55 R
53 R
55 R
38 R
34 R
80 R
72 R
65 R
4.2
4.1
3
23
30
24
62
72
16
42
51
4
4.0
1
4.0
Pseudomonas
fluorescens
3
4.0
4
4.4
1
10.4
10.2
9.6
3
4
EXPERIMENTAL
Esters of (R)- and (S)-(2,2-dimethyl-1,3-dioxolan-4-
yl)methanol; (R)-solketal and (S)-solketal esters (4,5 a-d)
NMR spectra were recorded at 300 MHz for H NMR
and 75.5 MHz for 13C NMR on a Varian Inova 300 MHz in
CDCl3 solution if not indicated else; ꢀ values are in parts per
million (ppm) relative to tetramethylsilane (TMS) as an
internal standard. Alcohol and ester concentrations were de-
termined by GC analysis on the Agilent Technologies model
6890N Network GC System gas-chromatograph equipped
with a flame ionisation detector (FID) and a chiral capillary
column MEGA-DEX DMP Beta, (MEGA, Legnano, Italy,
diameter 0.25 mm, length 25 m, thickness 0.25ꢀm).
General Procedure
The enantiomerically enriched (S)-solketal 2a or (R)-
solketal 2b (1.32 g, 10 mmol) was dissolved in anhydrous
methylene chloride (18 ml), DMAP (0.12 g, 1mmol), DCC
(2.27g, 11 mmol) and carboxylic acid 3a-d (10 mmol) was
added at room temperature while stirring. After 24 h, the
reaction mixture was filtered off by a thin pad of silica gel.
The deposit formed on silica surface was rinsed with anhy-

10 Letters in Organic Chemistry, 2014, Vol. 11, No. 1
Zniszczoꢀ and Walczak
Table 5. The Influence of Ratio Solketal : Acyl Donor 6b on Esterification of 1
Lipase
Ratio 1 : 6b
Time [h]
Yield of Ester [%]
ee
%
E
R
1
3
10
33
45
16
42
51
22
51
61
28
47
39
64
81
74
69
80
72
65
77
64
54
37
31
30
21
10.3
9.5
9.5
10.5
10.2
9.6
1:1
4
1
Pseudomonas fluorescens
1:2
1:4
3
4
1
9.6
8.9
8.2
2.5
2.5
2.2
2.2
3
4
0.5
1.0
0.5
1.0
1:2
1:6
Spawn from Mucor
circinelloides
Influence of solketal : vinyl butyrate ratio
on yield of (R)-solketal butyrate
100
80
60
01:02
01:01
01:04
40
20
0
0
20
40
60
80
Yield [%]
Fig. (1). Influence of solketal and vinyl butyrate ratio on yield of (R)-solketal butyrate.
26.8, 64.9, 66.4, 73.7, 109.5, 170.9. [ꢀ]25D = +2.0 (neat);
[ꢀ]25 D = +1.9 (neat) [26].
drous CH2Cl2 (10 ml). The combined filtrates were washed
with aqueous solution of sodium bicarbonate (3 x 15 ml)
and water (1ꢀ15 ml). The organic layer was dried over
anhydrous MgSO4 and after evaporation on rotary evapo-
rator at room temperature, the residual oil was purified
on silica gel packed column using ethyl acetate : n-hexane
as an eluent (3:7, v:v). Appropriate esters 4,5a-d were ob-
tained as colourless oils.
(R)-Solketal Propionate (4b)
1
3
Yield 79%; H NMR (CDCl3), ꢁ (ppm): 1.15 (t, J=7.5
Hz, 3H, CH3), 1.26 (s, 3H, CH3), 1.32 (s, 3H, CH3), 2.38 (q,
3
2
3
2H, J=7.5 Hz, CH2), 3.74 (dd, 1H, J=8.4 Hz, J=6.0 Hz,
H -5), 4.04-4.12 (m, 2H, H -5, H -6), 4.16-4.21 (dd, 1H,
a
b
b
3
2J=11.5 Hz, J=4.5 Hz, H -6), 4.29-4.37 (m, 1H, CH). 13C
a
(R)-Solketal Acetate (4a)
NMR (CDCl ), ꢁ (ppm): 9.0, 20.9, 25.5, 26.8, 64.9, 66.4,
3
73.7, 109.5, 170.9. [ꢀ]25 D = +4.4 (neat); [ꢀ]25 D = +4.7 (neat)
1
Yield 75%; H NMR (CDCl3), ꢁ (ppm): 1.38 (s, 3H,
[26].
CH3), 1.44 (s, 3H, CH3), 2.10 (s, 3H, CH3CO), 3.74 (dd,
2
3
(R)-Solketal Butyrate (4c)
1H, J=8.4Hz, J=6.0Hz, H -5), 4.03-4.11 (m, 2H, H -5,
a
b
2
3
1
H -6), 4.18 (dd,1H, J=11.4 Hz, J=4.5 Hz, H -6) 4.29-
Yield 83%; H NMR (CDCl3), ꢁ (ppm): 0.95 (t, 3H,
b
a
,
3J=7.5 Hz, CH3), 1.37 (s, 3H, CH3), 1.44 (s, 3H, CH3), 1.66
4.37 (m, 1H, CH). 13C NMR (CDCl ), ꢁ (ppm): 20.9, 25.5,
3

Lipases Aided Esterification of (2,2-Dimethyl-1,3-dioxolan-4-yl)methanol
Letters in Organic Chemistry, 2014, Vol. 11, No. 1 11
3
3
[2]
[3]
Dmitriev, G. S.; Zanaveskin, L. N. Synthesis of epichlorohydrin
from glycerol. Hydrochlorination of glycerol. Chem. Eng. Trans.,
2011, 24, 43-48.
Bell, B. M.; Briggs, J. R.; Campbell, R. M.; Chambers, S. M.;
Gaarenstroom, P. D.; Hippler, J. G.; Hook, B. D.; Kearns, K.; Ken-
ney; J. M.; Kruper, W. J.; Schreck, D. J.; Theriault, C. N.; Wolfe,
Ch. P. Glycerin as a renewable feedstock for epichlorohydrin pro-
duction. The GTE process. Clean-Soil, Air, Water, 2008, 36, 657-
661.
Zheng, Y.; Chen, X.; Shen, Y. Commodity chemicals derived from
glycerol, an important biorefinery feedstock. Chem. Rev., 2008,
108, 5253-5277.
Jurczak, J.; Pikul, S.; Bauer, T. (R)- and (S)-2,3-O-
isopropylideneglyceraldehyde in stereoselective organic synthesis.
Tetrahedron, 1986, 42, 447-488.
Xia, J.; Hui, Y. Z. The efficient synthesis of mixed diacyl phos-
pholipids with polyunsaturated fatty acid in sn-2 position of glyc-
erol. Tetrahedron: Asymmetry, 1997, 8, 3019-3021.
Lecollinet, G.; Auzely-Velty R.; Danel, M.; Benvegnu, T.;
Mackenzie, G.; Goodby, J. W.; Plusquellec, D. Synthetic ap-
proaches to novel archaeal tetraether glycolipid analogues. J. Org.
Chem., 1999, 64, 3139-3150.
Li Z.; Liu, G. Water-dispersible tetrablock copolymer synthesis,
aggregation, nanotube preparation, and impregnation. Langmuir,
2003, 19, 10480-10486.
Jing, G.; Falguieres, T.; Gruenberg, J.; Prestwich, G. D. Concise
synthesis of ether analogues of lysobisphosphatidic acid. Org. Lett.,
2005, 7, 3837-3840.
Gajewiak, J.; Tsukahara, R.; Fujiwara,Y.; Tigyi, G.; Prestwich, G.
D. Synthesis, pharmacology, and cell biology of sn-2-aminooxy
analogues of lysophosphatidic acid. Org. Lett., 2008, 10, 1111-
1114.
Nelson, W. L.; Burke, T. R. Absolute configuration of glycerol
derivatives. 5. Oxprenolol enantiomers. J. Org. Chem., 1978, 43,
3641-3645.
(sextet, 2H, J=7.5 Hz, CH2), 2.34 (t, 2H, J=7.5 Hz, CH2),
3.74 (dd, 1H, 2J=8.4 Hz, 3J=6.0 Hz, H -5), 4.06-4.08 (m, 2H,
a
H -5, H -6), 4.11-4.16 ( dd, 1H, 2J=11.4 Hz, 3J=4.5 Hz, H -
b
b
a
6), 4.28-4.36 (m, 1H, CH). 13C NMR (CDCl3), ꢀ (ppm):
13.8, 18.5, 25.5, 26.8, 36.1, 64.6, 66.5, 73.8, 109.9, 173.6.
[ꢀ]25D = +4.9 (neat); [ꢀ]25 D = +5.1 (neat) [26].
(R)-Solketal Valerate (4d)
[4]
[5]
[6]
[7]
1
Yield 89%; H NMR (CDCl3), ꢀ (ppm): 0.92 (t, 3H,
3J=7.5 Hz, CH3), 1.36 (quintet, 2H, 3J=7.5 Hz, CH2), 1.37
(s, 3H, CH3), 1.44 (s, 3H, CH3), 1.66 (kwintet, 2H, J=7.5
Hz, CH2), 2.34 (t, 2H, 3J=7.5 Hz, CH2), 3.74 (dd, 1H,
3
2J=8.4 Hz, J=6.3 Hz, H -5), 4.06-4.12 (m, 2H, H -5, H -
a
b
b
2
3
6), 4.17 (dd, 1H, J=11.5 Hz, J=4.6 Hz, H -6), 4.28-4.36
a
(m, 1H, CH). 13C NMR (CDCl3), ꢀ (ppm): 13.6, 22.3,
25.5, 26.8, 27.0, 31.0, 33.9, 70.3, 73.7, 96.2, 109.9,
173.7. [ꢀ]25D = +5.4 (neat); [ꢀ]25 = +5.7 (neat) [26].
D
[8]
Irreversible Esterification of Solketal (General Proce-
dure)
[9]
(R, S)-Solketal (0.95 mmol) was dissolved in anhydrous
diisopropyl ether (4 ml), and appropriate vinyl ester 6a-c
(1.90 mmol) was added followed by addition of enzyme
preparation in amounts 10-40 mg as indicated in (Tables 3
and 4). The resultant suspension was stirred at room tem-
perature. In time intervals samples of volume 80-100 ꢀl were
taken of, diluted with diisopropyl ether to the volume of 800
ꢀl and analysed on GC gas chromatograph system. The
analyses were carried out using the following temperature
program: oven temperature from 35 °C to 90 °C (5 °C/min),
next from 90 °C to 150 °C (12 °C/min), and then held at 150
°C for 5 min. Injector temperature was 200 °C and the detec-
tor 250 °C. Carrier gas was held with a flow rate of 1.2
mL/min. The retention times of the enantiomers of 1,2-O-
isopropylidene glycerol and its esters under these conditions
were: (R)- solketal: 13.80 min, (S)-solketal: 13.90 min, (S)-
solketal acetate: 14.50 min, (R)-solketal acetate: 14.60 min.,
(S)-solketal propionate: 15.80 min., (R)-solketal propionate
15.90 min., (S)-solketal butyrate: 17.50 min, (R)-solketal
butyrate: 17.60 min., (S)-solketal valerate: 20.20 min., (R)-
solketal valerate: 20.30 min.
[10]
[11]
[12]
Danilewicz, J. C.; Kemp, J. E. G. Absolute configuration by
asymmetric synthesis of (+)-1-( 4-acetamidophenoxy)-3-( isopro-
pylamino)-propan-2-o1 (Practolol). J. Med. Chem., 1973, 16, 168-
169.
[13]
Mequanint, K.; Patel, A.; Bezuidenhout, D. Synthesis, swelling
behavior, and biocompatibility of novel physically cross-linked po-
lyurethane-block-poly(glycerol methacrylate) hydrogels. Bio-
macromolecules, 2006, 7, 883-891.
[14]
[15]
[16]
[17]
Bigot,S.; Bricout, H.; Suisse, I.; Mortreux, A.; Castanet, Y. Synthe-
sis and surface properties of glycerol based C8 chain monoethers.
Ind. Eng. Chem. Res., 2011, 50, 9870-9875.
Hirth, G.; Walther, W. Synthèse des (R)- et (S)-O-isopropylidène-
1,2-glycérols. Détermination de la pureté optique. Helv. Chim.
Acta, 1985, 68, 1863-1871.
Thomas, B. N.; Lindemann, Ch. M.; Corcoran,R. C.; Cotant, C. L.;
Kirsch, J. E.; Persichini, P. J. Phosphonate lipid tubules II. J. Am.
Chem. Soc., 2002, 124, 1227-1233.
Jung, M. E.; Shaw, T. J. Total synthesis of (R)-glycerol acetonide
and the antiepileptic and hypotensive drug (-)-ꢁ-amino-ꢀ-
hydroxybutyric acid (GABOB): Use of vitamin C as a chiral star-
ting material. J. Am. Chem. Soc., 1980, 102, 6304-6311.
Lok, M. C.; Ward, J. P.; van Dorg, D. A. The synthesis of chiral
glycerides starting from D- and L-serine. Chem. Phis. Lipids, 1976,
16, 115-122.
CONFLICT OF INTEREST
[18]
[19]
The authors confirm that this article content has no
conflict of interest.
Kriefa, A.; Froidbise, A. Hemisynthesis of methyl pyrethroates
from ꢁ-alkoxy-alkylidene malonates and isopropylidenediphenyl-
sulfurane and isopropylidenetriphenylphosphorane. Tetrahedron,
2004, 60, 7637-7658.
ACKNOWLEDGEMENTS
The research was financially supported by the project
co-financed by the European Union from the European
Regional Development Fund in the framework of the Opera-
tional Program Innovative Economy Task: Biotransforma-
tion for pharmaceutical and cosmetic industry POIG.01.03.
01-00-158/09.
[20]
[21]
Smith, M. B.; March, J. Marche’s Advanced Organic Chemistry,
5th ed.; Wiley & Sons: New York 2001.
Ghanem, A.; Aboul-Enein, H. Y. Lipase-mediated chiral resolution
of racemates in organic solvents. Tetrahedron: Asymmetry., 2004,
15, 3331-3351.
[22]
[23]
[24]
Urdiales, E. G.; Alfonso, I.; Gotor, V. Enantioselective enzymatic
desymmetrizations in organic synthesis. Chem. Rev., 2005, 105,
313-354.
Chen, C-S.; Fujimoto, Y.; Girdaukas, G.; Sih, Ch. J. Quantitative
analyses of biochemical kinetic resolutions of enantiomers. J. Am.
Chem. Soc., 1982, 104, 7294-7299.
REFERENCES
[1]
Meher, L. C.; Sagar, D. V.; Naik, S. N. Technical aspects of bio-
diesel production by transesterification-a review. Renew. Sust. En-
ergy Rev., 2006, 10, 248-268.
Machado, A. C. O.; da Silva, A. A. T.; Borges, C. P.; Simas, A. B.
C.; Freire, D. M.G. Kinetic resolution of (R, S)-1,2-isopropylidene

12 Letters in Organic Chemistry, 2014, Vol. 11, No. 1
Zniszczoꢀ and Walczak
glycerol (solketal) ester derivatives by lipases. J. Mol. Cat. B:
Enzymatic, 2011, 69, 42-46.
Rodrigues, R. C.; Ortiz, C.; Berenguer-Murcia, A.; Torres, R.;
Fernandez-Lafuente, R. Modifying enzyme activity and selectivity
by immobilization. Chem. Soc. Rev., 2013, 42, 6290-6307.
[26]
Bear, E.; Fischer, H. O. L. Synthesis of a homologous series of
optically active normal aliphatic ꢀ-monoglycerides (L-series). J.
Am. Chem. Soc., 1945, 67, 2031-2037.
[25]