Lipase-mediated desymmetrization of glycerol with aromatic and aliphatic anhydrides

Article abstract of DOI:10.1016/j.tetasy.2004.09.033

Chirazyme L-2 (Candida antarctica) catalyzed esterification of glycerol with aromatic and aliphatic anhydrides in 1,4-dioxane is described. All the aromatic monoacylglycerols (MAGs) were produced as (R)-enantiomers, while aliphatic MAGs were obtained either as racemic mixtures or the (S)-enantiomers. The influence of substituted aromatic rings, chain length, and presence of a conjugated double bond in the acyl donor moiety on the enantiotopic selectivity as well as the efficiency of the enzyme was studied.

Full text of DOI:10.1016/j.tetasy.2004.09.033

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 15 (2004) 3551–3559
Lipase-mediated desymmetrization of glycerol with aromatic and
aliphatic anhydrides
Daniela I. Batovska,a,b Shuichirou Tsubota,a Yasuo Kato,a Yasuhisa Asanoa,* and
Makoto Ubukatab,*
aBiotechnology Research Center, Toyama Prefectural University, 5180 Kurokawa, Kosugi, Toyama 939-0398, Japan
bHokkaido University, Graduate School of Agriculture, Kita-9, Nishi-9, Kita-ku, Sapporo 060-8589, Japan
Received 9 August 2004; accepted 13 September 2004
Abstract—Chirazyme L-2 (Candida antarctica) catalyzed esterification of glycerol with aromatic and aliphatic anhydrides in 1,4-
dioxane is described. All the aromatic monoacylglycerols (MAGs) were produced as (R)-enantiomers, while aliphatic MAGs were
obtained either as racemic mixtures or the (S)-enantiomers. The influence of substituted aromatic rings, chain length, and presence
of a conjugated double bond in the acyl donor moiety on the enantiotopic selectivity as well as the efficiency of the enzyme was
studied.
ꢀ 2004 Elsevier Ltd. All rights reserved.
1. Introduction
the efficiency and enantioselectivity of lipases can be af-
fected by alteringthe size of the acyl group or varying
the substituents in aromatic ring, present in the mole-
cule.5–8
Monoacylglycerols (MAGs) are known as emulsifiers
with antimicrobial properties, which are widely em-
ployed in the food, pharmaceutical, and cosmetic indus-
tries. In their enantiomerically pure forms, these
compounds are important synthetic intermediates and
buildingblocks with their synthesis becomingthe focus
of much attention over the last decade.
Recently, we have used Chirazyme (Candida antarctica)
for an efficient esterification of glycerol with benzoic
anhydride in 1,4-dioxane.9 (R)-a-MBG was obtained
with high enantiomeric excesses on a large scale.10 We
also found benzoic anhydride was the better acyl donor
than the vinyl and methyl esters of benzoic acid.11
For the syntheses of chiral MAGs enzymatic ap-
proaches, such as the kinetic resolution of racemic gly-
cerol derivatives or desymmetrization of the prochiral
glycerol, 1,3-propanediols and their derivatives have
been developed.1–3 These methods are based upon the
ability of the lipases to distinguish between enantiomeric
and enantiotopic groups and usually employ an organic
solvent as media. Most often, the acyl donor in these
reactions is either a short-, medium-, or long-chain fatty
acid or vinyl ester. The influence of the acyl donor struc-
ture on the enantioselectivity of lipases in MAGs synthe-
ses has hardly been reported.1,4 On the other hand,
many examples in the literature show that in general
Acid anhydrides are readily available chemicals and can
be easily used as highly reactive and non-water-produc-
12–14
ingacyl donors for enzyme esterifications.
As an
extension of our work we used substituted aromatic
anhydrides as well as short- and medium-chain fatty
acid anhydrides to accomplish the lipase-catalyzed este-
rification of glycerol and studied the effect of the acyl
donor on the enantioselectivity of Chirazyme. Some cor-
relations between the acyl donor structure and lipase
efficiency were also observed.
2. Results and discussion
The lipase-catalyzed asymmetrization of the prochiral
molecule of glycerol was accomplished via acylation to
its primary hydroxyl groups, as shown in Tables 1 and 2.
*
Correspondingauthors. Tel.: +81 766 56 7500x530; fax: +81 766 56
2498 (Y.A.); tel./fax: +81 11 706 3638 (M.U.); e-mail addresses:
asano@pu-toyama.ac.jp; m-ub@for.agr.hokudai.ac.jp
0957-4166/$ - see front matter ꢀ 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2004.09.033

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D. I. Batovska et al. / Tetrahedron: Asymmetry 15 (2004) 3551–3559
Table 1. Lipase-catalyzed esterification of glycerol with aromatic anhydrides
O
O
O
Chirazyme L-2
1,4-Dioxane
HO
OH
+
R
O
OH
R
O
R
OH
OH
Compound
R
Yield
(%)
Reaction
time (h)
Enantiomeric
excess (%)
Absolute
configuration
1
2
3
4
5
6
16
65
1
24
36
39
72
48
48
14
21
100
63
29
14
R
R
R
R
R
R
23
1
H3C
H3CO
Cl
15
7
8
17
21
48
15
66
74
R
R
O2N
O2N
O2N
Aromatic and aliphatic acid anhydrides were used as
acyl donors. The aromatic acid anhydrides had a substi-
tuted ringat the p-position and either one or two meth-
ylene groups or a double bond between the aromatic
and acyl parts. The aliphatic anhydrides bore straight
or branched chains ranging in length from 3 to 14 car-
bons. Most of the acyl donors are commercially avail-
able. We synthesized myristic, cyclohexanecarboxylic,
sorbic, and all the aromatic acid anhydrides from the
correspondingacids or chlorides. To prepare authentic
samples of MAGs, we first obtained their acetonides
from the reaction of racemic or chiral 2,2-dimethyl-
1,3-dioxolane-4-methanol and acyl chlorides or anhy-
drides. The resultingderivatives were further depro-
tected with Amberlyst 15 (wet).
2.1. Effect of the structure of the acyl donor on enantio-
selectivity of Chirazyme
2.1.1. Aromatic acid anhydrides
2.1.1.1. Influence of the substituted aromatic ring
present in the acid anhydrides. Chirazyme showed dis-
tinct pro-R selectivity in the esterification of glycerol
with aromatic anhydrides (Table 1). The lipase preferred
the bulkiest, 3,5-dinitrobenzoic anhydride and trans-
formed it into 8 with an e.e. of 74%. Duringthe reaction,
this value dropped to 30%, which may be due to an acyl
migration. The rest of the substituted aromatic anhy-
drides resulted in MAGs with lesser e.e. With respect
to their p-substituents, they are put in order of decreas-
ingvalues of e.e., as follows: NO 2 > CH3 > CH3O > Cl
(Fig. 1). Comparison of the Hammett constants and
van der Waals radii of the substituents did not reveal
a strongcorrelation between their electronic effects
and size and the enantioselectivity of the enzyme.16
Under the followingconditions: 100mM lygcerol,
100mM acid anhydride, 1,4-dioxane (5mL), 15ꢁC,
Chirazyme (25mg) was active toward all the anhydrides.
In a controlled experiment under the same conditions
without an enzyme, no acylation was observed. The pro-
gress of the enzyme esterification concerning the yield
and e.e. of MAGs was monitored with GC or HPLC.
The e.e.ꢀs of the MAGs were measured on chiral col-
umns after derivatization into acetonides.11,15 A model
reaction of ketalization of two racemic MAGs, mono-
pivaloyl glycerol, and monoheptanoylglycerol showed
that using( )-10-camphorsulfonic acid and 20%
acetone dimethylacetal did not cause an asymmetric
transformation.
2.1.1.2. Influence of an aliphatic chain introduced
between the benzene ring and acyl function. When the
acyl part of aromatic anhydrides was separated from
the benzene ringwith a methylene group, MAG 1 with
an e.e. of 14% was obtained. Introducinga second meth-
ylene group at the same place gave an almost two-fold
rise in the enantioselectivity with an e.e. of 21% for
the resultingcompound 2. The presence of a double
bond conjugated with both the benzene ring and acyl
function, drastically increased the enantioselectivity

D. I. Batovska et al. / Tetrahedron: Asymmetry 15 (2004) 3551–3559
Table 2. Lipase-catalyzed esterification of glycerol with aliphatic acid anhydrides
3553
O
O
O
Chirazyme L-2
1,4-Dioxane
HO
OH
+
R
O
OH
R
O
R
OH
OH
Compound
R
Yield (%) Reaction time (min) Enantiomeric excess (%) Absolute configuration
9
80
43
180
120
Racemic mixture
Racemic mixture
H3C
10
11
12
13
14
H3C
H3C
99
69
24
48
540
120
60
Racemic mixture
CH3
Racemic mixture
H3C
H3C
13
11
S
S
H3C
90
CH3
CH3
CH3
15
H3C
H3C
47
120
29
S
S
16
17
18
19
20
21
22
15
71
28
32
35
15
13
30
360
90
Racemic mixture
83
H3C
H3C
H3C
H3C
H3C
H3C
Racemic mixture
Racemic mixture
Racemic mixture
Racemic mixture
Racemic mixture
240
180
240
240
23
60
600
73
S
100
90
80
70
60
50
40
30
20
10
2.1.2. Aliphatic acid anhydrides
2.1.2.1. Influence of the chain length. The behavior
of the lipase toward the esterification of glycerol with ali-
phatic anhydrides was quite surprising. While the short-
chain propionic, butyric, and isobutyric anhydrides
yielded racemic mixtures of MAGs, the anhydrides with
five carbons in each of their chains, n-pentanoic, i-penta-
noic, and pivalic anhydrides gave MAGs with a preferen-
tial (S)-configuration (Table 1). Amongst them the
highest e.e. achieved was with the bulky pivalic anhydride
as a donor, although it still remained low (Fig. 2). In the
enzyme literature, we found a few examples showingan
increase in the e.e. of lipase-catalyzed esterifications when
0
0
5,8
increasingthe chain length in the acyl donor moiety.
10
20
30
40
50
60
70
We therefore decided to use longer aliphatic anhydrides
bearing6–14 carbons in their chains. However, instead
of the expected rise in e.e. all these reactions produced
racemic mixtures of MAGs. It is noteworthy to notice
that the aliphatic anhydride of cyclohexanecarboxylic
acid having six carbons in each ring, transformed glycerol
to the (S)-MAG with high e.e. (Fig. 2).
Reaction time, h
Figure 1. E.e. of MAGs, obtained from the lipase-catalyzed esterifi-
cation of glycerol with aromatic anhydrides. Compounds: ( ): 1; ( ):
Ç
2; ( ): 3; ( ): 4; (d): 5; ( ): 6; (-): 7; (j): 8.
+
Ã
of the lipase. Thus, for monocinnamoyl glycerol 3, an
e.e. of 100% was achieved (Fig. 1).
2.1.2.2. Influence of conjugated double bonds present
in the aliphatic chain. We supposed that the opposite

3554
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D. I. Batovska et al. / Tetrahedron: Asymmetry 15 (2004) 3551–3559
90
80
70
60
50
80
60
40
20
0
0
100
200
300
400
500
600
Reaction time, min
40
30
20
10
0
Figure 2. E.e. of MAGs, obtained from the lipase-catalyzed esterifi-
cation of glycerol with aliphatic anhydrides. Compounds: (j): 13; ( ):
Ç
14; ( ): 15; ( ): 17; ( ): 23.
Ã
configurations observed for the aromatic and aliphatic
MAGs were due to the OHÁ Á Áp or CHÁ Á Áp interactions
between the p electrons of the aromatic anhydrides
and the active site of lipase.16 We were interested in
whether insertingdouble bonds in the chains of aliphatic
anhydrides would reverse the enantiotopic selectivity of
Chirazyme and lead to aliphatic MAGs with an (R)-con-
figuration. To verify this possibility, we selected crotonic
and sorbic anhydrides, which are aliphatic compounds,
but contain one or two double bonds in their chains,
respectively. In the presence of crotonic anhydride as
acyl donor, the lipase-catalyzed esterification of glycerol
did not divert from the usual progress and monocroto-
nyl glycerol 11 was obtained as a racemic mixture.
However, with sorbic anhydride as the donor, the
enantioselectivity of Chirazyme was definitely pro-S
and the highest e.e. of 83% determined for monosorboyl
glycerol 17 (Table 1, Fig. 2).
0
1000
2000
3000
4000
Reaction time, min
Figure 3. Time course of the lipase-catalyzed reaction of glycerol with
some aromatic and aliphatic anhydrides. Compounds: ( ): 2; ( ): 3;
(-): 8; (j): 9; ( ): 17; ( ): 23.
+
ꢀ
Ã
or a conjugated double bond, p-metoxybenzoic and cin-
namic anhydrides gave the lowest yields of MAGs.
3. Conclusions
Chirazyme showed distinct pro-R selectivity toward the
esterification of glycerol with aromatic anhydrides and
pro-S or no selectivity when the acyl donors were ali-
phatic anhydrides. The introduction of a conjugated
double bond in the acid donor moiety drastically in-
creased the enantiotopic selectivity of the enzyme. Steric
and electronic effects of the acid anhydride moieties were
found to affect the efficiency of Chirazyme.
2.2. Effect of the structure of the acyl donor on chirazyme
efficiency
The activity of Chirazyme was not very high at 15ꢁC
and in most cases, the yields of MAGs obtained were
low to moderate. However, we found that the chemical
racemization was suppressed at this temperature.11
Additionally to avoid any racemization, we did not
use a base for removingthe generated acid, which also
contributed to the lower yields.
4. Experimental
4.1. Analytical methods
1H and 13C NMR spectra were recorded on JEOL LA-
400 and JEOL EX-270 spectrometers for solutions in
CDCl3 or DMSO-d6 with TMS as the internal standard
and J values are given in hertz (Hz). HPLC analyses
were carried out on Waters LC Module 1 equipped with
UV/VIS spectrophotometer and Hitachi, equipped with
UV detector L-400, intelligent pump L-6200 using ODS-
80Ts column (Tosoh), Nova-Pakꢂ C18 column (Waters)
and chiral columns Chiralcel OJ (Daicel). Gas chroma-
tograms were recorded on a Shimadzu GC-14B and
Shimadzu GC-2010 usingpacked PEG 20 m column
(GLScience) and chiral columns a-DEX 120 (Supelco)
0.25 · 30m and WCOT fused silia (Varian) 0.25,
0.25 · 25m. Meltingpoints were determined on Mettler
FP5 and are uncorrected. All chemical reactions were
qualitatively monitored by thin layer chromatography
using Merck silica gel plates Kieselgel 60 F254 (Kanto
Chem.). The spots were visualized under UV, iodine or
by sprayingwith molibdate–sulfate solution containing
85% H3PO4.
The enzyme reactions of glycerol with aliphatic anhy-
drides completed within 4h. It was observed that when
increasingthe carbon number, the yields of the MAGs
decreased. The steric hindered MAGs—monoisobuty-
ryl-, monoisopentanoyl-, and monopivaloyl glycerols
were obtained in higher yields than their isomers with
straight chains. Inserting a double bond, conjugated
with the acyl function of aliphatic anhydrides made
them react slower, but with high yield. The yield of
MAG however, decreased when an additional double
bond, conjugated to the first one, was introduced.
In comparison with aliphatic anhydrides, the aromatic
acyl donors esterified glycerol much slower (Tables 1
and 2, Fig. 3). Electronic effects were observed to influ-
ence the reactivity of the carboxylic group connected
with the substituted aromatic ring. Thus, for having in
their molecule a strongelectron donatingsubstituent

D. I. Batovska et al. / Tetrahedron: Asymmetry 15 (2004) 3551–3559
3555
4.2. Materials
5. For 23, HPLC (Chiralcel OJ-RH), eluent 40%
CH3CN: 10mM H3PO4, flow rate 0.4mL/min.
An immobilized lipase from Candida antarctica (Chira-
zyme L-2 lyo. c.f.) was provided by Roche Diagnostics.
Monocaprin, monostearin, and monopalmitin were
purchased from Tokyo Kasei. Cyclohexanecarboxylic,
myristic, hydrocinnamic, p-methoxybenzoic, and p-chlo-
4.4. Chemical synthesis of MAGs
4.4.1. Synthesis of (RS)-1,2-isopropylidene derivatives
4.4.1.1. General procedure for synthesis of (RS)-1,2-
isopropylidene derivatives from the corresponding acyl-
chlorides or anhydrides. Acyl chloride (10mmol) or
acid anhydride (11mmol) was added to a solution of
2,2-dimethyl-1,3-dioxolane-4-methanol (10mmol) in
pyridine (10mL) and stirred for 24h at rt. After evapo-
ration of the solvent, the residue was partitioned
between water (10mL) and EtOAc (30mL). The organic
layer was successively washed with 5% CuSO4Æ5H2O
(3 · 50mL), saturated NaHCO3 aq (3 · 50mL) and sat-
urated NaCl aq (50mL), dried over Na2SO4 and then
evaporated. All the products were further purified by
column chromatography over silica gel with eluent n-
hexane:EtOAc. The yields obtained were over 90%.
robenzoic anhydrides were synthesized from the corre-
17
spondingacids or acid chlorides in pyridine.
Both
sorbic and cinnamic acid anhydrides were obtained by
reaction of carboxylic acids with triphosgene.18 Phenyl-
acetic anhydride was synthesized by reaction between
phenylacetic acid and ethyl ethynyl ether.19 p-Methyl-
benzoic, p-nitrobenzoic and 3,5-dinitrobenzoic anhy-
drides were obtained from the correspondingacyl
chlorides and NaHCO3 usingphase-transfer catalyst in
CH3CN.20 Amberlyst 15J (wet) was from Organo. All
other chemicals were from commercial sources and used
without further purification.
4.3. General procedure for enzymatic acylation of glycerol
(2,2-Dimethyl-1,3-dioxolane-4-yl)methyl phenylacetate,
colorless oil; H NMR (CDCl3): d 7.36–7.27 (m, 5H),
1
To a solution of glycerol (100mM) and acid anhydride
(100mM) in 1,4-dioxane (5mL) was added CHIRA-
ZYME L-2 lyo. c.f. (25mg). The reaction mixture was
magnetically stirred at 15ꢁC. The enzymatic esterifica-
tion of glycerol with aliphatic and aromatic acid
anhydrides was monitored with GC and HPLC,
respectively, after periodically withdrawingof aliquots
from the reaction mixtures. The enantiomeric purity of
the obtained MAGs was determined after their derivati-
zation into acetonides and GC or HPLC with chiral col-
umns used. The authentic samples of MAGs were
synthesized by chemical means as stated below in Sec-
tion 4.4 and characterized on the basis of their spectral
data. Samples of chiral MAGs were prepared from com-
mercial (R)- and (S)-2,2-dimethyl-1,3-dioxolane-4-meth-
anols prior to use.
4.34–4.28 (m, 1H), 4.18 (dd, 1H, J = 4.6, 11.5), 4.13
(dd, 1H, J = 5.6, 11.5), 4.03 (dd, 1H, J = 6.4, 8.3), 3.70
(dd, 1H, J = 6.1, 8.3), 3.67 (s, 2H), 1.41 (s, 3H), 1.37
(s, 3H); 13C NMR (CDCl3): d 173.0, 135.2, 129.6,
129.3, 128.6, 128.4, 127.3, 73.5, 66.2, 64.3, 41.1, 30.1,
28.3, 25.4; Rt 28.61 (S), 28.83 (R).
(2,2-Dimethyl-1,3-dioxolane-4-yl)methyl hydrocinnamate,
1
colorless oil; H NMR (CDCl3): d 7.31–7.27 (m, 2H),
7.22–7.19 (m, 3H), 4.27 (m, 1H), 4.15 (dd, 1H, J = 4.6,
11.5), 4.09 (dd, 1H, J = 5.8, 11.5), 4.03 (dd, 1H,
J = 6.4, 8.4), 3.68 (dd, 1H, J = 6.2, 8.4), 2.96 (t, 2H,
J = 7.6), 2.68 (t, 2H, J = 7.6), 1.42 (s, 3H), 1.36 (s,
3H); 13C NMR (CDCl3): d 172.6, 140.3, 128.5, 128.3,
127.9, 127.7, 126.3, 109.8, 73.5, 66.7, 66.3, 35.6, 30.8,
26.7, 24.4; Rt 27.3 (S), 29.2 (R).
The followingconditions for determination of the e.e. of
the monoacylglycerols after their derivatization into
acetonides were used.
Dimethyl-1,3-dioxolane-4-yl)methyl cinnamate, white
crystals, mp 44.2ꢁC; H NMR (CDCl3): d 7.71 (d, 1H,
1
J = 15.9), 7.51–7.37 (m, 5H), 6.47 (d, 2H, J = 15.9),
4.44–4.36 (m, 1H), 4.31 (dd, 1H, J = 4.6, 11.3), 4.22
(dd, 1H, J = 5.9, 11.6), 4.12 (dd, 1H, J = 6.5, 8.4), 3.80
(dd, 1H, J = 5.9, 8.1), 1.46 (s, 3H), 1.39 (s, 3H); 13C
NMR (CDCl3): d 166.5, 145.3, 134.2, 130.3, 128.8,
128.0, 117.4, 109.8, 74.9, 73.8, 66.4, 27.3, 26.8; Rt
11.08 (R), 12.50 (S).
1. For the aromatic MAGs: 1, GC (a-DEX 120) with
temperature gradient 100–220ꢁC; 2, 4, 5, 6, and 7:
HPLC (Chiralcel OJ), eluent n-hexane:i-propanol
95: 5 (v/v) at 254nm with the flow rates as follows,
compounds 4 and 6, 0.3mL/min; 2, 0.4mL/min; 5,
0.5mL/min; 7, 0.75mL/min; 3, eluent n-hexane:i-pro-
panol 83:17 (v/v), 0.5mL/min and 8, eluent n-hex-
ane:i-propanol 70:30 (v/v), 0.9mL/min.
2. For the short-chain aliphatic MAGs: GC (a-DEX
120) under isocratic temperatures as follows: 9, 12,
and 15, 90ꢁC; 10, 13 and 14, 100ꢁC.
3. For the medium-chain aliphatic MAGs with GC
(WCOT fused silia): 16, with temperature gradient
100–130ꢁC, 5ꢁ/min; 18, 140ꢁC; 19, 150ꢁC and 20,
160ꢁC; 21, 170ꢁC; 22, with temperature gradient
150–180ꢁC, 5ꢁ/min.
4. For 11, HPLC (Chiralcel OJ), eluent n-hexane:i-pro-
panol 70:30 (v/v), 0.75mL/min and 17, eluent n-hex-
ane:i-propanol 95:5 (v/v), 0.9mL/min.
(2,2-Dimethyl-1,3-dioxolane-4-yl)methyl p-methylbenz-
1
oate, white crystals, mp 46.9ꢁC; H NMR (CDCl3): d
7.95 (d, 2H, J = 8.1), 7.24 (d, 2H, J = 8.1), 4.45 (m,
1H), 4.38 (dd, 1H, J = 4.9, 11.1), 4.35 (dd, 1H, J = 5.6,
10.9), 4.15 (dd, 1H, J = 6.5, 8.5), 3.88 (dd, 1H, J = 6.0,
8.4), 2.41 (s, 3H), 1.46 (s, 3H), 1.39 (s, 3H); 13C NMR
(CDCl3): d 166.4, 143.8, 129.7, 129.4, 129.1, 128.9,
127.0, 109.8, 73.7, 69.4, 64.8, 26.7, 25.4, 21.6; Rt 22.3
(S), 25.2 (R).
(2,2-Dimethyl-1,3-dioxolane-4-yl)methyl p-methoxyben-
1
zoate, white crystals, mp 39.8ꢁC; H NMR (CDCl3): d
8.02 (d, 2H, J = 9.0), 6.92 (d, 2H, J = 9.0), 4.45 (m,

3556
D. I. Batovska et al. / Tetrahedron: Asymmetry 15 (2004) 3551–3559
1H), 4.37 (dd, 1H, J = 4.8, 11.6), 4.34 (dd, 1H, J = 5.5,
11.6), 4.14 (dd, 1H, J = 6.4, 8.5), 3.87 (dd, 1H, J = 5.9,
8.5), 3.86 (s, 3H), 1.46 (s, 3H), 1.39 (s, 3H); 13C NMR
(CDCl3): d 166.1, 163.5, 131.7, 129.6, 122.2, 113.6,
109.8, 73.8, 68.5, 66.4, 64.7, 55.4, 26.7, 25.4; Rt 25.9
(S), 31.8 (R).
(2,2-Dimethyl-1,3-dioxolane-4-yl)methyl n-pentanoate,
colorless oil; H NMR (CDCl3): d 4.35–4.29 (m, 1H),
1
4.16 (dd, 1H, J = 4.8, 11.6), 4.11–4.06 (m, 2H), 3.74
(dd, 1H, J = 6.2, 8.4), 2.35 (t, 2H, J = 7.3), 1.69–1.58
(m, 2H), 1.44 (s, 3H), 1.39–1.31 (m, 2H), 1.37 (s, 3H),
0.92 (t, 3H, J = 7.3); 13C NMR (CDCl3): d 173.6,
110.8, 73.6, 66.3, 64.5, 33.8, 26.9, 26.7, 25.4, 22.2, 13.7;
Rt 30.40 (S), 30.82 (R).
(2,2-Dimethyl-1,3-dioxolane-4-yl)methyl p-chlorobenzo-
1
ate, white crystals, mp 49.8ꢁC; H NMR (CDCl3): d
7.99 (d, 2H, J = 6.6), 7.42 (d, 2H, J = 8.4), 4.46 (t, 1H,
J = 5.7), 4.40 (dd, 1H, J = 4.5, 11.4), 4.35 (dd, 1H, J =
5.4, 11.5), 4.15 (dd, 1H, J = 6.5, 8.4), 3.87 (dd, 1H,
J = 5.9, 8.5), 1.46 (s, 3H), 1.39 (s, 3H); 13C NMR
(CDCl3): d 165.5, 139.6, 131.1, 128.8, 128.2, 109.9,
73.6, 66.3, 65.3, 26.7, 25.3; Rt 22.4 (S), 25.8 (R).
(2,2-Dimethyl-1,3-dioxolane-4-yl)methyl isopentanoate,
col- orless oil; H NMR (CDCl3): d 4.39–4.29 (m, 1H),
1
4.17 (dd, 1H, J = 4.9, 11.5), 4.12–4.06 (m, 2H), 3.75
(dd, 1H, J = 6.1, 8.3), 2.24 (d, 2H, J = 6.8), 2.14–2.08
(m, 1H), 1.44 (s, 3H), 1.37 (s, 3H), 0.96 (d, 6H,
J = 6.6); 13C NMR (CDCl3): d 172.9, 110.8, 73.6, 66.3,
64.4, 43.1, 26.7, 26.7, 25.6, 25.4, 22.3; Rt 34.01 (R),
34.49 (S).
(2,2-Dimethyl-1,3-dioxolane-4-yl)methyl p-nitrobenzo-
1
ate, white crystals, mp 57.4ꢁC; H NMR (CDCl3): d
8.30 (d, 2H, J = 8.5), 8.24 (d, 2H, J = 8.8), 4.52–4.45
(m, 2H), 4.40 (dd, 1H, J = 6.7, 12.6), 4.17 (dd, 1H,
J = 6.5, 10.3), 3.88 (dd, 1H, J = 5.5, 8.7), 1.46 (s, 3H),
1.39 (s, 3H); 13C NMR (CDCl3): d 164.5, 150.7, 135.1,
130.8, 123.6, 110.1, 73.4, 66.2, 66.0, 26.7, 25.2; Rt 24.2
(S), 27.8 (R).
(2,2-Dimethyl-1,3-dioxolane-4-yl)methyl pivalate, color-
less oil; H NMR (CDCl3): d 4.30 (t, 1H, J = 5.7), 4.13
(dd, 1H, J = 5.0, 11.5), 4.11 (dd, 1H, J = 5.0, 6.5), 4.07
(dd, 1H, J = 6.4, 8.3), 3.73 (dd, 1H, J = 6.1, 8.3), 1.44
(s, 3H), 1.33 (s, 3H), 1.22 (s, 9H); 13C NMR (CDCl3):
d 178.2, 109.6, 73.6, 66.3, 64.1, 38.8, 27.1, 26.6, 25.4;
Rt 27.67 (S), 28.31 (R).
1
(2,2-Dimethyl-1,3-dioxolane-4-yl)methyl 3,5-dinitroben-
1
zoate, white crystals, mp 74.8ꢁC; H NMR (CDCl3): d
(2,2-Dimethyl-1,3-dioxolane-4-yl)methyl caproate, col-
orless oil; 1H NMR (CDCl3): d 4.35–4.29 (m, 1H),
4.17 (dd, 1H, J = 4.9, 11.7), 4.11 (d, 1H, J = 5.4), 4.07
(dd, 1H, J = 1.9, 5.8), 3.74 (dd, 1H, J = 6.3, 8.5), 2.35
(t, 2H, J = 7.6), 1.67–1.60 (m, 2H), 1.44 (s, 3H), 1.37
(s, 3H), 1.35–1.28 (m, 4H), 0.90 (t, 3H, J = 7.1); 13C
NMR (CDCl3): d 173.6, 109.8, 73.6, 66.3, 64.5, 34.0,
31.2, 26.6, 25.4, 24.5, 22.3, 13.9; Rt 25.15 (R), 25.50 (S).
9.24–9.18 (m, 3H), 4.50–4.46 (m, 3H), 4.22–4.16 (m,
1H), 3.90–3.85 (m, 1H), 1.48 (s, 3H), 1.40 (s, 3H); 13C
NMR (CDCl3): d 166.2, 148.6, 133.4, 129.4, 122.5,
110.2, 73.2, 67.0, 66.1, 26.8, 25.3; Rt 23.08 (S), 27.06 (R).
(2,2-Dimethyl-1,3-dioxolane-4-yl)methyl n-propanoate,
1
colorless oil; H NMR (CDCl3): d 4.34–4.30 (m, 1H),
4.18 (dd, 1H, J = 4.5, 15.5), 4.12–4.07 (m, 2H), 3.75
(dd, 1H, J = 6.2, 8.4), 2.38 (q, 2H, J = 7.6), 1.44 (s,
3H), 1.37 (s, 3H), 1.15 (t, 3H, J = 7.6); 13C NMR
(CDCl3): d 174.2, 109.8, 73.6, 66.2, 64.6, 27.3, 26.6,
25.3, 9.0; Rt 24.50 (S), 25.00 (R).
(2,2-Dimethyl-1,3-dioxolane-4-yl)methyl sorbate, color-
1
less oil; H NMR (CDCl3): d 7.33–7.29 (m, 1H), 6.20–
6.14 (m, 2H), 5.81 (d, 1H, J = 15.3), 4.40–4.32 (m,
1H), 4.24 (dd, 1H, J = 4.6, 11.5), 4.15 (dd, 1H, J = 5.1,
11.6), 4.08 (d, 1H, J = 6.6), 3.77 (dd, 1H, J = 6.1, 8.2),
1.86 (d, 3H, J = 4.9), 1.44 (s, 3H), 1.38 (s, 3H); 13C
NMR (CDCl3): d 166.9, 145.7, 139.8, 129.6, 118.1,
109.8, 73.7, 66.4, 64.6, 26.8, 25.5, 18.8; Rt 5.78 (S),
6.12 (R).
(2,2-Dimethyl-1,3-dioxolane-4-yl)methyl n-butanoate, col-
1
orless oil; H NMR (CDCl3): d 4.39–4.29 (m, 1H), 4.17
(dd, 1H, J = 4.9, 11.5), 4.12–4.06 (m, 2H), 3.75 (dd, 1H,
J = 6.1, 8.3), 2.34 (t, 2H, J = 6.8), 1.67 (6th, 2H, J = 7.6),
1.44 (s, 3H), 1.37 (s, 3H), 0.95 (t, 3H, J = 7.3); 13C NMR
(CDCl3): d 173.4, 109.8, 73.6, 66.2, 64.4, 35.9, 26.6, 25.3,
18.3, 13.5; Rt 27.30 (S), 27.70 (R).
(2,2-Dimethyl-1,3-dioxolane-4-yl)methyl heptanoate, col-
orless oil; 1H NMR (CDCl3): d 4.33–4.31 (m, 1H), 4.18–
4.15 (m, 1H), 4.11–4.06 (m, 2H), 3.76–3.72 (m, 1H), 2.34
(t, 2H, J = 5.8), 1.63–1.60 (m, 2H), 1.43 (s, 3H), 1.37 (s,
3H), 1.29 (s, 6H), 0.90–0.84 (m, 3H); 13C NMR
(CDCl3): d 173.5, 109.7, 73.6, 66.2, 64.4, 34.0, 31.3,
28.7, 26.6, 25.3, 24.8, 22.4, 13.9; Rt 19.69 (R), 19.96 (S).
(2,2-Dimethyl-1,3-dioxolane-4-yl)methyl crotonate, col-
orless oil; 1H NMR (CDCl3): d 7.08–6.95 (m, 1H),
5.88 (dq, 1H, J = 15.4, 1.6), 4.39–4.29 (m, 1H), 4.22
(dd, 1H, J = 4.6, 11.6), 4.14 (dd, 1H, J = 5.7, 11.1),
4.09 (dd, 1H, J = 6.2, 8.4), 3.76 (dd, 1H, J = 5.9, 8.4),
1.89 (dd, 1H, J = 1.9, 6.8), 1.44 (s, 3H), 1.37 (s, 3H);
13C NMR (CDCl3): d 166.0, 145.3, 122.1, 109.8, 73.7,
66.4, 64.5, 26.8, 25.5, 18.1; Rt 5.14 (S), 5.56 (R).
(2,2-Dimethyl-1,3-dioxolane-4-yl)methyl caprylate, white
crystals, mp 27.4ꢁC; 1H NMR (CDCl3): d 4.35–4.28 (m,
1H), 4.17 (dd, 1H, J = 4.6, 11.5), 4.10 (d, 1H, J = 5.8),
4.07 (dd, 1H, J = 2.2, 5.8), 3.74 (dd, 1H, J = 6.1, 8.6),
2.34 (t, 2H, J = 7.3), 1.70–1.60 (m, 2H), 1.44 (s, 3H),
1.37 (s, 3H), 1.29 (s, 8H), 0.88 (t, 3H, J = 6.6); 13C
NMR (CDCl3): d 173.7, 109.8, 73.6, 66.3, 64.5, 34.1,
31.6, 29.0, 28.9, 26.7, 25.4, 24.9, 22.6, 14.0; Rt 20.12
(R), 20.33 (S).
(2,2-Dimethyl-1,3-dioxolane-4-yl)methyl isobutanoate,
1
colorless oil; H NMR (CDCl3): d 4.35–4.29 (m, 1H),
4.18–4.06 (m, 3H), 3.76 (dd, 1H, J = 6.3, 8.4), 2.65–
2.55 (m, 1H), 1.44 (s, 3H), 1.37 (s, 3H), 1.18 (d, 6H,
J = 6.8); 13C NMR (CDCl3): d 176.9, 109.7, 73.6, 66.3,
64.3, 33.9, 26.6, 25.3, 18.9, 18.7; Rt 27.90 (S), 28.50 (R).

D. I. Batovska et al. / Tetrahedron: Asymmetry 15 (2004) 3551–3559
3557
(2,2-Dimethyl-1,3-dioxolane-4-yl)methyl laurate, white
crystals, mp 32.5ꢁC; 1H NMR (CDCl3): d 4.35–4.28
(m, 1H), 4.17 (dd, 1H, J = 4.6, 11.5), 4.11 (d, 1H,
J = 5.6), 4.07 (dd, 1H, J = 2.2, 5.6), 3.74 (dd, 1H,
J = 6.1, 8.6), 2.34 (t, 2H, J = 7.6), 1.67–1.59 (m, 2H),
1.44 (s, 3H), 1.37 (s, 3H), 1.26 (s, 16H), 0.88 (t, 3H,
J = 6.6); 13C NMR (CDCl3): d 173.7, 109.8, 73.6, 66.3,
64.5, 34.1, 31.9, 29.6, 29.4, 29.3, 29.2, 29.1, 26.7, 25.4,
24.9, 22.7, 14.1; Rt 42.94 (R), 43.39 (S).
77 (11.6), 65 (4.4), 43 (4.1); HREIMS m/z 224.1034
[M]+ (calcd for C12H16O4 224.2584).
1-O-(Cinnamoyl)glycerol 3, colorless oil; 1H NMR
(CDCl3): d 7.71 (d, 1H, J = 16.2), 7.54–7.51 (m, 2H),
7.41–7.38 (m, 3H), 6.47 (d, 1H, J = 15.9), 4.35 (dd,
1H, J = 4.3, 11.6), 4.29 (dd, 1H, J = 5.7, 11.3), 4.07–
4.00 (m, 1H), 3.75 (dd, 1H, J = 3.5, 11.6), 3.66 (dd,
1H, 5.7, 11.3), 2.80 (br s, 1H). 2.36 (br s, 1H); 13C
NMR (CDCl3): d 167.2, 145.8, 133.9, 130.5, 128.8,
128.1, 117.1, 70.3, 65.4, 63.3.
(2,2-Dimethyl-1,3-dioxolane-4-yl)methyl myristate, white
crystals, mp 44.7ꢁC; 1H NMR (CDCl3): d 4.35–4.29 (m,
1H), 4.17 (dd, 1H, J = 4.6, 11.5), 4.11 (d, 1H, J = 5.6),
4.07 (dd, 1H, J = 2.0, 5.8), 3.74 (dd, 1H, J = 6.3, 8.5),
2.34 (t, 2H, J = 7.6), 1.64–1.59 (m, 2H), 1.44 (s, 3H),
1.37 (s, 3H), 1.26 (s, 20H), 0.88 (t, 3H, J = 6.6); 13C
NMR (CDCl3): d 173.7, 109.8, 73.6, 66.3, 64.5, 34.1,
31.9, 29.7, 29.6, 29.5, 29.4, 29.3, 29.2, 29.1, 26.7, 25.4,
24.9, 22.7, 14.1; Rt 42.29 (R), 43.45 (S).
1-O-(p-Methylbenzoyl)glycerol 4, white crystals, mp
67.8ꢁC; 1H NMR (CDCl3): d 7.94 (d, 2H, J = 8.0),
7.23 (d, 2H, J = 8.0), 4.40 (dd, 1H, J = 5.2, 11.6), 4.38
(dd, 1H, J = 5.8, 11.7), 4.09–4.03 (m, 1H), 3.76 (dd,
1H, J = 3.8, 11.6), 3.68 (dd, 1H, J = 5.9, 11.7), 3.22 (br
s, 1H), 2.40 (s, 3H); 13C NMR (CDCl3): d 167.1,
144.1, 129.7, 129.2, 126.0, 70.4, 65.5, 63.4, 21.6.
(2,2-Dimethyl-1,3-dioxolane-4-yl)methyl cyclohexancar-
bonyl glycerol, colorless oil: H NMR (DMSO) d 4.25–
1-O-(p-Methoxybenzoyl)glycerol 5, white crystals, mp
50.0ꢁC; 1H NMR (CDCl3): d 8.01 (d, 2H, J = 9.0),
6.96 (d, 2H, J = 9.0), 4.43 (dd, 1H, J = 4.9, 11.7), 4.39
(dd, 1H, J = 6.0, 11.6), 4.08–4.04 (m, 1H), 3.87 (s,
3H), 3.78–3.74 (m, 1H), 3.71–3.67 (m, 1H), 2.67 (d,
1H, J = 5.4), 2.20 (br s, 1H); 13C NMR (CDCl3): d
166.9, 163.8, 131.9, 121.9, 113.8, 70.5, 65.6, 63.4, 55.5.
1
4.20 (m, 1H), 4.07 (dd, 1H, J = 4.2, 11.7), 3.98 (dd, 2H,
J = 4.1, 11.2), 3.64 (t, 1H, J = 6.3), 1.82–1.78 (m, 2H),
1.66–1.63 (m, 2H), 1.58–1.55 (m, 1H), 1.38–1.35 (m,
2H), 1.31 (s, 3H), 1.25 (s, 3H), 1.24–1.16 (m, 3H); 13C
NMR (CDCl3) d 176.1, 103.5, 73.2, 68.7, 64.2, 42.3,
29.0, 28.9, 27.1, 26.9, 26.4, 24.6, 24.2; Rt 4.49 (R), 4.98
(S).
1-O-(p-Chlorobenzoyl)glycerol 6, white crystals, mp
86.3ꢁC; 1H NMR (CDCl3): d 7.98 (d, 2H, J = 8.3),
7.41 (d, 2H, J = 8.6), 4.41 (dd, 1H, J = 5.9, 11.7), 4.08
(t, 1H, J = 6.0), 3.78 (dd, 2H, J = 3.9, 11.5), 3.69 (dd,
1H, J = 5.9, 11.5), 2.75 (br s, 1H), 2.31 (br s, 1H); 13C
NMR (CDCl3): d 166.1, 139.9, 128.8, 128.0, 70.3, 65.9,
63.4.
4.4.1.2. Ketalization of monocaprin21 (2,2-Di-
methyl-1,3-dioxolane-4-yl)methyl caprate, colorless oil:
1H NMR d 4.35–4.29 (m, 1H), 4.17 (dd, 1H, J = 4.6,
11.5), 4.11 (d, 1H, J = 5.8), 4.07 (dd, 1H, J = 2.2, 5.4),
3.74 (dd, 1H, J = 6.1, 8.3), 2.33 (t, 2H, J = 7.6), 1.67–
1.59 (m, 2H), 1.44 (s, 3H), 1.37 (s, 3H), 1.26 (s, 12H),
0.88 (t, 3H, J = 6.6); 13C NMR (CDCl3) d 173.6,
109.8, 73.6, 66.3, 64.5, 34.1, 31.8, 29.4, 29.2, 29.1, 26.6,
25.4, 24.8, 22.6, 14.1; Rt 29.78 (R), 30.16 (S); EIMS
271 [MÀ15]+ (100.0), 228 (3.4), 227 (1.3), 199 (1.2),
185 (3.2), 171 (7.1), 155 (17.2), 129 (6.9), 116 (11.7),
101 (27.9), 85 (6.9), 57 (10.5), 55 (10.1), 43 (26.7), 41
(19.6); HREIMS m/z 271.1880 [MÀ15]+ (calcd for
C15H27O4 271.3792).
1-O-(p-Nitrobenzoyl)glycerol 7, white crystals, mp
106.2ꢁC; 1H NMR (DMSO-d6): d 8.35 (d, 2H,
J = 9.0), 8.22 (d, 2H, J = 8.8), 5.09 (d, 1H, J = 5.4),
4.74 (t, 1H, J = 5.7), 4.36 (dd, 1H, J = 3.8, 11.1), 4.22
(dd, 1H, J = 3.8, 11.1), 3.86 (dd, 1H, J = 5.4), 3.46
(dd, 1H, J = 5.4, 11.0), 3.42 (dd, 1H, J = 6.3, 11.0);
13C NMR (DMSO-d6): d 164.9, 150.6, 135.1, 130.8,
123.5, 70.0, 66.5, 63.3.
4.4.2. Deprotection of the isopropylidene deriva-
1-O-(3,5-Dinitrobenzoyl)glycerol 8, white crystals, mp
118.8ꢁC; H NMR (DMSO-d6): d 9.06–8.97 (m, 3H),
1
1
tives.22 1-O-(Phenylacetyl)glycerol 1, colorless oil; H
NMR (CDCl3): d 7.36–7.27 (m, 5H), 4.23 (dd, 1H,
J = 4.4, 11.5), 4.17 (dd, 1H, J = 6.1, 11.7), 3.93–3.89
(m, 1H), 3.71–3.67 (m, 1H), 3.68 (s, 2H), 3.57–3.52 (m,
1H), 2.39 (t, 1H, J = 4.6), 1.94 (s, 1H); 13C NMR
(CDCl3): d 173.3, 140.2, 129.2, 128.7, 126.3, 70.0, 65.3,
62.4, 41.8, 35.7, 30.9.
5.26 (d, 1H, J = 5.4), 4.82 (t, 1H, J = 5.4), 4.46 (dd,
1H, J = 3.2, 11.3), 4.29 (dd, 1H, J = 6.2, 11.3), 3.85–
3.79 (m, 1H); 13C NMR (DMSO-d6): d 162.5, 148.2,
132.6, 128.8, 122.5, 69.0, 68.1, 62.4.
1-O-(Propionyl)glycerol 9, colorless oil; 1H NMR
(CDCl3): d 4.22 (dd, 1H, J = 4.4, 11.7), 4.16 (dd, 1H,
J = 6.1, 11.7), 3.96–3.93 (m, 1H), 3.74–3.68 (m, 1H),
3.64–3.58 (m, 1H), 2.46 (br s, 1H), 2.42–2.36 (m, 2H),
2.00 (br s, 1H), 1.16 (t, 3H, J = 7.6); 13C NMR (CDCl3):
d 172.3, 70.1, 65.3, 65.2, 20.8, 9.1.
1-O-(Hydrocinnamoyl)glycerol 2, colorless oil; 1H
NMR (CDCl3): d 7.32–7.20 (m, 5H), 4.18 (dd, 1H,
J = 4.6, 11.7), 4.13 (dd, 1H, J = 6.2,11.6), 3.88–3.83
(m, 1H), 3.61 (dd, 1H, J = 4.0, 11.6), 3.50 (dd, 1H,
J = 5.7, 11.6), 2.97 (t, 2H, J = 7.6), 2.70 (t, 2H,
J = 7.7), 2.47 (br s, 1H), 1.69 (br s, 1H); 13C NMR
(CDCl3): d 173.3, 140.2, 128.6, 128.3, 126.4, 65.3, 63.2,
35.7, 30.9; EIMS 224 [M]+ (46.3), 206 (7.7), 193 (10.3),
150 (7.9), 133 (25.6), 105 (51.9), 104 (100.0), 91 (52.7),
1-O-(Butyryl)glycerol 10, colorless oil; 1H NMR
(CDCl3): d 4.22 (dd, 1H, J = 4.6, 11.5), 4.16 (dd, 1H,
J = 6.1, 11.7), 3.97–3.91 (m, 1H), 3.73–3.67 (m, 1H),
3.63–3.58 (m, 1H), 2.55 (br s, 1H), 2.35 (t, 2H,

3558
D. I. Batovska et al. / Tetrahedron: Asymmetry 15 (2004) 3551–3559
J = 7.6), 2.12 (br s, 1H), 1.70–1.63 (m, 2H), 0.96 (t, 3H,
J = 7.3); 13C NMR (CDCl3): d 172.3, 72.1, 65.3, 65.2,
30.8, 19.8, 13.1.
(CDCl3): d 174.4, 70.2, 65.1, 63.3, 34.1, 31.3, 28.7,
24.8, 22.4, 13.9.
1-O-(Capryloyl)glycerol 19, white crystals, mp 35.6ꢁC;
1H NMR (CDCl3): d 4.21 (dd, 1H, J = 4.6, 11.7), 4.14
(dd, 1H, J = 6.1, 11.7), 3.97–3.90 (m, 1H), 3.73–3.68
(m, 1H), 3.63–3.58 (m, 1H), 2.57 (br s, 1H), 2.36 (t,
2H, J = 7.6), 2.13 (br s, 1H), 1.65–1.60 (m, 2H), 1.30–
1.28 (m, 8H), 0.88 (t, 3H, J = 7.1); 13C NMR (CDCl3):
d 174.4, 70.2, 65.1, 63.3, 34.1, 31.6, 29.0, 28.8, 24.8,
22.5, 13.9.
1-O-(Crotonyl)glycerol 11, colorless oil; 1H NMR
(CDCl3): d 7.08–6.99 (m, 1H), 5.88 (d, 1H, J = 1.6,
15.7), 4.27 (dd, 1H, J = 4.9, 11.6), 4.21 (dd, 1H,
J = 5.9, 11.9), 3.97–3.86 (m, 1H), 3.71 (dd, 1H, J = 4.3,
11.3), 3.61 (dd, 1H, J = 5.7, 11.6), 2.57 (br s, 1H), 2.13
(br s, 1H), 1.91 (dd, 3H, J = 1.6, 6.8); 13C NMR
(CDCl3): d 166.8, 146.1, 122.0, 70.3, 65.1, 63.3, 18.2.
1-O-(Isobutyryl)glycerol 12, colorless oil; 1H NMR
(CDCl3): d 4.22 (dd, 1H, J = 4.6, 11.5), 4.16 (dd, 1H,
J = 5.9, 11.5), 3.97–3.91 (m, 1H), 3.73–3.67 (m, 1H),
3.63–3.57 (m, 1H), 2.66–2.56 (m, 1H), 2.48 (br s,
1H), 2.05 (br s, 1H), 1.19 (d, 6H, J = 7.0); 13C NMR
(CDCl3): d 172.3, 72.1, 65.3, 65.2, 30.8, 19.8, 19.5.
1-O-(Lauroyl)glycerol 21, white crystals, mp 47.4ꢁC; 1H
NMR (CDCl3): d 4.21 (dd, 1H, J = 4.6, 11.7), 4.14 (dd,
1H, J = 6.1, 10.0), 3.97–3.90 (m, 1H), 3.63 (d, 1H,
J = 11.2), 3.60 (dd, 1H, J = 5.6, 11.2), 2.63 (br s, 1H),
2.35 (t, 2H, J = 7.8), 2.21 (br s, 1H), 1.68–1.59 (m,
2H), 1.26 (s, 16H), 0.88 (t, 3H, J = 6.6); 13C NMR
(CDCl3): d 174.4, 70.2, 65.1, 63.3, 34.1, 31.9, 29.5,
29.4, 29.3, 29.2, 29.1, 24.9, 22.6, 14.1.
1-O-(Pentanoyl)glycerol 13, colorless oil; 1H NMR
(CDCl3): d 4.21 (dd, 1H, J = 4.6, 11.5), 4.15 (dd, 1H,
J = 6.1, 11.5), 3.97–3.90 (m, 1H), 3.73–3.67 (m, 1H),
3.64–3.57 (m, 1H), 2.72–2.67 (m, 1H), 2.36 (t, 2H,
J = 7.6), 2.31–2.24 (m, 1H), 1.66–1.59 (m, 2H), 1.40–
1.31 (m, 2H), 0.92 (t, 3H, J = 7.3); 13C NMR (CDCl3):
d 173.4, 70.2, 65.1, 63.3, 33.8, 26.9, 22.2, 13.6.
1-O-(Myristoyl)glycerol 22, white crystals, mp 56.2ꢁC;
1H NMR (CDCl3): d 4.21 (dd, 1H, J = 4.6, 11.7), 4.15
(dd, 1H, J = 6.1, 11.7), 3.96–3.93 (m, 1H), 3.71–3.69
(m, 1H), 3.61–3.59 (m, 1H), 2.48 (br s, 1H), 2.35 (t,
2H, J = 7.6), 2.04 (br s, 1H), 1.63 (t, 2H, J = 7.3), 1.26
(s, 20H), 0.88 (t, 3H, J = 6.6); 13C NMR (CDCl3): d
172.6, 70.2, 65.1, 63.3, 34.1, 31.9, 29.6, 29.4, 29.3, 29.2,
29.1, 24.9, 22.6, 14.1.
1
1-O-(Isopentanoyl)glycerol 14, colorless oil; H NMR
(CDCl3): d 4.22 (dd, 1H, J = 4.4, 11.5), 4.16 (dd, 1H,
J = 6.1, 11.4), 3.97–3.91 (m, 1H), 3.73–3.68 (m, 1H),
3.64–3.59 (m, 1H), 2.63–2.60 (m, 1H), 2.24 (d, 2H,
J = 7.1), 2.15–2.06 (m, 2H), 0.97 (d, 6H, J = 6.6); 13C
NMR (CDCl3): d 172.4, 70.4, 65.1, 63.3, 40.8, 23.6,
22.2, 22.0.
1
1-O-(Cyclohexanecarbonyl)glycerol 23, colorless oil; H
NMR (CDCl3): d 4.18 (dd, 1H, J = 5.1, 11.5), 4.14 (dd,
1H, J = 5.6, 11.5), 3.95–3.88 (m, 1H), 3.72–3.65 (m, 1H),
3.63–3.55 (m, 1H), 3.08 (br s, 1H), 2.73 (br s, 1H), 2.39–
2.31 (m, 1H), 1.93–1.89 (m, 2H), 1.80–1.72 (m, 2H),
1.68–1.62 (m, 1H), 1.49–1.37 (m, 2H), 1.33–1.20 (m,
3H); 13C NMR (CDCl3): d 173.4, 70.2, 65.1, 63.3,
33.8, 26.9, 22.2, 13.6.
1-O-(Pivaloyl)glycerol 15, colorless oil; 1H NMR
(CDCl3): d 4.22 (dd, 1H, J = 4.6, 11.7), 4.16 (dd, 1H,
J = 5.9, 11.7), 3.97–3.91 (m, 1H), 3.73–3.67 (m, 1H),
3.63–3.57 (m, 1H), 1.23 (s, 9H); 13C NMR (CDCl3): d
172.5, 72.1, 65.1, 63.3, 39.5, 22.5, 22.4, 22.2.
Acknowledgements
1-O-(Caproyl)glycerol 16, colorless oil; 1H NMR
(CDCl3): d 4.21 (dd, 1H, J = 4.6, 11.4), 4.15 (dd, 1H,
J = 6.1, 11.7), 3.97–3.90 (m, 1H), 3.73–3.68 (m, 1H),
3.63–3.57 (m, 1H), 2.67 (br s, 1H), 2.35 (t, 2H,
J = 7.8), 2.25 (br s, 1H), 1.71–1.60 (m, 2H), 1.36–1.29
(m, 4H), 0.90 (t, 3H, J = 7.0); 13C NMR (CDCl3): d
174.6, 70.2, 65.1, 63.3, 34.1, 31.2, 24.5, 22.2, 13.8.
The scholarship from JSPS for the post-doctoral re-
search of Dr. Batovska is greatly acknowledged. The
authors are also thankful to Dr. Takao Kishimoto,
Hokkaido University for all his technical assistance
and proper advices. This work was supported in part
by a Grant-in-Aid for Scientific Research provided by
the Japanese Society for the Promotion of Science.
1-O-(Sorboyl)glycerol 17, colorless oil; 1H NMR
(CDCl3): d 7.33–7.28 (m, 1H), 6.21–6.18 (m, 2H), 5.80
(d, 1H, J = 15.1), 4.32 (dd, 1H, J = 4.7, 11.5), 4.27 (dd,
1H, J = 5.6, 11.5), 4.05–3.97 (m, 1H), 3.75 (dd, 1H,
J = 3.5, 11.6), 3.68 (dd, 1H, 5.7, 11.5), 2.65 (br s, 1H),
2.21 (br s, 1H), 1.87 (d, 3H, J = 4.3); 13C NMR (CDCl3):
d 165.5, 146.2, 140.4, 129.5, 117.8, 70.4, 65.2, 63.3, 18.8.
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