Stereospecific and regioselective opening of an oxirane system. A new efficient entry to 1- or 3-monoacyl- and 1- or 3-monoalkyl-sn-glycerols

Article abstract of DOI:10.1016/j.tetlet.2005.01.093

Acyl or alkyl glycidols in the presence of trifluoroacetic anhydride (TFAA) and trifluoroacetate anions, undergo a regioselective and stereospecific opening of the oxirane system to produce the bis(trifluoroacetylated) derivatives, from which the corresponding 1(3)-monoacyl-sn-glycerols or 1(3)-monoalkyl-sn-glycerols can be obtained directly in high purity (>99%) and in quantitative yields.

Full text of DOI:10.1016/j.tetlet.2005.01.093

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 1601–1605
Stereospecific and regioselective opening of an oxirane system.
A new efficient entry to 1- or 3-monoacyl- and 1- or
3
-monoalkyl-sn-glycerols
a,
*
b,c,
*
Stephan D. Stamatov and Jacek Stawinski
a
Department of Chemical Technology, University of Plovdiv, 24 Tsar Assen Street, Plovdiv 4000, Bulgaria
Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University, S-106 91 Stockholm, Sweden
b
c
Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznan, Poland
Received 1 November 2004; revised 7 January 2005; accepted 19 January 2005
Available online 1 February 2005
Abstract—Acyl or alkyl glycidols in the presence of trifluoroacetic anhydride (TFAA) and trifluoroacetate anions, undergo a
regioselective and stereospecific opening of the oxirane system to produce the bis(trifluoroacetylated) derivatives, from which the
corresponding 1(3)-monoacyl-sn-glycerols or 1(3)-monoalkyl-sn-glycerols can be obtained directly in high purity (>99%) and
in quantitative yields.
Ó 2005 Elsevier Ltd. All rights reserved.
6
1. Introduction
(e.g., BF ÆOEt ) further limits the number of suitable
3
2
synthetic procedures.
The importance of stereochemically pure 1(3)-mono-
acyl-sn-glycerols (MAG) and their 1(3)-monoalkyl-sn-
These problems are most acute in the classical synthesis
1
7
8
analogues (MALKG) as physiological effectors per se
or as chiral building blocks in the asymmetric synthesis
of 1(3)-MAG or 1(3)-MALKG where 1,2(2,3)-isopro-
pylidene-sn-glycerol derivatives are commonly used as
starting materials. The prolonged treatment with con-
centrated mineral acids at elevated temperature (condi-
tions that are typically required for acetal cleavage in
these approaches), adversely affects the purity of the iso-
lated 1(3)-MAG due to extensive side-product forma-
tion (e.g., acyl migration, formation of cyclic systems,
2
3
of various bioactive lipids and agents for biochemical
4
or medicinal intervention, has been well documented.
Despite the apparent structural simplicity, access to the
aforementioned classes of lipid mediators is rather lim-
ited as the presence of two adjacent hydroxyl functions
makes 1(3)-monoacyl-sn-glycerols highly susceptible to
7
racemization, etc.). Although various reagent systems,
9
5
acyl migration. This process, which is promoted by
for example, dimethylboronbromide or trifluoroacetic
acid with triethyl borate-2,2,2-trifluoroethanol (8:1 v/
acids, bases or heat, not only results in loss of chirality
at C-2, but also poses severe problems in isolation and
storage of these compounds. For derivatives bearing
polyunsaturated systems (e.g., oleoyl or arachidonoyl
moieties), a high propensity to autooxidation and
decomposition in the presence of even mild Lewis acids
1
0
v) have been advocated as superior to mineral acids
for the removal of the isopropylidene group, these
procedures require painstaking chromatography, which
often has a detrimental effect on the stereochemical
1
1
purity of compounds isolated.
To overcome complications inherent in most protocols
involving protection/deprotection steps, two procedures
based on a titanium(IV) isopropoxide-promoted acidoly-
sis/or phenolysis of optically active glycidols were pro-
Keywords: 1(3)-Monoacyl-sn-glycerols; 1(3)-Monoalkyl-sn-glycerols;
Glycidyl oleate; 2-(Hexadecyloxymethyl)oxirane; Trifluoroacetic
anhydride.
1
2
posed for accessing unprotected 1(3)-monoacyl- /or
1
3
*
Corresponding authors. Tel.: +46 8 16 24 85; fax: +46 8 15 49 08;
e-mail: js@organ.su.se
1(3)-monoaryl-sn-glycerols in one-pot reactions. In
the most recent modification, involving a synthesis of
0
040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.01.093

1602
S. D. Stamatov, J. Stawinski / Tetrahedron Letters 46 (2005) 1601–1605
1
4
1
(
(3)-hexadecyl-sn-glycerol,
TBDPS) ether derivative of a chiral glycidol was used
as a substrate and, after opening the oxirane system with
-hexadecanol using boron trifluoride etherate as cata-
a
tert-butydiphenylsilyl
Having developed the reaction conditions for the con-
version of acyl glycidols into 1-acylglycerols, the reac-
tions were next carried out on enantiomerically pure
glycidol derivatives, to investigate the stereochemical
outcome of this transformation (Scheme 1). S-(+)-Gly-
cidol oleate 1 and R-(ꢁ)-glycidol oleate 2 were subjected
separately to treatment as above, with TFAA and
1
lyst, the TBDPS group was removed by means of tetra-
butylammonium fluoride. Unfortunately, in comparison
with approaches based on 1,2-isopropylideneglycerol
derivatives, these methods although simple, are rather
inefficient and provide the target compounds in low
+
ꢁ
Bu N TFA and after evaporation of the solvents and
4
passing a solution of the residue in toluene through a
small silica gel pad to remove the trifluoroacetate salt,
bis(trifluoroacetate) derivatives 5 and 6, respectively,
1
2
(
ꢀ
e.g., ꢀ25% for 1-acyl-sn-glycerols) to moderate (e.g.,
1
4
54–70% for 1-alkyl-sn-glycerols) yields.
1
13
were obtained in excellent yields. H and C NMR
1
7
As part of our studies on the development of new syn-
thetic methodologies for glycerolipids based on glycidol
derivatives, we developed a very efficient synthesis of 2-
acylglycerols via opening of the oxirane system of gly-
analyses confirmed that opening of the oxirane system
occurred with complete regioselectivity and the optical
rotations measured indicated the stereospecificity of this
process.
1
5
cidyl esters using trifluoroacetic anhydride (TFAA).
Here, we report that opening the oxirane system in acyl
glycidols with TFAA in the presence of trifluoroacetate
anions can be carried out without concomitant acyl
group migration, thus providing an efficient entry to 1-
acyl glycerols.
Conjugates 5 and 6 were then subjected to deprotection
with methanol and pyridine as described above, and
after removal of all volatile materials under vacuum, iso-
merically homogenous 1-oleoyl-sn-glycerol 9 and 3-
oleoyl-sn-glycerol 10 (purity >99%, H and C NMR
spectroscopy) were obtained in >90% overall yields.
Since compound 9, obtained from S-(+)-glycidol 1,
was identified as 1-acyl-sn-glycerol, and compound
10, obtained from R-(ꢁ)-glycidol 2, was identified as
3-acyl-sn-glycerol, this established the overall transfor-
mation to have occurred with complete retention of con-
figuration at the C-2 carbon of the glycerol backbone.
1
13
First, opening of the oxirane ring of acyl glycidols was
investigated on racemic glycidyl oleate (all compounds
as in Scheme 1, but racemic). It was found that in
THF/CH Cl (1:1, v/v) at 80 °C, in the presence of
2
2
TFAA (2 equiv) and tetrabutylammonium trifluoroace-
+
tate (Bu N TFA , 3 equiv) glycidyl oleate was quanti-
ꢁ
4
tatively converted within 5 h into racemic 1-oleoyl-2,3-
1
13
bis(trifluoroacetyl) glycidol (TLC, H and C NMR
analyses). The reaction seemed to be rather general as
other glycidol derivatives (linoleoyl, palmitoyl, stearoyl,
benzoyl-, isopropyl-, or methyl) also underwent quanti-
tative conversions into the corresponding bis(trifluoro-
acetates) without detectable migration of the fatty acid
residues from C-1 to C-2.
We also found that the reagent system TFAA/
Bu N TFA opens the oxirane system of alkyl glycidols
+
ꢁ
4
completely regioselectively and stereospecifically, as
exemplified by the efficient conversion of S-(+)-hexade-
cyl glycidol 3 into 1-hexadecyl-sn-glycerol 11 (94% yield)
with the intermediacy of bis(trifluoroacetyl) derivative 7,
and R-(ꢁ)-hexadecyl glycidol 4 into 1-hexadecyl-sn-
glycerol 12 (92% yield) with the intermediacy of bis(tri-
fluoroacetyl) derivative 8.
Since trifluoroacetate esters are known to undergo
1
5,16
smooth transesterification with alcohols,
fluoroacetates) of type 5, obtained in CH Cl /pentane
the bis(tri-
We carried out also some additional experiments to pro-
vide evidence on a possible mechanism for this transfor-
2
2
were treated (20 min) with pyridine (10 equiv) and meth-
anol (250 equiv) to provide racemic 1-acylglycerols.
1
13
mation. Thus, H and C NMR spectroscopy revealed
that TFAA alone effected opening of the oxirane system
of acyl glycidols of type 1 with migration of the acyl
group to produce the corresponding 2-acyl glycerols,
while alkyl glycidols of type 3, were completely stable
OCOCF3
OCOCF3
OR
1
5
under these conditions. On the other hand, in the
absence of TFAA, oleoyl glycidol 1 underwent reaction
with tetra-n-butylammonium trifluoroacetate to pro-
duce, after deprotection of the trifluoroacetyl groups,
a mixture of 1-monoacylglycerol 9 and 2-acylglycerol
in a ratio of 85:15. In all instances where instead of
TFAA, other carboxylic acid anhydrides (e.g., acetic or
benzoic anhydride) with a controlled excess (e.g., 3
Step A:
Step B:
5
- 8
Yields: 95 - 97%
OH
OH
OR
O
OR
- 4
1
9 - 12
Overall yields: 92 - 95%
+
ꢁ
equiv) of Bu N TFA were used, the target bis(trifluoro-
4
1
2
3
4
= S-(+), R = C17H33CO
= R-(-), R = C17H33CO
= S-(+), R = C16H33
= R-(-), R = C16H33
5, 9 = 1-oleoyl-sn-glycerol
6, 10 = 3-oleoyl-sn-glycerol
7, 11 = 1-hexadecyl-sn-glycerol
8, 12 = 3-hexadecyl-sn-glycerol
acetates) of type 5 or 7 were identified as the only prod-
ucts of the reaction. Reactions with acyl donors other
+
than that of TFAA/Bu N TFA were sluggish and
ꢁ
4
+
N TFA
ꢁ
are impractical, since even for a rather reactive reagent
system, for example, tetra-n-butylammonium acetate/
acetic anhydride, the reaction occurred to only ca.
85% after 24 h.
Scheme 1. Reagents and conditions: (i) step A: Bu
4
(
3.0 equiv)/TFAA (2.0 equiv), THF/CH
ii) step B: pyridine (10 equiv)/MeOH (250 equiv), CH
20 min.
2
Cl
2
= 1:1, v/v, 80 °C, ꢀ5 h;
(
2
Cl /pentane, rt,
2
ꢀ

S. D. Stamatov, J. Stawinski / Tetrahedron Letters 46 (2005) 1601–1605
1603
The above observations suggest that opening of the oxi-
rane system in acyl and alkyl glycidols probably pro-
ceeds via a one-step synchronous mechanism involving
nucleophilic attack of a trifluoroacetate anion on the
primary carbon of the oxirane ring, with simultaneous
electrophilic catalysis exerted by TFAA, as depicted in
Scheme 2. Since in this mechanism no bond breaking
takes place at the chiral center of the glycidol, the trans-
formation should be stereospecific and occur with reten-
tion of configuration. In addition, the simultaneous
nucleophile and electrophile catalysis provided by this
reagent system should facilitate opening of the oxirane
ring and prevent an acyl migration during the course
of the reaction.
solvent. The support was washed with toluene
(100 mL), fractions containing the product were com-
bined, the solvent was removed under reduced pressure,
and the residue was kept under high vacuum at room
temperature for 2–3 h to provide bis(trifluoroacetate)
1
5–8 (purity >99%, H NMR spectroscopy).
Step B: To a solution of 5–8 in pentane/CH Cl (3:1, v/v,
2
2
5.0 mL), a mixture of pyridine (0.8 mL, 10 mmol) and
methanol (10.1 mL, 250 mmol) in the same solvent sys-
tem (5.0 mL) was added at 0 °C and the reaction was left
at room temperature for 20 min. The solvents were
evaporated under reduced pressure (bath temp 50 °C)
and the residue was kept under high vacuum at room
temperature for 2–3 h to give the deprotected glycerol-
1
In conclusion, we have developed an efficient synthetic
strategy based on a novel, stereospecific transformation
of chiral glycidyl derivatives possessing acyl- (e.g., 1, 2)
or alkyl- (e.g., 3, 4) moieties into 1(3)-acyl- (e.g., 5, 6) or
derivative 9–12 (purity >99%, H NMR spectroscopy).
2.1. 1-Oleoyl-2,3-bis(trifluoroacetyl)-sn-glycerol 5
1
7
(3)-alkyl-2,3(1,2)-bis(trifluoroacetyl)-sn-glycerols (e.g.,
, 8) with complete retention of configuration, from
Obtained from (S)-(+)-2-(oleoyloxymethyl)oxirane (1;
0.338 g; 1.00 mmol). Yield: 0.532 g (97%, yellowish
oil); Rf 2(0pentane/toluene/EtOAc = 40:50:10, v/v/
v) = 0.60; ½aꢂ ꢁ3.49 (c 10.14, CHCl ). Anal. Calcd for
which isomerically pure 1(3)-monoacyl- (9, 10) or 1(3)-
monoalkyl-sn-glycerols (11, 12) can be retrieved directly.
The main features of this new protocol are (i) highly reg-
iospecific and practically quantitative syntheses of 1(3)-
monoacyl- or 1(3)-monoalkyl-sn-glycerols under mild
conditions; (ii) the compounds 5–8 and 9–12 produced
are of high purity, which alleviates problems of addi-
tional purification, and thus the risk of acyl migration
and other side-reactions is eliminated; (iii) bis(trifluoro-
acetates) 5–8 can be envisaged as either, convenient stor-
age forms or intermediate frameworks for 9–12; (iv) the
novel strategy also introduces the above types of gly-
cidyl conjugates 1–4 as versatile, bifunctional building
blocks of potential interest for the synthesis of asymmet-
ric lipid mediators; (v) the method makes use of com-
mercially available reactants and it is easy to scale up.
D
3
C H O F (548.57): C, 54.74; H, 6.98. Found: C,
2
5
38
6 6
1
54.64; H, 7.03. H NMR dH (in ppm, CDCl3,
400 MHz): 0.88 (t, J = 6.6 Hz, 18-CH , 3H); 1.30 (m,
4-7-CH , 12-17-CH , 20H); 1.62 (m, 3-CH , 2H); 2.02
3
2
2
2
(m, 8-CH , 11-CH , 4H); 2.34 (t, J = 7.5 Hz, 2-CH ,
2
2
2
2H); 4.25 (dd, J = 6.0, 5.9 Hz, RC(O)OCH H CH-
a
b
CH OC(O), 1H); 4.48 (dd, J = 4.2, 4.0 Hz, RC(O)O-
2
CH H CHCH OC(O), 1H); 4.54 (dd, J = 6.6, 6.6 Hz,
a
b
2
C(O)OCH CHCH H OC(O)CF , 1H); 4.66 (dd,
3
2
a
b
J = 3.5, 3.7 Hz, C(O)OCH CHCH H OC(O)CF , 1H);
2
a
b
3
5.35 (m, CH@CH, 2H); 5.51 (m, OCH CHOC(O)CF ,
2
3
1
3
1H). C NMR dC (in ppm, CDCl , 100 MHz): 14.30
3
(18-CH ); 22.89 (17-C); 24.92 (3-C); 27.36, 27.43
(11-C, 8-C); 29.22–29.98 (4-C-7-C, 12-C-15-C); 32.12
3
(
(
16-C); 33.99 (2-C); 129.90, 130.26 (9-C, 10-C); 173.16
1-C): oleoyl fragment; 114.44 (d, J = 285.3 Hz, 2-C);
2
. General procedure for the synthesis of 5–8 and 9–12
156.85 (d, J = 43.5 Hz, 1-C): trifluoroacetyl fragment;
0.81 (1-C); 64.69 (3-C); 72.58 (2-C): glycerol fragment.
6
Step A: A solution of glycidyl derivative 1–4 (1.00
mmol) in alcohol-free dichloromethane/THF (1:1, v/v,
2.2. 3-Oleoyl-1,2-bis(trifluoroacetyl)-sn-glycerol 6
2
.0 mL) was added to a mixture of tetra-n-butylammo-
nium trifluoroacetate (1.066 g; 3.00 mmol) and trifluoro-
acetic anhydride (TFAA, 0.278 mL; 2.00 mmol) in the
same solvent system (3.0 mL), and the reaction was kept
under argon, in a pressure-proof glass ampoule at 80 °C
Obtained from (R)-(ꢁ)-2-(oleoyloxymethyl)oxirane (2;
0.338 g; 1.00 mmol). Yield: 0.521 g (95%, yellowish
oil). While all other physicochemical and spectral char-
20
acteristics were identical with those of 5, ½aꢂ +3.54 (c
D
(
bath) for 5 h. The solvents and unreacted TFAA were
11.28, CHCl ).
3
removed under reduced pressure (bath temp 50 °C),
the residue was taken up in toluene (5.0 mL) and passed
through a silica gel pad (ꢀ5 g) prepared in the same
2.3. 1-Hexadecyl-2,3-bis(trifluoroacetyl)-sn-glycerol 7
Obtained from (S)-(+)-2-(hexadecyloxymethyl)oxirane
(
3; 0.299 g; 1.00 mmol). Yield: 0.468 g (92%, colourless
oil); Rf 20(pentane/toluene/EtOAc = 40:50:10, v/v/v) =
.76; ½aꢂ ꢁ9.55 (c 10.89, CHCl ). Anal. Calcd for
-O(O)CCF3
0
D
3
O
RO
C H O F (508.53): C, 54.32; H, 7.53. Found: C,
5
2
3
38
5 6
O
O
1
F3C
O
O
4.40; H, 7.47. H NMR dH (in ppm, CDCl3,
F3C
O
CF3
F3C
OR
4
00 MHz): 0.88 (t, J = 6.6 Hz, 16-CH , 3H); 1.26 (m,
3
O
O
3-15-CH , 26H); 1.55 (m, 2-CH , 2H); 3.46 (m,
2 2
1-CH , 2H); 3.67 (dd, J = 2.2, 2.2 Hz, C(O)OCH CH-
CH H OR, 2H); 4.57 (dd, J = 6.8, 6.8 Hz, ROCH CH-
2
2
R = C17H33CO; C16H33
a
b
2
Scheme 2.
CH H OC(O)CF , 1H); 4.67 (dd, J = 3.1, 3.1 Hz,
a b 3

1604
S. D. Stamatov, J. Stawinski / Tetrahedron Letters 46 (2005) 1601–1605
1
3
ROCH CHCH H OC(O)CF , 1H); 5.42 (m, OCH -
2
CHOH, 1H). C NMR d (in ppm, CDCl , 100 MHz):
C 3
2
a
b
3
1
3
CHOC(O)CF , 1H). C NMR dC (in ppm, CDCl3,
14.33 (16-CH ); 22.91 (15-C); 26.30 (3-C); 29.58–29.91
(4-C-14-C); 32.14 (2-C); 72.77 (1-C): hexadecyl fragment;
64.55 (3-C); 70.60 (2-C); 72.09 (1-C): glycerol fragment.
3
3
1
00 MHz): 14.30 (16-CH ); 22.90 (15-C); 26.13 (3-C);
3
29.57–29.90 (4-C-14-C); 32.14 (2-C); 72.39 (1-C): hexa-
decyl fragment; 114.51 (q, J = 283.1 Hz, 2-C); 157.12
(
(
q, J = 20.6 Hz, 1-C): trifluoroacetyl fragment; 65.35
3-C); 67.72 (1-C); 73.76 (2-C): glycerol fragment.
2.8. 3-Hexadecyl-sn-glycerol 12
Obtained from (R)-(ꢁ)-2-(hexadecyloxymethyl)oxirane
(4; 0.299 g; 1.00 mmol) via 8. Yield: 0.291 g (92%). Iden-
tical physicochemical and spectral characteristics with
2
.4. 3-Hexadecyl-1,2-bis(trifluoroacetyl)-sn-glycerol 8
20
14
25
Obtained from (R)-(ꢁ)-2-(hexadecyloxymethyl)oxirane
4; 0.299 g; 1.00 mmol). Yield: 0.478 g (94%, colourless
those of 11. ½aꢂ +2.72 (c 3.66, THF); lit. ½aꢂD +2.69
D
(
(c 3.5, THF).
20
oil). With the exception of ½aꢂ +9.67 (c 10.03, CHCl3),
D
all other physicochemical and spectral characteristics
were identical with those of 7.
Acknowledgements
2
.5. 1-Oleoyl-sn-glycerol 9
Financial support from the Swedish Natural Science
Research Council and the Swedish Foundation for
Strategic Research is gratefully acknowledged.
Obtained from (S)-(+)-2-(oleoyloxymethyl)oxirane (1;
.338 g; 1.00 mmol) via 5. Yield: 0.338 g (95%,
0
calculated on 1); white solid; mp 34.5–36 °C (identical
with that of a commercial sample from Fluka); R (pen-
tane/toluene/EtOAc = 30:20:50,
References and notes
f
20
v/v/v) = 0.34;
1.32 (c 11.76, CHCl ). Anal. Calcd for C H O
½aꢂ
D
ꢁ
1. Tyler, M. I.; Howden, M. E. H. Naturwissenschaften 1985,
3
21 40 4
7
2, 373–375; Ikegawa, N.; Ikegawa, T. Jp Patent
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1191619; CAN 106:72911, 1986; Murase, T.; Hase, T.;
Tokimitsu, I. Jp Patent 2001354558; CAN 136:48454,
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Arguin, C.; Pande, S. V.; Steff, A.-M.; Hugo, P. Cell
Death Differ. 2001, 8, 1103–1112; Philippoussis, F.;
Arguin, C.; Fortin, M.; Steff, A.-M.; Hugo, P. Immunol.
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Academic: New York, 1983.
(
356.54): C, 70.74; H, 11.31. Found: C, 70.66; H,
1
1
1.40. H NMR dH (in ppm, CDCl , 400 MHz): 0.87
3
6
(
CH , 20H); 1.62 (m, 3-CH , 2H); 2.00 (m, 8-CH ,
t, J = 6.6 Hz, 18-CH , 3H); 1.28 (m, 4-7-CH , 12-17-
3 2
2
2
2
2
1
s, OH, 2H); 3.59 (dd, J = 5.9, 5.9 Hz, C(O)OCH CH-
1-CH , 4H); 2.34 (t, J = 7.5 Hz, 2-CH , 2H); 2.92 (br
2 2
2
CH H OH, 1H); 3.69 (dd, J = 3.8, 4.0 Hz,
a
b
C(O)OCH CHCH H OH, 1H); 3.93 (m, OCH CHOH,
b
2
a
2
1
H); 4.16 (m, C(O)OCH H CHCH OH, 2H); 5.34 (m,
a b 2
1
3
CH@CH, 2H).
C NMR dC (in ppm, CDCl3,
2
3
. Eibl, H.; Woolley, P. Chem. Phys. Lipids 1988, 47, 47–53;
Chacko, G. K.; Hanahan, D. J. Biochim. Biophys. Acta
1
2
1
1
6
00 MHz): 14.32 (18-CH ); 22.89 (17-C); 25.11 (3-C);
3
7.37, 27.43 (11-C, 8-C); 29.30–29.98 (4-C-7-C, 12-C-
5-C); 32.12 (16-C); 34.36 (2-C); 129.93, 130.26 (9-C,
0-C); 174.53 (1-C): oleoyl fragment; 63.56 (3-C);
5.39 (1-C); 70.48 (2-C): glycerol fragment.
1
1
968, 164, 252–271; Sonnet, P. E. Chem. Phys. Lipids
991, 58, 35–39; Lipid Technologies and Applications;
Gunston, F. D., Padley, F. B., Eds.; Marcel Dekker: New
York, 1997.
. Urata, K.; Takaishi, N. J. Am. Oil Chem. Soc. 1996, 73,
2
.6. 3-Oleoyl-sn-glycerol 10
8
4
19–830; Weber, N. Prog. Biochem. Pharmacol. 1988, 22,
8–57; Kabara, J. J.; Vrable, R.; Jie, M. S. F. L. K. Lipids
Obtained from (R)-(ꢁ)-2-(oleoyloxymethyl)oxirane (2;
.338 g; 1.00 mmol) via 6. Yield: 0.335 g (94%). Identical
physicochemical and spectral characteristics with those
1977, 12, 753–759; Houte, H.; Partali, V.; Sliwka, H.-R.;
Quartey, E. G. K. Chem. Phys. Lipids 2000, 105, 105–113;
Carballeira, N. M. Prog. Lipid Res. 2002, 41, 437–456;
Von Minden, H. M.; Morr, M.; Milkereit, G.; Heinz, E.;
Vill, V. Chem. Phys. Lipids 2002, 114, 55–80.
0
20
20
of 9. ½aꢂ +1.28 (c 10.64, CHCl ); ½aꢂ ꢁ3.33 (c 7.33,
D
3
D
9
22
D
pyridine); lit. ½aꢂ ꢁ3.2 (c 5, pyridine).
4
. Brohult, A.; Brohult, J.; Brohult, S. Experientia 1973, 29,
8
1–82; Parang, K.; Wiebe, L. I.; Knaus, E. E. Curr. Med.
2
.7. 1-Hexadecyl-sn-glycerol 11
Chem. 2000, 7, 995–1039; Han, S.-Y.; Cho, S.-H.; Kim,
S.-Y.; Seo, J.-T.; Moon, S.-J.; Jhon, G.-J. Bioorg. Med.
Chem. Lett. 1999, 9, 59–64; Ferraboschi, P.; Colombo, D.;
Compostella, F.; Reza-Elahi, S. Synlett 2001, 9, 1379–
1382; Kurz, M.; Scriba, G. K. E. Chem. Phys. Lipids 2000,
107, 143–157; Will, D. W.; Brown, T. Tetrahedron Lett.
Obtained from (S)-(+)-2-(hexadecyloxymethyl)oxirane
3; 0.299 g; 1.00 mmol) via 7. Yield: 0.297 g (94%); white
(
1
4
solid; mp 62.9–63.9 °C; lit. mp 63.0–64.0 °C; R (pen-
f
2
0
tane/toluene/EtOAc = 30:20:50,
1
v/v/v) = 0.26;
½aꢂ
D
4
25
1
992, 33, 2729–2732; Chang, C.-M.; Bodmeier, R. Int. J.
Pharmacol. 1997, 147, 135–142.
5. Mattson, F. H.; Volpenhein, R. A. J. Lipid Res. 1962,
ꢁ
2.10 (c 3.00, THF); lit. ½aꢂ ꢁ2.68 (c 3.5, THF). Anal.
D
Calcd for C H O (316.52): C, 72.10; H, 12.74. Found:
1
9
40
3
1
C, 72.00; H, 12.80. H NMR dH (in ppm, CDCl3,
3
5
, 281–296; Martin, J. B. J. Am. Chem. Soc. 1953, 75,
483–5486; Boswinkel, G.; Derksen, J. T. P.; Riet, K. V.
4
1
00 MHz): 0.88 (t, J = 7.1 Hz, 16-CH , 3H); 1.25 (m, 3-
5-CH , 26H); 1.57 (qnt, J = 7.5 Hz, 2-CH , 2H); 2.30
3
2
2
T.; Cuperus, F. P. J. Am. Oil Chem. Soc. 1996, 73, 707–
11.
(
CH , OCH CHCH H OH, 4H); 3.64 (dd, J = 5.1,
br s, OH, 2H); 3.40–3.57 (m, overlapping with dd, 1-
7
2
2
a
b
6. Gras, J.-L.; Bonfanti, J.-F. Synlett 2000, 248–250.
7. Baer, E.; Fisher, H. O. L. J. Am. Chem. Soc. 1945, 67,
2031–2037; Hartman, L. J. Chem. Soc. 1959, 4134–4135;
5
.1 Hz, OCH CHCH H OR, 1H); 3.72 (dd, J = 3.8,
2 a b
3
.8 Hz, OCH CHCH H OR, 1H); 3.85 (m, OCH -
b
2
a
2

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