Enantioselective syntheses of xylo-C18-phytosphingosines using double stereodifferentiation

Article abstract of DOI:10.1055/s-2003-36261

The concept of double stereodifferentiation in Sharpless asymmetric dihydroxylation has been studied and the results obtained are applied to the diastereoselective syntheses of xylo-isomers of C₁₈-phytosphingosine. The diastereomeric mixture obtained could be separated by column chromatography. Thus, the L-xylo-(2R,3S,4S)-C₁₈- and D-xylo-(2S,3R,4R)-C₁₈-phytosphingosines as their tetraacetate derivatives were synthesized in diastereomerically pure form.

Full text of DOI:10.1055/s-2003-36261

PAPER
129
Enantioselective Syntheses of xylo-C -Phytosphingosines using Double
1
8
Stereodifferentiation
S
R
ynthese
s
of xylo
o
-C -Phytosp
d
hingosines ney A. Fernandes, Pradeep Kumar*
1
8
Division of Organic Chemistry: Technology, National Chemical Laboratory, Pune 411 008, India
Fax +91(20)5893614; E-mail: tripathi@dalton.ncl.res.in
Received 19 July 2002; revised 2 October 2002
Abstract: The concept of double stereodifferentiation in Sharpless
asymmetric dihydroxylation has been studied and the results ob-
tained are applied to the diastereoselective syntheses of xylo-iso-
mers of C -phytosphingosine. The diastereomeric mixture
18
obtained could be separated by column chromatography. Thus, the
L-xylo-(2R,3S,4S)-C - and D-xylo-(2S,3R,4R)-C -phytosphing-
18
18
osines as their tetraacetate derivatives were synthesized in dia-
stereomerically pure form.
Key words: dihydroxylation, diastereoselectivity, stereoselective
synthesis, sphingolipids, amino alcohols
Sphingolipids constitute a class of widely ranging natural
products. Although known for more than 100 years, the
finding that defects in sphingolipid metabolism lead to
several inherited human diseases and that sphingolipids
are involved in essentially all aspects of cell regulation
have led to an explosion of interest in sphingolipids,1
namely sphingomyelins, gangliosides, cerebrosides and
other complex cellular lipid homologues. These have
long-chain bases as the backbone, i.e. sphingosine (1),
phytosphingosine (2) and the biosynthetic precursor of
both, sphinganine (3) (Figure 1) which are most abundant
long-chain amino alcohols with generally 18 or 20 carbon
atoms.
Figure 2 C -phytosphingosine isomers
1
8
and -Galactosyl and glucosylphytoceramides possess
very high tumor inhibitory potency.1
0c
Phytosphingosine (2) exists abundantly as one of the mo-
lecular species of sphingolipids in microorganisms, plants Most synthetic studies have been focused primarily on the
and many mammalian tissues such as brain, hair, intes- preparation of ribo- or arabino-phytosphingosines
2
3
4
5
6
7
tine, uterus, liver, skin, kidney and in blood plasma.
(Figure 2), the stereochemistry of the C-2 position being
8
It was first isolated from mushrooms in 1911 and its either derived from the chiral pool materials, particularly
9
a
9b
11
structure was elucidated by Oda and by Carter et al. In serine, or by asymmetric synthesis. To our knowledge,
addition to its structural function as the long-chain base of only eight syntheses of lyxo- or xylo-phytosphingosines,
either racemic12 or enantiomerically pure,
11,13
have been
sphingolipids in membranes, phytosphingosine itself is a
bioactive lipid; for example, phytosphingosine (2) is a po-
tential heat stress signal in yeast cells
derivatives exhibit important physiological activities. -
described to date. No report on the asymmetric synthesis
1
0a,b
and some of its
of L-xylo-(2R,3S,4S)-C -phytosphingosine (4) was
1
8
1
4
known until our preliminary communication described
the first diastereoselective synthesis of this isomer.
Figure 1 Sphingolipid bases
Synthesis 2003, No. 1, 30 12 2002. Article Identifier:
1
©
437-210X,E;2003,0,01,0129,0135,ftx,en;T08102ss.pdf.
Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881

1
30
R. A. Fernandes, P. Kumar
PAPER
The osmium-catalyzed asymmetric dihydroxylation (AD)
1
5,16
developed by Sharpless
has evolved as one of the most
powerful methods for enantioselective oxidation of ole-
fins. Like many other reactions including the Sharpless
asymmetric epoxidation and the AD of olefins, the pre-ex-
isting chiral information in the substrate has a marked in-
fluence on the stereoselective outcome of the reaction.
Several applications of the asymmetric dihydroxylation in
the double stereodifferentiation reaction of chiral olefins
have been documented in the literature. Among the re-
ported examples are the preparation of intermediates for
1
7
the synthesis of immunosuppresant FK-506 and mycala-
1
8
mide B, the synthesis of insect juvenile hormone ep-
1
9
20
oxide, modified pyrimidine nucleobases, and the
synthesis of polyhydroxylated indolizidine alkaloid,
2
1
castanospermine.
As part of our ongoing research aimed at developing
enantioselective syntheses of naturally occurring lac-
2
2a–c
14,22d–f
22g
tones,
clure,
amino alcohols,
diolmycins and posti-
2
2h
we have recently employed the Sharpless
asymmetric dihydroxylation and the regioselective nu-
cleophilic opening of cyclic sulfites/sulfates as one of the
key steps in synthesis. Herein we have exploited the con-
cept of double stereodifferentiation in the Sharpless asym-
metric dihydroxylation of enantiomerically enriched
terminal olefins 16 and 17 with different chiral ligands.
We also report the application of the results obtained to-
ward the diastereoselective synthesis of L-xylo-
Scheme 1
(
2R,3S,4S)-C - and D-xylo-(2S,3R,4R)-C -phytosphin-
18 18
gosines.
ic ratio of 18:19 (5:1) was observed with the use of
DHQD) -PHAL ligand (Table 1). The poor diastereose-
lectivity observed in the former case may be because of
opposite influences of the chiral reagent and substrate
(
With a view to exploit the concept of double stereodiffer-
entiation, we prepared the enantiomerically enriched ter-
minal olefins 16 and 17 following the reaction steps
shown in Scheme 1. The commercially available pentade-
can-1-ol (11) was oxidized to the aldehyde and
subsequently treated with (ethoxycarbonylmethyl-
ene)triphenylphosphorane to give the Wittig product 12.
The dihydroxylation of olefin 12 using (DHQ) -PHAL
ligand under the Sharpless asymmetric dihydroxylation
conditions gave the diol 13 in 94% yield and 99% ee.
Protection of the diol followed by lithium aluminum hy-
dride reduction of the ester 14 gave compound 15 in ex-
cellent yield. The primary alcohol 15 was oxidized to the
aldehyde under the normal Swern oxidation conditions.
Subsequent Wittig reaction furnished the olefin 16. Simi-
larly the enantiomer of 16, i.e. 17 was prepared from 12
2
(
mismatched case) while the latter could be regarded as
matched case where the chirality information of the re-
agent and the substrate probably act synergistically and
therefore, a high degree of diastereoselection was ob-
tained. The use of (DHQD) -AQN ligand showing a mar-
2
2
ginal improvement in the diastereomeric ratio of 18:19
1
5
23
(
6:1) could be regarded as another example of matched
case (Table 1). Similar results were obtained with olefin
7 giving diastereomers 20 and 21 in a 5.45:1 ratio with
the use of (DHQ) -PHAL ligand and in a 1:2 ratio with
1
2
(
DHQD) -PHAL ligand (Table 1). Interestingly, when the
2
olefin 17 was subjected to the Sharpless asymmetric dihy-
droxylation reaction conditions using pyridine instead of
cinchona alkaloid as ligand, the diastereomers 20 and 21
were obtained in a 4.3:1 ratio showing a relative good di-
astereoselection (Table 1). This could be explained on the
basis of the chirality present in the substrate, which has
significant influence on diastereoselection and the stereo-
chemical course of the reaction. It may be pertinent to
mention here that although a few examples of matched
and mismatched double diastereoselection in the AD of
chiral olefins have been reported, the levels of diastereo-
selection observed in the AD of chiral monosubstituted
olefin are not as high as those observed for the other olefin
substitution classes.25
via -dihydroxylation using (DHQD) -PHAL and follow-
ing the reaction sequence as shown in Scheme 1.
2
Having obtained the enantiomerically enriched terminal
olefins 16 and 17, we subjected them to the Sharpless
asymmetric dihydroxylation reaction by varying the
ligands
stereodifferentiation are given in Table 1.
Thus when the olefin 16 was subjected to the Sharpless
asymmetric dihydroxylation using (DHQ) -PHAL ligand,
the diastereomers 18 and 19 were obtained in a 1:2 ratio,
whereas a considerable enhancement in the diastereomer-
employed.
The
results
of
double
2
4
2
Synthesis 2003, No. 1, 129–135 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Syntheses of xylo-C -Phytosphingosines
131
1
8
Table 1 Double Stereodifferentiation in AD of Olefin 16 and 17
Substrate
Ligand
18
1
19
2
20
–
21
–
Yield (%) Diastereomeric Mixture
16
16
16
(DHQ) PHAL
89
92
69
22 [ ]D20 17.3 (c = 1, CHCl3)
23 [ ]D20 19.5 (c = 1, CHCl3)
18 pure diastereomer
2
(DHQD) PHAL
5
1
–
–
2
(DHQD) AQN
6
1
–
–
2
20
[
]D
20.1 (c = 1, CHCl3)
17
(DHQ) PHAL
–
–
5.45
1
70
20 pure diastereomer
2
20
[
]D +20.3 (c = 1, CHCl3)
1
7
7
(DHQD) PHAL
–
–
–
–
1
2
1
92
83
24 [ ]D20 +18.2 (c = 1, CHCl3)
25 [ ]D20 +18.7 (c = 1, CHCl3)
2
1
Pyridine
4.3
Further we extended the above results towards the dia- Protection of the primary hydroxyl group of 18 was car-
stereoselective synthesis of L-xylo-(2R,3S,4S)-C - and D- ried out using pivaloyl chloride and pyridine at 0 °C to
1
8
xylo-(2S,3R,4R)-C -phytosphingosines. The diastereo- give 26. The C-2 hydroxyl was then converted into the
1
8
meric mixture of 18:19 in 6:1 ratio was separated by flash azido functionality through mesylation followed by the
2
6
column chromatography on TLC mesh silica gel to give nucleophilic displacement with LiN to give 27 with in-
3
1
8 in diastereomerically pure form in 69% yield. The pure version of configuration at C-2. The protection of the pri-
diastereomer 18 was converted into L-xylo-(2R,3S,4S)- mary hydroxyl group as a pivaloate was advantageous
C -phytosphingosine 4 as its tetraacetate derivative 29 as over other protecting groups since both pivaloate depro-
1
8
shown in Scheme 2.
tection and azide reduction could be accomplished togeth-
er under the same conditions. Thus, the lithium aluminum
hydride reduction of 27 gave the amino alcohol 28 in ex-
cellent yield. In an attempt to obtain amino alcohol 28 by
an alternative approach, the terminal olefin 16 was sub-
jected to the Sharpless asymmetric aminohydroxylation
reaction using (DHQ) -PHAL ligand, however, it gave a
2
complex mixture of compounds which could not be isolat-
ed. Deprotection of the acetonide in 28 was effected with
6
N HCl in MeOH to give the hydrochloride salt of
(
2R,3S,4S)-2-amino-1,3,4-trihydroxyoctadecane. This
was subsequently acetylated using acetic anhydride in py-
ridine with a catalytic amount of DMAP to give the tet-
raacetate 29 of L-xylo-(2R,3S,4S)-C -phytosphingosine
18
(
4) in diastereomerically pure form. In a similar manner
the diastereomeric mixture of 20:21 (5.45:1) was separat-
ed by column chromatography on TLC mesh silica gel26
and pure diastereomer 20 was converted into the tetra-
acetate 30 of D-xylo-(2S,3R,4R)-C -phytosphingosine
18
(
5).
The configurational assignments of xylo-C -phytosphin-
1
8
gosines 4 and 5 were made on the basis of spectroscopic
and optical rotation data of the corresponding
phytosphingosine acetates.1
3b
Thus, the absolute
(
2R,3S,4S)-configuration of the tetraacetate 29 arising
Scheme 2
Synthesis 2003, No. 1, 129–135 ISSN 0039-7881 © Thieme Stuttgart · New York

1
32
R. A. Fernandes, P. Kumar
PAPER
from its mode of formation, was confirmed by the sign of Ethyl (2R,3S)-2,3-Dihydroxyheptadecanoate (13)
To a mixture of K Fe(CN) (9.98 g, 30.4 mmol), K CO (4.20 g,
its specific rotation which was opposite to the sign of the
3
6
2
3
rotation of the known (2S,3R,4R)-enantiomer (30).13e The
30.4 mmol) and (DHQ) -PHAL (79 mg, 102 mol, 1 mol%) in t-
2
BuOH–H O (1:1, 120 mL) cooled at 0 °C was added OsO (410 L,
2
4
relative configuration of the three asymmetric carbons
0
.1 M solution in toluene, 0.40 mol%) followed by methanesulfona-
1
13
was established by comparison of the H and C NMR
mide (964 mg, 10.1 mmol). After stirring for 5 min at 0 °C, the ole-
fin 12 (3.0 g, 10.1 mmol) was added in one portion. The reaction
mixture was stirred at 0 °C for 24 h and then quenched with solid
Na SO (5.0 g). The stirring was continued for an additional 45 min
data of the acetates with those of authentic samples.1
3e
In summary, we have exploited the concept of double
stereodifferentiation in Sharpless asymmetric dihydroxy-
lation reaction and applied the results obtained toward the
2
3
and then the solution was extracted with EtOAc (5 30 mL). The
combined organic phases were washed with 10% aq KOH, brine,
dried (Na SO ) and concentrated. Silica gel column chromatogra-
diastereoselective synthesis of xylo-isomers of C -
1
8
2
4
phytosphingosine. The diastereomeric mixture obtained phy of the crude product using petroleum ether–EtOAc (3:2) as
2
0
could be separated by the TLC mesh silica gel column eluent gave 13 (3.15 g, 94%) as a white solid; mp 77–78 °C; [ ]
D
1
0.1 (c = 1, CHCl3).
chromatography. Thus, the L-xylo-(2R,3S,4S)-C - and D-
1
8
–
1
xylo-(2S,3R,4R)-C -phytosphingosines as their tetra- IR (CHCl ): 3372, 2916, 1712, 1463, 1293, 1088, 491 cm .
1
8
3
acetate derivatives were synthesized in diastereomerically
pure form.
1H NMR (200 MHz, CDCl3): = 0.85 (t, J = 6.4 Hz, 3 H), 1.2 1.3
(m, 24 H), 1.31 (t, J = 8.0 Hz, 3 H), 1.52 1.62 (m, 2 H), 3.1 (br s, 2
H), 3.82 3.88 (m, 1 H), 4.05 4.08 (m, 1 H), 4.24 (q, J = 8.0 Hz, 2
H).
Solvents were purified and dried by standard procedures before use;
petroleum ether of boiling range 60–80 °C was used. Melting points
are uncorrected. Optical rotations were measured using sodium D
line on a Jasco P-1020 microprocessor based polarimeter. IR spec-
13C NMR (50 MHz, CDCl3): = 13.9, 14.0, 22.5, 25.6, 29.2, 29.5
(
overlapping 8 C), 31.8, 33.3, 61.5, 72.5, 73.3, 173.5.
EIMS: m/z (%) = 329 ([M+
1], 0.64), 312 (0.7), 257 (4.12), 239
1
tra were recorded on ATI Mattson RS-1 FT-IR spectrometer. H
(
1.5), 104 (100), 76 (8.5), 57 (2.5).
NMR and 13C NMR spectra were recorded on Bruker AC-200 spec-
trometer. The chemical shifts were expressed in ppm ( ) downfield
Anal. Calcd for C H O (330.5): C, 69.05; H, 11.58. Found: C,
1
9
38
4
6
8.94; H, 11.67.
from TMS with residual CDCl ( = 7.27) as internal standard. Mass
3
spectra were obtained with a TSQ 70, Finningen MAT mass spec-
trometer. Elemental analyses were carried out on a Carlo Erba
CHNS-O analyzer.
Ethyl (2R,3S)-2,3-O-Isopropylideneheptadecanoate-2,3-diol
14)
To a solution of the diol 13 (8.0 g, 24.2 mmol), p-TsOH (200 mg)
in acetone (200 mL) was added 2,2-dimethoxypropane (3.53 g, 4.20
mL, 33.9 mmol) and the mixture was stirred overnight. Solid
(
Ethyl (E)-Heptadec-2-enoate (12)
A two-necked round bottom flask was charged with pentadecan-1-
ol (11; 8.0 g, 35.0 mmol) in CH Cl (200 mL) under N and then
NaHCO (1.0 g) was added and the mixture was stirred for 30 min.
3
2
2
2
The mixture was filtered through a pad of neutral alumina and con-
centrated. Silica gel column chromatography using petroleum
ether–EtOAc (24:1) gave 14 (8.79 g, 98%) as a colorless liquid;
cooled in an ice-bath. DMSO (5.50 g, 5 mL, 70.4 mmol) and P O
2
5
(10.0 g, 70.4 mmol) were added sequentially. The reaction mixture
was stirred and allowed to warm to r.t until the TLC showed com-
plete disappearance of the starting material (45 min). The flask was
2
0
[
]D
10.9 (c = 1, CHCl3).
–
1
cooled to 0 °C and Et N (17 mL) was added dropwise over one
IR (neat): 2927, 1746, 1214, 1097, 462 cm .
3
minute. The stirring was continued for 45 min in ice bath and anoth-
er 45 min at r.t. The mixture was quenched with 10% aq HCl (150
mL) and the solution extracted with EtOAc (3 50 mL). The com-
bined organic extracts were washed with brine, dried (Na SO ), fil-
tered and concentrated in vacuum to give pentadecanal as a pale
yellow oil, which was used in the next step without further purifica-
tion. To a solution of (ethoxycarbonylmethylene)triphenylphos-
phorane (14.0 g, 40.3 mmol) in anhyd THF (100 mL) was added
dropwise a solution of pentadecanal in THF (10 mL) at r.t. and the
mixture was refluxed for 12 h. The solvent was removed under re-
duced pressure and the crude product was purified on a silica gel
column using petroleum ether–EtOAc (9:1) as eluent to give 12
1H NMR (200 MHz, CDCl3): = 0.87 (t, J = 6.4 Hz, 3 H), 1.2 1.3
(m, 24 H), 1.31 (t, J = 8.0 Hz, 3 H), 1.43 (s, 3 H), 1.46 (s, 3 H), 1.68–
1
.75 (m, 2 H), 4.10 4.19 (m, 2 H), 4.25 (q, J = 8.0 Hz, 2 H).
2
4
13C NMR (50 MHz, CDCl3): = 14.2, 14.3, 22.9, 25.8 (overlapping
2
3
C), 27.3, 29.7 (overlapping 3 C), 29.9 (overlapping 6 C), 32.1,
3.8, 61.2, 79.4, 79.4, 110.8, 171.1.
EIMS: m/z (%) = 369 ([M+ 1], 1.3), 355 ([M+ 15], 100), 341
(7.7), 297 (34.6), 239 (10.2), 144 (21.8), 109 (43.6), 59 (11.5).
Anal. Calcd for C H O (370.6): C, 71.30; H, 11.42. Found: C,
2
2
42
4
7
1.44; H, 11.38.
(
9.34 g, 90%) as a colorless oil.
(
2S,3S)-2,3-O-Isopropylideneheptadecane-1,2,3-triol (15)
–
1
IR (neat): 2926, 1717, 1653, 1461, 1269, 1183, 1043, 758, 420 cm .
To a stirred suspension of LiAlH (615 mg, 16.2 mmol) in anhyd
4
1H NMR (200 MHz, CDCl3): = 0.88, (t, J = 7.4 Hz, 3 H), 1.23
Et O (100 mL) at 0 °C was added dropwise a solution of 14 (4.0 g,
2
1
0.8 mmol) in Et O (10 mL). The reaction mixture was allowed to
1
.3 (m, 22 H), 1.32 (t, J = 8.0 Hz, 3 H), 1.35 1.46 (m, 2 H), 2.2 (dd,
2
warm to r.t. and stirred overnight. Excess LiAlH was destroyed by
Jallylic = 6.0 Hz, 2 H), 4.20 (q, J = 8.0 Hz, 2 H), 5.8 (dt, Jtrans = 16.0
Hz, 1 H), 6.97 (dt, Jtrans = 16.0 Hz, Jallylic = 6.0 Hz, 1 H).
4
slow addition of 10% aq NaOH (2 mL) and EtOAc (20 mL). The
white precipitate was filtered through a pad of neutral alumina and
washed with MeOH (3 100 mL). The filtrate was concentrated and
the residue was purified by silica gel column chromatography using
1
3
C NMR (50 MHz, CDCl ): = 13.6, 13.8, 22.3, 27.7, 28.9, 29.1,
3
2
1
9.4 (overlapping 7 C), 31.6 (overlapping 2 C), 59.4, 121.0, 148.5,
65.8.
petroleum ether–EtOAc (4:1) as eluent to give 15 (3.30 g, 93%) as
+
20
EIMS: m/z (%) = 296 ([M ], 14.9), 251 (35), 250 (36.3), 199 (28.6),
a white solid; mp 45–46 °C; [ ]
D
16.5 (c = 1, MeOH).
1
55 (40), 127 (99), 101 (100), 83 (25), 69 (7.1), 55 (5.9).
–1
IR (CHCl ): 3440, 2926, 1460, 1361, 1216, 764, 667 cm .
3
Anal. Calcd for C H O (296.5): C, 76.97; H, 12.24. Found: C,
19
36
2
7
7.01; H, 12.16.
Synthesis 2003, No. 1, 129–135 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Syntheses of xylo-C -Phytosphingosines
133
1
8
1H NMR (200 MHz, CDCl3): = 0.88 (t, J = 7.2 Hz, 3 H), 1.2 1.3
quenched with solid Na SO (3.0 g). The stirring was continued for
2
3
(
m, 24 H), 1.4 (s, 3 H), 1.41 (s, 3 H), 1.52 1.56 (m, 2 H), 2.17 (br
an additional 45 min and then the solution was extracted with
EtOAc (5 30 mL). The combined organic phases were washed
s, 1 H), 3.55 3.63 (m, 1 H), 3.7 3.85 (m, 2 H), 3.93 4.07 (m, 1 H).
1
3
with brine, dried (Na SO ) and concentrated. Silica gel column
2 4
C NMR (50 MHz, CDCl ): = 13.9, 22.6, 25.2, 25.4, 25.8, 26.5,
3
chromatography of the crude product using petroleum ether–ace-
tone (7:3) as eluent gave the diols 18–24 as white solids in 89–92%
yield.
2
1
7.0, 27.3, 29.2, 29.5 (overlapping 5 C), 31.8, 33.1, 62.3, 77.2, 81.7,
08.5.
+
+
EIMS: m/z (%) = 329 ([M + 1], 1.3), 314 ([M
27), 231 (2.6), 109 (12.8), 95 (14.1), 59 (1.3).
15], 100), 297
(
1
8
This compound was prepared following the above procedure and
using (DHQD) AQN (1.50 mol%) and OsO (0.80 mol%). The dia-
Anal. Calcd for C H O (328.5): C, 73.12; H, 12.27. Found: C,
20
40
3
7
2.96; H, 12.36.
2
4
stereomeric mixture of 18 and 19 in 6:1 ratio was separated by flash
column chromatography on TLC mesh silica gel using petroleum
ether–EtOAc (7:3) as eluent to give 18 (69%) as a white solid; mp
(
3S,4S)-3,4-O-Isopropylideneoctadec-1-ene-3,4-diol (16);
Typical Procedure
To a solution of oxalyl chloride (1.74 g, 1.20 mL, 13.7 mmol) in an-
hyd CH Cl (75 mL) cooled at 78 °C was added dropwise DMSO
2
0
5
4–56 °C; [ ]D
20.1 (c = 1, CHCl3).
–1
2
2
IR (CHCl ): 3358–3250, 2924, 1465, 1382, 1220, 760, 479 cm .
3
(
2.14 g, 1.95 mL, 27.4 mmol) in CH Cl (5 mL) over 20 min. The
2 2
1
H NMR (200 MHz, CDCl ): = 0.88 (t, J = 6.4 Hz, 3 H), 1.23 1.3
3
reaction mixture was stirred for 30 min at 78 °C and a solution of
alcohol 15 (3.0 g, 9.13 mmol) in CH Cl (10 mL) was added drop-
wise at 60 °C over 20 min. The mixture was stirred for 30 min
when a copious white precipitate was obtained. Et N (4.21 g, 5.80
(
m, 24 H), 1.38 (s, 3 H), 1.40 (s, 3 H), 1.52 1.58 (m, 2 H), 2.62 (br
2
2
s, 2 H), 3.55 3.76 (m, 4 H), 3.8 4.0 (m, 1 H).
1
3
C NMR (50 MHz, CDCl ): = 14.0, 22.6, 26.1, 27.1, 27.3, 29.3,
3
3
mL, 41.0 mmol) was added dropwise and stirred for 1 h allowing the
temperature to rise to r.t. The mixture was quenched with 5% aq
HCl (100 mL) and extracted with EtOAc. The combined organic
phases were washed with brine, dried (Na SO ) and concentrated to
give the crude aldehyde, which was used in the next step without
further purification. To a suspension of methyltriphenylphosphoni-
um iodide (5.0 g, 12.4 mmol) in anhyd THF (10 mL) was added
NaHMDS (14 mL, 14.0 mmol, 1 M in THF) and stirred overnight
at r.t. The precipitated solids were allowed to settle and the super-
natant liquid was added through a syringe to the solution of the al-
dehyde in anhyd THF (15 mL). The mixture was stirred at r.t. for 18
29.6 (overlapping 8 C), 31.9, 34.2, 63.9, 72.7, 79.4, 81.2, 108.7.
+
+
EIMS: m/z (%) = 359 ([M + 1], 1.2), 343 ([M 15], 100), 297
84.6), 269 (21.8), 109 (28), 95 (55.3), 83 (42.2), 59 (17.0).
(
2
4
Anal. Calcd for C H O (358.6): C, 70.34; H, 11.80. Found: C,
21 42
4
7
0.36; H, 11.73.
2
0
The diastereomeric mixture of 20:21 (5.45:1) was separated by
flash column chromatography on TLC mesh silica gel using petro-
leum ether–EtOAc (7:3) as eluent to give pure diastereomer 20
2
0
(
7
0
%
)
a
s
a
w
h
i
t
e
s
o
l
i
d
;
m
p
4
9
–
5
0
°
C
;
[
]
+
2
0
.
3
(
c
=
1
,
C
H
C
l
)
.
h and then quenched with sat. aq NH Cl. The aqueous layer was ex-
D
3
4
tracted with EtOAc (3 30 mL). The combined organic extracts
The spectroscopic data were the same as described for compound
18.
were washed (brine), dried (Na SO ) and concentrated. Purification
2
4
of the residue by silica gel column chromatography using petroleum
ether–EtOAc (24:1) gave 16 (2.28 g, 77%) as a pale yellow oil;
2
2 (1:2 Diasteromeric Mixture of 18/19)
20
[
]D
4.6 (c = 1, CHCl3].
20
Mp 53–55 °C; [ ]D
17.3 (c = 1, CHCl3).
–
1
IR (neat): 2926, 2855, 1460, 1361, 1217, 1048, 764, 639 cm .
–1
IR (CHCl ): 3420–3300, 2923, 1465, 1378, 1245, 861, 487 cm .
3
1H NMR (200 MHz, CDCl3): = 0.88 (t, J = 7.2 Hz, 3 H), 1.2 1.3
1H NMR (200 MHz, CDCl3): = 0.86 (t, J = 6.4 Hz, 3 H), 1.2 1.3
(
(
1
m, 24 H), 1.41 (s, 6 H), 1.52 1.56 (m, 2 H), 3.6 3.7 (m, 1 H), 3.98
t, J = 8.0 Hz, 1 H), 5.2 5.4 (m, 2 H), 5.7 5.9 (m, 1 H).
(
3
m, 24 H), 1.37 (s, 6 H), 1.51 1.56 (m, 2 H), 3.18 (br s, 2 H), 3.61
.76 (m, 2 H), 3.85 4.09 (m, 3 H).
3
C NMR (50 MHz, CDCl ): = 14.6, 23.2, 26.6, 27.5, 27.8, 29.9,
13
3
C NMR (50 MHz, CDCl ): = 13.4, 22.1, 25.4, 25.5, 26.4, 26.8,
3
3
1
0.1, 30.2 (overlapping 7 C), 32.5 (overlapping 2 C), 81.3, 83.3,
08.9, 118.8, 136.3.
2
8
8.8, 29.1, 29.6, 29.9 (overlapping 5 C), 31.4, 33.2, 67.0, 76.7, 80.0,
0.8, 108.1.
EIMS: m/z (%) = 324 ([M ], 1.3), 309 ([M+ 15], 50), 225 (21.8),
+
+
+
EIMS: m/z (%) = 359 [M + 1], 1.2), 343 ([M 15], 100), 297 (91),
69 (28.2), 109 (38.46), 95 (65.4), 83 (38.46), 59 (21.8).
1
23 (9), 109 (15.4), 98 (100), 83 (7.7), 57 (1.3).
2
Anal. Calcd for C H O (324.6): C, 77.70; H, 12.42. Found: C,
21
40
2
Anal. Calcd for C H O (358.6): C, 70.34; H, 11.80. Found: C,
21 42 4
7
7.50; H, 12.48.
7
0.23; H, 11.78.
(
3R,4R)-3,4-O-Isopropylideneoctadec-1-ene-3,4-diol (17)
2
3 (5:1 Diasteromeric Mixture of 18/19)
This compound was prepared from 12 following the typical proce-
dure described for compound 16. The ligand used in this case was
20
Mp 51–52 °C; [ ]D
IR (CHCl ): 3355–3253, 2923, 1460, 1375, 1215, 755, 481 cm .
1H NMR (200 MHz, CDCl3): = 0.87 (t, J = 6.4 Hz, 3 H), 1.2 1.3
m, 24 H), 1.38 (s, 3 H), 1.40 (s, 3 H), 1.50 1.54 (m, 2 H), 2.94 (br
s, 2 H), 3.6 3.8 (m, 4 H), 3.9 4.12 (m, 1 H).
13C NMR (50 MHz, CDCl
): = 13.2, 21.9, 25.5, 26.4, 26.8, 28.3,
19.5 (c = 1, CHCl3).
–
1
2
0
3
(DHQD) PHAL. Pale yellow oil; [ ]D +4.7 (c = 1, CHCl3).
2
The spectroscopic data were the same as described for compound
6.
(
1
Asymmetric Dihydroxylation of Compounds 16 and 17;
General Procedure
To a mixture of K Fe(CN) (7.60 g, 23.1 mmol), K CO (3.20 g,
3
28.6, 29.0, 29.4, 29.8 (overlapping 5 C), 31.3, 33.7, 63.5, 72.7, 79.3,
80.5, 107.8.
3
6
2
3
2
3.1 mmol) and the ligand (72 mg, 92.4 mol, 1.20 mol%) in
+
+
EIMS: m/z (%) = 359 ([M + 1], 1.2), 343 ([M
(
15], 100), 297
t-BuOH–H O (1:1, 90 mL) cooled at 0 °C was added OsO (468 L,
0
0
2
4
87.2), 269 (29.5), 109 (25.6), 95 (36.0), 83 (42.3), 59 (32.0).
.1 M solution in toluene, 0.60 mol%). After stirring for 5 min at
°C, the olefin 16 or 17 (2.50 g, 7.70 mmol) was added in one por-
Anal. Calcd for C H O (358.6): C, 70.34; H, 11.80. Found: C,
21 42
4
7
0.18; H, 11.92.
tion. The reaction mixture was stirred at 0 °C for 24 h and then
Synthesis 2003, No. 1, 129–135 ISSN 0039-7881 © Thieme Stuttgart · New York

1
34
R. A. Fernandes, P. Kumar
PAPER
2
4 (1:2 Diasteromeric Mixture of 20/21)
(100), 158 (24.3), 109 (11.5), 85 (43.6), 57 (21.8).
Anal. Calcd for C H O (442.7): C, 70.54; H, 11.38. Found: C,
2
0
Mp 48–50 °C; [ ]D +18.2 (c = 1, CHCl3).
2
6
50
5
IR (CHCl ): 3354–3252, 2924, 1467, 1377, 1216, 756, 478, 454
cm .
70.42; H, 11.25.
3
–
1
1H NMR (200 MHz, CDCl3): = 0.88 (t, J = 6.4 Hz, 3 H), 1.2 1.3
(2R,3S,4S)-2-Azido-1-O-pivaloyl-3,4-O-isopropylideneocta-
decane-1,3,4-triol (27)
(
m, 24 H), 1.38 (s, 3 H), 1.41 (s, 3 H), 1.51 1.55 (m, 2 H), 2.01 (br
To a solution of 26 (1.20 g, 2.70 mmol) in anhyd pyridine (3 mL)
and CH Cl (4 mL) was added DMAP (cat.), followed by MeSO Cl
s, 1 H), 2.62 (br s, 1 H), 3.55 3.81 (m, 3 H), 3.9 4.2 (m, 2 H).
13C NMR (50 MHz, CDCl3): = 13.3, 22.1, 25.3, 25.6, 26.4, 26.8,
2
2
2
(0.62 g, 0.42 mL, 5.40 mmol) and the reaction mixture was heated
2
8
8.7, 29.1, 29.5, 29.9 (overlapping 4 C), 31.4, 33.2, 33.8, 63.6, 76.7,
0.0, 80.9, 108.1.
to 60 °C for 5 h. It was then cooled, quenched with H O (10 mL),
2
and the aqueous phase was extracted with EtOAc (3 20 mL). The
EIMS: m/z (%) = 343 ([M+ 15], 7.7), 297 (100), 265 (16.7), 107
66.7), 95 (27.0), 83 (28.2), 59 (2.5).
combined organic extracts were washed (H O and then brine), dried
2
(
Na SO ) and concentrated to give the crude mesylate, which was
(
2 4
used for the next step without further purification. To the solution
Anal. Calcd for C H O (358.6): C, 70.34; H, 11.80. Found: C,
21
42
4
of mesylate in anhyd DMF (15 mL) was added LiN (530 mg, 10.8
3
7
0.50; H, 12.06.
mmol) and stirred at 80 °C for 12 h. The mixture was cooled and
treated with acetone. The solid material was filtered and washed
with acetone. The filtrate was concentrated and the residue was
purified by silica gel column chromatography using petroleum
2
5 (4.3:1 Diasteromeric Mixture of 20/21)
To a mixture of K Fe(CN) (7.60 g, 23.1 mmol), K CO (3.20 g,
3
6
2
3
2
3.1 mmol) and pyridine (31 L, 385 mol, 5 mol%) in t-BuOH–
ether–EtOAc (24:1) to give 27 (1.11 g, 88%) as a colorless oil;
H O (1:1, 90 mL) cooled at 0 °C was added OsO (468 L, 0.1 M
20
2
4
[
]D
22.8 (c = 1, CHCl3).
solution in toluene, 0.60 mol%). After stirring for 5 min at 0 °C, the
olefin 17 (2.50 g, 7.70 mmol) was added in one portion. The reac-
tion mixture was stirred at 0 °C for 24 h and then quenched with sol-
id Na SO (3.0 g). The stirring was continued for an additional 45
IR (neat): 2926, 2855, 2116, 1738, 1463, 1371, 1281, 1149, 1100,
–
1
4
87 cm .
1
2
3
H NMR (200 MHz, CDCl ): = 0.88 (t, J = 6.4 Hz, 3 H), 1.24 (s,
3
min and then the solution was extracted with EtOAc (4 30 mL).
The combined organic phases were washed with brine, dried
9
H), 1.25 1.3 (m, 24 H), 1.39 (s, 3 H), 1.44 (s, 3 H), 1.51 1.56 (m,
2
H), 3.47 (t, J = 6.2 Hz, 1 H), 3.65 3.69 (m, 1 H), 4.02 4.06 (m,
(
Na SO ) and concentrated. Silica gel column chromatography of
2 4
1 H), 4.32 4.36 (m, 2 H).
13C NMR (50 MHz, CDCl
): = 13.8, 22.5, 25.7, 26.3, 26.9 (over-
3
lapping 3 C), 27.2, 29.1, 29.4 (overlapping 8 C), 31.7, 32.7, 38.6,
the crude product using petroleum ether–acetone (7:3) as eluent
2
0
gave 25 (2.30 g, 83%) as a white solid; mp 50–52 °C; [ ]D +18.7
c = 1, CHCl3).
(
5
9.4, 64.0, 77.3, 80.2, 109.1, 177.4.
–
1
IR (CHCl ): 3350–3245, 2928, 1465, 1378, 1210, 766, 474 cm .
3
+
+
EIMS: m/z (%) = 469 ([M + 2], 1.0), 452 ([M
15], 3.9), 297
1
H NMR (200 MHz, CDCl ): = 0.87 (t, J = 6.4 Hz, 3 H), 1.2 1.33
3
(100), 280 (30.8), 214 (30.7), 109 (14.1), 85 (20.5), 57 (2.5).
(m, 24 H), 1.36 (s, 3 H), 1.40 (s, 3 H), 1.53 (m, 2 H), 2.94 (br s, 2
Anal. Calcd for C H N O (467.7): C, 66.77; H, 10.56; N, 8.98.
2
6
49
3
4
H), 3.55 3.75 (m, 4 H), 3.97 (m, 1 H).
Found: C, 66.55; H, 10.66; N, 8.89.
1
3
C NMR (50 MHz, CDCl ): = 13.9, 22.5, 25.9, 26.7, 27.1 (over-
3
lapping 3 C), 27.3, 29.2 (overlapping 4 C), 31.8 (overlapping 3 C),
4.1, 66.2, 71.5, 79.4, 80.5, 108.7.
EIMS: m/z (%) = 343 ([M+ 15], 7.9), 297 (100), 265 (17.9), 107
66.7), 95 (32.0), 83 (28.2), 59 (3.5).
(
2R,3S,4S)-2-Amino-3,4-O-isopropylideneoctadecane-1,3,4-
triol (28)
To a stirred suspension of LiAlH (244 mg, 6.41 mmol) in anhyd
3
4
Et O (20 mL) at 0 °C was added dropwise a solution of 27 (1.0 g,
2
warm to r.t. and stirred overnight. Excess LiAlH was destroyed by
slow addition of 10% aq NaOH (2 mL) and EtOAc (15 mL). The
white precipitate was filtered through a pad of neutral alumina and
washed with MeOH (3 50 mL). The filtrate was concentrated and
the residue was purified by silica gel column chromatography using
CHCl –MeOH (9:1) as eluent to give 28 (734 mg, 96%) as a white
solid; mp 55–57 °C; [ ]D
(
2
.14 mmol) in Et O (5 mL). The reaction mixture was allowed to
2
Anal. Calcd for C H O (358.6): C, 70.34; H, 11.80. Found: C,
21
42
4
4
7
0.44; H, 11.96.
(
1
2S,3R,4S)-1-O-Pivaloyl-3,4-O-isopropylideneoctadecane-
,2,3,4-tetrol (26)
To a solution of 18 (1.25 g, 3.48 mmol) in CH Cl (5 mL) and pyri-
2
2
3
dine (3 mL) at 0 °C was added dropwise pivaloyl chloride (443 mg,
.45 mL, 3.65 mmol) in CH Cl (2 mL) over 30 min. The reaction
20
24.3 (c = 1, MeOH).
0
2
2
–
1
IR (CHCl ): 3370, 3357, 2925, 1380, 758, 468 cm .
mixture was allowed to warm to r.t. and stirred overnight. H O (15
3
2
mL) was added and the aqueous layer was extracted with EtOAc (3
1H NMR (200 MHz, CDCl3): = 0.88 (t, J = 6.4 Hz, 3 H), 1.2 1.3
(m, 24 H), 1.40 (s, 6 H), 1.52 1.56 (m, 2 H), 2.9 3.3 (m, 4 H), 3.5
3.6 (m, 3 H), 3.91 3.94 (m, 1 H).
2
0 mL). The combined organic extracts were washed (H O and
2
then brine), dried (Na SO ) and concentrated. The residue was pu-
2
4
rified by silica gel column chromatography using petroleum ether–
13C NMR (50 MHz, CDCl
9.6 (overlapping 8 C), 31.8, 33.4, 53.7, 63.9, 78.0, 81.1, 108.7.
): = 14.0, 22.6, 26.1, 27.0, 27.3, 29.3,
3
2
0
acetone (9:1) to give 26 (1.43 g, 93%) as a colorless oil; [ ]D
7.2 (c = 1, CHCl3).
2
1
+
+
–
1
EIMS: m/z (%) = 357 ([M ], 1.0), 342 ([M 15], 14.0), 326 (16.7),
97 (16.6), 282 (16.8), 268 (37.1), 167 (1.3), 149 (1.4), 100 (100),
IR (neat): 3484, 2925, 1725, 1480, 1371, 1164, 1064, 458 cm .
1H NMR (200 MHz, CDCl3): = 0.88 (t, J = 6.4 Hz, 3 H), 1.23 (s,
2
60 (99.0).
9
2
H), 1.22 1.3 (m, 25 H), 1.37 (s, 3 H), 1.40 (s, 3 H), 1.53 1.59 (m,
H), 3.6 (t, J = 6.2 Hz, 1 H), 3.85 3.91 (m, 1 H), 3.99 4.03 (m, 1
Anal. Calcd for C H NO (357.6): C, 70.53; H, 12.12; N, 3.91.
2
1
43
3
Found: C, 70.62; H, 12.08; N, 3.85.
H) 4.14 4.19 (m, 1 H), 4.27 4.32 (m, 1 H).
13C NMR (50 MHz, CDCl3): = 13.8, 22.5, 25.9, 26.8 (overlapping
(2R,3S,4S)-2-Acetamido-1,3,4-triacetoxyoctadecane (29);
Typical Procedure
To a solution of 28 (780 mg, 2.18 mmol) in MeOH (15 mL) was
added aq 6 N HCl (3 mL) at r.t. and the mixture was stirred over-
3
7
C), 26.9, 27.2, 29.1 (overlapping 9 C), 31.7, 34.1, 38.6, 66.0, 71.3,
9.3, 80.3, 108.5, 178.7.
EIMS: m/z (%) = 427 ([M+
15], 84.6), 367 (3.8), 340 (1.0), 297
Synthesis 2003, No. 1, 129–135 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Syntheses of xylo-C -Phytosphingosines
135
1
8
night. Solid NaHCO (1.0 g) was added and the mixture was filtered
through a pad of neutral alumina and further eluted with MeOH (3
(9) (a) Oda, T. J. Pharm. Soc. Jpn. 1952, 72, 142. (b)Carter,H.
E.; Hendrickson, H. S. Biochemistry 1963, 2, 389.
(10) (a) Dickson, R. C.; Nagiec, E. E.; Skrzypek, M.; Tillman, P.;
Wells, G. B.; Lester, R. L. J. Biol. Chem. 1997, 272, 30196.
(b) Schneiter, R. Bioessays 1999, 21, 1004. (c) Kobayashi,
E.; Motoki, K.; Yamaguchi, Y.; Uchida, T.; Fukushima, H.;
Koezuka, Y. Oncol. Res. 1995, 7, 529.
3
2
0 mL). The combined filtrate was concentrated to a white pow-
der of hydrochloride salt, which was subsequently acetylated with
Ac O (3 mL) in pyridine (5 mL) and in CH Cl (5 mL) containing
2
2
2
DMAP (cat.). After stirring for 12 h at r.t., the mixture was
quenched with H O (10 mL) and the aqueous layer was extracted
2
with EtOAc (4 20 mL). The combined organic extracts were
washed (H O and then brine), dried (Na SO ) and concentrated. Sil-
ica gel column chromatography of the crude product using petro-
(11) Martin, C.; Prunck, W.; Bortolussi, M.; Bloch, R.
Tetrahedron: Asymmetry 2000, 11, 1585; and references
cited therein.
2
2
4
leum ether–EtOAc (3:2) as eluent gave 29 (690 mg, 67%) as a waxy
(12) Sisido, K.; Tamura, H.; Kobata, H.; Takagisi, M.; Isida, T. J.
Org. Chem. 1970, 35, 350.
2
0
white solid; mp 51–52 °C; [ ]D
7.2 (c = 1.2, CHCl3).
–
1
(13) (a) Schmidt, R. R.; Maier, T. Carbohydr. Res. 1988, 174,
IR (CHCl ): 3297, 3290, 2925, 1744, 1662, 1226, 479 cm .
3
169. (b) Sugiyama, S.; Honda, M.; Komori, T. Liebigs Ann.
1H NMR (200 MHz, CDCl3): = 0.86 (t, J = 6.4 Hz, 3 H), 1.2 1.3
m, 24 H), 1.53 1.56 (m, 2 H), 2.03 (s, 3 H), 2.04 (s, 6 H), 2.07 (s,
H), 3.95 4.05 (m, 2 H), 4.3 4.55 (m, 1 H), 5.02 5.18 (m, 2 H),
Chem. 1990, 1069. (c) Li, Y. L.; Mao, X. H.; Wu, Y. L. J.
Chem. Soc., Perkin Trans. 1 1995, 1559. (d) Nakamura, T.;
Shiozaki, M. Tetrahedron Lett. 1999, 40, 9063. (e) Shirota,
O.; Nakanishi, K.; Berova, N. Tetrahedron 1999, 55, 13643.
(f) He, L.; Byun, H.-S.; Bittman, R. J. Org. Chem. 2000, 65,
(
3
5
.92 (d, J = 10.2 Hz, 1 H).
1
3
C NMR (50 MHz, CDCl ): = 13.5, 19.2, 20.4, 22.1, 22.2, 24.3,
8.8, 29.1 (overlapping 9 C), 30.0, 31.4, 48.0, 62.9, 71.3, 71.9,
3
7
618.
14) Fernandes, R. A.; Kumar, P. Tetrahedron Lett. 2000, 41,
0309.
15) (a) Becker, H.; Sharpless, K. B. Angew. Chem., Int. Ed. Engl.
996, 35, 448. (b) Kolb, H. C.; VanNiewenhze, M. S.;
2
1
(
(
69.5, 169.5, 169.8, 169.8.
1
+
EIMS: m/z (%) = 486 ([M + 1], 2.5), 426 (2.4), 292 (32.0), 144
(86.0), 102 (60.0), 84 (100).
1
Anal. Calcd for C H NO (485.67): C, 64.30; H, 9.75; N, 2.88.
Found: C, 64.57; H, 9.86; N, 2.95.
Sharpless, K. B. Chem. Rev. 1994, 94, 2483. (c) Sharpless,
K. B.; Amberg, W.; Bennani, Y. L.; Crispino, G. A.;
Hartung, J.; Jeong, K. S.; Kwong, H.-L.; Morikawa, K.;
Wang, Z.-M.; Xu, D.; Zhang, X.-L. J. Org. Chem. 1992, 57,
2768.
2
6
47
7
(
2S,3R,4R)-2-Acetamido-1,3,4-triacetoxyoctadecane (30)
This compound was prepared from 20 following the typical proce-
2
0
dure described for 29; waxy white solid; mp 53–55 °C; [ ] +7.2
(16) (a) Schroeder, M. Chem. Rev. 1980, 80, 187. (b) Hanson, R.
M. Chem. Rev. 1991, 91, 437.
D
1
3e
21
(
c = 1, CHCl ) {Lit. [ ]D +7.0 (c = 0.86, CHCl )}.
3
3
(
(
(
(
(
(
17) Ireland, R. E.; Wipf, P.; Roper, T. D. J. Org. Chem. 1990, 55,
284.
18) Hoffmann, R. W.; Schlapbach, A. Tetrahedron Lett. 1993,
4, 7903.
19) Rickards, R. W.; Thomas, R. D. Tetrahedron Lett. 1993, 34,
369.
20) Barvin, M. R.; Greenberg, M. M. J. Org. Chem. 1993, 58,
151.
21) Kim, N.-S.; Choi, J.-R.; Cha, J. K. J. Org. Chem. 1993, 58,
096.
22) (a) Pais, G. C. G.; Fernandes, R. A.; Kumar, P. Tetrahedron
999, 55, 13445. (b) Fernandes, R. A.; Kumar, P.
The spectroscopic data were the same as described for compound
9.
2
2
3
Acknowledgments
8
R.A.F. thanks CSIR, New Delhi, for financial assistance. We are
grateful to Dr. M. K. Gurjar, Head, Organic Chemistry, Technology
division for his support and encouragement. This is NCL Commu-
nication No 6629.
6
7
1
References
Tetrahedron: Asymmetry 1999, 10, 4349. (c) Fernandes, R.
A.; Kumar, P. Eur. J. Org. Chem. 2002, 2921.
(
1) For an excellent overview of sphingolipid functions, see:
a) Merrill, A. H. Jr.; Sweeley, C. C. Biochemistry of Lipids,
(
1
d) Fernandes, R. A.; Kumar, P. Tetrahedron: Asymmetry
999, 10, 4797. (e) Fernandes, R. A.; Kumar, P. Eur. J. Org.
(
Lipoproteins and Membranes; Vance, D. E.; Vance, J. E.,
Eds.; Elsevier: Amsterdam, 1996, Chap. 12, 309.
Chem. 2000, 3447. (f) Pandey, R. K.; Fernandes, R. A.;
Kumar, P. Tetrahedron Lett. 2002, 43, 4425. (g)Fernandes,
R. A.; Bodas, M. S.; Kumar, P. Tetrahedron 2002, 58, 1223.
(b) Vankar, Y. D.; Schmidt, R. R. Chem. Soc. Rev. 2000, 29,
201.
(
h) Fernandes, R. A.; Kumar, P. Tetrahedron 2002, 58, 6685.
(
(
(
(
2) Okabe, K.; Keeman, R. W.; Schmidt, G. Biochem. Biophys.
(
23) The enantiomeric excess of the corresponding dibenzoate
Res. Commun. 1968, 31, 137.
was determined by HPLC using Lichrocart 250-4 (4 mm ID
3) Takamatsu, K.; Mikami, M.; Kikuchi, K.; Nozawa, S.;
Iwamori, M. Biochim. Biophys. Acta 1992, 1165, 177.
4) Barenholz, Y.; Gatt, S. Biochem. Biophys. Res. Commun.
2
5 cm) HPLC-Cartridge (R. R.-Whelk-01), 10% i-PrOH in
hexane, 1 mL/min.
24) The diastereomeric ratio was determined by H NMR and
1
(
(
1967, 27, 319.
1
3
C NMR spectroscopy.
5) (a) Wertz, P. W.; Miethke, M. C.; Long, S. A.; Stauss, J. S.;
25) For examples of double diastereoselective asymmetric
dihydroxylation of chiral monosubstituted olefins, see:
Downing, D. T. J. Invest. Dertmatol. 1985, 84, 410.
(
b) Schmidt, R. R. In Liposome Dermatics; Braun-Falco, O.;
(a) Jirousek, M. R.; Cheung, A. W.-H.; Babine, R. E.; Sass,
Corting, H. C.; Maibach, H. I., Eds.; Springer-Verlag:
Berlin, 1992, 44–56.
P. M.; Schow, S. R.; Wick, M. M. Tetrahedron Lett. 1993,
3
5
4, 3671. (b) Sinha, S. C.; Keinan, E. J. Org. Chem. 1994,
9, 949. (c) Gurjar, M. K.; Mainkar, A. S.; Syamala, M.
(
6) (a) Karlsson, K. A.; Samuelsson, B. E.; Steen, G. O. Acta
Chem. Scand. 1968, 22, 136. (b) Karlsson, K. A. Acta
Chem. Scand. 1964, 18, 2395.
Tetrahedron: Asymmetry 1993, 4, 2343.
(
26) Taber, D. F. J. Org. Chem. 1982, 47, 1351.
(
(
7) Vance, D. E.; Sweeley, C. C. J. Lipid Res. 1967, 8, 621.
8) Zellner, J. Monatsh. Chem. 1911, 32, 133.
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