Synthesis of glycolipid clusters with pentaerythritol cores and different ethyleneoxy-spaced mannose residues as terminal carbohydrates

Article abstract of DOI:10.1002/1099-0690(200202)2002:4<669::aid-ejoc669>3.0.co;2-n

We describe the synthesis of polyantennary glycolipid clusters with pentaerythritol cores. A known protecting group strategy permits the introduction of different hydrophobic moieties and the selective coupling with ethyleneoxy spacers of different lengths. After glycosidation, substances with one, two or three mannose residues as terminal carbohydrate headgroups were isolated. These polyantennary mannosides can be used as attractive tools for targeting of liposomes towards the macrophage mannose receptor.

Full text of DOI:10.1002/1099-0690(200202)2002:4<669::aid-ejoc669>3.0.co;2-n

FULL PAPER
Synthesis of Glycolipid Clusters with Pentaerythritol Cores and Different
Ethyleneoxy-Spaced Mannose Residues as Terminal Carbohydrates
Matthias Schmidt,[a] Bodo Dobner,[a] and Peter Nuhn*[a]
Keywords: Alkylation / Cluster compounds / Glycolipids / Glycosidation
We describe the synthesis of polyantennary glycolipid clus-
two or three mannose residues as terminal carbohydrate
ters with pentaerythritol cores. A known protecting group headgroups were isolated. These polyantennary mannosides
strategy permits the introduction of different hydrophobic
moieties and the selective coupling with ethyleneoxy spacers
of different lengths. After glycosidation, substances with one,
can be used as attractive tools for targeting of liposomes to-
wards the macrophage mannose receptor.
Complex carbohydrate structures are one of the basic distances to be introduced within the molecule in place of
constituents of biological membranes besides phospholip- the former cluster glycolipids with equal sugar domains or
ids. The importance of the carbohydrate domains in the spacer lengths.[11] In this case we have synthesized mono-,
context of glycoproteins and glycolipids as elements of all di- and trimannosylated glycolipids. The molecules differ in
surface recognition is manifested by their role in cellular the number of lipid anchors, in the length and number of
adhesion. Investigations into the interaction of natural gly- the ethyleneoxy spacers used in place of natural oligosacch-
coconjugates indicate that the structures of the terminal arides, and in the variety of terminal carbohydrate headg-
carbohydrate headgroups in the hydrophilic moiety and the roups. As the sugar domain we chose mannose, because of
different distances between the hydrophobic and the recog- our investigation into mannosylated liposomes as attractive
nition domains are responsible for the efficiency of ligand tools for targeting towards the macrophage mannose recep-
coupling to the receptor. Because of the complexity of the tor.
total retrosynthesis of natural oligosaccharides (Sialyl-
LewisX, for example),[1] interest in simply structured model pentaerythritol [2,2-bis(hydroxymethyl)propane-1,3-diol],
substances is growing.
of which diverse functional derivatives are known.[12,13] The
The core substance of our neoglycoconjugates is
On one hand, the development of neoglycoconjugates lipid anchor starting materials used in this work, O-hexa-
with two, three or more sugar compounds in the hydro- decyl-OЈ,OЈЈ-(p-methoxybenzylidene)pentaerythritol (1), O-
philic moiety evidence the cluster effect and hence a logar- benzyl-OЈ-hexadecylpentaerythritol (2), O-hexadecylpenta-
ithmic increase of the binding affinity. On the other hand, erythritol (3), di-O,OЈ-hexadecylpentaerythritol (4) and O-
studies of glycomimics with different ethyleneoxy spacers benzyl-OЈ-hexadecyl-OЈЈ-(p-methoxybenzyl)pentaerythritol
demonstrate a relationship between the spacer length and (5),[10] are shown in Scheme 1.
adhesion effects of the corresponding receptor.
There are actually two possible means to simulate effect-
ive ligandϪreceptor binding with carbohydrate-clustered
glycoconjugates. Beside the glycodendrimers,[2Ϫ5] highly
branched, complex and symmetrical macromolecules with
a core substance and multiple terminal sugar residues,[6,7]
which can be applied in, for example, antiadhesion ther-
apy,[8] the incorporation of neocluster glycolipids in large
unilamellar liposomes, as first reported by Lee et al.,[9]
promises to be a possible target strategy.
In continuation of our work on the study of cellular re-
sponse towards liposomes, we have developed a synthetic
strategy[10] that allows different carbohydrates with suitable
[a]
Institute of Pharmaceutical Chemistry, Martin Luther
University,
Wolfgang-Langenbeck-Str. 4, 06120 Halle/Saale, Germany
E-mail: nuhn@pharmazie.uni-halle.de
Scheme 1. Different functionalized O-hexadecylpentaerythritol de-
rivatives 1Ϫ5
Eur. J. Org. Chem. 2002, 669Ϫ674
WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002 1434Ϫ193X/02/0204Ϫ0669 $ 17.50ϩ.50/0
669

M. Schmidt, B. Dobner, P. Nuhn
FULL PAPER
The substances are characterized by different numbers of structures of the hydrophobic and spacer core substance be-
hexadecyl residues as a lipid anchor that can of course be tween small/short terminal binding domains and polyanten-
exchanged for other long alkyl chains Ϫ with branching, nary/voluminous ligands we can synthesize a host of syn-
for example[10]
Ϫ to achieve efficient and variable thons that promise to find neoglycoconjugates for optimal
hydrophilicϪlipophilic balance (HLB) values as possible ligandϪreceptor binding.
membrane components.
The selective protection of the hydroxy groups permits
the introduction of various headgroups with different
monosaccharides, such as -glucose, -galactose[10] or, in
this work, coupling with ethyleneoxy spacers of different
lengths to simulate a variety of binding epitopes. It should
be mentioned that the introduction of the spacer into the
core substances 3 and 4 can also be achieved without the
need for a protecting group strategy. The result of this reac-
tion is certainly a mixture of products, separation of which
is a problem because of the similarity of, for example, the
Rf values of mono- and dialkylated products.
As spacer material we chose the often used ethyleneoxy
derivatives,[14,15] the advantages of which are their uncom-
plicated chemical properties and their greater flexibility in
comparison to natural oligosaccharides. In Scheme 2 a
number of ethyleneoxy spacer derivatives are shown.
Scheme 3. Hydrophobic pentaerythritol derivatives 7Ϫ11 with dif-
ferent numbers and lengths of ethylene glycol spacers
Experience has shown that the main problem in the syn-
thesis of glycolipid clusters is the introduction of the ter-
minal carbohydrate headgroups into the molecule, because
of the relatively low yields of glycosidation reactions. In-
vestigations in our group into the effectivities of the triflate
method, the KoenigsϪKnorr method and the imidate
method for the synthesis of cluster glycolipids demonstrated
that the triflate method afforded the best results with the
highest yields and anomeric purities.[20] Nevertheless, in the
reactions of the intermediates 7Ϫ11, mixtures of the ex-
pected mono-, di- and (in the cases of 9Ϫ11) also triglycosi-
dated products were obtained. Certainly, separation of the
acetylated intermediate glycolipids could not be achieved
with conventional methods such as column or flash chro-
matography. Therefore, prior deprotection of the acetylated
sugar compounds and subsequent separation of the unpro-
tected final compounds by use of a preparative, centrifu-
gally accelerated, radial, thin layer chromatograph
(Chromatotron, Harrison Research) afforded a range of
glycolipids with different numbers of terminal mannose
headgroups and various spacer lengths (Scheme 4).
Scheme 2. Halogenated ethyleneoxy derivatives 6aϪ6g of different
lengths with protecting groups as spacer material
All compounds were fully characterized by 1H NMR and
ESI-MS. The final products 12Ϫ16 had to be reacetylated
for final structure elucidation for the reasons given.
The introduction of the halogenated ethylene glycol de-
rivatives 6 into the hydrophobic core substances (Scheme 1)
was achieved by simple O-alkylation. The terminal hydroxy
group was blocked by different protecting groups. The THP
Initial biochemical investigation has shown that these po-
protecting group can be selectively removed by catalytic lyantennary mannosides can be used as attractive tools for
amounts of pyridinium p-toluenesulfonate (PPTS)[16] and liposome-targeting toward the macrophage mannose recep-
the p-methoxybenzyl (PMB) group by treatment with ceric tor. The neoglycolipids were asymmetrically incorporated
ammonium nitrate (CAN),[17] while the O-benzyl ether can into liposomes and subsequently investigated in detail by
be reduced to the free hydroxy group by palladium-cata- flow cytometry. It was shown that the degree of mannosyl-
lysed hydrogenolysis.[18,19] With this selective deprotection, ation and the linkage moiety between the acyl chain and
the introduction of various carbohydrate headgroups is the headgroups resulted in increases in macrophage binding
possible.
and uptake, respectively. This suggests that molecular re-
According to this procedure, a range of amphiphilic mo- cognition of mannose residues by the mannose-specific
lecules characterized by one or two hexadecyl chains and 175KDa receptor may occur prior to endocytosis which en-
ethyleneoxy spacers of different lengths was achieved in ables it’s use as target device for therapeutic reason.[21] Fur-
good yield (Scheme 3). With the possibility of varying the ther biochemical investigations will follow soon.
670
Eur. J. Org. Chem. 2002, 669Ϫ674

Glycolipid Clusters with Pentaerythritol Cores
FULL PAPER
ive ions): m/z ϭ 501.70 [M ϩ 23]ϩ. Rf (CHCl3/Et2O, 8:2) ϭ 0.59.
Yield 56%; m.p. 55Ϫ57 °C (heptane). C29H50O5 (478.71): calcd. C
72.76, H 10.53; found C 72.73, H 10.59.
O-Benzyl-OЈ-hexadecylpentaerythritol (2): Compound 2 was syn-
thesized according to ref[1] 1H NMR (CDCl3, 400 MHz): δ ϭ
.
0.84Ϫ0.87 (t, 3 H, ϪCH3), 1.23Ϫ1.28 (s, 26 H, ϪCH2Ϫ),
1.50Ϫ1.56 (m, 2 H, ϪOCH2CH2Ϫ), 2.64 (t, 2 H, ϪOH), 3.36Ϫ3.40
(t, 2 H, ϪOCH2CH2Ϫ), 3.49 (s, 2 H, ϪCCH2OϪ), 3.53 (s, 2 H,
ϪCCH2OBn), 3.64 (d,
2 H, HOCH2CϪ), 3.66 (d, 2 H,
HOCH2CϪ), 4.49 (s, 2 H, ϪOCH2C6H5), 7.27Ϫ7.33 (m, 5 H,
ϪC6H5). MS (ES, positive ions): m/z ϭ 473.69 [M ϩ 23]ϩ. Rf
(CHCl3/Et2O, 8:2) ϭ 0.26. Yield 28%. C28H50O4 (450.70): calcd. C
74.62, H 11.18; found C 74.58, H 11.29.
O-Hexadecylpentaerythritol (3): Concentrated HCl (50 mL) was ad-
ded dropwise to a solution of 1 (0.1 mol) in 500 mL of EtOH. The
mixture was heated at 80 °C for 3 h and neutralized with NaOH
while still warm. After cooling, the mixture was repeatedly parti-
tioned with ethyl acetate. The organic phases were dried with
Na2SO4 and the solvents were evaporated under reduced pressure.
The oily residue was resuspended in heptane/diethyl ether (90:10)
1
to provide 3 as a pure crystalline material (28.1 g, 78%). H NMR
(CDCl3, 400 MHz): δ ϭ 0.84Ϫ0.86 (t, 3 H, ϪCH3), 1.23Ϫ1.26 (s,
26 H, ϪCH2Ϫ), 1.50Ϫ1.55 (m, 2 H, ϪOCH2CH2Ϫ), 2.53 (s, 3 H,
ϪOH), 3.38Ϫ3.42 (t,
2 H, ϪOCH2CH2Ϫ), 3.45 (s, 2 H,
ϪOCH2CϪ), 3.69 (s, 6 H, ϪCH2OH). MS (ES, positive ions): m/
z ϭ 383.57 [M ϩ 23]ϩ. Rf (CHCl3/MeOH 8:2) ϭ 0.68; m.p. 71
°C. C21H44O4 (360.57): calcd. C 69.95, H 12.30; found C 69.83,
H 12.38.
Synthesis of the Spacers: 2-Bromo-1-(tetrahydro-2H-pyran-2-yl-
oxy)ethane (6a),[23] 5-chloro-1-(tetrahydro-2H-pyran-2-yloxy)-3-
oxapentane (6b),[24] 8-chloro-1-(tetrahydro-2H-pyran-2-yloxy)-3,6-
dioxaoctane (6c),[25] 1-chloro-7-phenyl-3,6-dioxaheptane (6d)[26]
and 1-chloro-10-phenyl-3,6,9-trioxadecane (6e)[27] were synthesized
according to the literature. 5-Chloro-3-oxapentanol (0.1 mol) or 8-
chloro-3,6-dioxaoctanol (0.1 mol) were dissolved together with p-
methoxybenzyl bromide (0.1 mol) in THF (100 mL), and tBuOK
(0.1 mol) was added at 0 °C. The mixture was stirred for 24 h, the
solid was filtered off and the organic phase was concentrated. The
oily residue was purified by flash chromatography (petroleum
ether/EtO2) to obtain 6f or 6g, respectively, in good yields.
Scheme 4. Different glycosidated mannosides 12Ϫ16 with variation
in the hydrophobic and spacer moieties
Experimental Section
General: 1H NMR spectra were recorded with a Bruker AC 500
spectrometer at a frequency of 400 MHz with TMS as internal
standard. Mass spectra were obtained with a Finnigan MAT 710
spectrometer. The ionization was effected at 4.5 kV both in negative
and positive modes. Elemental analyses were performed with a
CHNS-932 apparatus (LECO Corporation). Column chromato-
graphy was carried out with silica gel 60 (0.04Ϫ0.2 mm; Merck)
and preparative, centrifugally accelerated, radial, thin layer chro-
matography with a Chromatotron (Harrison Research). All reac-
tions were performed under argon. Solvents were dried before use.
All chemicals were purchased from Aldrich and Fluka.
1-Chloro-7-(p-methoxyphenyl)-3,6-dioxaheptane (6f): MS (ES, pos-
itive ions): m/z ϭ 267.72 [M ϩ 23]ϩ. Rf (CHCl3) ϭ 0.65. Yield
74%. C12H17ClO3 (244.72): calcd. C 58.90, H 7.00; found C 58.86,
H 6.95.
1-Chloro-10-(p-methoxyphenyl)-3,6,9-trioxadecane (6g): MS (ES,
positive ions): m/z ϭ 311.77 [M ϩ 23]ϩ. Rf (CHCl3) ϭ 0.57. Yield
68%. C14H21ClO4 (288.77): calcd. C 58.23, H 7.33; found C 58.75,
H 7.18.
Synthesis of the Starting Materials: Di-O,OЈ-hexadecylpenta-
erythritol (4)[22] and O-benzyl-OЈ-(p-methoxybenzyl)-OЈЈ-hexade-
cylpentaerythritol (5)[10] were synthesized according to the literat-
ure.
Introduction of the Spacers into the Hydrophobic Core Substances
O,OЈ-Dihexadecyl-OЈЈ-(8-hydroxy-3,6-dioxaoctyl)pentaerythritol
O-Hexadecyl-OЈ,OЈЈ-(p-methoxybenzylidene)pentaerythritol
Compound 1 was synthesized according to ref.[1] 1H NMR (CDCl3, ded dropwise to a solution of 4 (0.01 mol), tBuOK (0.011 mol) and
400 MHz): δ ϭ 0.84Ϫ0.88 (t, 3 H, ϪCH3), 1.24Ϫ1.28 (s, 26 H, catalytic amounts of tetrabutylammonium iodide (TBAI) in 50 mL
(1): (7): Compound 6e (0.01 mol), dissolved in THF (10 mL), was ad-
ϪCH2Ϫ), 1.54Ϫ1.58 (m, 2 H, ϪOCH2CH2Ϫ), 2.81 (s, 1 H, ϪOH), of THF. The mixture was heated at 65 °C for 24 h. After cooling
3.25 (s, 2 H, ϪOCH2CϪ), 3.35Ϫ3.38 (t, 2 H, ϪOCH2CH2Ϫ), to room temperature, the mixture was diluted with CHCl3. The
3.38Ϫ3.50 (d, 2 H, ϪCCH2OCHϪ), 3.72Ϫ3.74 (d, 2 H, Jeq,ax
ϭ
organic phase was washed with water and dried with Na2SO4, and
11.8 Hz, ϪCCH2OCHϪ), 3.78 (s, 3 H, ϪOCH3), 4.11Ϫ4.13 (d, 2 the solvents were evaporated. The intermediate 7/I was dissolved
H, ϪCCH2OH), 5.36 (s, 1 H, ϪCHϪ), 6.85Ϫ6.89 (m, 2 H, in 20 mL of EtOH and removal of the O-benzyl group was achieved
ϪC6H4OCH3), 7.38Ϫ7.40 (m, 2 H, ϪC6H4OCH3). MS (ES, posit-
by palladium-catalysed hydrogenolysis for 12 h. After filtration, the
Eur. J. Org. Chem. 2002, 669Ϫ674
671

M. Schmidt, B. Dobner, P. Nuhn
Synthesis of the Final Compounds
FULL PAPER
solvents were evaporated and the residue was purified by flash
chromatography (petroleum ether/CHCl3) to provide the mono-O-
alkylated product 7 (3.01 g, 42%). MS (ES, positive ions): m/z ϭ
740.16 [M ϩ 23]ϩ. Rf (CHCl3/MeOH, 8:2) ϭ 0.89. C43H88O7
(717.16): calcd. C 72.02, H 12.37; found C 71.95, H 12.46.
General Method for the Synthesis of Compounds 12؊16 by Trans-
glycosidation with TMS Triflate: TMS triflate was added to a solu-
tion of penta-O-acetyl--mannopyranose in dry CH2Cl2 and mo-
lecular sieves and the mixture was stirred for 4 h at 20 °C under
argon. The glycosyl acceptors 7Ϫ11 were added and the mixture
was stirred for 8 h at room temperature (the TMS triflate/glycosyl
donor/glycosyl acceptor ratio was 2.2:2.2:1 in the cases of 7 and 8
and 3.3:3.3:1 in the cases of 9, 10 and 11). The mixture was neutral-
ized with triethylamine (TEA), filtered and washed with water, and
the organic phase was dried with Na2SO4. After concentration, the
residue was dissolved in MeOH and a catalytic amount of NaOMe
was added. The mixture was stirred for 12 h and then the solvent
was removed. The residue was purified by preparative, centrifugally
accelerated, radial, thin layer chromatograph (Chromatotron) to
separate the mono-, di- and particularly triglycosylated final com-
pounds 12؊16.
O,OЈ-Dihexadecyl-OЈЈ-(8-hydroxy-3,6-dioxaoctyl)-OЈЈЈ-(2-hydroxy-
ethyl)pentaerythritol (8): The intermediate 7/I (0.01 mol), isolated
by flash chromatography (petroleum ether/CHCl3), tBuOK (0.011
mol) and catalytic amounts of TBAI were dissolved in 50 mL of
THF. A solution of 6a (0.01 mol), dissolved in 10 mL of THF was
added dropwise to this mixture, which was heated at 65 °C for 24 h.
After cooling to room temperature, the mixture was diluted with
CHCl3. The organic phase was washed with water and dried with
Na2SO4, and the solvents were evaporated. The residue was dis-
solved in 20 mL of EtOH and removal of the O-benzyl group was
achieved by palladium-catalysed hydrogenolysis for 12 h. After fil-
tration, the mixture was stirred with catalytic amounts of PPTS for
4 h. After concentration, the residue was purified by flash chroma-
tography (petroleum ether/EtO2) to provide compound 8 (2.74 g,
36%). MS (ES, positive ions): m/z ϭ 784.22 [M ϩ 23]ϩ. Rf (CHCl3/
MeOH 8:2) ϭ 0.83. C45H92O8 (761.22): calcd. C 71.00, H 12.18;
found C 70.89, H 12.27.
O,OЈ-Dihexadecyl-OЈЈ-[8-(α-
D
-mannopyranosidoyloxy)-3,6-dioxa-
octyl]-OЈЈЈ-[2-(α-
D
-mannopyranosidoyloxy)ethyl]pentaerythritol
(12a): MS (ES, positive ions): m/z ϭ 1108.50 [M ϩ 23]ϩ. Rf
(CHCl3/MeOH, 8:2) ϭ 0.32. Yield 16%. [α]2D0 ϭ ϩ14.9 (c ϭ 1.8,
MeOH). C57H112O18 (1085.50): calcd. C 63.07, H 10.40; found C
63.02, H 10.48.
O-Hexadecyl-OЈ,OЈЈ-bis(8-hydroxy-3,6-dioxaoctyl)pentaerythritol
(9): Compound 6e (0.025 mol), dissolved in THF (10 mL), was
added dropwise to a solution of 2 (0.01 mol), tBuOK (0.025 mol)
and catalytic amounts of TBAI in THF (50 mL). The mixture was
heated at 65 °C for 24 h. After cooling to room temperature, the
mixture was diluted with CHCl3. The organic phase was washed
with water and dried with Na2SO4, and the solvents were evapor-
ated. The intermediate 9/I was dissolved in 20 mL of EtOH and
removal of the O-benzyl group was achieved by palladium-cata-
lysed hydrogenolysis for 12 h. After filtration, the solvents were
evaporated and the residue was purified by flash chromatography
(petroleum ether/CHCl3) to provide the bis-O-alkylated product 9
(2.93 g, 47%). MS (ES, positive ions): m/z ϭ 647.89 [M ϩ 23]ϩ. Rf
(CHCl3/MeOH, 8:2) ϭ 0.81. C33H68O10 (624.89): calcd. C 63.43,
H 10.97; found C 63.37, H 11.04.
O,OЈ-Dihexadecyl-OЈЈ-(2-hydroxyethyl)-OЈЈЈ-[8-(α-D-mannopyrano-
sidoyloxy)-3,6-dioxaoctyl]pentaerythritol (12b): MS (ES, positive
ions): m/z ϭ 946.36 [M ϩ 23]ϩ. Rf (CHCl3/MeOH, 8:2) ϭ 0.54.
Yield 19%. [α]2D0 ϭ ϩ15.2 (c ϭ 2.1, MeOH). C51H102O13 (923.36):
calcd. C 66.34, H 11.13; found C 66.31, H 11.16.
O,OЈ-Dihexadecyl-OЈЈ-(α-D-mannopyranosidoyl)-OЈЈЈ-[8-(α-D-
mannopyranosidoyloxy)-3,6-dioxaoctyl]pentaerythritol (13a): MS
(ES, positive ions): m/z ϭ 1064.45 [M ϩ 23]ϩ. Rf (CHCl3/MeOH,
8:2) ϭ 0.34. yield 18%. [α]2D0 ϭ ϩ12.7 (c ϭ 2.7, MeOH). C55H108O17
(1041.45): calcd. C 63.43, H 10.45; found C 63.31, H 10.52.
O,OЈ-Dihexadecyl-OЈЈ-[8-(α-
octyl]pentaerythritol (13b): MS (ES, positive ions): m/z ϭ 902.30
[M ϩ 23]ϩ. Rf (CHCl3/MeOH, 8:2) ϭ 0.57. Yield 21%. [α]2D0
D-mannopyranosidoyloxy)-3,6-dioxa-
ϭ
ϩ11.3 (c ϭ 2.1, MeOH). C49H98O12 (879.30): calcd. C 66.93, H
11.23; found C 66.86, H 11.26.
O-Hexadecyl-OЈ-(8-hydroxy-3,6-dioxaoctyl)pentaerythritol
Compound 6c (0.012 mol), dissolved in THF (10 mL), was added
dropwise to a solution of 1 (0.01 mol), tBuOK (0.012 mol) and
(10):
O-Hexadecyl-OЈ-(α-D-mannopyranosidoyl)-OЈЈ,OЈЈЈ-bis[8-(α-D-
catalytic amounts of TBAI in THF (50 mL). The mixture was mannopyranosidoyloxy)-3,6-dioxaoctyl]pentaerythritol (14a): MS
heated for 24 h at 65 °C. After cooling to room temperature, the (ES, positive ions): m/z ϭ 1134.32 [M ϩ 23]ϩ. Rf (CHCl3/MeOH,
mixture was diluted with CHCl3. The organic phase was washed
8:2) ϭ 0.07. Yield 11%. [α]2D0 ϭ ϩ26.4 (c ϭ 3.1, MeOH). C51H98O25
with water and dried with Na2SO4, and the solvents were evapor- (1111.32): calcd. C 55.12, H 8.89; found C 55.07, H 8.93.
ated. The intermediate 10/I was dissolved in 100 mL of EtOH (100
O-Hexadecyl-OЈ,OЈЈ-bis[8-(α-
octyl]pentaerythritol (14b): MS (ES, positive ions): m/z ϭ 972.18
[M ϩ 23]ϩ. Rf (CHCl3/MeOH, 8:2) ϭ 0.16. Yield 14%. [α]2D0
ϩ17.8 (c ϭ 2.5, MeOH). C45H88O20 (949.18): calcd. C 56.94, H
9.34; found C 56.85, H 9.42.
D-mannopyranosidoyloxy)-3,6-dioxa-
mL) and removal of the O-(p-methoxybenzylidene) and THP
groups was achieved by heating the mixture with HCl (2 , 10
mL) for 3 h. After cooling to room temperature, the mixture was
neutralized and diluted with water and CHCl3. The organic phase
was separated and dried with Na2SO4. After concentration, the res-
idue was purified by flash chromatography (petroleum ether/
CHCl3) to provide the mono-O-alkylated product 10 (2.21 g, 45%).
MS (ES, positive ions): m/z ϭ 515.73 [M ϩ 23]ϩ. Rf (CHCl3/MeOH
8:2) ϭ 0.86. C27H56O7 (492.73): calcd. C 65.82, H 11.46; found C
65.73, H 11.56.
ϭ
rac-O-Hexadecyl-OЈ-(8-hydroxy-3,6-dioxaoctyl)-OЈЈ-[8-(α-D-
mannopyranosidoyloxy)-3,6-dioxaoctyl]pentaerythritol (14c): MS
(ES, positive ions): m/z ϭ 810.03 [M ϩ 23]ϩ. Rf (CHCl3/MeOH,
8:2) ϭ 0.47. Yield 18%. [α]2D0 ϭ ϩ4.9 (c ϭ 1.9, MeOH). C39H78O15
(787.03): calcd. C 59.52, H 9.99; found C 59.47, H 10.03.
O-Hexadecyl-OЈ-(5-hydroxy-3-oxapentyl)pentaerythritol (11): Com-
pound 11 was synthesized like compound 10 by use of 6b as spacer
derivative. MS (ES, positive ions): m/z ϭ 471.68 [M ϩ 23]ϩ. Rf
(CHCl3/MeOH 8:2) ϭ 0.87. Yield 51%. C25H52O6 (448.68): calcd.
C 66.92, H 11.68; found C 66.85, H 11.76.
O-Hexadecyl-OЈ,OЈЈ-bis(α-D-mannopyranosidoyl)-OЈЈЈ-[8-(α-D-
mannopyranosidoyloxy)-3,6-dioxaoctyl]pentaerythritol (15a): MS
(ES, positive ions): m/z ϭ 1002.16 [M ϩ 23]ϩ. Rf (CHCl3/MeOH,
8:2) ϭ 0.09. Yield 12%. [α]2D0 ϭ ϩ22.6 (c ϭ 2.4, MeOH). C45H86O22
(979.16): calcd. C 55.20, H 8.85; found C 55.16, H 8.91.
672
Eur. J. Org. Chem. 2002, 669Ϫ674

Glycolipid Clusters with Pentaerythritol Cores
FULL PAPER
rac-O-Hexadecyl-OЈ-α-
D
-mannopyranosidoyl-OЈЈ-[8-(α-
D
-manno- O-Acetyl-OЈ-[8ЈЈ-(2Ј,3Ј,4Ј,6Ј-tetra-O-acetyl-α-
D-mannopyrano-
pyranosidoyloxy)-3,6-dioxaoctyl]pentaerythritol (15b): MS (ES, pos-
sidoyloxy)3ЈЈ,6ЈЈ-dioxaoctyl]-OЈЈ,OЈЈЈ-dihexadecylpentaerythritol
itive ions): m/z ϭ 840.02 [M ϩ 23]ϩ. Rf (CHCl3/MeOH, 8:2) ϭ (18b): MS (ES, positive ions): m/z ϭ 1112.49 [M ϩ 23]ϩ. 1H NMR
0.19. Yield 16%. [α]2D0 ϭ ϩ6.1 (c ϭ 3.3, MeOH). C39H76O17
(817.02): calcd. C 57.33, H 9.38; found C 57.28, H 9.42.
(CDCl3, 400 MHz): δ ϭ 0.81Ϫ0.88 (t, 6 H, ϪCH3), 1.24Ϫ1.27 (s,
52 H, ϪCH2Ϫ), 1.53Ϫ1.57 (m, 4 H, ϪOCH2CH2Ϫ), 1.99Ϫ2.15 (5
s, 15 H,
5
COCH3), 3.37Ϫ3.88 (m, 24 H, ϪOCH2CH2Ϫ,
2.1 and
O-Hexadecyl-OЈ-[8-(α-D-mannopyranosidoyloxy)-3,6-dioxaoctyl]-
ϪOCH2CϪ, ϪOCH2CH2OϪ), 4.07Ϫ4.11 (dd,
J
ϭ
pentaerythritol (15c): MS (ES, positive ions): m/z ϭ 677.87 [M ϩ
23]ϩ. Rf (CHCl3/MeOH, 8:2) ϭ 0.52. Yield 20%. [α]2D0 ϭ ϩ13.8
(c ϭ 2.7, MeOH). C33H66O12 (654.87): calcd. C 60.52, H 10.16;
found C 60.49, H 10.17.
12.2 Hz, 1 H, 6-H), 4.14Ϫ4.19 (m, 1 H, 5-H), 4.24Ϫ4.27 (dd, J ϭ
5.2 and 12.2 Hz, 1 H, 6Ј-H), 4.69 (d, J ϭ 1.6 Hz, 1 H, 1-Hα),
5.21Ϫ5.37 (m, 3 H, 2-H, 4-H, 3-H).
O-(2Ј,3Ј,4Ј,6Ј-Tetra-O-acetyl-α-
[8ЈЈ-(2Ј,3Ј,4Ј,6Ј-tetra-O-acetyl-α-
D
-mannopyranosidoyl)-OЈ,OЈЈ-bis-
-mannopyranosidoyloxy)-3ЈЈ,6ЈЈ-
O-Hexadecyl-OЈ,OЈЈ-bis(α-D-mannopyranosidoyl)-OЈЈЈ-[5-(α-D-
D
mannopyranosidoyloxy)-3-oxapentyl]pentaerythritol (16a): MS (ES,
positive ions): m/z ϭ 958.11 [M ϩ 23]ϩ. Rf (CHCl3/MeOH, 8:2) ϭ
0.09. Yield 11%. [α]2D0 ϭ ϩ24.5 (c ϭ 2.5, MeOH). C43H82O21
(935.11): calcd. C 55.23, H 8.84; found C 55.24, H 8.81.
dioxaoctyl]-OЈЈЈ-hexadecylpentaerythritol (19a): MS (ES, positive
ions): m/z ϭ 1638.77 [M ϩ 23]ϩ. 1H NMR (CDCl3, 400 MHz):
δ ϭ 0.83Ϫ0.88 (t, 3 H, ϪCH3), 1.24Ϫ1.27 (s, 26 H, ϪCH2Ϫ),
1.53Ϫ1.58 (m, 2 H, ϪOCH2CH2Ϫ), 1.97Ϫ2.14 (4 s, 36 H, 12
COCH3), 3.39Ϫ3.87 (m, 34 H, ϪOCH2CH2Ϫ, ϪOCH2CϪ,
ϪOCH2CH2OϪ), 4.10Ϫ4.12 (dd, J ϭ 2.3 and 12.2 Hz, 3 H, 6-H),
4.15Ϫ4.19 (m, 3 H, 5-H), 4.23Ϫ4.29 (dd, J ϭ 5.3 and 12.2 Hz, 3
H, 6Ј-H), 4.77 (d, J ϭ 1.7 Hz, 3 H, 1-Hα), 5.21Ϫ5.34 (m, 9 H, 2-
H, 4-H, 3-H).
rac-O-Hexadecyl-OЈ-(α-D-mannopyranosidoyl)-OЈЈ-[5-(α-D-manno-
pyranosidoyloxy)-3-oxapentyl]pentaerythritol (16b): MS (ES, posit-
ive ions): m/z ϭ 795.96 [M ϩ 23]ϩ. Rf (CHCl3/MeOH, 8:2) ϭ 0.20.
Yield 15%. [α]2D0 ϭ ϩ3.7 (c ϭ 1.9, MeOH). C37H72O16 (772.96):
calcd. C 57.49, H 9.39; found C 57.47, H 9.44.
O-Acetyl-OЈ,OЈЈ-bis[8ЈЈ-(2Ј,3Ј,4Ј,6Ј-tetra-O-acetyl-α-D-manno-
O-Hexadecyl-OЈ-[5-(α-D-mannopyranosidoyloxy)-3-oxapentyl]-
pyranosidoyloxy)-3ЈЈ,6ЈЈ-dioxaoctyl]-OЈЈЈ-hexadecylpentaerythritol
(19b): MS (ES, positive ions): m/z ϭ 1350.51 [M ϩ 23]ϩ. 1H NMR
(CDCl3, 400 MHz): δ ϭ 0.85Ϫ0.88 (t, 3 H, ϪCH3), 1.24Ϫ1.28 (s,
26 H, ϪCH2Ϫ), 1.53Ϫ1.59 (m, 2 H, ϪOCH2CH2Ϫ), 1.89Ϫ2.11 (5
pentaerythritol (16c): MS (ES, positive ions): m/z ϭ 633.82 [M ϩ
23]ϩ. Rf (CHCl3/MeOH, 8:2) ϭ 0.55. Yield 19%. [α]2D0 ϭ ϩ16.1
(c ϭ 3.2, MeOH). C31H62O11 (610.82): calcd. C 60.96, H 10.23;
found C 61.00, H 10.21.
s, 27 H,
9
COCH3), 3.42Ϫ3.85 (m, 34 H, ϪOCH2CH2Ϫ,
2.2 and
ϪOCH2CϪ, ϪOCH2CH2OϪ), 4.03Ϫ4.08 (dd,
J
ϭ
Analytical Data for the Reacetylated Glycolipids
12.2 Hz, 2 H, 6-H), 4.12Ϫ4.17 (m, 2 H, 5-H), 4.23Ϫ4.28 (dd, J ϭ
5.3 and 12.1 Hz, 2 H, 6Ј-H), 4.76 (d, J ϭ 1.7 Hz, 2 H, 1-Hα),
5.20Ϫ5.37 (m, 6 H, 2-H, 4-H, 3-H).
O-[8ЈЈ-(2Ј,3Ј,4Ј,6Ј-tetra-O-acetyl-α-
3ЈЈ,6ЈЈ-dioxaoctyl]-OЈ-[2Ј,3Ј,4Ј,6Ј-tetra-O-acetyl-α-
D
-mannopyranosidoyloxy)-
-mannopyrano-
D
sidoyloxyethyl]-OЈЈ,OЈЈЈ-dihexadecylpentaerythritol (17a): MS (ES,
positive ions): m/z ϭ 1444.80 [M ϩ 23]ϩ. 1H NMR (CDCl3,
400 MHz): δ ϭ 0.84Ϫ0.87 (t, 6 H, ϪCH3), 1.23Ϫ1.27 (s, 52 H,
ϪCH2Ϫ), 1.54Ϫ1.58 (m, 4 H, ϪOCH2CH2Ϫ), 1.94Ϫ2.14 (4 s, 24
H, 8 COCH3), 3.41Ϫ3.87 (m, 28 H, ϪOCH2CH2Ϫ, ϪOCH2CϪ,
ϪOCH2CH2OϪ), 4.05Ϫ4.10 (dd, J ϭ 2.2 and 12.2 Hz, 2 H, 6-H),
4.15Ϫ4.19 (m, 2 H, 5-H), 4.24Ϫ4.29 (dd, J ϭ 5.3 and 12.2 Hz, 2
H, 6Ј-H), 4.87 (d, J ϭ 1.8 Hz, 2 H, 1-Hα), 5.23Ϫ5.37 (m, 6 H, 2-
H, 4-H, 3-H).
rac-O-(8Ј-Acetoxy-3Ј,6Ј-dioxaoctyl)-OЈ-acetyl-OЈЈ-[8ЈЈ-(2Ј,3Ј,4Ј,6Ј-
tetra-O-acetyl-α-D-mannopyranosidoyloxy)-3ЈЈ,6ЈЈ-dioxaoctyl]-OЈЈЈ-
hexadecylpentaerythritol (19c): MS (ES, positive ions): m/z ϭ
1
1062.26 [M ϩ 23]ϩ. H NMR (CDCl3, 400 MHz): δ ϭ 0.84Ϫ0.90
(t, 3 H, ϪCH3), 1.24Ϫ1.28 (s, 26 H, ϪCH2Ϫ), 1.54Ϫ1.58 (m, 2 H,
ϪOCH2CH2Ϫ), 1.93Ϫ2.15 (6 s, 18 H, 6 COCH3), 3.39Ϫ3.87 (m,
34 H, ϪOCH2CH2Ϫ, ϪOCH2CϪ, ϪOCH2CH2OϪ), 4.06Ϫ4.09
(dd, J ϭ 2.3 and 12.2 Hz, 1 H, 6-H), 4.15Ϫ4.19 (m, 1 H, 5-H),
4.24Ϫ4.27 (dd, J ϭ 5.1 and 12.2 Hz, 1 H, 6Ј-H), 4.76 (d, J ϭ
1.8 Hz, 1 H, 1-Hα), 5.24Ϫ5.37 (m, 3 H, 2-H, 4-H, 3-H).
O-(Acetoxyethyl)-OЈ-[8ЈЈ-(2Ј,3Ј,4Ј,6Ј-tetra-O-acetyl-α-D-manno-
pyranosidoyloxy)-3ЈЈ,6ЈЈ-dioxaoctyl]-OЈЈ,OЈЈЈ-dihexadecyl-
pentaerythritol (17b): MS (ES, positive ions): m/z ϭ 1156.54 [M ϩ
23]ϩ. 1H NMR (CDCl3, 400 MHz): δ ϭ 0.83Ϫ0.87 (t, 6 H, ϪCH3),
1.24Ϫ1.28 (s, 52 H, ϪCH2Ϫ), 1.51Ϫ1.57 (m, 4 H, ϪOCH2CH2Ϫ),
O,OЈ-Bis(2Ј,3Ј,4Ј,6Ј-tetra-O-acetyl-α-
D-mannopyranosidoyl)-OЈЈ-
[8ЈЈ-(2Ј,3Ј,4Ј,6Ј-tetra-O-acetyl-α- -mannopyranosidoyloxy)-3ЈЈ,6ЈЈ-
D
dioxaoctyl]-OЈЈЈ-hexadecylpentaerythritol (20a): MS (ES, positive
ions): m/z ϭ 1506.61 [M ϩ 23]ϩ. 1H NMR (CDCl3, 400 MHz):
δ ϭ 0.83Ϫ0.89 (t, 3 H, ϪCH3), 1.23Ϫ1.27 (s, 26 H, ϪCH2Ϫ),
1.54Ϫ1.58 (m, 2 H, ϪOCH2CH2Ϫ), 1.98Ϫ2.12 (4 s, 36 H, 12
COCH3), 3.38Ϫ3.79 (m, 22 H, ϪOCH2CH2Ϫ, ϪOCH2CϪ,
ϪOCH2CH2OϪ), 4.03Ϫ4.10 (dd, J ϭ 2.3 and 12.2 Hz, 3 H, 6-H),
4.13Ϫ4.19 (m, 3 H, 5-H), 4.22Ϫ4.27 (dd, J ϭ 5.2 and 12.2 Hz, 3
H, 6Ј-H), 4.67 (d, J ϭ 1.8 Hz, 3 H, 1-Hα), 5.23Ϫ5.37 (m, 9 H, 2-
H, 4-H, 3-H).
1.92Ϫ2.11 (5 s, 15 H,
5 COCH3), 3.37Ϫ3.79 (m, 28 H,
ϪOCH2CH2Ϫ, ϪOCH2CϪ, ϪOCH2CH2OϪ), 4.07Ϫ4.10 (dd, J ϭ
2.3 and 12.2 Hz, 1 H, 6-H), 4.14Ϫ4.19 (m, 1 H, 5-H), 4.24Ϫ4.29
(dd, J ϭ 5.2 and 12.2 Hz, 1 H, 6Ј-H), 4.84 (d, J ϭ 1.8 Hz, 1 H, 1-
Hα), 5.22Ϫ5.35 (m, 3 H, 2-H, 4-H, 3-H).
O-(2Ј,3Ј,4Ј,6Ј-tetra-O-acetyl-α-
D-mannopyranosidoyl)-OЈ-[8ЈЈ-
(2Ј,3Ј,4Ј,6Ј-tetra-O-acetyl-α- -mannopyranosidoyloxy)-3ЈЈ,6ЈЈ-
D
dioxaoctyl]-OЈЈ,OЈЈЈ-dihexadecylpentaerythritol (18a): MS (ES, pos-
itive ions): m/z ϭ 1400.75 [M ϩ 23]ϩ. 1H NMR (CDCl3, 400 MHz):
rac-O-Acetyl-OЈ-(2Ј,3Ј,4Ј,6Ј-tetra-O-acetyl-α-
D-mannopyrano-
sidoyl)-OЈЈ-[8ЈЈ-(2Ј,3Ј,4Ј,6Ј-tetra-O-acetyl-α- -mannopyranosidoyl-
D
δ ϭ 0.84Ϫ0.88 (t, 6 H, ϪCH3), 1.25Ϫ1.29 (s, 52 H, ϪCH2Ϫ), oxy)-3ЈЈ,6ЈЈ-dioxaoctyl]-OЈЈЈ-hexadecylpentaerythritol (20b): MS
1
1.52Ϫ1.58 (m, 4 H, ϪOCH2CH2Ϫ), 1.89Ϫ2.09 (4 s, 24 H, 8 (ES, positive ions): m/z ϭ 1118.35 [M ϩ 23]ϩ. H NMR (CDCl3,
COCH3), 3.42Ϫ3.87 (m, 24 H, ϪOCH2CH2Ϫ, ϪOCH2CϪ, 400 MHz): δ ϭ 0.84Ϫ0.88 (t, 3 H, ϪCH3), 1.24Ϫ1.29 (s, 26 H,
ϪOCH2CH2OϪ), 4.04Ϫ4.11 (dd, J ϭ 2.2 and 12.2 Hz, 2 H, 6-H), ϪCH2Ϫ), 1.52Ϫ1.58 (m, 2 H, ϪOCH2CH2Ϫ), 1.92Ϫ2.11 (5 s, 27
4.15Ϫ4.20 (m, 2 H, 5-H), 4.24Ϫ4.29 (dd, J ϭ 5.3 and 12.1 Hz, 2 H, 9 COCH3), 3.38Ϫ3.85 (m, 22 H, ϪOCH2CH2Ϫ, ϪOCH2CϪ,
H, 6Ј-H), 4.74 (d, J ϭ 1.7 Hz, 2 H, 1-Hα), 5.25Ϫ5.43 (m, 6 H, 2-
H, 4-H, 3-H).
ϪOCH2CH2OϪ), 4.07Ϫ4.11 (dd, J ϭ 2.1 and 12.3 Hz, 2 H, 6-H),
4.15Ϫ4.19 (m, 2 H, 5-H), 4.22Ϫ4.27 (dd, J ϭ 5.3 and 12.2 Hz, 2
Eur. J. Org. Chem. 2002, 669Ϫ674
673

M. Schmidt, B. Dobner, P. Nuhn
FULL PAPER
H, 6Ј-H), 4.81 (d, J ϭ 1.7 Hz, 2 H, 1-Hα), 5.21Ϫ5.41 (m, 6 H, 2-
H, 4-H, 3-H).
[1]
[2]
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[5]
[6]
[7]
[8]
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O,OЈ-Diacetyl-OЈЈ-[8ЈЈ-(2Ј,3Ј,4Ј,6Ј-tetra-O-acetyl-α-D-manno-
pyranosidoyloxy)-3ЈЈ,6ЈЈ-dioxaoctyl]-OЈЈЈ-hexadecylpentaerythritol
1
(20c): MS (ES, positive ions): m/z ϭ 930.10 [M ϩ 23]ϩ. H NMR
(CDCl3, 400 MHz): δ ϭ 0.82Ϫ0.89 (t, 3 H, ϪCH3), 1.24Ϫ1.27 (s,
26 H, ϪCH2Ϫ), 1.53Ϫ1.61 (m, 2 H, ϪOCH2CH2Ϫ), 1.95Ϫ2.09 (5
s, 18 H,
6
COCH3), 3.43Ϫ3.88 (m, 22 H, ϪOCH2CH2Ϫ,
2.2 and
ϪOCH2CϪ, ϪOCH2CH2OϪ), 4.05Ϫ4.10 (dd,
J
ϭ
12.2 Hz, 1 H, 6-H), 4.15Ϫ4.19 (m, 1 H, 5-H), 4.26Ϫ4.29 (dd, J ϭ
5.2 and 12.2 Hz, 1 H, 6Ј-H), 4.84 (d, J ϭ 1.8 Hz, 1 H, 1-Hα),
5.20Ϫ5.37 (m, 3 H, 2-H, 4-H, 3-H).
O-Hexadecyl-OЈ-[5ЈЈ-(2Ј,3Ј,4Ј,6Ј-tetra-O-acetyl-α-
pyranosidoyloxy)-3ЈЈ-oxapentyl)]-OЈЈ,OЈЈЈ-bis(2Ј,3Ј,4Ј,6Ј-tetra-
O-acetyl-α- -mannopyranosidoyl)pentaerythritol (21a): MS (ES,
d-manno-
D
positive ions): m/z ϭ 1462.55 [M ϩ 23]ϩ. 1H NMR (CDCl3,
400 MHz): δ ϭ 0.84Ϫ0.88 (t, 3 H, ϪCH3), 1.24Ϫ1.29 (s, 26 H,
ϪCH2Ϫ), 1.53Ϫ1.57 (m, 2 H, ϪOCH2CH2Ϫ), 1.98Ϫ2.11 (4 s, 36
H, 12 COCH3), 3.41Ϫ3.87 (m, 18 H, ϪOCH2CH2Ϫ, ϪOCH2CϪ,
ϪOCH2CH2OϪ), 4.08Ϫ4.11 (dd, J ϭ 2.3 and 12.3 Hz, 3 H, 6-H),
4.15Ϫ4.21 (m, 3 H, 5-H), 4.26Ϫ4.31 (dd, J ϭ 5.3 and 12.1 Hz, 3
H, 6Ј-H), 4.81 (d, J ϭ 1.8 Hz, 3 H, 1-Hα), 5.19Ϫ5.35 (m, 9 H, 2-
H, 4-H, 3-H).
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[12]
S. Hanessian, D. Qui, H. Praphanjan, G. V. Reddy, B. Lou,
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[13]
[14]
rac-O-Acetyl-OЈ-(2Ј,3Ј,4Ј,6Ј-tetra-O-acetyl-α-
D-mannopyrano-
sidoyl)-OЈЈ-[5ЈЈ-(2Ј,3Ј,4Ј,6Ј-tetra-O-acetyl-α- -mannopyranosidoyl-
D
lxoxy)-3ЈЈ-oxapentyl]-OЈЈЈ-hexadecylpentaerythritol (21b): MS (ES,
positive ions): m/z ϭ 1174.30 [M ϩ 23]ϩ. 1H NMR (CDCl3,
400 MHz): δ ϭ 0.82Ϫ0.87 (t, 3 H, ϪCH3), 1.24Ϫ1.28 (s, 26 H,
ϪCH2Ϫ), 1.52Ϫ1.58 (m, 2 H, ϪOCH2CH2Ϫ), 1.93Ϫ2.14 (5 s, 27
H, 9 COCH3), 3.37Ϫ3.85 (m, 18 H, ϪOCH2CH2Ϫ, ϪOCH2CϪ,
ϪOCH2CH2OϪ), 4.07Ϫ4.11 (dd, J ϭ 2.2 and 12.3 Hz, 2 H, 6-H),
4.14Ϫ4.19 (m, 2 H, 5-H), 4.23Ϫ4.28 (dd, J ϭ 5.1 and 12.2 Hz, 2
H, 6Ј-H), 4.69 (d, J ϭ 1.8 Hz, 2 H, 1-Hα), 5.26Ϫ5.42 (m, 6 H, 2-
H, 4-H, 3-H).
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[18]
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[20]
O,OЈ-Diacetyl-OЈЈ-[5ЈЈ-(2Ј,3Ј,4Ј,6Ј-tetra-O-acetyl-α-D-manno-
pyranosidoyloxy)-3ЈЈ-oxapentyl]-OЈЈЈ-hexadecylpentaerythritol
1
(21c): MS (ES, positive ions): m/z ϭ 886.05 [M ϩ 23]ϩ. H NMR
[21]
[22]
[23]
A. Al-arifi, M. Schmidt, J. Langner, D. Riemann, P. Nuhn, J.
Pharm. Sci., submitted.
(CDCl3, 400 MHz): δ ϭ 0.84Ϫ0.87 (t, 3 H, ϪCH3), 1.24Ϫ1.28 (s,
26 H, ϪCH2Ϫ), 1.51Ϫ1.57 (m, 2 H, ϪOCH2CH2Ϫ), 1.94Ϫ2.12 (5
S. Chierici, P. Boullanger, L. Marrone-Brignone, R. M. Mo-
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186608.
s, 18 H,
6
COCH3), 3.40Ϫ3.88 (m, 18 H, ϪOCH2CH2Ϫ,
2.3 and
ϪOCH2CϪ, ϪOCH2CH2OϪ), 4.04Ϫ4.08 (dd,
J
ϭ
12.2 Hz, 1 H, 6-H), 4.13Ϫ4.18 (m, 1 H, 5-H), 4.26Ϫ4.29 (dd, J ϭ
5.3 and 12.3 Hz, 1 H, 6Ј-H), 4.75 (d, J ϭ 1.7 Hz, 1 H, 1-Hα),
5.21Ϫ5.38 (m, 3 H, 2-H, 4-H, 3-H).
[24]
[25]
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Acknowledgments
This work was supported by the Deutsche Forschungsgemeinschaft
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Received August 29, 2001
(Sonderforschungsbereich 197).
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