Synthesis of oligoarabinofuranosides from the mycobacterial cell wall

Article abstract of DOI:10.1002/ejoc.200300303

Oligoarabinofuranosides 1-4, fragments of the arabinan components found in the mycobacterial cell wall have been synthesized. 1 and 2 are representative of the structural features of the internal core of arabinogalactan, arabinomannan and lipoarabinomanna

Full text of DOI:10.1002/ejoc.200300303

FULL PAPER
Synthesis of Oligoarabinofuranosides from the Mycobacterial Cell Wall
Karine Marotte,[a] Sylvie Sanchez,[a] Toufiq Bamhaoud,[b] and Jacques Prandi*[a]
Keywords: Carbohydrates / Natural products / Oligoarabinofuranosides / Glycosylation
Oligoarabinofuranosides 1−4, fragments of the arabinan
components found in the mycobacterial cell wall have been
achieved for the elaboration of glycosidic linkages between
arabinofuranoside units: α-glycosides were obtained by par-
synthesized. 1 and 2 are representative of the structural fea- ticipation of an ester or carbonate group on the 2-position,
tures of the internal core of arabinogalactan, arabinomannan
and lipoarabinomannans. 3 is the capping motif of the lipo-
arabinomannan of Mycobacterium tuberculosis and M. bovis
BCG while 4 is the hexasaccharide found at the non-redu-
cing end of arabinogalactan. Complete stereocontrol was
while β-arabinofuranosides were secured by an internal
aglycon delivery approach.
( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2003)
Introduction
Tuberculosis remains a major worldwide health problem
taking millions of lives annually. Mycobacterium tubercu-
losis, the causative agent of human tuberculosis, and M.
leprae, responsible for leprosy, are the two major pathogens
of the mycobacterium genus. The development of new
drugs against these infections implies a more precise defi-
nition of therapeutic targets. Among them, the mycobacter-
ial arabinan biosynthetic pathway[1] has already been iden-
tified as the site of action of ethambutol, a first line antitu-
berculosis drug.[2Ϫ5] It is a very promising target as -arabi-
nose is not used by the human host. In the mycobacterial
cell wall, -arabinose is found in arabinogalactan (AG) and
lipoglycans: lipoarabinomannan (LAM) and arabinoman-
nan (AM).[6,7] AG is the major component by weight of the
cell wall, it is covalently linked to the peptidoglycan and
carries at its ends, the mycolic acids.[8] LAM is a major
antigen with various biological properties, depending on the
mycobacterial species.[9Ϫ11] Although the structural models
of the arabinan domain of AG and LAM show small differ-
ences, in these compounds, -arabinose occurs as oligomers
of furanosides. The core of the arabinan domain is a chain
with α-(1Ǟ5)-linked units (squares, see Figure 1) and α-
(1Ǟ3)-α-(1Ǟ5) branching points (diamonds). At the end of
the domain are found β-(1Ǟ2)-arabinofuranosides (tri-
angles). Two structures have been characterized at the non-
reducing end of the arabinan chains. In AG, only branched
hexasaccharidic Ara6 motifs were found while in LAM,
both linear Ara4 and branched Ara6 were identified (see
Figure 1. Schematic representation of mycobacterial arabinans
dotted lines, Figure 1). In LAM, the terminal units (tri-
angles) are substituted on the 5-position by small motifs,
called caps, which have been shown to be dependent on the
mycobacterial species and crucial for biological activity.
The caps of LAM isolated from M. tuberculosis and M.
bovis BCG are mono-, di- and tri-α-(1Ǟ2)-
mannopyranosides,[12Ϫ14] while caps of LAM of M. smeg-
matis, a nonpathogenic species, are inositol phosphates.[15]
In AG, about two thirds of both last units (triangles and
circles) are esterified on their 5-position by the mycolic
acids.[5,16] The development of an arabinosyl transferase as-
say[4,17,18] has followed the isolation of a mycobacterial
arabinose donor.[19] It allows in vitro testing of inhibitors with
synthetic oligoarabinofuranosidic acceptors and prompted
renewed
interest
in
oligoarabinofuranoside
con-
struction.[18,20Ϫ27]
Completing our previous work,[22,23] we describe here the
preparation of oligoarabinofuranosides 1Ϫ4, representative
of all structural features found in mycobacterial arabinans
(Figure 2). Compounds 1Ϫ4 were efficiently obtained from
previously reported building blocks 5Ϫ12 (Figure 3) pre-
pared from 1,2,5-orthoesters of -arabinose.[27] We have
now in hand a comprehensive system for the stereoselective
synthesis of any possible glycosidic linkage between oligo-
arabinofuranosidic units.
[a]
Institut de Pharmacologie et de Biologie Structurale du CNRS,
205 route de Narbonne, 31077 Toulouse Cedex 5, France
[b]
´
Laboratoire de Chimie Organique et Bioorganique, Universite
Chouaib Doukkali,
B. P. 20, El Jadida, Morroco
Eur. J. Org. Chem. 2003, 3587Ϫ3598
DOI: 10.1002/ejoc.200300303
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K. Marotte, S. Sanchez, T. Bamhaoud, J. Prandi
FULL PAPER
Synthesis of Fragments of the Internal Arabinan
Core
Two pentasaccharides, 1 and 2, found in the internal core
of the arabinan domain of AG and LAMs were made. As
only α-glycosidic bonds are found in this part, synthetic
work was straightforward and required only α-donors 8 and
12 (Figure 3). 8 was used for the introduction of the 5-gly-
cosylated units while 12 was chosen for introduction of the
3,5-branching points. Compound 12 was obtained in quan-
titative yield by benzoylation of the known alcohol 11[21]
with benzoyl chloride in pyridine.
The synthesis of both 1 and 2 began with glycosylation
of acceptor 5 with 1.1 equiv. of thioglycoside donor 8 under
N-iodosuccinimide (NIS) and catalytic trimethylsilyl tri-
Figure 2. Structural formulas and ring lettering conventions for
targeted oligosaccharides 1Ϫ4
Scheme 1. Synthesis of 1: a: 1.0 equiv. 5, 1.1 equiv. 8, 1.3 equiv.
˚
NIS, 0.1 equiv. TMSOTf, CH2Cl2, molecular sieves (4 A), Ϫ15 °C,
40 min, 90%; b: HCl, MeOH/Et2O, room temp., overnight, 86%; c:
1.0 equiv. 15, 1.1 equiv. 8, 1.3 equiv. NIS, 0.1 equiv. TMSOTf,
˚
CH2Cl2, molecular sieves (4 A), Ϫ15 °C, 1 h, 77%; d: same as b,
36 h, 90%; e: 1.0 equiv. 18, 1.2 equiv. 8, 1.3 equiv. NIS, 0.1 equiv.
˚
TMSOTf, CH2Cl2, molecular sieves (4 A), Ϫ15 °C, 1 h, 90%; f:
same as b, 24 h, 79%; g: 1.0 equiv. 20, 1.2 equiv. 8, 1.3 equiv. NIS,
˚
0.1 equiv. TMSOTf, CH2Cl2, molecular sieves (4 A), Ϫ15 °C, 1 h,
90%; h: Bu4NF, THF, room temp., 3 h, then MeONa, MeOH,
room temp., 1.5 h, then H2, Pd(OH)2/C, MeOH, 0.08  HCl, 6 h,
65% (three steps)
Figure 3. Building blocks 5Ϫ13 used for the construction of oligo-
saccharides 1Ϫ4
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Synthesis of Oligoarabinofuranosides from the Mycobacterial Cell Wall
FULL PAPER
fluoromethanesulfonate (TMSOTf)[28] activation in CH2Cl2
at Ϫ15 °C (Scheme 1). α-Disaccharide 14 was obtained in
90% isolated yield and as a single anomer (δ1B-H
ϭ
3
5.28 ppm, J1B,2B Ͻ 0.5 Hz; δC-1B ϭ 105.9 ppm).[29] Re-
moval of the tert-butyldiphenylsilyl group with commercial
tetrabutylammonium fluoride (Bu4NF) in THF (1  solu-
tion) gave disaccharide 15 but in a disappointing 60% yield.
The main by-product, isolated in 25% yield from the reac-
tion, was diol 16, where the 2B-benzoyl group has been re-
moved together with the 5B-silyl group (see Figure 2 for the
lettering of the rings of oligoarabinofuranosides). This very
easy debenzoylation was probably induced by the proximity
of the 5B-hydroxy group, liberated during the desilylation
reaction, and the slightly basic nature of the reagent. To
eliminate this side-reaction, commercial Bu4NF solution in
THF was treated with trifluoroacetic acid until neutrality
(pH paper). This reagent was found to give much cleaner
reaction in the deprotection of 14 but a considerable loss of
reactivity was observed. 15 was obtained in 80% yield but
the reaction took 24 h at room temp to go to completion.
Finally, desilylation with HCl in a 1:1 diethyl ether/meth-
anol solution[30] was found to be very convenient in terms
of selectivity and reaction time, 15 was thus obtained from
14 in 86% yield after overnight reaction at room tempera-
ture.
Scheme 2. Synthesis of 2: a: 1.0 equiv. 15, 1.1 equiv. 12, 1.3 equiv.
˚
NIS, 0.1 equiv. TMSOTf, CH2Cl2, molecular sieves (4 A), Ϫ15 °C,
1 h, 81%; b: Bu4NF, THF, room temp., 3 h, 95%; c: 1.0 equiv. 23,
3 equiv. 8, 4.0 equiv. NIS, 0.1 equiv. TMSOTf, CH2Cl2, molecular
˚
sieves (4 A), Ϫ15 °C, 1 h, 81%; d: Bu4NF, THF, room temp., 3 h,
then NaOMe, MeOH, room temp., 1.5 h, then H2, Pd/C, MeOH,
overnight, 63% (three steps)
(IAD)[33,34]
for
a
general
synthesis
of
β-
For the synthesis of linear pentasaccharide 1, 15 was gly- arabinofuranosides.[21Ϫ23] Examples of its use for the syn-
cosylated with 1.1 equiv. of thioglycoside 8 to give trisacch- thesis of β--fructofuranosides have been described.[35,36]
aride 17 in 77% yield (Scheme 1). Two more cycles of desi-
We first tested the method for the formation of β-(1Ǟ5)-
lylation/glycosylation with compound 8 gave linear tetra- linkage between arabinofuranosidic units. According to the
saccharide 19 (81% for the two steps from 17) and pentasac- described protocol,[33,37] acceptor with a free 5-OH group 5
charide 21 (71% from 19). Finally, compound 1 was isolated (1 equiv.) and β-donor 9 (1.05 equiv.) were treated with 1.5
in 65% yield after three steps of deprotection [commercial equiv. of 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ)
Bu4NF in THF, sodium methoxide in methanol and cata- in CH2Cl2 to give acetal 25, isolated in 66% yield as a mix-
lytic hydrogenation in acidic methanol with Pd(OH)2/C as ture of diastereoisomers on the acetalic carbon atom
catalyst].
(Scheme 3). Intramolecular glycosylation of 25 was pro-
Branched pentasaccharide 2 was also prepared from 15 moted by 1.2 equiv. of iodonium dicollidine perchlorate
by using thioglycoside donor 12 instead of 8 for the intro- (IDCP) in CH2Cl2 and gave the β-(1Ǟ5)-linked diarabino-
duction of the branching unit C of 2. Trisaccharide 22 was furanoside 26 in 79% isolated yield. In order to obtain such
obtained in 81% yield by reaction of 15 with 1.1 equiv. of a yield, it was found necessary to hydrolyze some 4-meth-
12 under NIS/catalytic TMSOTf activation (Scheme 2). In oxybenzaldehyde derivatives, still present after treatment
this case also, the reaction was completely stereoselective and extraction of the glycosylation reaction. This was done
and only the α-product was isolated (δ1C-H ϭ 5.04 ppm, by hydrolysis with catalytic amounts of DDQ in wet aceto-
3J1C,2C ϭ 1.5 Hz, δC-1C ϭ 105.7 ppm). The TIPS group of nitrile.[38] No other disaccharide was isolated and assign-
22 was removed (commercial Bu4NF in THF, 95%) and the ment of the β-(D) configuration to the new anomeric center
1
resulting diol 23 was bis(α-glycosylated) with 3 equiv. of was unambiguously deduced from H and 13C NMR spec-
thioglycoside donor 8 to afford pentaarabinofuranoside 24 troscopic data of 26 in CDCl3. The signal for 1B-H (see
in 81% yield. A three-step deprotection sequence (Bu4NF Scheme 3) was found at δ ϭ 4.91 ppm in the 1H NMR spec-
3
in THF, NaOMe in MeOH and hydrogenolysis with Pd/C trum, with a J1B,2B coupling constant of 4.5 Hz while C-1B
as catalyst) gave pentasaccharide 2 in 63% overall yield.
resonated at δ ϭ 102.1 ppm, which are typical values for β-
arabinofuranosides.[29]
To obtain the β-(1Ǟ2)-linked diarabinofuranoside 27,
the very same sequence of reactions was carried out with
β-donor 9 and acceptor with a free 2-OH group 6. Treat-
Synthesis of β-Arabinofuranosides
After the internal core of mycobacterial arabinans, we ment of 6 with 1.1 equiv. of 9 and 1.5 equiv. of DDQ in
embarked on the more challenging synthesis of the terminal CH2Cl2 gave a mixture of acetals (75%). IDCP-promoted
β-(1Ǟ2)-linkage. Among the numerous methods described intramolecular glycosylation afforded the disaccharide 28 in
for the preparation of 1,2-cis-glycosidic linkages,[31,32] we 70% yield. Once again, the reaction was completely stereo-
chose to look at Ogawa’s internal aglycon delivery approach selective and only the β-anomer was isolated (δ1B-H
ϭ
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K. Marotte, S. Sanchez, T. Bamhaoud, J. Prandi
FULL PAPER
arabinofuranoside acceptor having a hydroxy group in 5B-
position. 13 was prepared according to a procedure first
described by Ley.[39,40] To obtain the diarabinofuranoside
coupling partner, the strategy described above for the prep-
aration of 28 was applied with the pivalate-protected ac-
ceptor 7 (Figure 3) instead of 6 to allow selective un-
masking of the 5B-position of the intermediate β-(1Ǟ2)-
diarabinofuranoside. Coupling of building blocks 7 and 9
was done as above with Ogawa’s 2-steps procedure and gave
29 in 63% overall yield (Scheme 3). The 2B-hydroxy group
of 29 was protected as an acetate with acetic anhydride in
pyridine and removal of the TBDPS group of 30 with
Bu4NF in THF gave diarabinofuranoside 31, isolated in
76% yield for the two steps. Tetrasaccharide 32 was ob-
tained from glycosylation of 31 with 1.5 equiv. of thiodi-
mannoside 13 promoted by NIS and catalytic TMSOTf in
CH2Cl2. 32 was isolated in 77% yield as a 4:1 α/β mixture
on the C-1C anomeric center. Despite the absence of a par-
ticipating group on the 2C-position of the thiomannosidic
donor 13, an acceptable diastereoselectivity was obtained
for the glycosylation at Ϫ15 °C, the difficult α-mannosyl-
ation of the 5-position of a β-arabinofuranoside has been
reported during the synthesis of a related compound.[41] As
chromatographic separation of the two anomers could not
be obtained at this stage, the mixture of tetrasaccharides
was deacylated with sodium methoxide in methanol to a
mixture of triols, from which the required α-anomer 33 was
isolated. Finally, hydrogenolysis of the benzyl ethers (H2,
Pd/C, 65%) gave 3, the tetrasaccharidic cap of LAM of M.
tuberculosis and M. bovis BCG.
Scheme 3. a: 1.0 equiv. 5, 1.05 equiv. 9, 1.5 equiv. DDQ, CH2Cl2,
˚
molecular sieves (4 A), room temp., 3 h, 66%; b: 1.2 equiv. IDCP,
Synthesis of the Terminal Hexasaccharide of the
Arabinan Core of Arabinogalactan
˚
CH2Cl2, molecular sieves (4 A), room temp., 2 h, 79%; c: 1.0 equiv.
˚
6, 1.2 equiv. 9, 1.5 equiv. DDQ, CH2Cl2, molecular sieves (4 A),
room temp., 2 h, 75% then 1.2 equiv. IDCP, CH2Cl2, molecular
˚
sieves (4 A), room temp., 2 h, 70%; d: Bu4NF, THF, room temp.,
The last characteristic structural feature of mycobacterial
arabinans is 4, the terminal hexaarabinoside found at the
non-reducing end of the arabinan domain of AG. In light
of the symmetric structure of 4, the most convergent ap-
proach was chosen for its synthesis and involved two suc-
cessive bis(glycosylations). Firstly, for the introduction of
the two α-(1Ǟ3)- and α-(1Ǟ5)-arabinofuranosides (units C
and D, Figure 2) on disaccharide AϪB, and later in the
1 h then H2, Pd/C, EtOAc/MeOH, room temp., 60%, 2 steps; e: 1.0
equiv. 7, 1.1 equiv. 9, 1.5 equiv. DDQ, CH2Cl2, molecular sieves (4
˚
A), room temp., 2.5 h, 84%, then 1.2 equiv. IDCP, CH2Cl2, molecu-
˚
lar sieves (4 A), room temp., 2 h, 75%; f: Ac2O, pyridine, room
temp., overnight; g: Bu4NF, THF, room temp., 1 h, 75%, 2 steps;
h: 1.0 equiv. 31, 1.4 equiv. 13, 1.7 equiv. NIS, 0.15 equiv. TMSOTf,
˚
CH2Cl2, molecular sieves (4 A), Ϫ15 °C, 1 h, 77%; i: NaOMe,
MeOH, room temp., 5 h, 50%; j: H2, Pd/C, MeOH, room temp.,
1 h, 65%
3
5.14 ppm, J1B,2B ϭ 4.5 Hz, δC-1B ϭ 101.4 ppm). This com- synthesis, for the simultaneous formation of the two β-
pound was deprotected in two steps: silyl groups were re- (1Ǟ2)-arabinosides E and F. This approach has been suc-
moved with Bu4NF in THF and benzyl ethers were hydro- cessfully applied for the preparation of a related pentaarabi-
genolyzed with H2 and 10% Pd/C. This gave a 60% yield of noside motif.[23] Fmoc-protected α-donor 10 was selected
the β-(1Ǟ2)-diarabinofuranoside 28.
for the introduction of units C and D on disaccharide AϪB
(Figure 1). The Fmoc group will participate during the gly-
cosylation, securing the requested α-configuration for the
CǞB and DǞB linkages, while it can be easily and selec-
tively removed in the presence of benzoate and pivalate es-
ters.[42] This will allow the unmasking of the 2-hydroxy
Synthesis of the Caps of the LAM of
Mycobacterium tuberculosis[22]
With the β-(1Ǟ2)-diarabinofuranoside in hand, 3, the groups of units C and D prior to the β-glycosylations. Di-
major tetrasaccharidic caps of the LAM of M. tuberculosis saccharide 34 was obtained in 87% yield from coupling of
and M. bovis BCG were accessible. A convergent strategy 5 with 1.2 equiv. of thioglycoside donor 12 under NIS/cata-
was chosen and involved coupling dimannosidic thioglyco- lytic TMSOTf activation (Scheme 4). The TIPS group was
side donor 13 (Figure 3) with an appropriate β-(1Ǟ2)-di- removed (commercial Bu4NF, THF) and diarabinofurano-
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Synthesis of Oligoarabinofuranosides from the Mycobacterial Cell Wall
FULL PAPER
side 35 was isolated in 98% yield. Treatment of acceptor nals corresponding to β-arabinofuranosides were found in
1
35 with 2.7 equiv. of thioglycoside α-donor 10 under NIS/ the NMR spectra. The first one was observed in the H
TMSOTf activation afforded the tetrasaccharide 36 which NMR spectrum at δ ϭ 5.11 ppm (3J1F,2F ϭ 4.7 Hz) and was
was not isolated in pure form. Crude 36 was dissolved in a correlated to a carbon signal at δC ϭ 101.6 ppm, while the
4:1 THF/Et3N mixture to achieve the deprotection of the other β-anomeric proton resonated at δ ϭ 5.21 ppm
Fmoc groups and diol 37 was isolated in 75% for the two (3J1E,2E ϭ 4.7 Hz) and was correlated with a carbon signal
steps. This bis(α-glycosylation) was completely selective and at δ ϭ 102.2 ppm. Although moderate, this yield might have
this was ascertained from the NMR spectroscopic data. been anticipated from calculations made using our previous
Two new anomeric signals were observed in the NMR spec- results for the formation of β-(1Ǟ2)-arabinofuranosides.
tra. In the 1H NMR spectrum, 1C-H was found as a doub- Extrapolation from the observed yields for synthesis of 27
let (3J1C,2C ϭ 1.1 Hz) at δ ϭ 4.98 ppm while 1D-H res- and 29 would have given 27 and 39%, respectively, for the
onated as a broad singlet at δ ϭ 5.07 ppm. These two pro- bis(β-glycosylation). This result clearly shows the limitation
ton signals were correlated with carbon signals found at δ ϭ of Ogawa’s internal aglycon delivery approach for the con-
108.5 (C-1C) and 108.3 (C-1D) ppm in the 13C NMR spec- struction of more complex oligoarabinofuranosidic struc-
trum.[29] 37 was then treated with 3 equiv. of β-donor 9 and tures by simultaneous polyglycosylations. Final deprotec-
3 equiv. of DDQ in CH2Cl2 to yield a mixture of dia- tion of 38 in three steps [Bu4NF/THF, NaOMe in MeOH
stereoisomeric bis(acetals) in 83% yield isolated yield. This and H2 with Pd(OH)2/C] gave the terminal hexaarabino-
mixture was treated with IDCP (3 equiv.) for 24 h at room furanoside of arabinogalactan 4 in 30% overall yield.
temperature. After DDQ treatment, the expected hexasac-
charide 38 was obtained in a moderate yield of 33%, no
other hexasaccharide was isolated. Two new anomeric sig-
Conclusion
Oligosaccharides 1Ϫ4, representative of the structural di-
versity found in the arabinans of the mycobacterial cell wall
have been synthesized. Their elaboration relies on the ef-
ficient preparation of the various required building blocks
and the complete control of the stereochemical outcome of
the glycosylation reactions. Monoarabinofuranosidic units,
donors and acceptors, were all derived from 1,2,5-orthoes-
ters of -arabinose.[27] Esters or carbonates efficiently di-
rected the formation of α-glycosides while the more chal-
lenging synthesis of β-arabinofuranosides was solved by an
internal aglycon delivery approach. Together with our pre-
vious results,[22,23] we have now a comprehensive glycosyl-
ation system which allows the synthesis of any possible oli-
goarabinofuranosidic structure and makes these com-
pounds readily accessible for biochemical studies.
Experimental Section
General: All reactions were run under argon in oven-dried glass-
ware. Anhydrous solvents were distilled before use. Commercial re-
agents were used as received. Chromatographic separations were
run on silica gel (35Ϫ70 µm) obtained from SDS (Peypin, France).
NMR spectra were recorded with Bruker AM 250, Avance DPX
400 and DMX 500 spectrometers, working at 250 MHz (400 MHz
1
and 500 MHz, respectively) for H NMR and 62.89 MHz (100.62
and 125.72 MHz, respectively) for 13C NMR. All chemical shifts
are expressed in ppm from internal tetramethylsilane. Assignment
of signals for oligosaccharides were deduced from HOHAHA and
HMQC experiments. Optical rotations were measured at 25 °C with
a PerkinϪElmer 41 polarimeter. Elemental analyses were obtained
from the Laboratoire de Chimie de Coordination du CNRS at Tou-
louse (France). High resolution mass data were obtained from the
Scheme 4. a: 1 equiv. 5, 1.2 equiv. 12, 1.3 equiv. NIS, 0.1 equiv.
˚
TMSOTf, CH2Cl2, molecular sieves (3 A), 0 °C to room temp., 1 h,
87%; b: Bu4NF, THF, room temp., 2 h, 98%; c: 1.0 equiv. 35, 2.7
equiv. 10, 4.0 equiv. NIS, 0.1 equiv. TMSOTf, CH2Cl2, molecular
˚
sieves (3 A), 0 °C to room temp., 1 h; d: 4:1 THF/Et3N, room temp.,
´
Centre d’Etudes Structurale et d’Analyse des Molecules Or-
2 h, 75%, 2 steps; e: 1.0 equiv. 37, 3 equiv. 9, 3 equiv. DDQ,
´
ganiques at Talence (France) and the Centre de Spectrometrie de
˚
CH2Cl2, molecular sieves (4 A), 0 °C to room temp., 4 h, then 3.0
´
Masse of Universite Claude Bernard at Lyon (France).
˚
equiv. IDCP, CH2Cl2, molecular sieves (4 A), room temp., 24 h,
27%, 2 steps; f: Bu4NF, THF, room temp., overnight, then MeONa,
MeOH, room temp., 22 h, then H2, Pd(OH)2/C, MeOH, 0.08 
HCl, 30% (three steps)
General Procedure for α-Glycosylation with NIS/TMSOTf: Ac-
ceptor (0.02Ϫ0.2  solution) and thioglycoside donor (1.1Ϫ1.3
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K. Marotte, S. Sanchez, T. Bamhaoud, J. Prandi
FULL PAPER
equiv.) were dissolved in CH2Cl2 in the presence of activated pow-
dered molecular sieves (3 or 4 A). The mixture was stirred for 20
10% Pd(OH)2/C at room temperature (1Ϫ4 h). The reaction mix-
ture was neutralized with aqueous K2CO3 and filtered. Concen-
tration of the filtrate and chromatography gave the product.
˚
min at room temperature. The temperature was lowered to Ϫ15 °C
before addition of NIS (1.3 equiv.) and TMSOTf (0.1 equiv. as a 1
 solution in toluene or CH2Cl2). After completion of the reaction
(TLC), the mixture was neutralized with a few drops of Et3N and
hydrolyzed with dilute aqueous Na2S2O3 solution. The aqueous
phase was extracted twice with CH2Cl2 and the combined organic
phases were dried with MgSO4. Evaporation of the solvent and
chromatography gave the product.
Ethyl 2-O-Benzoyl-3,5-O-(1,1,3,3-tetraisopropyldisiloxan-1,3-diyl)-
1-thio-α-D-arabinofuranoside (12): Ethyl 3,5-O-(1,1,3,3-tetraisopro-
pyldisiloxane-1,3-diyl)-1-thio-α--arabinofuranoside (11)[21] (1.60 g,
3.66 mmol) was dissolved in pyridine (7 mL) and treated at room
temperature with benzoyl chloride (640 µL, 5.51 mmol) for 3 h. The
pyridine was evaporated and the residue partitioned between
CH2Cl2 and water. The organic phase was decanted and the water
phase extracted once with CH2Cl2. Chromatography (petroleum
ether/ethyl acetate, 15:1) gave 12 as a colorless oil (1.96 g, quantita-
tive). [α]2D5 ϭ ϩ27 (c ϭ 1.20 in chloroform). 1H NMR (250 MHz,
General Procedure for β-Glycosylation: Acceptor (0.04Ϫ0.05 ) and
donor (1.05Ϫ1.2 equiv.) were dissolved in CH2Cl2, powdered mo-
˚
lecular sieves (4 A) was added and the reaction mixture was stirred
3
for 20 min at room temperature. The temperature was lowered to
0 °C before addition of DDQ (1.5 equiv.) and the reaction was left
at room temp. After completion (TLC), the reaction mixture was
CDCl3, 20 °C): δ ϭ 0.90Ϫ1.17 [m, 28 H, (CH3)2CH], 2.28 (t, J ϭ
7.5 Hz, 3 H, SCH2CH3), 2.57Ϫ2.82 (m, 2 H, SCH2CH3), 4.03 (dd,
3
3
2J5,5 ϭ 12.5, J5,4 ϭ 4.0 Hz, 1 H, 5-H), 4.09 (dd, J5,4 ϭ 3 Hz, 1
treated according to Ogawa’s protocol:[33] neutralization with an H, 5-H), 4.15 (m, 1 H, 4-H), 4.56 (dd, J3,4 ϭ 8, J3,2 ϭ 5.5 Hz, 1
3
3
3
ascorbic acid/citric acid/NaOH solution, filtration through Celite
(CH2Cl2 elution) and washings of the organic phase with water and
brine. Chromatography of the residue gave the mixture of acetals.
These acetals were taken up in CH2Cl2 containing powdered molec-
H, 3-H), 5.30 (d, J1,2 ϭ 3.5 Hz, 1 H, 1-H), 5.42 (dd, 1 H, 2-H),
7.42Ϫ8.08 (m, 5 H, Ar-H) ppm. 13C NMR (62.89 MHz, CDCl3,
20 °C): δ ϭ 12.4, 12.7, 13.1, 13.3, 13.4, 13.5 [(CH3)2CH], 14.7
(SCH2CH3), 16.9, 17.0, 17.2, 17.3, 17.4 [CH(CH3)2], 25.3
(SCH2CH3), 61.0 (C-5), 75.2 (C-4), 80.1 (C-3), 83.7 (C-2), 86.4 (C-
1), 129.3, 129.7, 133.3 (Ar), 165.5 (COOPh) ppm. C26H44O6SSi
(540.9): calcd. C 57.74, H 8.20; found C 57.58, H 8.22.
˚
ular sieves (4 A) and stirred for 20 min at room temperature before
addition of IDCP (1.2 equiv.). After completion of the reaction
(TLC, 2Ϫ24 h), the mixture was filtered through Celite (CH2Cl2
elution) and the organic phase was hydrolyzed with saturated aque-
ous Na2S2O3 solution, washed once with water and dried with
MgSO4. After evaporation of the solvent, the residue was filtered
through silica, taken up in wet acetonitrile (CH3CN/H2O, 9:1) and
treated with DDQ (0.1 equiv.) at room temperature for 4 h.[38]
Evaporation of the solvents and chromatography gave the product.
8-(Methoxycarbonyl)octyl
benzyl-5-O-tert-butyldiphenylsilyl-α-
benzyl-α- -arabinofuranoside (14): From 5 (99.1 mg, 0.19 mmol)
and 8 (133.0 mg, 0.21 mmol). Chromatography with petroleum
ether/EtOAc (5:1) gave 14 as a colorless oil (187.6 mg, 90%). [α]2D5
2-O-Benzoyl-5-O-(2-O-benzoyl-3-O-
D
-arabinofuranosyl)-3-O-
D
ϭ
ϩ65 (c ϭ 1.09 in chloroform). 1H NMR (250 MHz, CDCl3, 20 °C):
δ ϭ 0.97 [s, 9 H, C(CH3)3], 1.23Ϫ1.40 (m, 8 H, octyl CH2),
1.53Ϫ1.64 (m, 4 H, octyl CH2), 2.29 (t, 3J ϭ 7.5 Hz, 2 H, CH2CO),
3.46 (td, 2J ϭ 9.5, 3J ϭ 7.0 Hz, 1 H, octyl OCH2), 3.66 (s, 3 H,
CH3O), 3.67Ϫ3.79 (m, 4 H, 5A-H, 2 ϫ 5B-H, octyl OCH2), 3.92
Preparation of Neutralized Bu4NF: Commercial 1  solution of
Bu4NF in THF was treated dropwise with CF3COOH until a pH
of 7 was obtained according to a pH paper.
General Procedure for Desilylation with Bu4NF: The silyl ether was
dissolved in THF (0.02Ϫ0.05 ) and treated at room temperature
with a 1  solution of Bu4NF in THF (1.2Ϫ1.5 equiv. for each silyl
group). After completion of the reaction (TLC), the solvent was
evaporated. CH2Cl2/water extraction and chromatography gave
the product.
2
3
(dd, J5A,5A ϭ 11.5, J5A,4A ϭ 4 Hz, 1 H, 5A-H), 4.05Ϫ4.18 (m, 3
H, 3A-H, 3B-H, 4B-H), 4.33 (m, 1 H, 4A-H), 4.45, 4.59, 4.63, 4.77
(4d, 2J ϭ 12.0 Hz, 4 ϫ 1 H, benzyl CH2), 5.13 (s, 1 H, 1A-H), 5.28
(s, 1B-H), 5.38 (d, 3J2A,3A ϭ 1.5 Hz, 1 H, 2A-H), 5.43 (d, 3J2B,3B ϭ
0.7 Hz, 1 H, 2B-H), 7.12Ϫ8.10 (m, 20 H, Ar-H) ppm. 13C NMR
(62.89 MHz, CDCl3, 20 °C): δ ϭ 19.3 [C(CH3)3], 24.9, 26.0, 26.7,
29.1, 29.2, 29.4 (octyl CH2), 34.1 (CH2CO), 51.4 (CH3O), 63.0,
65.4, 67.5 (octyl OCH2), 72.0, 72.3 (benzyl CH2), 81.4, 81.9, 82.1,
83.0, 83.3, 83.7, 105.9 (C-1B), 106.1 (C-1A), 127.7, 127.8, 128.3,
128.4, 128.5, 129.5, 129.6, 129.8, 133.3, 133.6 (Ar) ppm.
C64H74O13Si (1079.4) calcd. C 71.22, H 6.91; found C 71.04, H 6.64.
General Procedure for Desilylation with HCl in Methanol: The silyl
ether (final concentration 0.009Ϫ0.015 ) was treated at room tem-
perature with a 0.28  solution of HCl in diethyl ether/methanol
(1:1, v/v). After completion of the reaction, the mixture was neu-
tralized with saturated aqueous NaHCO3. CH2Cl2/water extraction
and chromatography gave the product.
8-(Methoxycarbonyl)octyl
2-O-Benzoyl-5-O-(2-O-benzoyl-3-O-
-arabinofuranoside
benzyl-α- -arabinofuranosyl)-3-O-benzyl-α-
D
D
General Procedure for Debenzoylation: The oligosaccharide (0.1 )
was dissolved in a 0.1  solution of sodium methoxide in methanol
at room temperature. In some cases, a small amount of THF was
added to effect complete solubilisation of the product. The mixture
was left at room temperature until completion of the reaction
(2Ϫ22 h) and neutralized with Hϩ resin. Filtration of the resin,
concentration of the filtrate and chromatography gave the product.
(15): From 14 (124.1 mg, 0.11 mmoles) by treatment with HCl in
MeOH/Et2O according to the General Procedure. Chromatography
with petroleum ether/EtOAc (2:1) gave 15 as a colorless oil
(83.6 mg, 86%). [α]2D5 ϭ ϩ82 (c ϭ 0.49 in chloroform). 1H NMR
(250 MHz, CDCl3, 20 °C): δ ϭ 1.25Ϫ1.40 (m, 8 H, octyl CH2),
1.55Ϫ1.66 (m, 4 H, octyl CH2), 2.29 (t, 3J ϭ 7.5 Hz, 2 H, CH2CO),
2
3
3.47 (td, J ϭ 9.5, J ϭ 7 Hz, 1 H, octyl OCH2), 3.49Ϫ3.61 (m, 1
H, 5B-H), 3.66 (s, 3 H, CH3O), 3.67Ϫ3.83 (m, 3 H, 5A-H, 5B-H,
General Procedures for Debenzylation
2
3
octyl OCH2), 3.92 (dd, J5A,5A ϭ 11.5, J5A,4A ϭ 5.5 Hz, 1 H, 5A-
Procedure A: Benzyl ether (0.15 ) was dissolved in methanol and
hydrogenolyzed in the presence of 10% Pd/C overnight at room
temperature. Filtration of the mixture, concentration of the filtrate
and chromatography gave the product.
H), 3.97 (br. d, 3J3B,4B ϭ 5.5 Hz, 1 H, 3B-H), 4.07 (m, 1 H, 4B-H),
4.16 (br. d, J3A,4A ϭ 6.0 Hz, 1 H, 3A-H), 4.34 (m, 1 H, 4A-H),
3
4.47, 4.62, 4.65, 4.82 (4d, 2J ϭ 12.0 Hz, 4 ϫ 1 H, benzyl CH2),
5.16 (s, 1 H, 1A-H), 5.28 (s, 1 H, 1B-H), 5.39 (m, 2 H, 2A-H, 2B-
H), 7.14Ϫ8.08 (m, 20 H, Ar-H) ppm. 13C NMR (62.89 MHz,
CDCl3, 20 °C): δ ϭ 24.9, 26.0, 29.1, 29.2, 29.4 (octyl CH2), 34.1
Procedure B: Benzyl ether (0.04Ϫ0.13 ) was dissolved in a 0.08 
methanolic solution of HCl and hydrogenolyzed in the presence of
3592
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2003, 3587Ϫ3598

Synthesis of Oligoarabinofuranosides from the Mycobacterial Cell Wall
FULL PAPER
(CH2CO), 61.9 (C-5B), 67.6 (octyl OCH2), 72.2, 72.3 (benzyl CH2),
8-(Methoxycarbonyl)octyl 2-O-Benzoyl-5-O-{2-O-benzoyl-5-O-[2-
81.4, 81.7, 82.0, 82.8, 83.2, 83.3, 106.0 (C-1B), 106.2 (C-1A), 127.7, O-benzoyl-5-O-(2-O-benzoyl-3-O-benzyl-5-O-tert-butyldiphenylsilyl-
127.9, 128.4, 128.5, 129.7, 129.8, 133.3, 133.5 (Ar) ppm. C48H56O13 α- -arabinofuranosyl)-3-O-benzyl-α- -arabinofuranosyl]-3-O-
benzyl-α- -arabinofuranosyl}-3-O-benzyl-α- -arabinofuranoside (19):
D
D
(840.9): calcd. C 68.56, H 6.71; found C 68.59, H 6.89.
D
D
From 18 (143.0 mg, 0.12 mmol) and 8 (92.0 mg, 0.15 mmol). Chro-
matography with petroleum ether/EtOAc (3:1) gave 19 as a color-
8-(Methoxycarbonyl)octyl 2-O-Benzoyl-5-O-[2-O-benzoyl-5-O-(2-O-
benzoyl-3-O-benzyl-5-O-tert-butyldiphenylsilyl-α-
furanosyl)-3-O-benzyl-α- -arabinofuranosyl]-3-O-benzyl-α-
binofuranoside (17): From 15 (100.0 mg, 0.12 mmol) and
D
-arabino-
less oil (189.7 mg, 90%). [α]2D5 ϭ ϩ91 (c ϭ 0.49 in chloroform). H
1
D
D
-ara-
NMR (500 MHz, CDCl3, 25 °C): δ ϭ 0.95 [s, 9 H, C(CH3)3],
1.22Ϫ1.39 (m, 8 H, octyl CH2), 1.53Ϫ1.65 (m, 4 H, octyl CH2),
2.29 (t, 3J ϭ 7.7 Hz, 2 H, CH2CO), 3.45 (td, 2J ϭ 9.9, 3J ϭ 6.8 Hz,
8
(82.0 mg, 0.13 mmol). Chromatography with petroleum ether/
EtOAc (4:1) gave 17 a colorless oil (129 mg, 77%). [α]2D5 ϭ ϩ76 (c ϭ
0.89 in chloroform). 1H NMR (400 MHz, CDCl3, 20 °C): δ ϭ 0.96
[s, 9 H, C(CH3)3], 1.22Ϫ1.39 (m, 8 H, octyl CH2), 1.56Ϫ1.66 (m,
4 H, octyl CH2), 2.29 (t, 3J ϭ 7.5 Hz, 2 H, CH2CO), 3.45 (td, 2J ϭ
2
3
1 H, octyl OCH2), 3.63 (dd, J5C,5C ϭ 11.4, J5C,4C ϭ 3.5 Hz, 1 H,
5C-H), 3.65 (s, 3 H, CH3O), 3.65Ϫ3.75 (m, 5 H, 5A-H, 2 ϫ 5D-
3
H, 5B-H, octyl OCH2), 3.81 (dd, J5C,4C ϭ 3.9 Hz, 1 H, 5C-H),
2
3
3.84 (dd, J5B,5B ϭ 11.4, J5B,4B ϭ 3.9 Hz, 1 H, 5B-H), 3.92 (dd,
2
9.7, 3J ϭ 6.7 Hz, 1 H, octyl OCH2), 3.66 (dd, J5B,5B ϭ 11.3,
2J5A,5A ϭ 11.4, J5A,4A ϭ 4.1 Hz, 1 H, 5A-H), 4.01Ϫ4.07 (m, 3 H,
3C-H, 3D-H, 4D-H), 4.09 (br. d, J3B,4B ϭ 5.8 Hz, 1 H, 3B-H),
3
3J5B,4B ϭ 3.6 Hz, 5B-H), 3.66 (s, 3 H, CH3O), 3.68Ϫ3.73 (m, 4 H,
3
3
5A-H, 2 ϫ 5C-H, octyl OCH2), 3.84 (dd, J5B,4B ϭ 3.8 Hz, 1 H,
4.11 (m, 1 H, 4C-H), 4.15 (m, 1 H, 3A-H), 4.16 (m, 1 H, 4B-H),
4.32 (m, 1 H, 4A-H), 4.39, 4.40, 4.48, 4.53, 4.54, 4.61, 4.61, 4.78
(8d, 2J ϭ 12.2 Hz, 8 ϫ 1 H, benzyl CH2), 5.13 (s, 1 H, 1A-H), 5.22
(s, 1 H, 1D-H), 5.24 (s, 1 H, 1C-H), 5.28 (s, 1 H, 1B-H), 5.37 (m,
2
3
5B-H), 3.92 (dd, J5A,5A ϭ 11.2, J5A,4A ϭ 4.1 Hz, 1 H, 5A-H),
3
4.00Ϫ4.03 (m, 2 H, 3C-H, 4C-H), 4.09 (br. d, J3B,4B ϭ 5.4 Hz, 1
H, 3B-H), 4.15 (br. d, 3J3A,4A ϭ 4.6 Hz, 1 H, 3A-H), 4.17 (m, 1 H,
4B-H), 4.32 (m, 1 H, 4A-H), 4.40, 4.47, 4.47, 4.56, 4.61, 4.78 (6d,
2J ϭ 12.2 Hz, 6 ϫ 1 H, benzyl CH2), 5.13 (s, 1 H, 1A-H), 5.25 (s,
1 H, 1C-H), 5.28 (s, 1 H, 1B-H), 5.38 (m, 2 H, 2A-H, 2C-H), 5.40
(d, 3J2B,3B ϭ 1.2 Hz, 1 H, 2B-H), 7.10Ϫ8.05 (m, 40 H, Ar-H) ppm.
13C NMR (125.78 MHz, CDCl3, 20 °C): δ ϭ 19.7 [C(CH3)3], 25.1,
26.1, 26.8, 29.2, 29.3, 29.4, 29.5 (octyl CH2), 34.2 (CH2CO), 51.6
(CH3O), 63.0 (C-5C), 65.3 (C-5B), 65.6 (C-5A), 67.7 (octyl OCH2),
72.0, 72.2, 72.4 (benzyl CH2), 81.6 (C-4A), 81.9 (C-2A), 82.0 (C-
2B), 82.1 (C-4B), 82.3 (C-2C), 83.0 (C-3C), 83.3 (C-3A, C-3B), 83.9
(C-4C), 106.0 (C-1A), 106.2 (C-1B, C-1C), 127.6, 127.7, 127.8,
128.0, 128.4, 128.5, 128.6, 129.5, 129.6, 129.8, 129.9, 133.3, 133.4,
135.7, 137.8, 137.9 (Ar), 164.7, 165.4, 165.7 (COOPh), 174.5 (CO-
OMe) ppm. C83H92O18Si (1405.7): calcd. C 70.92, H 6.60; found C
70.74, H 6.58.
3
2 H, 2C-H, 2D-H), 5.38 (d, J2A,3A ϭ 1.8 Hz, 1 H, 2A-H), 5.42 (d,
3J2B,3B ϭ 1.4 Hz, 1 H, 2B-H), 7.05Ϫ8.05 (m, 50 H, Ar-H) ppm.
13C NMR (125.78 MHz, CDCl3, 25 °C): δ ϭ 24.9, 25.9, 26.7 (CH2),
26.9 [C(CH3)3], 28.9, 29.3, 29.4, 29.6, 29.8 (CH2), 34.1 (CH2CO),
51.4 (CH3O), 62.8 (C-5D), 65.1 (C-5C), 65.2 (C-5B), 65.4 (C-5A),
67.5 (octyl OCH2), 71.9, 72.1, 72.2 (benzyl CH2), 81.3 (C-4A), 81.6
(C-2C, C-2D), 81.8 (C-4B, C-4C), 82.1 (C-2A), 82.6 (C-4D), 82.7
(C-2B), 83.1 (C-3A, C-3B), 83.7 (C-3C, C-3D), 105.8 (C-1A), 106.0
(C-1B, C-1C, C-1D), 127.6, 127.8, 128.1, 128.3, 128.4, 129.6, 129.7,
133.2, 135.5 (Ar) ppm. HRMS (FAB): C102H110O23SiNa: calcd.
1753.7105, found 1753.7103.
8-(Methoxycarbonyl)octyl 2-O-Benzoyl-5-O-{2-O-benzoyl-5-O-[2-
8-(Methoxycarbonyl)octyl 2-O-Benzoyl-5-O-[2-O-benzoyl-5-O-(2-O-
O-benzoyl-5-O-(2-O-benzoyl-3-O-benzyl-α-
benzyl-α- -arabinofuranosyl]-3-O-benzyl-α-
benzyl-α- -arabinofuranoside (20): 19 (160.0 mg, 92 µmol) was desi-
D
-arabinofuranosyl)-3-O-
benzoyl-3-O-benzyl-α-
D
-arabinofuranosyl)-3-O-benzyl-α-
D-arabino-
D
D-arabinofuranosyl}-3-O-
furanosyl]-3-O-benzyl-α-
D-arabinofuranoside (18): 17 (252.2 mg,
D
0.18 mmol) was desilylated with neutralized Bu4NF in THF ac-
cording to the general procedure. Chromatography with petroleum
lylated with HCl in MeOH/Et2O according to the General Pro-
cedure. Chromatography with petroleum ether/EtOAc (2:1) gave 20
ether/EtOAc (2:1) gave 18 as a colorless oil (189 mg, 90%). [α]2D5
ϭ
as a colorless oil (109.3 mg, 79%). [α]2D5 ϭ ϩ110 (c ϭ 1.09 in chloro-
ϩ79 (c ϭ 0.90 in chloroform). 1H NMR (400 MHz, CDCl3, 20 °C): form). H NMR (400 MHz, CDCl3, 25 °C): δ ϭ 1.24Ϫ1.39 (m, 8
1
δ ϭ 1.24Ϫ1.40 (m, 8 H, octyl CH2), 1.56Ϫ1.65 (m, 4 H, octyl CH2), H, octyl CH2), 1.56Ϫ1.65 (m, 4 H, octyl CH2), 1.68 (m, 1 H, 5D-
3
3
3
1.75 (dd, JOH,5C ϭ 8.6, JOH,5C ϭ 4.3 Hz, 1 H, 5C-OH), 2.29 (t, OH), 2.28 (t, J ϭ 7.5 Hz, 2 H, CH2CO), 3.41Ϫ3.54 (m, 2 H, 5D-
3J ϭ 7.5 Hz, 2 H, CH2CO), 3.46 (td, J ϭ 9.6, J ϭ 6.4 Hz, 1 H, H, octyl OCH2), 3.63Ϫ3.69 (m, 5 H, 5B-H, 5C-H, CH3O),
octyl OCH2), 2.52 (ddd, J5C,5C ϭ 12.4, J5C,4C ϭ 4.0 Hz, 5C-H),
2
3
2
3
2
3.69Ϫ3.76 (m, 3 H, 5A-H, 5D-H, octyl OCH2), 3.80 (dd, J5B,5B ϭ
3
2
3.66 (s, 3 H, CH3O), 3.66Ϫ3.77 (m, 4 H, 5A-H, 5B-H, 5C-H, octyl 11.4, J5B,4B ϭ 3.8 Hz, 1 H, 5B-H), 3.85 (dd, J5C,5C ϭ 11.3,
OCH2), 3.83 (dd, 2J5B,5B ϭ 11.5, 3J5B,4B ϭ 4.0 Hz, 1 H, 5B-H), 3.93
3J5C,4C ϭ 3.9 Hz, 1 H, 5C-H), 3.89Ϫ3.94 (m, 2 H, 3D-H, 5A-H),
2
3
3
(m, 1 H, 3C-H), 3.96 (dd, J5A,5A ϭ 13.0, J5A,4A ϭ 4.2 Hz, 1 H, 3.98 (m, 1 H, 4D-H), 4.06 (br. d, J3B,4B ϭ 5.3 Hz, 1 H, 3B-H),
5A-H), 3.99 (m, 1 H, 4C-H), 4.09 (br. d, 3J3B,4B ϭ 5.5 Hz, 1 H, 3B-
4.09 (br. d, J3C,4C ϭ 5.2 Hz, 1 H, 3C-H), 4.11Ϫ4.17 (m, 2 H, 3A-
3
3
H), 4.16 (br. d, J3A,4A ϭ 5.6 Hz, 1 H, 3A-H), 4.19 (m, 1 H, 4B- H, 4B-H), 4.18 (m, 1 H, 4C-H), 4.31 (m, 1 H, 4A-H), 4.40, 4.44,
H), 4.33 (m, 1 H, 4A-H), 4.41, 4.51, 4.57, 4.62, 4.65, 4.81 (6d, 2J ϭ
4.49, 4.56, 4.57, 4.61, 4.63, 4.77 (8d, 2J ϭ 12.1 Hz, 8 ϫ 1 H, benzyl
12.2 Hz, 6 ϫ 1 H, benzyl CH2), 5.14 (s, 1 H, 1A-H), 5.24 (s, 1 H,
CH2), 5.13 (s, 1 H, 1A-H), 5.21 (s, 1 H, 1D-H), 5.25 (s, 1 H, 1B-
3
3
1C-H), 5.30 (s, 1 H, 1B-H), 5.34 (d, J2C,3C ϭ 1.1 Hz, 1 H, 2C-H), H), 5.27 (s, 1 H, 1C-H), 5.33 (d, J2D,3D ϭ 1.1 Hz, 1 H, 2D-H),
3
3
3
5.39 (d, J2A,3A ϭ 1.5 Hz, 1 H, 2A-H), 5.43 (d, J2B,3B ϭ 1.2 Hz, 1
5.38 (b, 2 H, 2A-H, 2B-H), 5.42 (d, J2C,3C ϭ 1.1 Hz, 1 H, 2C-H),
H, 2B-H), 7.17Ϫ8.06 (m, 30 H, Ar-H) ppm. 13C NMR
7.15Ϫ8.05 (m, 40 H, Ar-H) ppm. 13C NMR (100.62 MHz, CDCl3,
(125.78 MHz, CDCl3, 20 °C): δ ϭ 25.1, 26.1, 29.2, 29.3, 29.4, 29.5 25 °C): δ ϭ 25.1, 26.1, 29.2, 29.3, 29.4, 29.5, 29.8 (octyl CH2), 34.2
(octyl CH2), 34.2 (CH2CO), 51.6 (CH3O), 62.0 (C-5C), 65.6 (C- (CH2CO), 51.6 (CH3O), 62.0 (C-5D), 65.6 (C-5A, C-5B), 65.7 (C-
5B), 65.7 (C-5A), 67.7 (octyl OCH2), 72.2, 72.5 (benzyl CH2), 81.6 5C), 67.7 (octyl OCH2), 72.1, 72.2, 72.4 (benzyl CH2), 81.6 (C-4A),
(C-4A), 81.8 (C-2B, C-2C), 82.1 (C-4B), 82.2 (C-2A), 82.8 (C-3C), 81.8 (C-2A), 81.9 (C-2B, C-2C, C-2D), 82.1 (C-4C), 82.3 (C-4B),
83.3 (C-3B), 83.4 (C-3A), 83.5 (C-4C), 106.1 (C-1A), 106.2 (C-1B), 82.8 (C-3D), 83.2 (C-3B), 83.4 (C-3A, C-3C), 83.4 (C-4D), 106.1
106.3 (C-1C), 127.7, 127.8, 128.0, 128.4, 128.5, 129.4, 129.5, 129.8, (C-1A), 106.2 (C-1C), 106.3 (C-1B, C-1D), 127.7, 127.8, 128.0,
129.9, 133.5, 133.6, 137.7, 138.0 (Ar), 165.3, 165.4, 165.7(COOPh), 128.4, 128.6, 129.5, 129.6, 129.7, 129.8, 129.9, 133.4, 133.5, 137.7,
174.5 (COOMe) ppm. HRMS (FAB): C67H74O18Na: calcd. 138.0 (Ar), 165.3, 165.4, 165.7 (COOPh), 174.5 (COOMe) ppm.
1189.4773, found 1189.4773.
HRMS (FAB): C86H92O23Na: calcd. 1515.5928, found 1515.5922.
Eur. J. Org. Chem. 2003, 3587Ϫ3598
www.eurjoc.org
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3593

K. Marotte, S. Sanchez, T. Bamhaoud, J. Prandi
FULL PAPER
8-(Methoxycarbonyl)octyl 2-O-Benzoyl-5-O-[2-O-benzoyl-5-O-{2-
O-benzoyl-5-O-[2-O-benzoyl-5-O-(2-O-benzoyl-3-O-benzyl-5-O-
(106.0 mg, 0.20 mmol) Chromatography with petroleum ether/
EtOAc (4:1) gave 22 as a colorless oil (190.8 mg, 81%). [α]2D5 ϭ ϩ58
(c ϭ 1.62 in chloroform). 1H NMR (400 MHz, CDCl3, 20 °C): δ ϭ
0.81Ϫ1.43 [m, 28 H, (CH3)2CH], 1.21Ϫ1.39 (m, 8 H, octyl CH2),
1.57Ϫ1.64 (m, 4 H, octyl CH2), 2.29 (t, 3J ϭ 7.7 Hz, 2 H, CH2CO),
tert-butyldiphenylsilyl-α-
binofuranosyl]-3-O-benzyl-α-
arabinofuranosyl]-3-O-benzyl-α-
D
-arabinofuranosyl)-3-O-benzyl-α-
D-ara-
D
-arabinofuranosyl}-3-O-benzyl-α-D-
D-arabinofuranoside (21): From 20
(72.6 mg, 49 µmol) and 8 (36.6 mg, 58 µmol). Chromatography 3.45 (td, 2J ϭ 9.7, 3J ϭ 6.6 Hz, 1 H, octyl OCH2), 3.60 (dd,
3
with petroleum ether/EtOAc (2:1) gave 21 as a colorless oil
2J5B,5B ϭ 11.0, J5B,4B ϭ 4.5 Hz, 1 H, 5B-H), 3.66 (s, 3 H, CH3O),
(89.6 mg, 90%). [α]2D5 ϭ ϩ81 (c ϭ 1.33 in chloroform). 1H NMR
3.73 (td, 1 H, octyl OCH2), 3.73 (m, 1 H, 5A-H), 3.83 (dd, 3J5B,4B ϭ
(500 MHz, CDCl3, 20 °C): δ ϭ 0.93 [s, 9 H, C(CH3)3], 1.23Ϫ1.38 4.6 Hz, 1 H, 5B-H), 3.86Ϫ3.96 (m, 4 H, 3C-H, 5A-H, 2 ϫ 5C-H),
3
3
3
(m, 8 H, octyl CH2), 1.54Ϫ1.63 (m, 4 H, octyl CH2), 2.29 (t, J ϭ 4.01 (br. d, J3B,4B ϭ 5.2 Hz, 1 H, 3B-H), 4.16 (br. d, J3A,4A
ϭ
2
3
7.7 Hz, 2 H, CH2CO), 3.43 (td, J ϭ 9.7, J ϭ 6.7 Hz, 1 H, octyl
OCH2), 3.65Ϫ3.67 (m, 3 H, 5B-H, 5C-H, 5D-H), 3.64 (s, 3 H, 4.43 (m, 1 H, 4C-H), 4.51, 4.62, 4.66, 4.79 (4d, J ϭ 12.0 Hz, 4 ϫ
CH3O), 3.67Ϫ3.74 (m, 4 H, octyl OCH2, 5A-H, 2 ϫ 5E-H),
5.0 Hz, 1 H, 3A-H), 4.20 (m, 1 H, 4B-H), 4.32 (m, 1 H, 4A-H),
2
3
1 H, benzyl CH2), 5.04 (d, J1C,2C ϭ 1.5 Hz, 1 H, 1C-H), 5.14 (s,
2
3
3.76Ϫ3.84 (m, 3 H, 5B-H, 5C-H, 5D-H), 3.90 (dd, J5A,5A ϭ 11.3, 1 H, 1A-H), 5.27 (s, 1 H, 1B-H), 5.38 (d, J2A,1A ϭ 1.4 Hz, 1 H,
3J5A,4A ϭ 4.0 Hz, 1 H, 5A-H), 3.98Ϫ4.10 (m, 7 H, 3B-H, 3C-H, 2A-H), 5.43 (d, J2C,1C ϭ 1.7 Hz, 1 H, 2C-H), 5.44 (d, J2B,1B
ϭ
3
3
3D-H, 3E-H, 4C-H, 4D-H, 4E-H), 4.11Ϫ4.16 (m, 2 H, 3A-H, 4B-
1.4 Hz, 1 H, 2B-H), 7.17Ϫ8.07 (m, 25 H, Ar-H) ppm. 13C NMR
H), 4.29 (m, 1 H, 4A-H), 4.36, 4.37, 4.40, 4.46, 4.49, 4.51, 4.52, (100.62 MHz, CDCl3, 20 °C):
4.59, 4.59, 4.76 (10d, J ϭ 12.2 Hz, 10 ϫ 1 H, benzyl CH2), 5.11 [(CH3)2CH], 17.0, 17.1, 17.4, 17.6 [(CH3)2CH], 25.1, 26.1, 29.2,
δ ϭ 12.5, 12.9, 13.3, 13.5
2
(s, 1 H, 1A-H), 5.20 (s, 1 H, 1E-H), 5.21 (s, 1 H, 1D-H), 5.22 (s, 1
29.3, 29.4, 29.5 (octyl CH2), 34.2 (CH2CO), 51.6 (CH3O), 61.4 (C-
5C), 65.6 (C-5A), 67.1 (C-5B), 67.7 (octyl OCH2), 72.1, 72.5
(benzyl CH2), 75.9 (C-3C), 81.0 (C-4C), 81.6 (C-4A), 81.6 (C-2B),
82.1 (C-4B), 82.3 (C-2A), 83.0 (C-3A), 83.7 (C-3B), 84.1 (C-2C),
H, 1C-H), 5.26 (s, 1 H, 1B-H), 5.33Ϫ5.37 (m, 3 H, 2C-H, 2D-H,
3
3
2E-H), 5.38 (d, J2A,3A ϭ 1.3 Hz, 1 H, 2A-H), 5.40 (d, J2B,3B
ϭ
1.3 Hz, 1 H, 2B-H), 7.09Ϫ8.03 (m, 60 H, Ar-H) ppm. 13C NMR
(125.78 MHz, CDCl3, 20 °C): δ ϭ 25.1, 26.1 (octyl CH2), 26.8 105.7 (C-1C), 106.0 (C-1A), 106.2 (C-1B), 127.7, 127.8, 128.0,
[C(CH3)3], 29.2, 29.3, 29.4, 29.5 (octyl CH2), 34.2 (CH2CO), 51.6 128.4, 128.5, 128.6, 129.6, 129.8, 129.9, 130.0, 133.4, 137.9, 133.4
(CH3O), 63.0 (C-5E), 65.2 (C-5A), 65.4 (C-5B, C-5C), 65.5 (C-5D), (Ar), 165.4 (COOPh), 174.5 (COOCH3) ppm. C72H94O19Si2
67.7 (octyl OCH2), 72.0, 72.1, 72.2, 72.4 (benzyl CH2), 81.6, 81.8,
81.9, 82.1, 82.3, 82.9, 83.1, 83.2, 83.3, 83.9, 106.0 (C-1A), 106.2 (C-
1B, C-1C, C-1D, C-1E), 127.6, 127.7, 127.8, 128.0, 128.3, 128.4,
128.5, 128.9, 129.5, 129.6, 129.8, 129.9, 133.3, 133.4, 135.7, 137.8,
137.9 (Ar), 165.3, 165.4 (COOPh) ppm. HRMS (FAB): C121H128O-
28SiNa: calcd. 2079.8259, found 2079.8262.
(1319.7): calcd. C 65.53, H 7.18; found C 65.54, H 6.79.
8-(Methoxycarbonyl)octyl 2-O-Benzoyl-5-O-[2-O-benzoyl-5-O-(2-O-
benzoyl-α-
D
-arabinofuranosyl)-3-O-benzyl-α-
D-arabinofuranosyl]-3-
O-benzyl-α-
D-arabinofuranoside (23): 22 (87.0 mg, 66 µmol) was de-
silylated with neutralized Bu4NF in THF according to the General
Procedure. Chromatography with petroleum ether/EtOAc (1:1) gave
8-(Methoxycarbonyl)octyl 5-O-[5-O-{5-O-[5-O-(α-
syl)-α- -arabinofuranosyl]-α- -arabinofuranosyl}-α-
furanosyl]-α- -arabinofuranoside (1): 21 (79.6 mg, 39 µmol) was
d
-Arabinofurano 23 as a colorless oil (67.5 mg, 95%). [α]2D5 ϭ ϩ108 (c ϭ 1.01 in
1
D
D
D
-arabino-
chloroform). H NMR (500 MHz, CDCl3, 25 °C): δ ϭ 1.25Ϫ1.38
3
D
(m, 8 H, octyl CH2), 1.52Ϫ1.60 (m, 4 H, octyl CH2), 2.30 (t, J ϭ
2
3
submitted to three steps of deprotection without purification of the
intermediate compounds. Desilylation (Bu4NF in THF), deben-
7.5 Hz, 2 H, CH2CO), 3.47 (td, J ϭ 9.7, J ϭ 6.8 Hz, 1 H, octyl
2
3
OCH2), 3.65 (s, 3 H, CH3O), 3.65 (dd, J5B,5B ϭ 11.0, J5B,4B
ϭ
zoylation and debenzylation (Procedure B) were run according to 3.5 Hz, 1 H, 5B-H), 3.68 (m, 1 H, 5C-H), 3.74 (td, 1 H, octyl
the General Procedures. Chromatography with dichloromethane/
OCH2), 3.74Ϫ3.84 (m, 3 H, 5A-H, 5B-H, 5C-H), 3.89Ϫ3.95 (m, 3
methanol (15:1) gave 1 as a colorless oil (21.5 mg, 65%, 3 steps). H, 5A-H, 3B-H, 4C-H), 4.09 (m, 1 H, 3C-H), 4.16 (br. d, 3J3A,4A ϭ
[α]2D5 ϭ ϩ111 (c ϭ 1.02 in methanol). 1H NMR (400 MHz, 6.5 Hz, 1 H, 3A-H), 4.17 (m, 1 H, 4B-H), 4.34 (m, 1 H, 4A-H),
CD3OD, 27 °C): δ ϭ 1.26Ϫ1.42 (m, 8 H, octyl CH2), 1.54Ϫ1.65
4.49, 4.64, 4.64, 4.82 (4d, 2J ϭ 12.2 Hz, 4 ϫ 1 H, benzyl CH2),
3
(m, 4 H, octyl CH2), 2.32 (t, J ϭ 7.4 Hz, 2 H, CH2CO), 3.41 (td, 4.98 (dd, 3J2C,3C ϭ 2.8, 3J2C,1C ϭ 0.8 Hz, 1 H, 2C-H), 5.16 (s, 1 H,
2J ϭ 9.6, 3J ϭ 6.5 Hz, 1 H, octyl OCH2), 3.65 (s, 3 H, CH3O),
1A-H), 5.27 (s, 1 H, 1C-H), 5.30 (s, 1 H, 1B-H), 5.39 (d, J2A,1A
ϭ
3
3
3.61Ϫ3.69 (m, 5 H, 5A-H, 5B-H, 5C-H, 5D-H, 5E-H), 3.69 (td, 1 1.6 Hz, 1 H, 2A-H), 5.40 (d, J2B,1B ϭ 1.3 Hz, 1 H, 2B-H),
2
3
H, octyl OCH2), 3.75 (dd, J5E,5E ϭ 11.9, J5E,4E ϭ 3.3 Hz, 1 H,
5E-H), 3.80Ϫ3.92 (m, 9 H, 3A-H, 3B-H, 3C-H, 3D-H, 3E-H, 5A-
7.16Ϫ8.10 (m, 25 H, Ar-H) ppm. 13C NMR (125.77 MHz, CDCl3,
25 °C): δ ϭ 29.4, 29.6, (octyl CH2), 34.0 (CH2CO), 51.6 (CH3O),
3
3
H, 5B-H, 5C-H, 5D-H), 3.95 (dd, J2A,3A ϭ 3.8, J2A,1A ϭ 1.8 Hz, 61.8 (C-5C), 66.0 (C-5B, C-5A), 67.6 (octyl OCH2), 72.0, 72.3
1 H, 2A-H), 3.97Ϫ4.02 (m, 6 H, 2B-H, 2C-H, 2D-H, 2E-H, 4A-H, (benzyl CH2), 76.7 (C-3C), 81.4 (C-4A), 81.6 (C-2B), 81.7 (C-4B),
4E-H), 4.06Ϫ4.11 (m, 3 H, 4B-H, 4C-H, 4D-H), 4.85 (s, 1 H, 1A- 81.8 (C-2A), 83.0 (C-4C), 83.2 (C-3A), 84.1 (C-3B), 86.3 (C-2C),
H), 4.95 (b, 4 H, 1B-H, 1C-H, 1D-H, 1E-H) ppm. 13C NMR 105.1 (C-1C), 105.8 (C-1A) ppm. C60H66O18 (1077.2): calcd. C
(100.62 MHz, CD3OD, 27 °C): δ ϭ 26.0, 27.1, 30.1, 30.3, 30.6 (oc-
tyl CH2), 34.8 (CH2CO), 52.0 (CH3O), 63.1 (C-5E), 68.1, 68.2, 68.3
(C-5A, C-5B, C-5C, C-5D), 68.9 (octyl OCH2), 78.8, 79.1 (C-3A,
C-3B, C-3C, C-3D, C-3E), 83.1, 83.2, 83.5, 83.6 (C-2A, C-2B, C-
2C, C-2D, C-2E, C-4E), 84.2 (C-4B, C-4C, C-4D), 86.0 (C-4A),
109.5 (C-1A), 109.6, 109.7 (C-1B, C-1C, C-1D), 176.1 (COOMe)
ppm. HRMS (FAB): C35H60O23Na: calcd. 871.3423, found
871.3463.
66.90, H 6.18; found C 66.29, H 6.04.
8-(Methoxycarbonyl)octyl 2-O-Benzoyl-5-O-{2-O-benzoyl-5-O-[2-
O-benzoyl-3,5-di-O-(2-O-benzoyl-3-O-benzyl-5-O-tert-butyldi-
phenylsilyl-α-
D
-arabinofuranosyl)-α-
D
-arabinofuranosyl]-3-O-
-arabinofuranoside
benzyl-α- -arabinofuranosyl}-3-O-benzyl-α-
D
D
(24): From 23 (106.4 mg, 0.10 mmol) and 8 (185.6 mg, 0.30 mmol).
Chromatography with petroleum ether/EtOAc, 3:1 gave 24 as a col-
orless oil (177.3 mg, 81%). [α]2D5 ϭ ϩ85 (c ϭ 1.36 in chloroform).
1H NMR (500 MHz, CDCl3, 25 °C): δ ϭ 0.87, 0.92 [s, 9 H,
8-(Methoxycarbonyl)octyl 2-O-Benzoyl-5-O-{2-O-benzoyl-5-O-[2-
O-benzoyl-3,5-O-(1,1,3,3-tetra-isopropyldisiloxan-1,3-diyl)-α-
binofuranosyl]-3-O-benzyl-α- -arabinofuranosyl}-3-O-benzyl-α-
arabinofuranoside (22): From 15 (150.0 mg, 0.18 mmol) and 12
D-ara- C(CH3)3], 1.22Ϫ1.38 (m, 8 H, octyl CH2), 1.55Ϫ1.64 (m, 4 H, octyl
3
2
3
D
D
-
CH2), 2.29 (t, J ϭ 7.6 Hz, 2 H, CH2CO), 3.44 (td, J ϭ 9.7, J ϭ
6.6 Hz, 1 H, octyl OCH2), 3.65 (s, 3 H, CH3O), 3.64Ϫ3.76 (m, 7
3594
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2003, 3587Ϫ3598

Synthesis of Oligoarabinofuranosides from the Mycobacterial Cell Wall
H, 5A-H, 5B-H, 2 ϫ 5D-H, 2 ϫ 5E-H, octyl OCH2), 3.77 (dd, Procedure, chromatography with petroleum ether/ethyl acetate (6:1)
FULL PAPER
3
2
2J5C,5C ϭ 11.5, J5C,4C ϭ 2.7 Hz, 1 H, 5C-H), 3.85 (dd, J5B,5B
ϭ
gave 250 mg of 25 (66%). Glycosylation: From 25 (173 mg,
11.5, J5B,4B ϭ 3.9 Hz, 1 H, 5B-H), 3.91 (dd, J5A,5A ϭ 11.5, 0.15 mmol) according to the General Procedure, chromatography
3J5A,4A ϭ 4.2 Hz, 1 H, 5A-H), 3.94 (dd, 3J5C,4C ϭ 4.6 Hz, 1 H, 5C-
with toluene/ethyl acetate (12:1) gave 26 as a colorless oil (116 mg,
H), 4.07 (br. d, 3J3E,4E ϭ 5.4 Hz, 1 H, 3E-H), 4.12 (br. d, 3J3D,4D ϭ 79%). [α]2D5ϭ ϩ21 (c ϭ 0.81 in chloroform). H NMR (250 MHz,
3
2
1
5.6 Hz, 1 H, 3D-H), 4.13Ϫ4.24 (m, 7 H, 3A-H, 3B-H, 3C-H, 4B-
CDCl3, 25 °C): δ ϭ 1.03 [s, 9 H, (CH3)3C], 1.24Ϫ1.39 and
H, 4C-H, 4D-H, 4E-H), 4.31 (m, 1 H, 4A-H), 4.42 (m, 1 H, 3C-
1.54Ϫ1.69 (2m, 12 H, octyl CH2), 2.30 (t, 3J ϭ 7.5 Hz, 2 H,
2
3
2
H), 4.41, 4.47, 4.49, 4.57, 4.60, 4.61, 4.69, 4.77 (8d, J ϭ 12.1 Hz, CH2CO), 2.62 (d, JOH,2B ϭ 9.5 Hz, 1 H, 2B-OH), 3.41 (dt, J ϭ
8 ϫ 1 H, benzyl CH2), 5.12 (s, 1 H, 1A-H), 5.24 (s, 1 H, 1B-H), 9.5, 3J ϭ 6.5 Hz, 1 H, octyl OCH2), 3.52 (dd, J5A,5A ϭ 11.0,
2
3
2
5.27 (s, 2 H, 1C-H, 1D-H), 5.34 (d, J2E,1E ϭ 1.1 Hz, 1 H, 2E-H), 3J5A,4A ϭ 6.5 Hz, 1 H, 5A-H), 3.66 (s, 3 H, CH3O), 3.67 (dt, J ϭ
5.37 (d, 3J2A,3A ϭ 1.6 Hz, 1 H, 2A-H), 5.39 (d, 3J2C,3C ϭ 3J2D,3D ϭ
9.5, 3J ϭ 6.5 Hz, 1 H, octyl OCH2), 3.74 (m, 2 H, 5B-H), 3.78 (br.
d, 3J3A,4A ϭ 6.0 Hz, 1 H, 3A-H), 3.87 (dd, 2J5A,5A ϭ 11.0, 3J5A,4A ϭ
3
1.5 Hz, 2 H, 2C-H, 2D-H), 5.44 (d, J2B,3B ϭ 1.6 Hz, 1 H, 2B-H),
5.48 (s, 1 H, 1E-H), 7.08Ϫ8.05 (m, 65 H, Ar-H) ppm. 13C NMR 3.5 Hz, 1 H, 5A-H), 3.92 (m, 1 H, 3B-H), 4.05 (m, 1 H, 4B-H),
(125.78 MHz, CDCl3, 25 °C):
δ
ϭ 25.5 (octyl CH2), 26.4 4.22 (m, 2 H, 2B-H, 4A-H), 4.56, 4.52, 4.72, 4.77 (4d, 2J ϭ 12.0 Hz,
3
[(CH3)3CSi), 27.2, 29.7 (octyl CH2), 34.6 (CH2CO), 52.0 (CH3O), 4 ϫ 1 H, benzyl CH2), 4.91 (d, J1B,2B ϭ 4.5 Hz, 1 H, 1B-H), 5.06
63.3 (C-5D, C-5E), 65.9 (C-5B), 66.0 (C-5C), 66.2 (C-5A), 68.1 (s, 1 H, 1A-H), 5.34 (d, J2A,1A ϭ 1.5 Hz, 1 H, 2A-H) ppm. 13C
3
(octyl OCH2), 72.3, 72.6, 72.8, 72.9 (benzyl CH2), 80.6 (C-3C), 82.0
(C-4A), 82.4 (C-2B), 82.5 (C-3B, C-4D, C-4E), 82.6 (C-2E), 82.8 29.2, 29.3, 34.1, 51.5, 65.4, 67.5, 68.0, 71.8, 72.1, 81.2, 81.8, 82.5,
(C-2C, C-2D), 83.2 (C-2A), 83.4 (C-3D, C-3E), 83.7 (C-3A), 84.2 83.3, 84.6, 102.1 (C-1B), 106.0 (C-1A), 127.6, 127.7, 127.9, 128.0,
NMR (62.89 MHz, CDCl3, 25 °C): δ ϭ 19.2, 24.9, 26.8, 29.1, 29.2,
(C-4C), 84.6 (C-4B), 106.0 (C-1E), 106.5 (C-1A), 106.6 (C-1B), 128.3, 128.4, 128.5, 129.7, 133.5, 135.6, 164.5, 171.6 ppm.
106.7 (C-1C), 106.9 (C-1D), 128Ϫ130.1, 130.3, 130.3, 130.4, 133.8, C57H70O12Si (975.3) calcd. C 70.19, H 7.23; found C 69.91, H 6.97.
136.1 (Ar) ppm. HRMS (FAB): C130H140O28Si2Na: calcd.
8-(Methoxycarbonyl)octyl 2-O-(3-O-Benzyl-5-O-tert-butyldiphenyl-
silyl-β- -arabinofuranosyl)-3-O-benzyl-5-O-tert-butyldiphenylsilyl-α-
-arabinofuranoside (27): From 6 (122 mg, 0.19 mmol) and 9
2227.8967, found 2227.8920.
D
8-(Methoxycarbonyl)octyl 5-O-{5-O-[3,5-di-O-(α-
D-Arabinofurano-
D
syl)-α-
D
-arabinofuranosyl]-α-
D
-arabinofuranosyl}-α-
D
-arabino-
(150 mg, 0.23 mmol). Chromatography with petroleum ether/ethyl
acetate (6:1) gave 27 (110 mg, 52%, 2 steps). [α]2D5 ϭ ϩ0.1 (c ϭ 1.02
in chloroform). 1H NMR (250 MHz, CDCl3, 25 °C): δ ϭ 1.01 and
1.02 (2 s, 2 ϫ 9 H, (CH3)3C], 1.21Ϫ1.34 and 1.52Ϫ1.64 (2 m, 12
H, octyl CH2), 2.28 (t, 3J ϭ 7.5 Hz, 2 H, CH2CO), 2.39 (d,
furanoside (2): 24 (33.6 mg, 15 µmol) was submitted to three steps
of deprotection without purification of the intermediate com-
pounds. Desilylation (Bu4NF in THF), debenzoylation and de-
benzylation (Procedure A) were run according to the General Pro-
cedures. Chromatography with dichloromethane/methanol (3:1)
2
3
3JOH,2B ϭ 8.5 Hz, 1 H, 2B-OH), 3.38 (dt, J ϭ 9.5, J ϭ 6.5 Hz, 1
gave 2 as a white solid (8.1 mg, 63%, 3 steps). [α]2D5 ϭ ϩ123 (c ϭ H, octyl OCH2), 3.64 (dt, 2J ϭ 9.5, 3J ϭ 6.5 Hz, 1 H, octyl OCH2),
0.77 in methanol). 1H NMR (500 MHz, D2O, 25 °C): δ ϭ 3.66 (s, 3 H, CH3O), 3.72 (dd, J5B,5B ϭ 12.0, J5B,4B ϭ 5.5 Hz, 1
2
3
2
3
1.21Ϫ1.32 (m, 8 H, octyl CH2), 1.49Ϫ1.58 (m, 4 H, octyl CH2), H, 5B-H), 3.72 (dd, J5A,5A ϭ 11.0, J5A,4A ϭ 5.5 Hz, 1 H, 5A-H),
2.32 (t, 3J ϭ 7.6 Hz, 2 H, CH2CO), 3.50 (td, 2J ϭ 9.9, 3J ϭ 6.7 Hz, 3.73 (dd, J5B,5B ϭ 12.0, J5B,4B ϭ 6.5 Hz, 1 H, 5B-H), 3.78 (dd,
2
3
2
3
3
1 H, octyl OCH2), 3.61 (s, 3 H, CH3O), 3.64 (dd, J5E,5E ϭ 12.2,
2J5A,5A ϭ 11.0, J5A,4A ϭ 3.5 Hz, 1 H, 5A-H), 3.88 (dd, J3B,4B
ϭ
3J5E,4E ϭ 2.4 Hz, 1 H, 5E-H), 3.65 (dd, J5D,5D ϭ 12.7, J5D,4D
ϭ
4.5, 3J3B,2B ϭ 4.5 Hz, 1 H, 3B-H), 3.89 (dd, 3J3A,4A ϭ 6.5, 3J3A,2A ϭ
2
3
2.6 Hz, 1 H, 5D-H), 3.67 (td, 1 H, octyl OCH2), 3.69 (dd, 2J5C,5C ϭ 3.0 Hz, 1 H, 3A-H), 4.03Ϫ4.14 (m, 2 H, 4A-H, 4B-H), 4.23 (m,
12.2, 3J5C,4C ϭ 2.9 Hz, 1 H, 5C-H), 3.71Ϫ3.81 (m, 5 H, 5A-H, 5B-
3J2B,OH ϭ 8.5, J2B,3B ϭ 4.5, J2B,1B ϭ 4.5 Hz, 1 H, 2B-H), 4.32
3
3
H, 5C-H, 5D-H, 5E-H), 3.82 (dd, 2J5B,5B ϭ 11.6, J5B,4B ϭ 5.9 Hz,
(dd, J2A,3A ϭ 3.0, J2A,1A ϭ 1.0 Hz, 1 H, 2A-H), 4.19, 4.46, 4.60,
3
3
3
1 H, 5B-H), 3.86Ϫ3.90 (m, 3 H, 3D-H, 3E-H, 5A-H), 3.92 (dd, 4.71 (4d, 2J ϭ 12.0 Hz, 4 ϫ 1 H, benzyl CH2), 4.96 (br. s, 1 H, 1A-
3J3C,4C ϭ 6.4, J3C,2C ϭ 3.7 Hz, 1 H, 3C-H), 3.95 (dd, J3B,4B
ϭ
H), 5.14 (d, J1B,2B ϭ 4.5 Hz, 1 H, 1B-H) ppm. 13C NMR
3
3
3
3
6.0, J3B,2B ϭ 3.0 Hz, 1 H, 3B-H), 3.97 (m, 1 H, 4E-H), 3.98 (dd,
(62.89 MHz, CDCl3, 25 °C): δ ϭ 19.1, 19.2 [(CH3)3C], 24.9, 26.0,
1 H, 2C-H), 4.02 (m, 1 H, 3A-H), 4.04 (m, 1 H, 4D-H), 4.05 (dd, 26.7, 29.0, 29.1, 29.4, 34.0 (CH2CO), 51.4 (OCH3), 63.6, 65.7 (C-
3
1 H, 2B-H), 4.06 (dd, J2D,3D ϭ 3.3 Hz, 1 H, 2D-H), 4.06 (dd,
5A, C-5B), 67.4 (octyl OCH2), 71.8, 72.1 (benzyl CH2), 77.4, 82.2,
82.5, 83.4, 84.9, 86.4, 101.4 (C-1B), 105.6 (C-1A), 127.46, 127.52,
127.6, 127.7, 128.1, 128.3, 129.6, 129.7, 132.9, 133.0, 133.2, 133.3,
3J2E,3E ϭ 3.5 Hz, 1 H, 2E-H), 4.08 (td, 1 H, 4C-H), 4.14 (td, 1 H,
4C-H), 4.22 (dd, 3J2A,3A ϭ 2.1 Hz, 1 H, 2A-H), 4.24 (td, 3J4A,3A
ϭ
3.0 Hz, 1 H, 4A-H), 4.95 (d, 3J1C,2C ϭ 1.8 Hz, 1 H, 1C-H), 5.01 (d, 135.5, 135.6, 137.7, 137.8, 174.3 (CO) ppm. C66H84O11Si2 (1109.6):
3J1B,2B ϭ 1.4 Hz, 1 H, 1B-H), 5.02 (d, J1D,2D ϭ 1.4 Hz, 1 H, 1D-
calcd. C 71.44, H 7.63; found C 71.15, H 7.52.
3
3
H), 5.05 (b, 1 H, 1A-H), 5.08 (d, J1E,2E ϭ 1.4 Hz, 1 H, 1E-H)
ppm. 13C NMR (125.78 MHz, D2O, 25 °C): δ ϭ 24.4, 24.6, 24.8,
25.2, 28.2, 28.3, 28.7, 28.8 (octyl CH2), 33.9 (CH2CO), 52.3
(CH3O), 61.9 (C-5D, C-5E), 66.6 (C-5B, C-5A), 67.0 (C-5C), 68.9
(octyl OCH2), 76.6 (C-3C), 76.7 (C-3D, C-3E), 76.8 (C-3B), 79.3
(C-2A), 80.9 (C-2C), 81.2 (C-2B, C-2D, C-2E), 81.8 (C-4C), 81.9
(C-4A), 82.4 (C-4B), 82.5 (C-3A), 84.1 (C-4E), 84.2 (C-4D), 107.3
(C-1E), 107.4 (C-1C), 107.5 (C-1D), 107.6 (C-1A), 107.7 (C-1B)
ppm. HRMS (FAB): C35H60O23Na: calcd. 871.3423, found
871.3462.
8-(Methoxycarbonyl)octyl 2-O-β- -Arabinofuranosyl-α-D-arabinofu-
D
ranoside (28): 27 (106 mg, 95 µmol) was desilylated with Bu4NF in
THF according to the General Procedure. The intermediate triol
was filtered through silica (petroleum ether/ethyl acetate, 1:2) and
hydrogenolyzed at room temperature (H2, 10% Pd/C, ethyl acetate/
methanol). Filtration of the mixture and chromatography (di-
chloromethane/methanol, 6:1) gave 28 (26 mg, 60%, 2 steps).
1
[α]2D5 ϭ Ϫ8 (c ϭ 1.13 in methanol). H NMR (250 MHz, D2O, 25
°C): δ ϭ 1.28Ϫ1.38 and 1.56Ϫ1.63 (2m, 8 H and 4 H, octyl CH2),
2.38 (t, 3J ϭ 7.5 Hz, 2 H, CH2CO), 3.55 (dt, 2J ϭ 9.5, 3J ϭ 6.5 Hz,
3
3
8-(Methoxycarbonyl)octyl
benzyl-5-O-tert-butyldiphenylsilyl-β-
binofuranoside (26). Formation of the Acetals: From 5 (210 mg,
2-O-Benzoyl-3-O-benzyl-5-O-(3-O-
1 H, octyl OCH2), 3.67 (dd, J5B,5B ϭ 12.5, J5B,4B ϭ 7.0 Hz, 1 H,
3
3
D
-arabinofuranosyl)-α- -ara-
D
5B-H), 3.68 (s, 3 H, CH3O), 3.71 (dd, J5A,5A ϭ 12.5, J5A,4A ϭ
5.0 Hz, 1 H, 5A-H), 3.75 (dt, 2J ϭ 9.5, 3J ϭ 6.5 Hz, 1 H, octyl
2
0.33 mmol) and 9 (176 mg, 0.34 mmol) according to the General OCH2), 3.75 (m, 2 H, 3A-H, 4A-H), 3.79 (dd, J5B,5B ϭ 12.5,
Eur. J. Org. Chem. 2003, 3587Ϫ3598
www.eurjoc.org
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3595

K. Marotte, S. Sanchez, T. Bamhaoud, J. Prandi
FULL PAPER
3J5B,4B ϭ 3.5 Hz, 1 H, 5B-H), 3.83 (dd, J5A,5A ϭ 12.5, J5A,4A
2
3
2
ϭ
6.0 Hz, 1 H, 3B-H), 4.52, 4.66 (2d, J ϭ 11.5 Hz, 2 ϫ 1 H, benzyl
3.0 Hz, 1 H, 5A-H), 4.07 (dd, J3B,2B ϭ 8.0, J3B,4B ϭ 7.0 Hz, 1 H, CH2), 4.60, 4.68 (2d, 2J ϭ 12.0 Hz, 2 ϫ 1 H, benzyl CH2), 4.80 (d,
3
3
3
3
3B-H), 4.11 (dd, 2J3A,2A ϭ 5.0, 3J3A,4A ϭ 5.0 Hz, 1 H, 3A-H), 4.13
3J1A,2A ϭ 1.0 Hz, 1 H, 1A-H), 4.91 (dd, J2B,3B ϭ 7.0, J2B,1B
ϭ
3
3
3
3
(dd, J2A,3A ϭ 5.0, J2A,1A ϭ 2.0, 1 H, 2A-H), 4.14 (dd, J2B,3B
ϭ
5.0 Hz, 1 H, 2B-H), 5.38 (d, J1B,2B ϭ 5.0 Hz, 1 H, 1B-H),
8.0, J2B,1B ϭ 4.5 Hz, 1 H, 2B-H), 5.08 (d, J1A,2A ϭ 2.0 Hz, 1 7.25Ϫ7.40 (m, 10 H, Ar-H) ppm. 13C NMR (62.89 MHz, CDCl3,
3
3
3
H, 1A-H), 5.09 (d, J1B,2B ϭ 4.5 Hz, 1 H, 1B-H) ppm. 13C NMR
25 °C): δ ϭ 20.5 (CH3CO), 24.8, 25.6, 25.9, 26.5, 27.0, 29.0, 29.1,
(62.89 MHz, D2O, 25 °C): δ ϭ 25.0, 25.9, 28.9, 29.0, 29.1, 29.3, 29.4, 34.0 (CH2CO), 38.7 [COC(CH3)3], 51.4 (OCH3), 63.0 and
34.4 (CH2CO), 52.7 (CH3O), 61.0 (C-5A), 63.5 (C-5B), 69.1 (octyl 63.4 (C-5A, C-5B), 67.7 (octyl OCH2), 72.1 and 72.6 (benzyl CH2),
OCH2), 74.6 (C-3B), 74.9 (C-3), 77.0 (C-2B), 82.7 (C-4B), 82.8 (C-
79.0, 79.2, 81.4, 83.3, 85.5, 99.3 (C-1B), 105.4 (C-1A), 127.6, 127.8,
4), 87.3 (C-2B), 101.1 (C-1B), 106.2 (C-1A), 178.1 (CO) ppm. 127.9, 128.4, 128.4, 137.4, 137.5, 170.3 (CH3CO), 174.3 (CO-
C20H36O11ϩ0.5H2O (452.5) calcd. C 52.05, H 8.08; found C 52.04,
OCH3), 178.1 [COC(CH3)] ppm. C41H58O13 (758.9): calcd. C 64.89,
H 8.03.
H 7.70; found C 64.94, H 7.62.
8-(Methoxycarbonyl)octyl 2-O-(3-O-Benzyl-5-O-tert-butyldiphenyl- 8-(Methoxycarbonyl)octyl 3-O-Benzyl-2-O-{3-O-benzyl-5-O-[2-O-
silyl-β-
furanoside (29): From
D
-arabinofuranosyl)-3-O-benzyl-5-O-pivaloyl-α-
(54 mg, 0.11 mmol) and
D
-arabino-
(77 mg,
(3,4,6-tri-O-benzyl-α-
D
-mannopyranosyl)-3,4,6-tri-O-benzyl-α-
D-
7
9
mannopyranosyl]-β- -arabinofuranosyl}-α-D
D
-arabinofuranoside (33):
0.12 mmol), chromatography with petroleum ether/ethyl acetate Glycosylation of diarabinoside 31 (46 mg, 61 µmoles) with diman-
(4:1) gave 29 as a colorless oil (65 mg, 63%, 2 steps). [α]2D5 ϭ ϩ9 noside 13 (82 mg, 85 µmoles) was carried out with NIS (23 mg, 104
(c ϭ 1.13 in chloroform). 1H NMR (250 MHz, CDCl3, 25 °C): δ ϭ µmoles) and TMSOTf (9 µL of a 1  solution in toluene, 9 µmol)
1.03 [s, 9 H, (CH3)3CSi], 1.15 [s, 9 H, (CH3)3CO], 1.28Ϫ1.31 and
according to the General Procedure. Chromatography with toluene/
1.52Ϫ1.64 (2m, 12 H, octyl CH2), 2.29 (t, 3J ϭ 7.5 Hz, 2 H, ethyl acetate (8:1) gave tetrasaccharide 32 (77 mg, 77%) as a 4:1 α/
3
2
CH2CO), 2.50 (d, JOH,2B ϭ 9.0 Hz, 1 H, 2B-OH), 3.38 (dt, J ϭ β-anomeric mixture on the C-1C anomeric center. This mixture
9.5, 3J ϭ 6.5 Hz, 1 H, octyl OCH2), 3.64 (dt, 2J ϭ 9.5, 3J ϭ 6.5 Hz, (100 mg, 60 µmol) was treated with a 0.5  NaOMe solution in
1 H, octyl OCH2), 3.66 (s, 3 H, CH3O), 3.75 (m, 2 H, 3A-H, 4A-
MeOH for 5 h at room temp before neutralization with solid
NH4Cl (3.5 mg, 66 µmol). CH2Cl2/water extraction and chroma-
H), 3.91 (dd, 3J3B,4B ϭ 4.5, 3J3B,2B ϭ 4.5 Hz, 1 H, 3B-H), 4.05 (dd,
2J5B,5B ϭ 11.0, 3J5B,4B ϭ 5.5 Hz, 1 H, 5B-H), 4.10 (m, 1 H, 4B-H), tography (toluene/acetone, 5:1) gave the 1C-H β-anomer of 33
2
3
4.10 (dd, J5A,5A ϭ 10.5, J5A,4A ϭ 6.0 Hz, 1 H, 5A-H), 4.13 (dd, (14 mg, 16%), an equimolar mixture of anomers (8 mg, 9%) and 33
2J5A,5A ϭ 10.5, J5A,4A ϭ 5.5 Hz, 1 H, 5A-H), 4.22 (dd, J5B,5B
ϭ
(46 mg, 50%). [α]2D5 ϭ ϩ25 (c ϭ 1.10 in chloroform). 1H NMR
3
2
3
3
11.0, J5B,4B ϭ 2.5 Hz, 1 H, 5B-H), 4.25 (m, J2B,OH ϭ 9.0, (250 MHz, CDCl3, 25 °C): δ ϭ 1.24Ϫ1.34 and 1.48Ϫ1.67 (2m, 12
3J2B,3B ϭ 4.5, J2B,1B ϭ 4.5 Hz, 1 H, 2B-H), 4.32 (dd, J2A,3A
ϭ
H, octyl CH2), 2.30 (t, J ϭ 7.5 Hz, 2 H, CH2CO), 2.34Ϫ2.40 (m,
3
3
3
2.5, 3J2A,1A ϭ 1.0 Hz, 1 H, 2A-H), 4.24 and 4.52 (2d, 2J ϭ 11.5 Hz, 2 H, 5A-OH, 2D-OH), 2.53 (d, JOH,2B ϭ 9.0 Hz, 1 H, 2B-OH),
3
2
2
3
2 ϫ 1 H, benzyl CH2), 4.62 and 4.72 (2d, J ϭ 12.0 Hz, 2 ϫ 1 H,
3.34 (dt, J ϭ 9.5, J ϭ 6.5 Hz, 1 H, 1 H, octyl OCH2), 3.51 (dt,
3
benzyl CH2), 4.94 (s, 1 H, 1A-H), 5.15 (d, J1B,2B ϭ 4.5 Hz, 1 H,
2J ϭ 9.5, 3J ϭ 6.5 Hz, 1 H, 1 H, octyl OCH2), 3.66 (s, 3 H, CH3O),
1B-H) ppm. 13C NMR (62.89 MHz, CDCl3, 25 °C): δ ϭ 18.9, 24.6, 3.66Ϫ4.27 (m, 22 H), 4.41Ϫ4.84 (m, 16 H, benzyl CH2), 4.94 (s, 1
25.7, 26.5, 26.8, 28.7, 28.8, 29.1, 33.7, 51.1, 63.0, 65.3, 67.2, 71.5
and 71.9 (benzyl CH2), 76.2, 79.1, 82.2, 83.5, 84.4, 86.1, 101.5 (C-
H, 1A-H), 4.98 (d, 3J1C,2C ϭ 2.0 Hz, 1 H, 1C-H), 5.12 (d, 3J1B,2B ϭ
3
4.5 Hz, 1 H, 1B-H), 5.13 (d, J1D,2D ϭ 2.0 Hz, 1 H, 1D-H),
1B), 105.5 (C-1A), 127.3, 127.4, 127.5, 127.96, 128.05, 129.5, 132.6, 7.10Ϫ7.40 (m, 40 H, Ar-H) ppm. 13C NMR (62.89 MHz, CDCl3,
132.7, 135.20, 135.25, 137.1, 174.0 (CH3OCO), 177.7 [(CH3)3CO]
ppm. C55H74O12Si (955.3): calcd. C 69.15, H 7.81; found C 68.89,
H 8.02.
25 °C): δ ϭ 24.9, 26.0, 29.0, 29.1, 29.4, 29.7, 34.0 (CH2CO), 51.5
(CH3O), 61.4 (C-5A), 67.4 (octyl OCH2), 68.4, 68.8, 68.9, 69.2,
71.4, 71.9, 72.0, 72.5, 73.3, 74.2, 74.5, 74.7, 75.1, 75.2, 79.8, 79.9,
80.1, 82.4, 82.9, 84.0, 87.9, 98.9 (C-1C), 101.0 (C-1B), 102.2 (C-
1D), 106.1 (C-1A), 127.4, 127.5, 127.5, 127.6, 127.6, 127.7, 127.8,
127.8, 127.9, 128.3, 128.4, 137.6, 137.9, 137.9, 138.0, 138.1, 138.2,
138.2, 138.3, 174.3 (COOCH3) ppm. C88H104O21 (1497.8): calcd. C
70.57, H 7.00; found C 70.44, H 6.84.
8-(Methoxycarbonyl)octyl 2-O-(2-O-Acetyl-3-O-benzyl-β-
D-arabino-
furanosyl)-3-O-benzyl-5-O-pivaloyl-α- -arabinofuranoside
D
(31): Disaccharide 29 (61 mg, 64 µmoles) was dissolved in pyridine
(1.2 mL) and treated with acetic anhydride (0.8 mL). The mixture
was left overnight at room temperature before hydrolysis with aque-
ous saturated NaHCO3 solution and extraction with CH2Cl2. The
organic phase was dried with MgSO4 and the solvent evaporated.
The residue was coevaporated three times with toluene to give
crude 30 (63 mg, 99%). This crude product was desilylated with
Bu4NF in THF in 1 h according to the General Procedure. Chro-
matography with toluene/ethyl acetate (4:1) gave 31 as a colorless
8-(Methoxycarbonyl)octyl 2-O-[5-O-(2-O-α-D-Mannopyranosyl-α-D-
mannopyranosyl)-β- -arabinofuranosyl]-α- -arabinofuranoside (3):
D
D
Compound 33 (12 mg, 8 µmol) in MeOH (2 mL) was hydro-
genolyzed according to Procedure A. Chromatography with ethyl
acetate/methanol/water (8:3:1) gave 3 as a white solid (4 mg, 65%).
[α]2D5 ϭ ϩ19 (c ϭ 0.40 in water). 1H NMR (500 MHz, D2O, 25 °C):
δ ϭ 1.28Ϫ1.37 and 1.56Ϫ1.63 (2m, 12 H, octyl CH2), 2.38 (t, 3J ϭ
1
oil (37 mg, 76%). [α]2D5 ϭ Ϫ21 (c ϭ 1.13 in chloroform). H NMR
2
3
(250 MHz, CDCl3, 25 °C): δ ϭ 1.18 (s, 9 H, tBu), 1.25Ϫ1.36 and 7.5 Hz, 2 H, CH2CO), 3.56 (dt, J ϭ 9.5, J ϭ 6.5 Hz, 1 H, octyl
1.50Ϫ1.66 (2 m, 12 H octyl CH2), 2.06 (s, 3 H, CH3CO), 2.18 (dd,
OCH2), 3.60 (t, 3J4D,3D ഠ 3J4D,5D ഠ 9.5 Hz, 1 H, 4D-H), 3.64 (ddd,
3JOH,5B ϭ 8.0, 3JOH,5B ϭ 5.0 Hz, 1 H, 5B-OH), 2.30 (t, 3J ϭ 7.5 Hz, 3J5C,4C ϭ 10.0, J5C,6C ϭ 6.0, J5C,6C ϭ 2.0 Hz, 1 H, 5C-H), 3.68
3
3
2
3
2
2 H, CH2CO), 3.39 (dt, J ϭ 9.5, J ϭ 6.5 Hz, 1 H, octyl OCH2), (s, 3 H, CH3O), 3.70 (dd, J5B,5B ϭ 9.5, 3J5B,4B ϭ 6.0 Hz, 1 H, 5B-
3.58 (ddd, 2J5B,5B ϭ 12.0, 3J5B,OH ϭ 8.0, 3J5B,4B ϭ 4.5 Hz, 1 H, 5B-
H), 3.60 (dt, 2J ϭ 9.5, 3J ϭ 6.5 Hz, 1 H, octyl OCH2), 3.66 (s, 3 H,
CH3O), 3.72 (ddd, 2J5B,5B ϭ 12.0, 3J5B,OH ϭ 5.0, 3J5B,4B ϭ 3.5 Hz, 1
H), 3.70 (dd, J6C,6C ϭ 12.0, J6C,5C ϭ 6.0 Hz, 1 H, 6C-H), 3.73
2
3
2
3
2
(dd, J5A,5A ϭ 12.0, J5A,4A ϭ 3.0 Hz, 1 H, 5A-H), 3.75 (dt, J ϭ
9.5, 3J ϭ 6.5 Hz, 1 H, octyl OCH2), 3.76 (dd, J6D,6D ϭ 12.0,
2
3
3
3
3
H, 5B-H), 3.86 (dd, J3A,4A ϭ 6.0, J3A,2A ϭ 3.0 Hz, 1 H, 3A-H), 3J6D,5D ϭ 6.0 Hz, 1 H, 6D-H), 3.77 (dd, J4C,5C ϭ 10.0, J4C,3C
ϭ
3
3
3
3
3
4.07 (ddd, J4B,3B ϭ 6.0, J4B,5B ϭ 4.5, J4B,5B ϭ 3.0 Hz, 1 H, 4B-
9.5 Hz, 1 H, 4C-H), 3.78 (ddd, J5D,4D ϭ 9.5, J5D,6D ϭ 6.0,
H), 4.10Ϫ4.21 (m, 3 H, 4A-H, 5A-H), 4.26 (dd, J2A,3A ϭ 3.0, 3J5D,6D ϭ 2.0 Hz, 1 H, 5D-H), 3.79 (dd, J6D,6D ϭ 12.0, J6D,5D
ϭ
3
2
3
3J2A,1A ϭ 1.0 Hz, 1 H, 2A-H), 4.35 (dd, J3B,2B ϭ 7.0, J3B,4B
ϭ
2.0 Hz, 1 H, 6D-H), 3.83 (dd, 2J5B,5B ϭ 9.5, 3J5B,4B ϭ 6.0 Hz, 1 H,
3
3
3596
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2003, 3587Ϫ3598

Synthesis of Oligoarabinofuranosides from the Mycobacterial Cell Wall
4B-H), 3.84 (dd, 3J3D,4D ϭ 9.5, 3J3D,2D ϭ 3.5 Hz, 1 H, 3D-H), 3.84 13C NMR (100.62 MHz, CDCl3, 20 °C): δ ϭ 24.8, 25.1, 29.0, 29.1,
FULL PAPER
2
3
(dd, J5A,5A ϭ 12.0, J5A,4A ϭ 3.0 Hz, 1 H, 5A-H), 3.89 (dd,
29.3 (octyl CH2), 34.0 (CH2CO), 51.4 (CH3O), 61.6 (C-5B), 66.0
(C-5A), 67.5 (octyl OCH2), 72.2 (benzyl CH2), 76.2 (C-3B), 81.3
2J6C,6C ϭ 12.0, J6C,5C ϭ 2.0 Hz, 1 H, 6C-H), 3.95 (dd, J4C,3C
ϭ
3
3
3
9.5, J3C,2C ϭ 3.5 Hz, 1 H, 3C-H), 4.02 (m, 1 H, 4B-H), 4.02 (dd, (C-4A), 81.8 (C-2A), 83.2 (C-3A), 84.2 (C4-B), 85.8 (C-2B), 105.2
3J2C,3C ϭ 3.5, J2C,1C ϭ 1.7 Hz, 1 H, 2C-H), 4.04 (dd, J4A,3A
ϭ
(C-1B), 105.9 (C-1A), 127.7, 128.5, 128.4, 129.7, 133.4, 133.5, 137.6
3
3
3
3
5.0, J4A,5A ϭ 3.0 Hz, 1 H, 4A-H), 4.07 (dd, J2D,3D ϭ 3.5, (Ar), 174.3 (COOCH3) ppm. C41H50O13 (750.8): calcd. C 65.59, H
3J2D,1D ϭ 2.0 Hz, 1 H, 2D-H), 4.09 (dd, J3A,4A ϭ 5.0, J3A,2A
ϭ
6.71; found C 65.51, H 6.45.
3
3
3
3
4.0 Hz, 1 H, 3A-H), 4.11 (dd, J2A,3A ϭ 4.0, J2A,1A ϭ 2.0 Hz, 1
H, 2A-H), 4.11 (dd, J3B,2B ϭ 8.0, J3B,4B ϭ 7.0 Hz, 1 H, 3B-H),
3
3
8-(Methoxycarbonyl)octyl 2-O-Benzoyl-5-O-[2-O-benzoyl-3,5-di-O-
3
3
(3-O-benzyl-5-O-pivaloyl-α-
D-arabinofuranosyl)-α-D-arabino-
4.14 (dd, J2B,3B ϭ 8.0, J2B,1B ϭ 4.5 Hz, 1 H, 1B-H), 5.02 (d,
3J1D,2D ϭ 2.0 Hz, 1 H, 1D-H), 5.10 (d, J1A,2A ϭ 2.0 Hz, 1 H, 1A-
3
furanosyl]-3-O-benzyl-α- -arabinofuranoside (37): Glycosylation of
D
H), 5.11 (d, 3J1B,2B ϭ 4.5 Hz, 1 H, 1B-H), 5.16 (d, 3J1C,2C ϭ 1.7 Hz,
1 H, 1B-H) ppm. 13C NMR (125.72 MHz, D2O, 25 °C): δ ϭ 24.9,
25.8, 28.8, 28.9, 29.2, 34.4 (CH2CO), 52.7 (OCH3), 61.1 (C-5A),
61.5 and 61.8 (C-6C, C-6D), 67.5 (C-4D), 67.6 (C-4C), 69.0 (C-
5B), 69.2 (OCH2 octyl), 70.6 (C-2D), 70.8 (C-3C), 70.9 (C-3D),
73.5 (C-5C), 73.9 (C-5D), 74.7 (C-3B), 75.2 (C-3A), 76.7 (C-2B),
79.4 (C-4B), 80.4 (C-2C), 83.1 (C-4A), 87.5 (C-2A), 98.8 (C-1C),
101.0 (C-1B), 103.0 (C-1D), 106.1 (C-1A), 174.3 (COOCH3) ppm.
HRMS (FAB): C32H56O21Na: calcd. 799.3212, found 799.3218.
35 (40.0 mg, 53 µmol) with 10 (85.0 mg, 0.14 mmol) was carried
out according to the General Procedure. After workup of the reac-
tion, the residue containing 36 was taken up in a 4:1 THF/Et3N
mixture and left at room temp for 2 h. Concentration and chroma-
tography with petroleum ether/EtOAc (3:1) gave 37 as a colorless
oil (54.3 mg, 75%, 2 steps). [α]2D5 ϭ ϩ100 (c ϭ 0.90 in chloroform).
1H NMR (400 MHz, CDCl3, 20 °C): δ ϭ 1.10Ϫ1.18 [m, 18 H, 2
ϫ C(CH3)3], 1.23Ϫ1.40 (m, 8 H, octyl CH2), 1.56Ϫ1.66 (m, 4 H,
3
octyl CH2), 2.29 (t, J ϭ 7.4 Hz, 2 H, CH2CO), 2.35 (d, 3JOH,2D
ϭ
3
4.8 Hz, 1 H, OH-2D), 2.52 (d, JOH,2C ϭ 5.9 Hz, 1 H, OH-2C),
8-(Methoxycarbonyl)octyl
(1,1,3,3-tetraisopropyldisiloxan-1,3-diyl)-α-
O-benzyl-α- -arabinofuranoside (34): From
2-O-Benzoyl-5-O-[2-O-benzoyl-3,5-O-
3.47 (td, 2J ϭ 9.6, 3J ϭ 6.6 Hz, 1 H, octyl OCH2), 3.66 (s, 3 H,
2
3
D
-arabinofuranosyl]-3- CH3O), 3.66 (dd, J5B,5B ϭ 11.4, J5B,4B ϭ 3.3 Hz, 1 H, 5B-H),
D
5
(230.0 mg,
3.69Ϫ3.77 (m, 4 H, 2C-H, 2D-H, 5A-H, octyl OCH2), 3.90 (dd,
2
3
3
0.45 mmol) and 12 (290.0 mg, 0.54 mmol). Chromatography with
petroleum ether/EtOAc (9:1) gave 34 as a colorless oil (385.0 mg,
2J5A,5A ϭ J5B,5B ϭ 11.4, J5A,4A ϭ J5B,4B ϭ 4.3 Hz, 1 H, 5A-H,
5B-H), 4.06Ϫ4.31 (m, 11 H, 3A-H, 3B-H, 3C-H, 3D-H, 4B-H, 4C-
H, 4D-H, 2 ϫ 5C-H, 2 ϫ 5D-H), 4.33 (m, 1 H, 4A-H), 4.41, 4.48,
87%). [α]2D5 ϭ ϩ37 (c ϭ 1.20 in chloroform). H NMR (400 MHz,
1
CDCl3, 20 °C): δ ϭ 0.90Ϫ1.16 [m, 28 H, (CH3)2CH], 1.25Ϫ1.40 4.50, 4.60, 4.61, 4.81 (6d, 2J ϭ 12.1 Hz, 6 ϫ 1 H, benzyl CH2),
(m, 8 H, octyl CH2), 1.56Ϫ1.65 (m, 4 H, octyl CH2), 2.30 (t, J ϭ 4.98 (d, J1C,2C ϭ 1.1 Hz, 1 H, 1C-H), 5.07 (b, 1 H, 1D-H), 5.15
3
3
2
3
3
7.7 Hz, 2 H, CH2CO), 3.45 (td, J ϭ 9.6, J ϭ 6.6 Hz, 1 H, octyl
(s, 1 H, 1A-H), 5.28 (d, J2B,3B ϭ 1.5 Hz, 1 H, 2B-H), 5.29 (s, 1 H,
3
OCH2), 3.66 (s, 3 H, CH3O), 3.68 (m, 1 H, 5A-H), 3.72 (td, 1 H, 1B-H), 5.39 (d, J2A,3A ϭ 1.2 Hz, 1 H, 2A-H), 7.19Ϫ8.09 (m, 25
2
3
octyl OCH2), 3.90 (dd, J5A,5A ϭ 11.2, J5A,4A ϭ 4.7 Hz, 1 H, 5A- H, Ar-H) ppm. 13C NMR (100.62 MHz, CDCl3, 20 °C): δ ϭ 25.0
3
H), 3.93Ϫ3.99 (m, 3 H, 3B-H, 2 ϫ 5B-H), 4.08 (br. d, J3A,4A
ϭ
(octyl CH2), 26.1, 27.1, 27.2, 27.3 [C(CH3)3], 29.2, 29.3, 29.5 (octyl
4.9 Hz, 1 H, 3A-H), 4.33 (m, 1 H, 4A-H), 4.45 (m, 1 H, 4B-H), CH2), 34.2 (CH2CO), 51.6 (CH3O), 63.4 (C-5C, C-5D), 65.9 (C-
4.64, 4.83 (2d, 2J ϭ 12.0 Hz, 2 ϫ 1 H, benzyl CH2), 5.08 (d,
5A, C-5B), 67.8 (octyl OCH2), 71.8, 72.1, 72.4, 72.5 (benzyl CH2),
3J1B,2B ϭ 1.6 Hz, 1 H, 1B-H), 5.12 (s, 1 H, 1A-H), 5.40 (d, 79.7, 79.9 (C-3B), 80.7, 81.6, 81.4, 81.6 (C-4A), 81.9 (C-2A), 82.1
3
3
3J2A,3A ϭ 1.4 Hz, 1 H, 2A-H), 5.48 (dd, J2B,3B ϭ 5.6, J2B,1B
ϭ
(C-4B), 83.1 (C-2B), 83.4 (C-3A), 84.3 (C-2C), 84.8 (C-2D), 105.8
1.6 Hz, 1 H, 2B-H), 7.28Ϫ8.09 (m, 15 H, Ar-H) ppm. 13C NMR (C-1B), 106.0 (C-1A), 108.3 (C-1D), 108.5 (C-1C), 127.8, 127.9,
(100.62 MHz, CDCl3, 20 °C):
(CH3)2CH], 17.3, 17.4, 17.8, 17.9 [(CH3)2CH], 25.4, 26.4, 29.5,
δ
ϭ 12.8, 13.2, 13.6, 13.9,
128.0, 128.2, 128.3, 128.5, 128.4, 128.7, 128.8, 129.3, 129.6, 129.9,
130.0, 133.6, 133.7, 137.6, 137.7, 137.8 (Ar), 165.8 (COOPh), 174.7
29.6, 29.7, 29.8 (octyl CH2), 34.5 (CH2CO), 51.9 (CH3O), 61.7 (C- (COOCH3), 178.3, 178.4 [(CH3)3CCO) ppm. HRMS (FAB):
5B), 67.6 (C-5A), 68.0 (octyl OCH2), 72.6 (benzyl CH2), 76.2 (C4-
B), 81.4 (C-3B), 81.9 (C-4A), 82.3 (C-2A), 84.1 (C-3A), 84.4 (C-
2B), 106.0 (C-1B), 106.3 (C-1A), 128.1, 128.3, 128.8, 128.9, 129.9,
130.1, 130.3, 133.6, 133.8, 138.2 (Ar), 165.8, 166.0 (COOPh), 174.8
(COOCH3) ppm.
C75H94O23Na: calcd. 1385.6083, found 1385.6085.
8-(Methoxycarbonyl)octyl 2-O-Benzoyl-5-O-{2-O-benzoyl-3,5-di-O-
[2-O-(2-O-benzoyl-3-O-benzyl-5-O-tert-butyldiphenylsilyl-β-
binofuranosyl)-3-O-benzyl-5-O-pivaloyl-α- -arabinofuranosyl]-α-
arabinofuranosyl}-3-O-benzyl-α- -arabinofuranoside (38): From 37
D-ara-
D
D-
D
8-(Methoxycarbonyl)octyl 2-O-Benzoyl-5-O-(2-O-benzoyl-α-
binofuranosyl)-3-O-benzyl-α- -arabinofuranoside (35):
D
-ara-
34
(100.0 mg, 73 µmol) and 9 (141.0 mg, 0.22 mmol) according to the
General Procedure. Chromatography with petroleum ether/EtOAc
D
(112.0 mg, 0.11 mmol) was desilylated with neutralized Bu4NF in (3:1) gave 38 as a colorless oil (45.5 mg, 27%). [α]2D5 ϭ ϩ40 (c ϭ
THF according to the General Procedure. Chromatography with 0.80 in chloroform). 1H NMR (400 MHz, CDCl3, 20 °C): δ ϭ 1.01,
petroleum ether/EtOAc (1:1) gave 35 as a colorless oil (83.3 mg,
1.02 [2 s, 18 H, 2 ϫ SiC(CH3)3], 1.08, 1.09 [2 s, 18 H, 2 ϫ
COC(CH3)3], 1.24Ϫ1.36 (m, 8 H, octyl CH2), 1.55Ϫ1.77 (m, 4 H,
1
98%). [α]2D5 ϭ ϩ93 (c ϭ 1.09 in chloroform). H NMR (400 MHz,
3
3
CDCl3, 20 °C): δ ϭ 1.27Ϫ1.40 (m, 8 H, octyl CH2), 1.58Ϫ1.65 (m, octyl CH2), 2.29 (t, J ϭ 7.5 Hz, 2 H, CH2CO), 2.53 (d, JOH,2F
ϭ
4 H, octyl CH2), 2.29 (t, 3J ϭ 7.5 Hz, 2 H, CH2CO), 3.47 (td, 2J ϭ
8.3 Hz, 1 H, 2F-OH), 2.81 (d, 3JOH,2E ϭ 7.8 Hz, 1 H, 2E-OH), 3.42
3
9.6, J ϭ 6.5 Hz, 1 H, octyl OCH2), 3.65 (s, 3 H, CH3O), 3.73 (m, (td, 2J ϭ 9.7, 3J ϭ 6.7 Hz, 1 H, octyl OCH2), 3.65 (s, 3 H, CH3O),
1 H, 5B-H), 3.74 (m, 1 H, 5A-H), 3.75 (td, 1 H, octyl OCH2), 3.84
3.67Ϫ3.77 (m, 9 H, 3C-H, 3D-H, 5A-H, 5B-H, 2 ϫ 5E-H, 2 ϫ 5F-
H, octyl OCH2), 3.85 (m, 2 H, A-H, B-H), 3.91 (m, 1 H, 3F-H),
2
3
(dd, J5B,5B ϭ 12.1, J5B,4B ϭ 3.3 Hz, 1 H, 5B-H), 3.92 (dd,
2J5A,5A ϭ 11.1, 3J5A,4A ϭ 5.0 Hz, 1 H, 5A-H), 4.05 (br. d, 3J3A,4A ϭ 3.93Ϫ4.17 (m, 14 H, 3A-H, 3B-H, 3E-H, 4B-H, 4C-H, 4D-H, 4E-
3
6.3 Hz, 1 H, 3A-H), 4.07 (m, 1 H, 4B-H), 4.15 (dd, J3B,4B ϭ 6.1, H, 4F-H, 2 ϫ 5C-H, 2 ϫ 5D-H, 2 ϫ benzyl CH2), 4.17Ϫ4.32 (m,
3J3B,2B ϭ 2.5 Hz, 1 H, 3B-H), 4.34 (m, 1 H, 4A-H), 4.64, 4.84 (2d,
6 H, 2C-H, 2D-H, 2E-H, 2F-H, 4A-H, benzyl CH2), 4.45, 4.54,
3
2J ϭ 12.1 Hz, 2 ϫ 1 H, benzyl CH2), 5.10 (d, J2B,1B ϭ 2.1 Hz, 1
4.62, 4.65, 4.70, 4.73, 4.74 (7 d, 2J ϭ 12.0 Hz, 7 ϫ 1 H, benzyl
3
H, 2B-H), 5.17 (s, 1 H, 1A-H), 5.31 (s, 1 H, 1B-H), 5.39 (d,
CH2), 5.01 (b, 1 H, 1D-H), 5.10 (s, 1 H, 1A-H), 5.11 (d, J1F,2F
ϭ
3J2A,1A ϭ 1.4 Hz, 1 H, 2A-H), 7.21Ϫ8.05 (m, 15 H, Ar-H) ppm. 4.7 Hz, 1 H, 1F-H), 5.17 (s, 1 H, 1C-H), 5.21 (d, J1E,2E ϭ 4.7 Hz,
3
Eur. J. Org. Chem. 2003, 3587Ϫ3598
www.eurjoc.org
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3597

K. Marotte, S. Sanchez, T. Bamhaoud, J. Prandi
FULL PAPER
[5]
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3
D. Chatterjee, Curr. Opinions Chem. Biol. 1997, 1, 579Ϫ588.
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1 H, 1E-H), 5.24 (d, J2B,3B ϭ 2.0 Hz, 1 H, 2B-H), 5.28 (s, 1 H,
3
1B-H), 5.35 (d, J2A,3A ϭ 1.3 Hz, 1 H, 2A-H), 6.95Ϫ8.02 (m, 55
H, Ar-H) ppm. 13C NMR (100.62 MHz, CDCl3, 20 °C): δ ϭ 24.6,
25.6 (octyl CH2), 26.4, 26.6, 26.7, 26.8 [C(CH3)3], 28.7, 28.8, 28.9,
29.0 (octyl CH2), 33.7 (CH2CO), 51.1 (CH3O), 62.6, 63.1 (C-5C,
C-5D), 65.3 (C-5A, C-5F), 65.4 (C-5E), 65.5 (C-5B), 67.2 (octyl
OCH2), 71.4, 71.5, 71.9, 72.0 (benzyl CH2), 77.1 (C-2E, C-2F), 79.4
(C-4C, C-4D), 81.0 (C-4A), 81.2 (C-4B), 81.5 (C-2A), 82.0 (C-4E),
82.1 (C-4F), 82.9 (C-3D), 83.1 (C-3A), 83.5 (C-3C), 83.9 (C-2B),
84.5 (C-3E), 84.6 (C-3F), 86.0 (C-2D), 86.5 (C-2C), 101.6 (C-1F),
102.2 (C-1E), 105.3 (C-1B), 105.5 (C-1A), 106.4 (C-1D), 106.6 (C-
1C), 127.1, 127.2, 127.3, 127.4, 127.5, 127.8, 127.9, 128.0, 128.1,
128.2, 128.7, 129.0, 129.4, 129.5, 132.5, 135.6, 132.7, 133.1, 135.2,
135.3, 136.9, 137.3, 137.5, 137.6 (Ar), 165.1, 165.4 (PhCO), 174.0
(COOCH3), 177.6 [(CH3)3CCO) ppm.
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8-(Methoxycarbonyl)octyl 5-O-[3,5-Di-O-(2-O-β-
D
-arabinofurano-
-arabino-
syl-α- -arabinofuranosyl)-α- -arabinofuranosyl]-α-D
D
D
´
M. McNeil, M. Daffe, P. J. Brennan, J. Biol. Chem. 1991,
furanoside (4): 38 (45.0 mg, 20 µmol) was submitted to three steps
of deprotection without purification of the intermediate com-
pounds. Desilylation (Bu4NF in THF), debenzoylation and de-
benzylation (Procedure B) were run according to the General Pro-
cedures. Chromatography with dichloromethane/methanol (2:1)
gave 4 as a colorless oil (5.8 mg, 30%, 3 steps). [α]2D5 ϭ ϩ45.5 (c ϭ
0.58 in methanol). 1H NMR (400 MHz, CD3OD, 20 °C): δ ϭ
1.28Ϫ1.42 (m, 8 H, octyl CH2), 1.55Ϫ1.65 (m, 4 H, octyl CH2),
2.32 (t, 3J ϭ 7.5 Hz, 2 H, CH2CO), 3.42 (td, 2J ϭ 9.5, 3J ϭ 6.4 Hz,
1 H, octyl OCH2), 3.66 (s, 3 H, CH3O), 3.60Ϫ3.68 (m, 5 H, 5A-H,
5C-H, 5D-H, 5E-H, 5F-H), 3.71 (m, 1 H, octyl OCH2), 3.70Ϫ3.84
(m, 6 H, 5A-H, 5B-H, 5C-H, 5D-H, 5E-H, 5F-H), 3.89Ϫ4.08 (m,
266, 13217Ϫ13223.
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[21]
[22]
´
´
[23]
15 H, 2A-H, 2B-H, 2E-H, 2F-H, 3A-H, 1C-H, 3D-H, 3E-H, 3F-
3
H, 4A-H, 4C-H, 4D-H, 4E-H, 4F-H, 5B-H), 4.13 (dd, J2D,3D
ϭ
[24]
[25]
[26]
3
3
5.2, J2D,1D ϭ 2.4 Hz, 1 H, 2D-H), 4.14 (dd, J2C,3C ϭ 4.9,
3J2C,1C ϭ 2.3 Hz, 1 H, 2C-H), 4.16 (dd, J3B,4B ϭ 2.8, J3B,2B
ϭ
3
3
1.3 Hz, 1 H, 3B-H), 4.19 (m, 1 H, 4B-H), 4.88 (m, 1 H, 1A-H),
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3J1E,2E ϭ 4.0 Hz, 1 H, 1E-H), 5.08 (d, J1C,2C ϭ 2.1 Hz, 1 H, 1C-
3
3864Ϫ3873.
3
H), 5.16 (d, J1D,2D ϭ 2.3 Hz, 1 H, 1D-H) ppm. 13C NMR
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(100.62 MHz, CD3OD, 20 °C): δ ϭ 26.0, 27.2, 30.1, 30.4, 30.7 (oc-
tyl CH2), 34.8 (CH2CO), 52.0 (CH3O), 62.3 (C-5F), 62.4 (C-5E),
64.3 (C-5D), 64.4 (C-5C), 67.4 (C-5A), 67.8 (C-5B), 68.9 (octyl
OCH2), 75.6, 75.7, 76.2, 76.4, 78.6 (C-3A), 78.7 (C-3C, C-3D, C-
3E, C-3F), 81.6 (C-3B), 82.9, 83.3, 83.7 (C-2A), 83.8, 83.9, 84.3,
84.6, 89.2 (C-2C), 89.4 (C-2D), 102.4 (C-1F), 102.5 (C-1E), 107.0
(C-1D), 107.4 (C-1C), 109.4 (C-1A), 109.5 (C-1B), 176.1 (CO-
OCH3) ppm.
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Acknowledgments
We thank the Centre National de la Recherche Scientifique
`
(CNRS) and the Ministere de l’Education Nationale, de la Recher-
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´
work by the Comite Mixte Inter Universitaire Franco-Marocain
(AI, 00/235/SVS) is gratefully acknowledged.
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Received May 16, 2003
3598
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Eur. J. Org. Chem. 2003, 3587Ϫ3598