Efficient routes to glucosamine-myo-inositol derivatives, key building blocks in the synthesis of glycosylphosphatidylinositol anchor substances

Article abstract of DOI:10.1016/S0040-4020(01)01241-8

Short synthetic routes to protected derivatives of 2-amino-2-deoxy-α-D-glucopyranosyl-(1→6)-D-myo-inositol are described. Various 2-azido-2-deoxy-glucosyl donors were synthesized, starting from D-glucal or glucosamine hydrochloride. Derivatives of 1,2- and 2,3- D-myo-inositol-camphanylidene acetals were prepared to function as glycosyl acceptors. The subsequent glycosylations produced useful building blocks for the synthesis of GPI-anchor substances.

Full text of DOI:10.1016/S0040-4020(01)01241-8

TETRAHEDRON
Pergamon
Tetrahedron 58 (2002) 1387±1398
Ef®cient routes to glucosamine-myo-inositol derivatives, key
building blocks in the synthesis of glycosylphosphatidylinositol
anchor substances
a
b,²
Jan Lindberg, Liselotte Ohberg, Per J. Gareggb and Peter Konradssona,p
È
a
È
È
Department of Chemistry/IFM, Linkoping University, SE-58183 Linko ping, Sweden
bDepartment of Organic Chemistry, Arrhenius Laboratory, Stockholm University, SE-106 91 Stockholm, Sweden
Received 2 March 2001; revised 21 November 2001; accepted 13 December 2001
AbstractÐShort synthetic routes to protected derivatives of 2-amino-2-deoxy-a-d-glucopyranosyl-(1!6)-d-myo-inositol are described.
Various 2-azido-2-deoxy-glucosyl donors were synthesized, starting from d-glucal or glucosamine hydrochloride. Derivatives of 1,2- and
2,3- d-myo-inositol-camphanylidene acetals were prepared to function as glycosyl acceptors. The subsequent glycosylations produced useful
building blocks for the synthesis of GPI-anchor substances. q 2002 Elsevier Science Ltd. All rights reserved.
1. Introduction
complete GPI-anchors2 and lipid-free inositol containing
oligosaccharides.3
The glycosyl phosphatidylinositol (GPI) anchoring system
(Fig. 1) attaches proteins to the cell surface.1 This system is
widely distributed among eucaryotes, especially in lower
organisms, such as protozoa. All GPI-anchors characterized
up to date contain an ethanolamine-PO4-6Manp(a1-2)
Manp(a1-6)Manp(a1-4)GlcNp(a1-6)Ins backbone (Fig. 1),
and several of these have been synthesized, both as
Protein-free inositol phosphoglycans (IPGs) have also been
proposed as second messengers to insulin. Two second mes-
sengers, diacylglycerol and a myo-inositol-1,2-cyclic phos-
phate-containing oligosaccharide are supposed to be released
by the action of a phosphatidylinositol speci®c phospho-
lipase C.4 The a-d-glucosamine (1!6) myo-inositol-1,2-cyclic
Figure 1. Common structure for GPI-anchors.
Keywords: glucosamine-myo-inositol; glycosylphosphatidylinositol; anchoring system.
Corresponding author. Tel.: 146-13-28-1728; fax: 146-13-28-1399; e-mail: petko@ifm.liu.se
È È È È
Present address: AstraZeneca Sodertalje, SE-151 85 Sodertalje, Sweden.
p
²
0040±4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(01)01241-8

1388
J. Lindberg et al. / Tetrahedron 58 (2002) 1387±1398
Scheme 1.
phosphate have been shown to be the minimum structural
motif for the IPGs to possess insulin-mimetic activity.5
The inositol acceptors were synthesized using the myo-
inositol camphanylidene acetals described by Pietrusiewicz
et al.7 This method provides rapid entry into chiral myo-
inositol derivatives. d-camphor is an inexpensive chiral
auxilliary and the comparably more expensive l-camphor
can be prepared in large scale from the less expensive
l-borneol by sodium hypochlorite oxidation.8 Resolution
and regioselective protection is performed in one-step by
reacting myo-inositol with d- or l-camphor dimethyl acetal
and precipitating the myo-inositol-2,3- or 1,2-camphor
acetal (1 or 4) from the reaction mixture. This camphor
acetal, besides acting as a chiral auxilliary, also moderates
the individual reactivity of the remaining hydroxyl groups,
making regioselective protecting group manipulations
possible (Fig. 3).
This work focuses on short routes to appropriately protected
myo-inositol glycosyl acceptors, ef®cient routes to suitable
glycosyl donors and subsequent glycosylation reactions. In
the previously reported synthesis of `disaccharide' 36
(Scheme 1) the yield in the glycosylation step was not satis-
factory. Pivaloylation of 1 produces the 1,4,5-pivaloyl
derivative 2, having a single free OH group in the 6-position
of the d-myo-inositol derivative.7 Position 6 is the intended
site for glycosylation (Fig. 3). This constitutes a two-step
procedure to a chiral glycosyl acceptor from myo-inositol.
One disadvantage is that since the remaining OH group of 2
reacts slowly in the esteri®cation step, it is likely to be an
unreactive glycosyl acceptor as well. Another disadvantage
is that using the pivaloyl derivative requires further
synthetic manipulation after the glycosylation step. This
has led us to investigate other glycosylation methods, glyco-
syl donors, glycosyl acceptors, solvents and combinations
thereof.
Derivative 4, which has been used in syntheses of IPGs,9,10
has the 1- and 2-hydroxyl groups protected by an acetal.
This acetal can be selectively removed later in the syn-
theses. Conversion of 4 into an appropriately protected
acceptor by differential protection of the 6-OH and the 3,
4 and 5-hydroxyls, respectively, provides an acceptor
suitable for synthesis of 1,2-cyclic phosphate derivatives.
This type of inositol derivatives can also, after deprotection
of the camphor acetal, be regioselectively phosphorylated at
the 1-OH.9,11 This constitutes a starting point for syntheses
of phospholipid containing GPI-substances.
For rational syntheses of these types of compounds (i.e.
IPGs) it is necessary to ®nd ef®cient routes to properly
protected derivatives of a-d-glucosamine (1!6) myo-inosi-
tol as depicted in Fig. 2. Such derivatives should have
persistent protecting groups R1 and a selectively removable
protecting group R2. Furthermore, R3 should be easily
removed in the presence of the other protecting groups.
2. Results and discussion
The methods described for preparing 1 and 4 involve
preparation and puri®cation of the camphor dimethyl acetal,
and subsequent trans-acetalization with myo-inositol.7 The
camphor dimethyl acetal can be prepared from camphor and
trimethyl orthoformate and then puri®ed by distillation from
sodium.12
Figure 2.
When preparing the myo-inositol 1,2-camphor acetal we
Figure 3. 2,3-d- and 1,2-l-camphanylidene acetals of d-myo-inositol.

J. Lindberg et al. / Tetrahedron 58 (2002) 1387±1398
1389
Scheme 2.
Scheme 3.
experienced dif®culties in reproducing the results obtained
by the original procedure (Scheme 2). We found that
residual DMSO from the ®rst step, producing a complex
mixture of myo-inositol camphor acetals, was crucial
for the result. In order to simplify the method, we have
developed an in situ preparation of the camphor dimethyl
acetal and subsequent reaction with myo-inositol, thus
avoiding the laborious puri®cation of the dimethyl acetal.
Using 7 equiv. of trimethyl orthoformate gives .95%
conversion of camphor into the dimethyl acetal. Evapo-
ration of solvent and excess trimethyl orthoformate gives
a crude camphor dimethyl acetal. Reaction with myo-inosi-
tol without any further puri®cation provides an ef®cient
method for preparing the chiral inositol derivatives 1 and 4.
Conversion of 4 into a glycosyl acceptor was effected by a
two-step sequence involving regioselective tritylation of
the 6-OH (the glycosylation site) and benzylation of the
remaining hydroxyls. Usually the 3-OH of 4 is the most
reactive towards bulky reagents.13 Surprisingly, the 6-OH
was found to be the most reactive towards triphenylmethyl
chloride in 1,4-dioxan, producing 5 as the major isomer in
33% yield, along with minor amounts of regioisomers and
multiply tritylated derivatives. Subsequent benzylation
produced 6 in 96% yield (Scheme 3).
The trityl group has been shown to activate secondary
alcohols in glycosylation reactions14 and has been used in
highly stereoselective glycosylations with thiocyano
donors.15 The selectively removable camphor acetal
protects the 1- and 2-hydroxyls to be phosphorylated later
in the syntheses. This strategy avoids the drawback of
protecting group manipulations in later stages of the syn-
theses. The moderate yield in the tritylation step is more
than compensated for by the short route and the ready
chromatographic separability of the isomers. Evidence for
the con®guration of 6 was provided by treatment with cyclo-
hexanone and a catalytic amount of TsOH to produce the
known derivative 716 (Scheme 4).
Scheme 4.
Scheme 5.

1390
J. Lindberg et al. / Tetrahedron 58 (2002) 1387±1398
Scheme 6.
Since glucosamine had to be a-linked to the inositol, a
nonparticipating azido-deoxy group, containing a masked
amino-functionality, was used at C-2 of the glycosyl
donor. Syntheses of such donors are shown in Schemes
5±7.
was developed. Phthalimide 14, readily available from
glucosamine hydrochloride by standard transformations,21
was transformed into the glycosyl donors 16 and 17
(Scheme 6), and 19±24 (Scheme 7).
Removal of the phthalimido protecting group using ethylene
diamine in n-butanol22 gave 15 in 91% yield. Subsequent
diazotransfer produced glycosyl donor 16 in 97% yield.
Reductive opening of the benzylidene acetal followed by
allylation yielded donor 19.5 The thioglycosides 16 and 19
were converted into the corresponding sulfoxide donors 17
and 20 by oxidation with m-CPBA. No epoxidation of the
allyl group was observed. Azide 18 was converted into the
thiocyano donors 21 and 22, the intention being to take
advantage of the tritylated inositol derivative by utilizing
the stereoselective glycosylation protocol developed by
Kochetkov et al.15 Acetylation or benzoylation, and con-
version of the resulting derivative to the corresponding
bromo sugar, followed by substitution with potassium thio-
cyanate produced 21 and 22 in 53 and 54% yield, respec-
tively. Hydrolysis of the thioglycoside23 19 and subsequent
reaction with trichloroacetonitrile24 produced donor 23.
Reaction of 19 with dimethyl(methylthio)sulfonium tetra-
¯uoroborate (DMTSB)25 produced donor 24.6 Attempts to
convert 19 into the bromo sugar by treatment with bromine
failed, because of addition of the formed ethylsulfenyl
bromide to the allylic double bond.
Thiophenyl donors 12 and 13 were synthesized from
d-glucal, which can be transformed into the derivative
2-azido-1,6-anhydroglucopyranose 8.17 Heating a mixture
of the diol 8 with trimethylthiophenylsilane (TMSSPh) in
dichloromethane, followed by addition of ZnI2 and molec-
Ê
ular sieves (4 A) gave 9 in 83% yield (a/bˆ2.2:1, deter-
mined by NMR). Compound 9 was then converted to a
4,6-O-benzylidene derivative, followed by benzylation, to
produce 10 in 72% yield. Subsequent reductive opening of
the 4,6-O-benzylidene acetal gave 11, which was either
p-methoxybenzylated or allylated to give 12 and 13 in an
overall yield of 55 and 59%, respectively. Alternative
routes, benzylation of 8 followed by either regioselective
removal of the 4-O-benzyl protecting group with TiCl4, or
conversion to a phenylthio-glycoside have been developed
by others.18
The syntheses of donors 16, 17 and 19±24 are outlined in
Schemes 6 and 7. Syntheses of donors 16, 19 and 24 have
been accomplished earlier by us, using the diazo-transfer
protocol developed by Vasella et al.,19 for introduction of
the 2-azido-2-deoxy-functionality. In order to make more
ef®cient use of the potentially hazardous tri¯uoromethane-
sulfonyl azide (TfN3),19,20 a different route to these donors
The results from the glycosylations of acceptors 2 and 6
with the various donors are outlined in Table 1. The
Scheme 7.

J. Lindberg et al. / Tetrahedron 58 (2002) 1387±1398
1391
Table 1.
to be controllable by varying the solvent and temperature for
the glycosylation.27,28 The best yield of 3 (entry vii), 63%
together with traces of the b-glycoside, were obtained when
the sulfoxide donor 20 was activated in toluene at 2708C,
following the original procedure by Kahne et al.
Entry Donor Acceptor
Promoter
Solvent
Result
3 (34%)
Decomposition
Decomposition
3 (17%)
i
ii
iii
iv
v
2
4
S2nCl2/AgOTf Ether
122
13
19
19
2
DMTST
DMTST
DMTST
MeOTf
T2MSOTf
T2f2O
DMTST
MeOTf
DMTST
DMTST
MeOTf
Tf2O
CH2Cl2
2
2
2
3
0
6
6
6
6
6
6
CH2Cl2
CH2Cl2
Ether
Ether
Toluene 3 (63%)
Ether
Ether
Ether
CH2Cl2
CH2Cl2
Glycosylation of acceptor 6 (Scheme 8, Table 1) was tested
using the donors 16, 17 and 19±22. Activation of 19
with DMTST in ether gave 25 in 25% yield along with
decomposed products (entry viii). Activation with MeOTf
in ether gave 25 in an acceptable yield of 58% (entry ix).
The use of dichloromethane in these glycosylations only
resulted in decomposition of the donor. When the benzyl-
idene derivative 16 was used in the glycosylation of 6, the
reaction was very slow in ether, even when the strong thio-
philic promoter DMTST was used. Changing the solvent to
dichloromethane resulted in a signi®cant improvement.
DMTST gave mainly decomposition (entry xi), but with
MeOTf as promoter, disaccharide 26 was produced in
57% yield (entry xii). Subsequent reductive opening of the
benzylidene acetal gave the building block 27 in 83% yield.
The sulfoxide donors 17 and 20 and the thiocyano donors 21
and 22 were also tested with this acceptor in toluene and
dichloromethane, but the only products isolated were the
b-glycosides in low yields (entries xiii±xvi).
3 (48%)
3 (43%)
vi
vii
viii
ix
x
xi
xii
xiii
xiv
xv
xvi
2
19
19
16
16
16
17
2
25 (25%)
25 (58%)
26 (traces)
Decomposition
26 (57%)
Toluene 26 (traces)
Toluene 25 (traces)
CH2Cl2
CH2Cl2
0
1
6
T6f2O
T6rClO4
TrClO4
2
22
Decomposition
Decomposition
glycosylation of acceptor 2 (Scheme 1) with the glycosyl
¯uoride 24, has previously been reported using dicyclo-
pentadienylzirconium dichloride (Cp2ZrCl2) in ether to
produce the disaccharide 3 in 48% yield.6 A threefold excess
of acceptor was used to achieve acceptable yields. The
anomeric glycosyl ¯uoride 24 can also be activated with
SnCl2/AgOTf in diethyl ether26 (entry i) This promoter
system gave a lower yield (34%). Azides 12 and 13 with
the unreactive thiophenyl anomeric group did not give
any product with dimethyl(methylthio)sulfonium tri¯uoro-
methanesulfonate (DMTST) as promoter (entries ii and iii).
The thioethyl donor 19 was, as expected, found to be more
reactive than the thiophenyl donor 13. Glycosylation with
DMTST as promoter in dichloromethane gave the disac-
charide in 17% yield along with decomposed products
(entry iv). When 19 was activated with MeOTf in ether
the yield was raised to 48% (entry v). Glycosylation of 2
with 23, promoted by TMSOTf (entry vi), gave 3 in 43%
yield together with the N-trichloroacetamido glucoside
(25%). Sulfoxide donors activated with tri¯uoromethane-
sulfonic anhydride at low temperatures have been used
with good results in glycosylations of unreactive hydroxyl
groups.27 The stereochemical outcome has also been shown
3. Conclusions
The glycosylation of acceptor 2 was most successful using
the sulfoxide donor 20 giving the protected compound 3.
The stereoselectivity was highest when toluene was used as
solvent. The donors 19, 23 and 24 also gave acceptable and
similar yields (43±48%) when ether was used as solvent.
When dichloromethane was used as solvent these donors
decomposed rather than reacting with the acceptor.
The glycosylation of acceptor 6 was most successful with
the donors 16 and 19 using MeOTf as promoter, producing
the derivatives 25 and 26. The more reactive donor 19 gave
the best yields in ether, while the less reactive 16 gave the
Scheme 8. Glycosylation of acceptor 6 (entries ix and xii, Table 1). For further glycosylations see entries viii±xvi (Table 1).

1392
J. Lindberg et al. / Tetrahedron 58 (2002) 1387±1398
Scheme 9.
best yields in dichloromethane, being unreactive when ether
was used as solvent. 26 was converted to the useful building
block 27, ready for further elongation at the 4-OH of the
glucose unit. The moderate yields in the glycosylation steps
is compensated for by the very short route to the glucosyl
acceptors 2 and 6.
rotations were recorded at room temperature with a
Perkin±Elmer 241 polarimeter. Melting points were
recorded with a Gallenkamp melting point apparatus.
FAB-mass spectra were recorded on a JEOL SX 102 Mass
Spectrometer using a 3-nitrobenzyl alcohol matrix. IR
spectra were recorded as ®lms on CaF2 crystals (syrups)
or as KBr pellets (solids) on a Perkin±Elmer SPECRUM
1000 FT-IR Spectrometer.
In conclusion both acceptors can be glycosylated to produce
appropriately protected glucosamine-inositol derivatives.
The route, using 6 as acceptor, gives a building block 27
with a protecting group pattern which enables both further
glycosylation of the 4-OH followed by selective deprotec-
tion of the camphanylidene acetal, and phosphorylation to
give a 1,2-cyclic phosphate on the myo-inositol ring
(Scheme 9),9,10 without any protecting group manipulations.
Regioselective phosphorylation of the 1-OH to produce
phospholipid-containing GPI-substances is also an
option.9,11 The route using 2 as an acceptor gives a building
block 3, which after further protecting group manipulations6
has been used in the syntheses of the core heptasaccharyl-
myo inositol29 found in Leishmania parasites and fragments
thereof.30
4.1.1. 1,2-O-(l-1,7,7-Trimethyl[2,2,1]bicyclohept-6-yl-
idene)-d-myo-inositol (4). To a solution of l-camphor
(31.0 g, 0.204 mol) in trimethyl orthoformate (155 mL,
1.41 mol) and methanol (31 mL) was added H2SO4
(0.30 mL). After 48 h, the mixture was neutralized with
NaOMe (650 mg) and concentrated. The residue was
dissolved in toluene (150 mL), the precipitated Na2SO4
®ltered off and the ®ltrate concentrated to give crude
l-camphor dimethyl acetal (41.8 g). To this crude camphor
acetal and myo-inositol (16.0 g, 88.8 mmol) in DMSO
(175 mL) was added H2SO4 (0.9 mL). The resulting mixture
was stirred for 3 h at 758C, neutralized with NEt3 (6 mL)
and concentrated under vacuum at 808C. To the residue was
added DMSO to a total weight of 78 g, and CHCl3
(270 mL), MeOH (17 mL), H2O (5.4 mL) and TsOH´H2O
(60 mg) were added. The mixture was stirred for 17 h,
neutralized with NEt3 (2 mL) and the resulting precipitate
was ®ltered off and washed with CHCl3 (2£200 mL) to give
crude 4 (18.5 g). The crude product was recrystallized from
MeOH (0.1% NEt3) to give 4 (11.2 g) containing minor
impurities of myo-inositol and the diastereomeric 2-endo-
1-exo-isomer. A second recrystallization from MeOH (0.1%
NEt3)/H2O gave pure 4 (10.9 g, 34.7 mmol, 39%). Mp 260±
2628C; [a]Dˆ244.0 (c 1.0, pyridine), Lit. for the enan-
tiomer.13 mp 231±2328C; [a]Dˆ144.3 (c 1.9, pyridine);
1H and 13C NMR were in accordance with those previously
reported.7
4. Experimental
4.1. General methods
Organic phases were dried over MgSO4, ®ltered and
concentrated in vacuo below 408C. NMR spectra were
recorded on Varian Mercury 300 (1H 300 MHz and 13C
75.4 MHz and Varian Inova 600 (1H 600 MHz) instruments
at 258C in CDCl3 with TMS as internal standard
(dˆ0.00 ppm). Signals were assigned by means of DEPT,
NOE difference and 2D spectra (COSY, DQF-PS COSY,
HETCOR, MHQC, HMBC and NOESY). TLC was
performed on Silica Gel F254 (E. Merck) with detection by
UV light and/or by charring with 8% aqueous H2SO4 or
AMC [ammonium molybdate 10 g, cerium(IV)sulfate 2 g,
dissolved in 10% H2SO4 (200 mL)] followed by heating at
,2508C. Silica gel MERCK 60 (0.040±0.063 mm) was
used for Flash Chromatography (FC). Silanized silica gel
(Kieselgel 60 silanisiert, 0.063±0.200 mm, E. Merck) was
used for reversed phase ¯ash chromatography. Optical
4.1.2.
6-O-Triphenylmethyl-1,2-O-(l-1,7,7-trimethyl-
[2,2,1]bicyclohept-6-ylidene)-d-myo-inositol (5). Acetal
4 (5.00 g, 15.9 mmol), triphenylmethyl chloride (6.00 g,
21.5 mmol) and N,N-diisopropylethylamine (6 mL) were
re¯uxed in 1,4-dioxan (200 mL). After 24 h, the mixture
was concentrated and dissolved in MeOH containing 1%
NEt3 (400 mL). Toluene (100 mL) and H2O (300 mL) was

J. Lindberg et al. / Tetrahedron 58 (2002) 1387±1398
1393
added. The phases were separated and the aqueous phase
was extracted twice with toluene (100 mL). The combined
organic layers were dried and concentrated. FC (toluene/
acetone 4:1, 0.1% NEt3) gave 5 (2.93 g, 5.26 mmol, 33%)
as a colorless syrup. Rf 0.15 (toluene/acetone 4:1); [a]Dˆ
133 (c 1.0, CHCl3); IR nmax cm21 1036, 1046, 1109, 1448,
identical to those previously published for the racemic
compound.16b
4.1.5. Phenyl 2-azido-2-deoxy-1-thio-d-glucopyranoside
(9). To a solution of 8 (410 mg, 2.19 mmol) in CH2Cl2
(15 mL) was added Me3SiSPh (1.44 mL, 7.60 mmol). The
mixture was heated until a clear solution was obtained and
1
2952, 3418; NMR: H (600 MHz, CDCl3), d 0.67 (3H, s,
Ê
CH3), 0.78 (3H, s, CH3), 0.92 (3H, s, CH3), 0.98 (1H, ddd,
Jˆ12.2, 9.3, 4.7 Hz), 0.99 (1H, d, Jˆ14.0 Hz), 1.25 (1H,
ddd, Jˆ12.2, 12.2, 4.7 Hz), 1.53±1.64 (2H, m), 1.66 (1H,
dd, Jˆ4.7, 4.7 Hz), 1.79 (1H, ddd, Jˆ12.9, 5.0, 2.9 Hz),
3.47 (1H, dd, Jˆ7.3, 3.9 Hz, H-1), 3.64±3.70 (2H, m,
H-3, 4), 3.93 (1H, dd, Jˆ9.1, 4.3 Hz, H-5), 3.96 (1H, dd,
Jˆ3.9, 3.9 Hz, H-2), 4.29 (1H, dd, Jˆ7.2, 4.3 Hz, H-6),
7.10±7.52 (15H, m, Ph); 13C (75 MHz, CDCl3), d 10.2
(CH3), 20.2 (CH3), 20.5 (CH3), 26.9 (CH2), 29.8 (CH2),
43.0 (CH2), 44.9 (CH), 48.0 (Cq), 51.2 (Cq), 70.4 (C-5),
73.8 (C-6), 74.4 (C-1), 74.5 (C-4), 74.8 (C-2), 77.5 (C-3),
88.8 (Ph3C), 117.5 (OCO), 127.5±129.3 (Ph), 144.2 (Ph);
Anal. Calcd for C35H40O6: C, 75.5; H, 7.2 Found: C, 75.3; H,
7.3.
then 4 A molecular sieves and ZnI2 (2.10 g, 6.58 mmol)
were added. The mixture was stirred at rt for 3 h, ®ltered
through Celite and concentrated. The residue was dissolved
in 70% aqueous HOAc (30 mL) and stirred at rt for 30 min,
concentrated and puri®ed on a silica gel column (toluene/
EtOAc 1:1!1:3) to give 9 (598 mg, 2.01 mmol, 92%,
(a/bˆ2.2:1, determined by NMR) as a colorless syrup.
[a]Dˆ1134 (c 1.0, CHCl3); IR nmax cm21 1067, 1263,
1
2111, 3358; The H and 13C NMR spectra were in accor-
dance with those previously reported.31
4.1.6. Phenyl 2-azido-3-O-benzyl-4,6-O-benzylidene-2-
deoxy-1-thio-d-glucopyranoside (10). To a mixture of 9
(310 mg, 0.104 mmol) and a,a-dimethoxytoluene (172 mL,
1.15 mmol) in DMF (6 mL), a catalytic amount of p-tolu-
enesulfonic acid was added. The reaction mixture was
heated to 508C and stirred overnight. The solution was
diluted with CH2Cl2 (20 mL), washed with aqueous satu-
rated NaHCO3 and water, dried, ®ltered and concentrated.
Puri®cation on a silica gel column (toluene/EtOAc 10:1)
gave phenyl 2-azido-4,6-O-benzylidene-2-deoxy-1-thio-d-
glucopyranoside (330 mg, 0.8 mmol, 75%) as a white
solid. Rf 0.47 (toluene/EtOAc 9:1); [a]Dˆ1165 (c 1.2,
CHCl3); IR nmax cm21 976, 1008, 1101, 1262, 1370, 2101,
3333; NMR: 1H (300 MHz, CDCl3) a-anomer, d 3.49 (1H,
dd, Jˆ9.3, 9.3 Hz, H-4), 3.69 (1H, dd, Jˆ10.3, 10.3 Hz,
H-6a), 3.81 (1H, dd, Jˆ9.9, 5.5 Hz, H-2), 3.95 (1H, dd,
Jˆ9.5, 9.5 Hz, H-3), 4.18 (1H, dd, Jˆ10.4, 5.0 Hz, H-6b),
4.33 (1H, ddd Jˆ9.9, 9.9, 4.9 Hz, H-5), 5.49 (1H, d,
Jˆ5.5 Hz, H-1), 5.50 (1H, s, CHPh), 7.22±7.52 (10H, m,
Ph); b-anomer, d 3.30 (1H, dd, Jˆ10.2, 9.1 Hz, H-2), 3.38
(1H, ddd, Jˆ9.6, 9.6, 4.9 Hz, H-5), 3.43 (1H, dd, Jˆ9.3,
9.3 Hz, H-6a), 3.68 (1H, dd, Jˆ9.1, 9.1 Hz, H-3), 3.73 (1H,
dd, Jˆ9.6, 9.6 Hz, H-4), 4.34 (1H, dd, Jˆ10.6, 4.8 Hz,
H-6b), 4.47 (1H, d, Jˆ10.2 Hz, H-1), 5.49 (1H, s, CHPh),
7.34±7.58 (10H, m, Ph); 13C (75 MHz, CDCl3) a-anomer, d
63.4 (C-5), 63.7 (C-2), 68.4 (C-6), 70.6 (C-3), 81.6 (C-4),
87.7 (C-1), 102.1 (CHPh), 126.3±136.8 (Ph); b-anomer, d
65.1 (C-2), 68.4 (C-6), 70.2 (C-5), 74.0 (C-3), 80.2 (C-4),
86.8 (C-1), 101.9 (CHPh), 126.3±136.7 (Ph). A solution of
phenyl 2-azido-4,6-O-benzylidene-2-deoxy-1-thio-d-gluco-
pyranoside (230 mg, 0.6 mmol) and benzyl bromide
(142 mL, 1.2 mmol) in DMF (4.5 mL) was added dropwise
to a cold (08C) stirred slurry of 50% sodium hydride (55 mg,
1.2 mmol) in DMF (3 mL). After 50 min the reaction was
quenched with methanol (5 mL), diluted with toluene,
washed with aqueous saturated NaHCO3 and water, dried,
®ltered, concentrated and puri®ed on a silica gel column
(toluene/EtOAc 20:1) to give 10 (273 mg, 0.57 mmol,
96%) as a white solid. Rf 0.67 (toluene/EtOAc 9:1);
[a]Dˆ159 (c 1.0, CHCl3); IR nmax cm21 1005, 1086,
1374, 2102, 2902; NMR: 1H (300 MHz, CDCl3) a-anomer,
d 3.74±3.80 (2H, m, H-4, 6a), 3.92±4.01 (2H, m, H-2, 3),
4.22, (1H, dd, Jˆ10.4, 4.9 Hz, H-6b), 4.42 (1H, ddd, Jˆ9.7,
9.7, 4.8 Hz, H-5), 4.83 (1H, d, Jˆ11.0 Hz, CH2Ph), 4.98
(1H, d, Jˆ10.7 Hz, CH2Ph), 5.57 (1H, d, Jˆ3.8 Hz, H-1),
4.1.3. 3,4,5-Tri-O-benzyl-6-O-triphenylmethyl-1,2-O-(l-
1,7,7-trimethyl[2,2,1]bicyclohept-6-ylidene)-d-myo-ino-
sitol (6). 5 (5.46 g, 9.81 mmol) in DMF (85 mL) was added
dropwise over 20 min to 60% NaH (2.8 g, 70 mmol) at 08C
under N2. The mixture was stirred for an additional 20 min
at 08C, benzyl bromide (7.7 mL, 65 mmol) was added and
the mixture were stirred at rt for 14 h. MeOH (5 mL) was
added dropwise and the mixture was diluted with toluene,
washed with H2O, dried, ®ltered and concentrated. FC (tolu-
ene) gave 6 (7.77 g, 9.39 mmol, 96%) as a colorless syrup.
Rf 0.51 (toluene); [a]Dˆ23.2 (c 1.4, CHCl3); IR nmax cm21
1070, 1096, 1453, 1496, 2928; NMR: 1H (600 MHz,
CDCl3), d 0.78 (3H, s, CH3), 0.82 (3H, s, CH3), 0.87±
0.98 (2H, m), 0.99 (3H, s, CH3), 1.18±1.32 (1H, m),
1.55±1.80 (4H, m), 3.30 (1H, dd, Jˆ7.9, 3.9 Hz, H-1),
3.82±3.84 (1H, m, H-3), 4.03 (1H, dd, Jˆ9.3, 5.0 Hz,
H-4), 4.09 (1H, dd, Jˆ9.3, 3.6 Hz, H-5), 4.11 (1H, dd,
Jˆ3.8, 2.9 Hz, H-2), 4.13 (1H, d, Jˆ12.2 Hz, CH2Ph),
4.30 (1H, dd, Jˆ7.9, 3.6 Hz, H-6), 4.33 (1H, d, Jˆ
11.8 Hz, CH2Ph), 4.58 (1H, d, Jˆ11.5 Hz, CH2Ph), 4.70
(1H, d, Jˆ12.2 Hz, CH2Ph), 4.78 (1H, d, Jˆ11.8 Hz,
CH2Ph), 4.79 (1H, d, Jˆ11.5 Hz, CH2Ph), 7.05±7.45
(30H, m, Ph); 13C (75 MHz, CDCl3), d 10.0 (CH3), 20.2
(CH3), 20.6 (CH3), 27.0 (CH2), 29.7 (CH2), 42.5 (CH2),
44.9 (CH), 47.8 (Cq), 51.2 (Cq), 71.2 (CH2Ph), 71.7
(CH2Ph), 72.2 (C-2), 72.4 (C-6), 73.4 (C-1), 73.5
(CH2Ph), 76.4 (C-5), 79.5 (C-4), 86.0 (C-3), 88.5
(Ph3CO), 116.7 (OCO), 126.8±129.2 (Ph), 138.2 (Ph),
138.9 (Ph), 139.1 (Ph), 139.2 (Ph), 144.2 (Ph); Anal.
Calcd for C56H58O6: C, 81.3; H, 7.1 Found: C, 81.4; H, 7.0.
4.1.4. 3,4,5-Tri-O-benzyl-1,2-O-cyclohexylidene-d-myo-
inositol (7).
6 (410 mg, 0.50 mmol), cyclohexanone
(2.0 mL, 19 mmol), trimethyl orthoformate (0.10 mL,
0.92 mmol) and p-toluene sulfonic acid monohydrate
(20 mg, 0.11 mmol) was dissolved in CH2Cl2. After 18 h,
the mixture was diluted with CH2Cl2, washed with NaHCO3
(sat), dried, ®ltered and concentrated. FC (CH2Cl2/acetone
97:3) gave crystalline 7 (144 mg, 0.27 mmol, 55%). [a]Dˆ
220 (c 1.0, CHCl3), Lit.16a [a]Dˆ218 (c 1.1, CHCl3); mp
1
96±988C, Lit.16b 96±988C; H and 13C NMR spectra were

1394
J. Lindberg et al. / Tetrahedron 58 (2002) 1387±1398
5.60 (1H, s, CHPh), 7.29±7.52 (15H, m, Ph); b-anomer, d
3.31±3.50 (2H, m, H-2, 5), 3.60±3.69 (2H, m, H-3, 4), 3.79
(1H, dd, Jˆ10.3, 10.3 Hz, H-6a), 4.80 (1H, dd, Jˆ10.6,
5.1 Hz, H-6b), 4.49 (1H, d, Jˆ10.2 Hz, H-1), 4.78 (1H, d,
Jˆ11.0 Hz, CH2Ph), 4.91 (1H, d, Jˆ11.0 Hz, CH2Ph), 5.57
(1H, s, CHPh), 7.28±7.58 (15H, m, Ph); 13C (75 MHz,
CDCl3) a-anomer, d 63.6 (C-2), 63.8 (C-5), 68.6 (C-6),
75.2 (CH2Ph), 77.9 (C-3), 82.7 (C-4), 87.9 (C-1), 101.5
(CHPh), 126.0±137.7 (Ph); b-anomer, d 64.7 (C-2), 68.5
(C-6), 70.5 (C-5), 75.2 (CH2Ph), 81.0 (C-3), 81.3 (C-4), 86.7
(C-1), 101.3 (CHPh 126.0±137.1 (Ph); HRMS Calcd for
C26H25O4N3S: [M1Na]1 498.1463 Found: [M1Na]1
498.1468.
1.9 Hz, H-6a), 3.73 (1H, dd, Jˆ9.2, 9.2 Hz, H-4), 3.79 (1H,
dd, Jˆ10.5, 3.6 Hz, H-6b), 3.80 (1H, dd, Jˆ9.0, 9.0 Hz,
H-3), 3.79 (3H, s, CH3O), 3.94 (1H, dd, Jˆ9.9, 5.5 Hz,
H-2), 4.34 (1H, ddd, Jˆ9.5, 3.6, 1.8 Hz, H-5), 4.44 (1H,
d, Jˆ11.8 Hz, CH2Ph), 4.47 (1H, d, Jˆ10.4 Hz, CH2Ph),
4.60 (1H, d, Jˆ12.1 Hz, CH2Ph), 4.73 (1H, d, Jˆ10.4 Hz,
CH2Ph), 4.91 (2H, s, CH2Ph), 5.60 (1H, d, Jˆ5.5 Hz, H-1),
6.82 (2H, d, Jˆ8.8 Hz, Ph), 7.08 (2H, d, Jˆ8.8 Hz, Ph),
7.24±7.52 (15H, m, Ph); b-anomer, d 3.33 (1H, dd, Jˆ
9.6, 9.6 Hz, H-2), 3.42±3.47 (1H, ddd, Jˆ9.6, 3.6, 2.0 Hz,
H-5), 3.48 (1H, dd, Jˆ9.1, 9.1 Hz, H-3), 3.58 (1H, dd,
Jˆ9.2, 9.2 Hz, H-4), 3.69±3.81 (2H, m, H-6a, 6b), 3.78
(3H, s, CH3O), 4.40 (1H, d, Jˆ9.9 Hz, H-1), 4.51 (1H, d,
Jˆ10.7 Hz, CH2Ph), 4.54 (1H, d, Jˆ11.8 Hz CH2Ph), 4.62
(1H, d, Jˆ11.8 Hz, CH2Ph), 4.71 (1H, d, Jˆ10.4 Hz,
CH2Ph), 4.85 (2H, s, CH2Ph), 6.82 (2H, d, Jˆ8.5 Hz, Ph),
7.11 (2H, d, Jˆ8.8 Hz, Ph), 7.23±7.61 (15H, m, Ph); 13C
(75 MHz, CDCl3) a-anomer, d 55.3 (CH3O), 64.1 (C-2),
68.3 (C-6), 71.9 (C-5), 73.5 (CH2Ph), 74.8 (CH2Ph), 75.7
(CH2Ph), 78.0 (C-4), 81.8 (C-3), 87.3 (C-1), 113.9 (Ph),
127.6±137.8 (Ph), 159.4 (CH3OPh); b-anomer, d 55.3
(CH3O), 65.1 (C-2), 68.8 (C-6), 73.4 (CH2Ph), 74.7
(CH2Ph), 75.9 (CH2Ph), 77.3 (C-4), 79.4 (C-5), 85.1
(C-3), 86.0 (C-1), 113.9 (Ph), 127.6±138.2 (Ph), 159.4
(CH3OPh); HRMS Calcd for C34H35O4N3S: [M1Na]1
620.2195 Found: [M1Na]1 620.2177.
4.1.7. Phenyl 2-azido-3,6-di-O-benzyl-2-deoxy-1-thio-d-
glucopyranoside (11). Sodium cyanoborohydride (800
mg, 13 mmol) was added to a stirred solution of 10
(280 mg, 0.59 mmol) in THF (15 mL). After 2 h, the
mixture was treated with etheral HCl until gas evolution
ceased. After an additional 30 min, the mixture was ®ltered
through Celite. The ®ltrate was concentrated and puri®ed on
a silica gel column (toluene/EtOAc 10:1) to give 11
(240 mg, 0.50 mmol, 85%) as a colorless syrup. Rf 0.53
(toluene/EtOAc 4:1); [a]Dˆ176 (c 1.1, CHCl3); IR nmax
1
cm21 1066, 2108; NMR: H (300 MHz, CDCl3) a-anomer,
d 3.62±3.77 (4H, m, H-3, 4, 6a, 6b), 3.89 (1H, dd, Jˆ9.9,
5.5 Hz, H-2), 4.33 (1H, ddd, Jˆ9.1, 4.5, 4.5 Hz, H-5), 4.49
(1H, d, Jˆ12.1 Hz, CH2Ph), 4.58 (1H, d, Jˆ12.1 Hz,
CH2Ph), 4.84 (1H, d, Jˆ11.3 Hz, CH2Ph), 4.94 (1H, d, Jˆ
11.3 Hz, CH2Ph), 5.56 (1H, d, Jˆ5.5 Hz, H-1), 7.24±7.52
(15H, m, Ph); b-anomer, d 3.31 (1H, dd, Jˆ9.5, 9.5 Hz,
H-2), 3.37 (1H, dd, Jˆ8.8, 8.8 Hz, H-3), 3.46 (1H, ddd,
Jˆ9.3, 4.9, 4.9 Hz, H-5), 3.63 (1H, dd, Jˆ9.6, 9.6 Hz,
H-4), 3.75 (1H, dd, Jˆ9.7, 4.6 Hz, H-6a), 3.78 (1H, dd,
Jˆ10.2, 4.8 Hz, H-6b), 4.44 (1H, d, Jˆ8.5 Hz, H-1), 4.55
(1H, d, Jˆ11.8 Hz, CH2Ph), 4.61 (1H, d, Jˆ11.8 Hz,
CH2Ph), 4.81 (1H, d, Jˆ11.0 Hz, CH2Ph), 4.90 (1H, d, Jˆ
11.0 Hz, CH2Ph), 7.25±7.58 (15H, m, Ph); 13C (75 MHz,
CDCl3) a-anomer, d 63.6 (C-2), 69.7 (C-6), 71.0 (C-5),
72.3 (C-4), 73.6 (CH2Ph), 75.4 (CH2Ph), 81.4 (C-3), 87.3
(C-1), 127.7±137.9 (Ph); b-anomer, d 64.5 (C-2), 70.3
(C-6), 72.0 (C-4), 73.8 (CH2Ph), 75.5 (CH2Ph), 78.0
(C-5), 84.6 (C-3), 86.3 (C-1), 127.7±137.9 (Ph); Anal.
Calcd for C26H27N3O4S: C, 65.4; H, 5.7 Found: C, 65.0;
H, 5.5.
4.1.9. Phenyl 4-allyl-2-azido-3,6-di-O-benzyl-2-deoxy-1-
thio-d-glucopyranoside (13). A solution of 11 (220 mg,
0.46 mmol) and allyl bromide (78 mL 0.92 mmol) in DMF
(3 mL) was added dropwise to a cold (08C), stirred slurry of
50% sodium hydride (50 mg, 0.92 mmol) in DMF (5 mL).
The reaction was quenched with methanol after 40 min,
diluted with toluene, washed with aqueous saturated
NaHCO3, water, dried, ®ltered, concentrated and puri®ed
on a silica gel column (toluene/EtOAc 10:1) to give 13
(230 mg, 0.44 mmol, 96%) as a white solid. Rf 0.82 (tolu-
ene/EtOAc 12:1); [a]Dˆ195 (c 1.0, CHCl3); IR nmax cm21
1
696, 746, 1054, 1072, 1151, 2107; NMR: H (300 MHz,
CDCl3) a-anomer, d 3.60 (1H, dd, Jˆ9.9, 8.8 Hz, H-4),
3.64 (1H, dd, Jˆ10.8, 2.1 Hz, H-6a), 3.76 (1H, dd, Jˆ9.5,
9.5 Hz, H-3), 3.77 (1H, dd, Jˆ11.0, 3.6 Hz, H-6b), 3.90
(1H, dd, Jˆ10.3, 5.4 Hz, H-2), 4.02 (1H, dd, Jˆ12.4, 5.7,
1.4, 1.4 Hz, CHCH2O), 4.26 (1H, dddd, Jˆ12.4, 5.5, 1.4,
1.4 Hz, CHCH2O), 4.32 (1H, ddd, Jˆ9.9, 3.6, 1.9 Hz, H-5),
4.46 (1H, d, Jˆ11.8 Hz, CH2Ph), 4.62 (1H, d, Jˆ12.1 Hz,
CH2Ph), 4.85 (1H, d, Jˆ10.4 Hz, CH2Ph), 4.89 (1H, d,
Jˆ10.7 Hz, CH2Ph), 5.11±5.24 (2H, m, CH2vCH), 5.58
(1H, d, Jˆ5.2 Hz, H-1), 5.77±5.90 (1H, m, CH2vCH),
7.24±7.54 (15H, m, Ph); b-anomer, d 3.27±3.48 (4H, m,
H-2, H-3, H-4, H-5), 3.70±3.81 (2H, m, H-6a, 6b), 4.07 (1H,
dddd, Jˆ12.4, 5.5, 1.4, 1.4 Hz, CHCH2O), 4.24 (1H, dddd,
Jˆ12.4, 5.8, 1.4, 1.4 Hz, CHCH2O), 4.40 (1H, d,
Jˆ10.2 Hz, H-1), 4.56 (1H, d, Jˆ12.1 Hz, CH2Ph), 4.64
(1H, d, Jˆ11.8 Hz, CH2Ph), 4.82 (2H, s, Ph), 5.10±5.23
(2H, m, CH2vCH), 5.78±5.91 (1H, m, CH2vCH), 7.21±
7.61 (15H, m, Ph); 13C (75 MHz, CDCl3) a-anomer, d 63.9
(C-2), 68.3 (C-6), 71.9 (C-5), 73.5 (CH2Ph), 73.9
(CHCH2O), 75.7 (CH2Ph), 78.1 (C-4), 81.7 (C-3), 87.3
(C-1), 117.1 (CH2vCH), 127.7±137.8 (Ph), 134.4
(CH2vCH); b-anomer, d 64.9 (C-2), 68.8 (C-6), 73.5
(CH2Ph), 73.8 (CHCH2O), 75.9 (CH2Ph), 77.3 (C-3),
79.4 (C-5), 84.9 (C-4), 85.9 (C-1), 117.1 (CH2vCH),
4.1.8. Phenyl 2-azido-3,6-di-O-benzyl-2-deoxy-4-O-p-
methoxybenzyl-1-thio-d-glucopyranoside (12). A solu-
tion of 11 (180 mg, 0.37 mmol) and p-methoxybenzyl
bromide (101 mL, 0.76 mmol) in DMF (4.5 mL) was
added dropwise to a cold (08C), stirred slurry of 50% sodium
hydride (40 mg, 0.76 mmol) in DMF (5 mL). The reaction
was quenched with methanol after 1 h, diluted with toluene,
washed with aqueous saturated NaHCO3 and water, dried,
®ltered and concentrated. The residue was ®rst puri®ed on a
silica gel column (toluene/EtOAc 24:1), followed by puri®-
cation on a reversed phase gel column using a gradient of
acetone/water (2:1!4:1). The residue was concentrated,
diluted with CH2Cl2, washed with water, dried, ®ltered
and concentrated to give 12 (204 mg, 0.34 mmol, 90%) as
a colorless syrup. Rf 0.56 (toluene/EtOAc 12:1); [a]Dˆ164
(c 1.0, CHCl3); IR nmax cm21 1082, 1250, 1514, 2109; NMR
1H (300 MHz, CDCl3) a-anomer, d 3.62 (1H, dd, Jˆ10.7,

J. Lindberg et al. / Tetrahedron 58 (2002) 1387±1398
1395
127.6±138.3 (Ph), 133.6 (CH2vCH); Anal. Calcd for
C29H31N3O4S: C, 67.3; H, 6.0 Found: C, 67.1; H, 6.1.
7.6, 7.6 Hz, CH3CH2), 3.08 (1H, ddd, Jˆ20.6, 7.6, 7.6 Hz,
CH3CH2), 3.49 (1H, ddd, Jˆ9.5, 9.5, 5.1 Hz, H-5), 3.74
(1H, dd, Jˆ9.6, 9.6 Hz, H-4), 3.76 (1H, dd, Jˆ10.1,
10.1 Hz, H-6a), 3.83 (1H, dd, Jˆ8.9, 8.9 Hz, H-3), 3.99
(1H, dd, Jˆ9.2, 9.2 Hz, H-2), 4.10 (1H, d, Jˆ9.8 Hz,
H-1), 4.35 (1H, dd, Jˆ10.5, 5.1 Hz, H-6b), 4.82 (1H, d,
Jˆ11.3 Hz, CH2Ph), 4.98 (1H, d, Jˆ11.3 Hz, CH2Ph),
5.53 (1H, s, CHPh), 7.28±7.45 (10H, m, Ph); Rf 0.26, d
1.32 (3H, dd, Jˆ7.6, 7.6 Hz, CH2CH3), 2.76 (1H, ddd, Jˆ
20.6, 7.6, 7.6 Hz, CH3CH2), 3.08 (1H, ddd, Jˆ20.6, 7.6,
7.6 Hz, CH3CH2), 3.52 (1H, ddd, Jˆ9.7, 9.7, 4.9 Hz, H-5),
3.79 (1H, d, Jˆ10.5 Hz, H-1), 3.81±3.84 (2H, m, H-3, H-4),
3.88 (1H, dd, Jˆ10.3, 10.3 Hz, H-6a), 4.05±4.11 (1H, m,
H-2), 4.34 (1H, dd, Jˆ10.5, 5.1 Hz, H-6b), 4.84 (1H, d,
Jˆ11.2 Hz, CH2Ph), 4.99 (1H, d, Jˆ11.6 Hz, CH2Ph),
5.57 (1H, s, CHPh), 7.26±7.49 (10H, m, Ph); 13C
4.1.10. Ethyl 2-amino-3-O-benzyl-4,6-O-benzylidene-2-
deoxy-1-thio-b-d-glucopyranoside (15). 1421 (7.21 g,
13.6 mmol) in n-butanol/ethylenediamine 5:1 (480 mL)
was stirred at 908C for 14 h, after which the mixture was
concentrated, dissolved in CHCl3/MeOH 10:1 and passed
through a short column of silica. FC (CH2Cl2/EtOAc 9:1)
and recrystallization from EtOAc/hexane gave 15 (4.96 g,
12.4 mmol, 91%) as white needles. Rf 0.28 (CH2Cl2/EtOAc
9:1); mp 147±1488C; [a]Dˆ245 (c 1.5, CHCl3); IR nmax
cm21 931, 1027, 1070, 1082, 1093, 1369, 1452, 1607,
1
2860; NMR: H (300 MHz, CDCl3), d 1.30 (3H, dd, Jˆ
7.6, 7.6 Hz, CH3CH2), 2.74 (2H, m, CH3CH2), 2.96 (1H,
dd, Jˆ10.0, 10.0 Hz, H-2), 3.51 (1H, ddd, Jˆ9.7, 9.7,
4.8 Hz, H-5), 3.57 (1H, dd, Jˆ9.1, 9.1 Hz, H-3), 3.78 (1H,
dd, Jˆ9.1, 9.1 Hz, H-6a), 3.79 (1H, dd, Jˆ10.2, 10.2 Hz,
H-4), 4.35 (1H, dd, Jˆ10.5, 5.2 Hz, H-6b), 4.42 (1H, d,
Jˆ10.1 Hz, H-1), 4.71 (1H, d, Jˆ11.5 Hz, CH2Ph), 5.03
(1H, d, Jˆ11.5 Hz, CH2Ph), 5.63 (1H, s, CHPh), 7.20±
7.65 (10H, m, Ph); 13C (75 MHz, CDCl3), d 15.3
(CH3CH2), 24.6 (CH3CH2), 56.1 (C-2), 68.7 (C-6), 70.6
(C-3), 74.9 (CH2Ph), 82.2 (C-4), 82.3 (C-5), 87.6 (C-1),
101.2 (CHPh), 126.0 (Ph), 127.9 (Ph), 128.2 (Ph), 128.3
(Ph), 128.5 (Ph), 129.0 (Ph), 137.4 (Ph), 138.3 (Ph); Anal.
Calcd for C22H27NO4S: C, 65.8; H, 6.8 Found: C, 66.0; H,
6.8.
(75 MHz, CDCl3) Rf 0.46,
d 7.5 (CH3CH2), 43.5
(CH3CH2), 59.5 (C-2), 68.2 (C-6), 71.0 (C-5), 75.0
(CH2Ph), 80.9 (C-3, 4), 90.7 (C-1), 101.4 (CHPh), 126.0
(Ph), 128.0 (Ph), 128.3 (Ph), 128.4 (Ph), 128.5 (Ph), 129.2
(Ph), 136.9 (Ph), 137.5 (Ph); Rf 0.26, d 7.4 (CH3CH2), 41.3
(CH3CH2), 59.5 (C-2), 68.1 (C-6), 71.3 (C-5), 74.9 (CH2Ph),
80.7 (C-3), 81.0 (C-4), 88.0 (C-1), 101.4 (CHPh), 126.0
(Ph), 128.0 (Ph), 128.2 (Ph), 128.4 (Ph), 128.5 (Ph), 129.2
(Ph), 136.9 (Ph), 137.5 (Ph); Anal. Calcd for C22H25N3O5S:
C, 59.6; H, 5.7 Found: C, 59.6; H 5.3.
4.1.13. Ethyl 4-O-allyl-2-azido-3,6-di-O-benzyl-2-deoxy-
1-thio-b-d-glucopyranoside S-oxide (20). To a stirred
solution of 196 (470 mg, 1.00 mmol) in CH2Cl2 (50 mL) at
2788C, was added m-CPBA (200 mg, 1.16 mmol). The
mixture was allowed to warm up to 2208C over 30 min.
The mixture was diluted with CH2Cl2, washed with aqueous
NaHCO3, dried, ®ltered and concentrated. FC (toluene/
EtOAc 1:1) and recrystallization from hexane produced 20
as a mixture of (R)- and (S)-sulfoxides (470 mg, 0.97 mmol,
97%). Rf 0.25, 0.21 (toluene/EtOAc 2:1); mp 65±668C
(from hexane); [a]Dˆ257 (c 1.0, CHCl3); IR nmax cm21
1027, 1086, 1276, 1359, 1455, 2113, 2912; NMR: 1H
(300 MHz, CDCl3) Rf 0.25, d 1.37 (3H, dd, Jˆ7.6,
7.6 Hz, CH3CH2), 2.82 (1H, ddd, Jˆ10.6, 7.6, 7.6 Hz,
CH3CH2), 3.04 (1H, ddd, Jˆ10.6, 7.6, 7.6 Hz, CH3CH2),
3.43±3.48 (1H, m, H-5), 3.51 (1H, dd, Jˆ8.7, 8.7 Hz, H-
4), 3.60 (1H, dd, Jˆ8.9, 8.9 Hz, H-3), 3.68 (1H, dd, Jˆ11.0,
3.8 Hz, H-6a), 3.73 (1H, dd, Jˆ11.0, 2.0 Hz, H-6b), 3.83
(1H, dd, Jˆ9.4, 9.4 Hz, H-2), 3.99 (1H, dd, Jˆ10.1,
10.1 Hz, H-1), 4.07 (1H, dddd, Jˆ12.3, 5.8, 1.4, 1.4 Hz,
CHCH2O), 4.25 (1H, dddd, Jˆ12.3, 5.8, 1.4, 1.4 Hz,
CHCH2O), 4.52 (1H, d, Jˆ12.3 Hz, CH2Ph), 4.59 (1H, d,
Jˆ12.3 Hz, CH2Ph), 4.87 (2H, s, CH2Ph), 5.11±5.23 (2H,
m, CH2vCH), 5.77±5.89 (1H, m, CH2vCH), 7.25±7.38
(10H, m, Ph); Rf 0.21, d 1.30 (3H, dd, Jˆ7.5, 7.5 Hz,
CH3CH2), 2.80 (1H, ddd, Jˆ10.6, 7.6, 7.6 Hz, CH3CH2),
3.10 (1H, ddd, Jˆ10.4, 7.6, 7.6 Hz, CH3CH2), 3.44 (1H,
dd, Jˆ9.8, 8.7 Hz, H-4), 3.52 (1H, ddd, Jˆ9.8, 5.1,
1.9 Hz, H-5), 3.64 (1H, dd, Jˆ9.5, 8.7 Hz, H-3), 3.70 (1H,
dd, Jˆ10.9, 5.5 Hz, H-6a), 3.70 (1H, d, Jˆ10.2 Hz, H-1),
3.77 (1H, dd, Jˆ10.9, 2.2 Hz, H-6b), 3.96 (1H, dd, Jˆ10.4,
9.6 Hz, H-2), 4.07 (1H, dddd, Jˆ12.4, 5.8, 1.5, 1.5 Hz,
CHCH2O), 4.26 (1H, dddd, Jˆ12.4, 5.8, 1.5, 1.5 Hz,
CHCH2O), 4.54 (1H, d, Jˆ12.0 Hz, CH2Ph), 4.60 (1H, d,
Jˆ12.0 Hz, CH2Ph), 4.89 (2H, s, CH2Ph), 5.12±5.24 (2H,
m, CH2vCH), 5.77±5.90 (1H, m, CH2vCH), 7.25±7.42
4.1.11. Ethyl 2-azido-3-O-benzyl-4,6-O-benzylidene-2-
deoxy-1-thio-b-d-glucopyranoside (16). To a solution of
NaN3 (8.0 g, 123 mmol) in H2O (20 mL) was added CH2Cl2
(25 mL). The resulting mixture was cooled to 08C under N2.
Tri¯uoromethanesulfonic anhydride (4.0 mL, 23 mmol)
was added over 30 min to the stirred two-phase mixture.
After an additional 2 h at 08C, the phases were separated
and the aqueous phase was extracted with CH2Cl2
(2£10 mL). The combined organic layers were washed
with sat. NaHCO3 (20 mL) and H2O (20 mL), dried with
MgSO4 and ®ltered. The resulting solution of tri¯yl azide
was added dropwise to a stirred solution of 15 (5.03 g,
12.5 mmol) and DMAP (4.65 g, 38 mmol) in CH2Cl2
(50 mL). After 16 h, the mixture was diluted with EtOAc
and concentrated. FC (toluene/EtOAc 12:1) and recrystalli-
zation from hexane gave 16 (5.18 g, 12.1 mmol, 97%). Rf
0.56 (toluene/EtOAc 12:1); IR nmax cm21 995, 1062, 1084,
1
1101, 1278, 1376, 1452, 2111; H and 13C NMR spectra
were identical to those previously reported.6
4.1.12. Ethyl 2-azido-3-O-benzyl-4,6-O-benzylidene-2-
deoxy-1-thio-b-d-glucopyranoside S-oxide (17). To a
stirred solution of 16 (428 mg, 1.00 mmol) in CH2Cl2
(50 mL) at 2608C, was added m-CPBA (200 mg, 1.16
mmol). The mixture was allowed to warm up to 2208C
over 25 min. The mixture was diluted with CH2Cl2, washed
with aqueous NaHCO3, dried, ®ltered and concentrated. FC
(toluene/EtOAc 1:1) and recrystallization from EtOAc/
hexane produced 17 as a mixture of (R)- and (S)-sulfoxides
(419 mg, 0.94 mmol, 94%). Rf 0.46, 0.26 (toluene/EtOAc
1:1); mp 142±1488C (from EtOAc/hexane); [a]Dˆ2192 (c
1.0, CHCl3); IR nmax cm21 1015, 1108, 1263, 1366, 1454,
1
2109, 2862; NMR: H (300 MHz, CDCl3) Rf 0.46, d 1.37
(3H, dd, Jˆ7.6, 7.6 Hz, CH2CH3), 2.84 (1H, ddd, Jˆ20.6,

1396
J. Lindberg et al. / Tetrahedron 58 (2002) 1387±1398
(10H, m, Ph); 13C (75 MHz, CDCl3) Rf 0.25, d 7.2
(CH3CH2), 43.1 (CH3CH2), 61.0 (C-2), 68.4 (C-6), 73.6
(CH2Ph), 73.8 (CHCH2O), 75.8 (CH2Ph), 77.0 (C-4), 80.1
(C-5), 84.8 (C-3), 90.7 (C-1), 117.3 (CH2vCH), 127.7±
128.5 (Ph), 134.2 (CH2vCH), 137.6 (Ph), 137.9 (Ph); Rf
0.21, d 7.2 (CH3CH2), 41.3 (CH3CH2), 59.9 (C-2), 69.0
(C-6), 73.6 (CH2Ph), 74.0 (CHCH2O), 75.7 (CH2Ph), 77.5
(C-4), 80.6 (C-5), 84.9 (C-3), 87.7 (C-1), 117.6 (CH2vCH),
127.7±128.5 (Ph), 134.1 (CH2vCH), 137.9 (Ph), 138.0
(Ph); Anal. Calcd for C25H31N3O5S: C, 61.8; H, 6.4
Found: C, 62.0; H 6.3.
2.83 (2H, m, CH3CH2), 3.51±3.73 (5H, m, H-2, 3, 5, 6a,
6b), 4.39 (1H, d, Jˆ10.2 Hz, H-1), 4.46 (2H, s, CH2Ph),
4.63 (1H, d, Jˆ11.0 Hz, CH2Ph), 4.77 (1H, d, Jˆ10.7 Hz,
CH2Ph), 5.29 (1H, dd, Jˆ9.9, 9.3 Hz, H-4), 7.15±7.25
(10H, m, Ph), 7.41±7.46 (2H, m, Ph), 7.56±7.66 (1H, m,
Ph), 7.94±7.98 (2H, m, Ph); 13C (75 MHz, CDCl3), d 15.1
(CH3CH2), 24.7, (CH3CH2), 65.9 (C-2), 69.7, 71.4, 73.6,
75.3, 78.0, 82.4, 84.4, 127.6±129.8 (Ph), 133.4 (Ph),
137.1 (Ph), 137.7 (Ph), 165.2 (PhCO). To a stirred solution
of this derivative (353 mg, 0.66 mmol) in CH2Cl2 (5 mL)
was added bromine (115 mg, 0.72 mmol). After 10 min,
cyclohexene was added to the mixture until the yellow
color disappeared, and the mixture was concentrated. The
resulting bromo sugar was stirred with KSCN(210 mg,
2.16 mmol) and 18-crown-6 ether (23 mg, 0.087 mmol) in
dry acetone (3 mL) for 3 h. The mixture was ®ltered through
Celite and concentrated. FC (gradient toluene!toluene/
EtOAc 20:1) gave 22 (193 mg, 0.36 mmol, 55%) as a color-
less syrup. Rf 0.35 (toluene/EtOAc 12:1); [a]Dˆ271 (c 0.6,
CHCl3); IR nmax cm21 1067, 1256, 1451, 1732, 2114, 2160,
4.1.14. 4-O-Acetyl-2-azido-3,6-di-O-benzyl-2-deoxy-b-d-
glucopyranosyl thiocyanate (21). To a stirred solution
of 186 (495 mg, 1.15 mmol) in pyridine (5 mL) was added
acetic anhydride (0.25 mL, 2.6 mmol). After 10 min, the
mixture was diluted with CH2Cl2, washed with H2O and
0.1 M HCl, dried ®ltered and concentrated. FC (toluene/
EtOAc 12:1) gave ethyl 4-O-acetyl-2-azido-3,6-di-O-
benzyl-2-deoxy-thio-b-d-glucopyranoside (538 mg, 1.14
mmol, 99%) as a colorless syrup. Rf 0.68 (toluene/EtOAc
1
2916; NMR: H (300 MHz, CDCl3), d 3.62 (2H, d, Jˆ
1
4:1); NMR: H (300 MHz, CDCl3), d 1.32 (3H, dd, Jˆ7.6,
4.4 Hz), 3.72±3.84 (3H, m), 4.49 (2H, s, CH2Ph), 4.56
(1H, d, Jˆ9.6 Hz, H-1), 4.65 (1H, d, Jˆ10.7 Hz, CH2Ph),
4.76 (1H, d, Jˆ11.0 Hz CH2Ph), 5.36 (1H, dd, Jˆ9.9,
9.1 Hz, H-4), 7.13±7.26 (10H, m, Ph), 7.41±7.47 (2H, m,
Ph), 7.57±7.63 (1H, m, Ph), 7.94±7.98 (2H, m, Ph); 13C
(75 MHz, CDCl3), d 65.8 (C-2), 68.9, 70.5, 73.8, 75.5,
79.4, 82.0, 83.9, 107.8 (SCN), 127.7±129.9 (Ph), 133.6
(Ph), 136.6 (Ph), 137.4 (Ph), 165.0 (PhCO); HRMS Calcd
for C28H26N4O5S: [M1Na]1 553.1522 Found: [M1Na]1
553.1495.
7.6 Hz, CH3CH2), 1.84 (3H, s), 2.66±2.83 (2H, m,
CH3CH2), 3.42±3.56 (5H, m, H-2, 3, 5, 6a, 6b), 4.28±4.34
(1H, m, H-1), 4.49 (2H, s, CH2Ph), 4.65 (1H, d, Jˆ11.3 Hz,
CH2Ph), 4.83 (1H, d, Jˆ11.3 Hz, CH2Ph), 4.96±5.04 (1H,
m, H-4), 7.24±7.36 (10H, m, Ph); 13C (75 MHz, CDCl3), d
15.1 (CH3CH2), 20.7 (CH3CO), 24.7, (CH3CH2), 65.8 (C-2),
69.7, 70.8, 73.6, 75.2, 77.6, 82.5, 84.3, 127.7±128.5 (Ph),
137.5 (Ph), 137.8 (Ph), 169.6 (CH3CO). To a stirred solution
of this derivative (346 mg, 0.73 mmol) in CH2Cl2 (5 mL)
was added bromine (124 mg, 0.78 mmol). After 10 min,
cyclohexene was added to the mixture until the yellow
color disappeared, and the mixture was concentrated. The
resulting bromo sugar was stirred with KSCN(227 mg,
2.34 mmol) and 18-crown-6 ether (20 mg, 0.076 mmol) in
dry acetone (3 mL) for 3 h. The mixture was ®ltered through
Celite and concentrated. FC (toluene/EtOAc 20:1) gave 21
(184 mg, 0.39 mmol, 54%) as a colorless syrup. Rf 0.41
(toluene/EtOAc 12:1); [a]Dˆ254 (c 0.8, CHCl3); IR nmax
cm21 1062, 1224, 1365, 1455, 1747, 2114, 2160, 2873;
4.1.16. O-(4-O-Allyl-2-azido-3,6-di-O-benzyl-2-deoxy-b-
d-glucopyranosyl) trichloroacetimidate (23). To a stirred
mixture of 196 (140 mg, 0.30 mmol), H2O (10 mL) and
TfOH (7 mL) in acetonitrile (25 mL) at 08C was added a
solution of tetrabutylammonium periodate (52 mg, 0.12
mmol) in acetonitrile (3 mL). After 1 h, aqueous NaHCO3
(sat.) was added (15 mL) and the mixture was extracted with
CH2Cl2. The organic layer was washed with 5% Na2S2O3
and brine, dried, ®ltered and concentrated. FC (toluene/
EtOAc 6:1) gave 4-O-allyl-2-azido-3,6-di-O-benzyl-2-
deoxy-d-glucopyranose (106 mg, 0.25 mmol, 84%). Rf
1
NMR: H (300 MHz, CDCl3), d 1.85 (3H, s, CH3CO),
3.48±3.66 (4H, m), 3.72 (1H, dd, Jˆ9.6, 9.6 Hz), 4.48
(1H, d, Jˆ9.9 Hz, H-1), 4.52 (2H, s, CH2Ph), 4.67 (1H, d,
Jˆ11.3 Hz, CH2Ph), 4.83 (1H, d, Jˆ11.3 Hz, CH2Ph), 5.07
(1H, dd, Jˆ9.6, 9.6 Hz, H-4), 7.25±7.38 (10H, m, Ph); 13C
(75 MHz, CDCl3), d 20.7 (CH3CO), 65.7 (C-2), 68.9, 70.1,
73.7, 75.5, 79.1, 82.1, 83.7, 107.8 (SCN), 127.9±128.6 (Ph),
137.0 (Ph), 137.5 (Ph), 169.3 (CH3CO); HRMS Calcd for
C23H24N4O5S: [M1Na]1 491.1365 Found: [M1Na]1
491.1383.
1
0.38 (toluene/EtOAc 4:1); H NMR were in accordance
with that previously published.32 To a stirred solution
of 4-O-allyl-2-azido-3,6-di-O-benzyl-2-deoxy-d-glucopyra-
nose (127 mg, 0.30 mmol) in dry CH2Cl2 (4.5 mL) were
added K2CO3 (413 mg, 3.0 mmol) and trichloroacetonitrile
(0.60 mL, 6.0 mmol). After 3 h, the reaction mixture was
diluted with dry toluene, ®ltered through Celite and concen-
trated. The residue was puri®ed on a silica gel column (light
petroleum 45±60/EtOAc 4:1, 1% NEt3) to give 23 (132 mg,
0.23 mmol, 78%) as a colorless syrup. Rf 0.35 (light petro-
leum 40±65/EtOAc 4:1); IR nmax cm21 1060, 1286, 1674,
2113; NMR: 1H (300 MHz, CDCl3), d 3.48 (1H, dd, Jˆ9.6,
8.8 Hz, H-3), 3.52±3.65 (2H, m, H-4, 5), 3.64 (1H, dd,
Jˆ9.1, 9.1 Hz, H-2), 3.69±3.78 (2H, m, H-6a, 6b), 4.11
(1H, dddd, Jˆ12.4, 5.5, 1.4, 1.4 Hz, CHCH2O), 4.29 (1H,
dddd, Jˆ12.4, 5.8, 1.4, 1.4 Hz, CHCH2O), 4.57 (1H, d,
Jˆ12.1 Hz, CH2Ph), 4.66 (1H, d, Jˆ12.1 Hz, CH2Ph),
4.86 (1H, d, Jˆ11.0 Hz, CH2Ph), 4.90 (1H, d, Jˆ11.0 Hz,
CH2Ph), 5.14±5.25 (2H, m, CH2vCH), 5.64 (1H, d,
Jˆ8.5 Hz, H-1), 5.80±5.93 (1H, m, CH2vCH), 7.26±7.43
4.1.15. 2-Azido-4-O-benzoyl-3,6-di-O-benzyl-2-deoxy-b-
d-glucopyranosyl thiocyanate (22). To a stirred solution
of 186 (371 mg, 0.86 mmol) in pyridine (5 mL) was added
benzoyl chloride (0.20 mL, 1.7 mmol) and DMAP (20 mg,
0.16 mmol). After 30 min, the mixture was diluted with
CH2Cl2, washed with H2O and 0.1 M HCl, dried ®ltered
and concentrated. FC (toluene/EtOAc 12:1) gave ethyl
2-azido-4-O-benzoyl-3,6-di-O-benzyl-2-deoxy-thio-b-d-
glucopyranoside (448 mg, 0.84 mmol, 98%) as a colorless
1
syrup. Rf 0.72 (toluene/EtOAc 4:1); NMR: H (300 MHz,
CDCl3), d 1.34 (3H, dd, Jˆ7.4, 7.4 Hz, CH3CH2), 2.72±

J. Lindberg et al. / Tetrahedron 58 (2002) 1387±1398
1397
(10H, m, Ph), 8.76 (1H, s, NH); 13C (75 MHz, CDCl3), d
65.7 (C-2), 67.9 (C-6), 73.4 (CH2Ph), 73.8 (CHCH2O), 75.6
(CH2Ph), 76.1 (C-5), 77.0 (C-4), 82.8 (C-3), 90.6 (CCl3),
96.8 (C-1), 117.1 (CH2vCH), 127.7±128.5 (Ph), 134.4
(CH2vCH), 137.8 (Ph), 138.0 (Ph), 161.1 (Cl3CNHO);
Anal. Calcd for C25H27Cl3N4O5: C, 52.7; H, 4.8 Found: C,
52.9; H, 4.8.
67.8 (C-60), 70.4 (C-50), 72.5 (CH2Ph), 73.3 (CH2Ph), 73.5
(CHCH2O), 73.9 (C-1), 74.7 (CH2Ph), 75.2 (CH2Ph), 75.2
(CH2Ph), 76.1 (C-6), 77.0 (C-2), 78.1 (C-40, 5), 79.8 (C-30),
80.6 (C-3), 80.7 (C-4), 95.7 (C-10), 116.0 (CH2vCH), 118.0
(OCO), 127.6±128.5 (Ph), 135.0 (CH2vCH), 138.0±138.6
(Ph); Anal. Calcd for C60H69N3O10: C, 72.6; H, 7.0 Found:
C, 72.7; H 6.8.
4.1.17. 6-O-(4-Allyl-2-azido-3,6-di-O-benzyl-2-deoxy-a-
d-glucopyranosyl)-1,4,5-tri-O-trimethylacetyl-2,3-O-(d-
1,7,7-trimethyl[2.2.1]bicyclohept-6-ylidene)-d-myo-ino-
sitol (3). 20 (38 mg, 0.078 mmol) in toluene (1 mL) under
argon was cooled to 2788C. Tri¯uoromethanesulfonic
anhydride (0.014 mL, 0.083 mmol) was added, and the
resulting mixture stirred for 5 min at 2788C. 2 (75 mg,
0.133 mmol) and di-t-butyl-methyl aminopyridine (19 mg,
0.093 mmol) dissolved in toluene (1 mL) were added. The
reaction mixture was allowed to warm up to 08C over
15 min. After an additional 30 min at 08C, the mixture
was diluted with toluene, washed with NaHCO3, dried,
®ltered and concentrated. FC (toluene/EtOAc 25:1) gave 3
(48 mg, 0.049 mmol, 63%) as a colorless syrup. Rf 0.62
(toluene/EtOAc 12:1); 1H and 13C NMR spectra were
identical to those previously reported.6
4.1.19. 6-O-(2-Azido-3-O-benzyl-4,6-O-benzylidene-2-
deoxy-b-d-glucopyranosyl)-3,4,5-tri-O-benzyl-1,2-O-(l-
1,7,7-trimethyl[2,2,1]bicyclohept-6-ylidene)-d-myo-
inositol (26). To a stirred mixture of 16 (2.30 g, 5.38 mmol),
Ê
6 (5.20 g, 6.30 mmol) and 4 A molecular sieves in CH2Cl2
(100 mL) under argon was added methyl tri¯uoromethane-
sulfonate (2.8 mL, 25 mmol). After 28 h, NEt3 (7 mL) was
added, and after an additional 15 min the mixture was
®ltered through Celite and concentrated. FC (petroleum
ether 65±75/EtOAc gradient 19:1±9:1) gave 26 (2.97 g,
3.13 mmol, 58%) as a colorless syrup. Rf 0.57 (toluene/
EtOAc 12:1); [a]Dˆ147 (c 0.9, CHCl3); IR nmax cm21
1
1035, 1094, 1453, 2107, 2872, 2941; NMR: H (600 MHz,
CDCl3), d 0.86 (3H, s, CH3), 0.87 (3H, s, CH3), 1.07 (3H, s,
CH3), 1.21 (1H, ddd, Jˆ12.0, 9.3, 4.6 Hz), 1.39 (1H, ddd,
Jˆ12.2, 12.2, 4.7 Hz), 1.46 (1H, d, Jˆ12.6 Hz), 1.68±1.74
(1H, m), 1.75 (1H, dd, Jˆ4.5, 4.5 Hz), 1.86 (1H, ddd, Jˆ
12.9, 9.3, 3.6 Hz), 1.91 (1H, ddd, Jˆ12.9, 4.7, 2.9 Hz), 3.35
(1H, dd, Jˆ10.3, 3.6 Hz, H-20), 3.42 (1H, dd, Jˆ10.0,
7.5 Hz, H-4), 3.66±3.71 (2H, m, H-60a, 40), 3.78 (1H, dd,
Jˆ8.3, 3.9 Hz, H-2), 3.81 (1H, dd, Jˆ8.1, 8.1 Hz, H-3), 3.99
(1H, dd, Jˆ10.2, 7.0 Hz, H-5), 4.00 (1H, dd, Jˆ7.0, 5.7 Hz,
H-6), 4.01 (1H, dd, Jˆ9.7, 9.7 Hz, H-30), 4.16±4.21 (2H, m,
H-50, 60b), 4.27 (1H, dd, Jˆ5.7, 3.9 Hz, H-1), 4.67 (1H, d,
Jˆ10.8 Hz, CH2Ph), 4.68 (1H, d, Jˆ11.1 Hz, CH2Ph), 4.69
(1H, d, Jˆ11.8 Hz, CH2Ph), 4.70 (1H, d, Jˆ10.8 Hz,
CH2Ph), 4.73 (1H, d, Jˆ11.8 Hz, CH2Ph), 4.76 (1H, d, Jˆ
11.1 Hz, CH2Ph), 4.78 (1H, d, Jˆ10.8 Hz, CH2Ph), 4.91
(1H, d, Jˆ11.1 Hz, CH2Ph), 5.56 (1H, s, CHPh), 5.58
(1H, d, Jˆ3.9 Hz, H-10), 7.03±7.46 (25H, m, Ph); 13C
(75 MHz, CDCl3), d 9.7 (CH3), 20.4 (CH3), 20.6 (CH3),
27.0 (CH2), 29.8 (CH2), 44.9 (CH2), 45.2 (CH), 47.9 (Cq),
51.6 (Cq), 62.6 (C-50), 63.0 (C-20), 68.8 (C-60), 72.6
(CH2Ph), 74.0 (C-1), 74.7 (CH2Ph), 74.8 (CH2Ph), 75.4
(CH2Ph), 75.4 (C-30), 75.9 (C-6), 76.9 (C-2), 77.9 (C-5),
80.6 (C-3), 80.6 (C-4), 83.0 (C-40), 95.9 (C-10), 101.3
(CHPh), 118.1 (OCO), 126.2 (Ph), 127.5±128.4 (Ph),
137.5 (Ph), 137.8 (Ph), 137.9 (Ph), 138.3 (Ph), 138.5 (Ph);
Anal. Calcd for C57H63N3O10: C, 72.0; H, 6.7 Found: C,
72.2; H 6.8.
4.1.18. 6-O-(4-Allyl-2-azido-3,6-di-O-benzyl-2-deoxy-a-
d-glucopyranosyl)-3,4,5-tri-O-benzyl-1,2-O-(l-1,7,7-tri-
methyl[2,2,1]bicyclohept-6-ylidene)-d-myo-inositol (25).
To a stirred mixture of 19 (100 mg, 0.22 mmol), 6
Ê
(190 mg, 0.23 mmol) and 4 A molecular sieves in diethyl
ether (5 mL) under argon was added methyl tri¯uoro-
methanesulfonate (0.120 mL, 1.1 mmol). After 18 h, NEt3
(0.4 mL) was added, and after an additional 15 min the
mixture was ®ltered through Celite and concentrated. FC
(petroleum ether 65±75/EtOAc gradient 19:1!9:1) gave
25 (116 mg, 0.12 mmol, 56%) as a colorless syrup. Rf
0.49 (toluene/EtOAc 12:1); [a]Dˆ153 (c 0.5, CHCl3); IR
nmax cm21 1038, 1212, 1453, 1728, 1789, 2106, 2933;
1
NMR: H (600 MHz, CDCl3), d 0.84 (3H, s, CH3), 0.87
(3H, s, CH3), 1.06 (3H, s, CH3), 1.21 (1H, ddd, Jˆ12.0,
9.2, 4.6 Hz), 1.37 (1H, ddd, Jˆ12.2, 12.2, 4.7 Hz), 1.46
(1H, d, Jˆ12.9 Hz), 1.67±1.73 (1H, m), 1.74 (1H, dd, Jˆ
4.6, 4.6 Hz), 1.88±1.92 (2H, m), 3.33 (1H, dd, Jˆ10.4,
3.6 Hz, H-20), 3.37 (1H, dd, Jˆ11.1, 2.0 Hz, H-60a), 3.41
(1H, dd, Jˆ11.1, 2.6 Hz, H-60b), 3.42 (1H, dd, Jˆ9.7,
7.4 Hz, H-4), 3.62 (1H, dd, Jˆ10.0, 9.0 Hz, H-40), 3.78
(1H, dd, Jˆ8.1, 3.9 Hz, H-2), 3.80 (1H, dd, Jˆ7.4,
7.4 Hz, H-3), 3.90 (1H, dd, Jˆ10.4, 9.0 Hz, H-30), 3.98
(1H, dd, Jˆ9.9, 7.0 Hz, H-5), 3.99 (1H, dddd, Jˆ12.6,
7.2, 1.6, 1.6 Hz, CHCH2O), 4.01 (1H, ddd, Jˆ9.7, 2.6,
2.0 Hz, H-50), 4.01 (1H, dd, Jˆ6.6 Hz, H-6), 4.22 (1H,
dddd, Jˆ12.6, 5.6, 1.5, 1.5 Hz, CHCH2O), 4.28 (1H, dd,
Jˆ6.1, 4.6 Hz, H-1), 4.37 (1H, d, Jˆ12.2 Hz, CH2Ph),
4.55 (1H, d, Jˆ12.2 Hz, CH2Ph), 4.64 (1H, d, Jˆ10.6 Hz,
CH2Ph), 4.68 (1H, d, Jˆ12.0 Hz, CH2Ph), 4.69 (1H, d, Jˆ
10.9 Hz, CH2Ph), 4.72 (1H, d, Jˆ10.9 Hz, CH2Ph), 4.73
(1H, d, Jˆ12.0 Hz, CH2Ph), 4.79 (1H, d, Jˆ10.9 Hz,
CH2Ph), 4.82 (1H, d, Jˆ10.8 Hz, CH2Ph), 4.85 (1H, d,
Jˆ10.8 Hz, CH2Ph), 5.07±5.20 (2H, m, CH2vCH), 5.55
(1H, d, Jˆ3.6 Hz, H-10), 5.75±5.88 (1H, m, CH2vCH),
7.22±7.44 (25H, m, Ph); 13C (75 MHz, CDCl3), d 9.8
(CH3), 20.4 (CH3), 20.6 (CH3), 27.0 (CH2), 29.9 (CH2),
44.8 (CH2), 45.1 (CH), 47.9 (Cq), 51.6 (Cq), 63.2 (C-20),
4.1.20. 6-O-(2-Azido-3,6-di-O-benzyl-2-deoxy-b-d-gluco-
pyranosyl)-3,4,5-tri-O-benzyl-1,2-O-(l-1,7,7-trimethyl-
[2,2,1]bicyclohept-6-ylidene)-d-myo-inositol (27). To a
mixture of 26 (1.92 g, 2.02 mmol) and NaBH3CN(1.35 g,
21.5 mmol) in THF (30 mL) at 08C was added ether
saturated with HCl until only traces of starting material
remained according to TLC. NEt3 (5 mL) was added, the
mixture ®ltered through Celite and concentrated. FC
(toluene/EtOAc 20:1) gave 27 (1.59 g, 1.67 mmol, 83%)
as a colorless syrup. Rf 0.37 (toluene/EtOAc 12:1); [a]Dˆ
133 (c 1.1, CHCl3); IR nmax cm21 1037, 1111, 1453, 1729,
1
2105, 2918; NMR: H (600 MHz, CDCl3), d 0.84 (3H, s,
CH3), 0.87 (3H, s, CH3), 1.06 (3H, s, CH3), (1H, ddd, Jˆ
12.2, 9.3, 4.7 Hz), 1.37 (1H, ddd, Jˆ12.2, 12.2, 4.7 Hz),

1398
J. Lindberg et al. / Tetrahedron 58 (2002) 1387±1398
8. Stevens, R. V.; Chapman, K. T.; Weller, H. N. J. Org. Chem.
1980, 45, 2030±2032.
1.46 (1H, d, Jˆ12.9 Hz), 1.67±1.73 (1H, m), 1.74 (1H, dd,
Jˆ4.5, 4.5 Hz), 1.85±1.92 (2H, m), 3.30 (1H, dd, Jˆ9.7,
3.6 Hz, H-20), 3.43 (1H, dd, Jˆ9.7, 7.5 Hz, H-4), 3.44 (1H,
dd, Jˆ10.7, 4.3 Hz, H-60a), 3.49 (1H, dd, Jˆ10.6, 3.8 Hz,
H-60b), 3.73 (1H, dd, Jˆ9.2, 9.2 Hz, H-40), 3.78 (1H, dd,
Jˆ9.9, 8.8 Hz, H-30), 3.79±3.82 (2H, m, H-2, 3), 3.98 (1H,
dd, Jˆ9.7, 7.2 Hz, H-5), 4.00 (1H, ddd, Jˆ9.2, 4.3, 3.8 Hz,
H-50), 4.02 (1H, dd, Jˆ7.2, 6.1 Hz, H-6), 4.28 (1H, dd,
Jˆ6.1, 3.8 Hz, H-1), 4.40 (1H, d, Jˆ12.2 Hz, CH2Ph),
4.47 (1H, d, Jˆ12.2 Hz, CH2Ph), 4.64 (1H, d, Jˆ10.8 Hz,
CH2Ph), 4.68 (1H, d, Jˆ12.2 Hz, CH2Ph), 4.69 (1H, d, Jˆ
10.8 Hz, CH2Ph), 4.73 (1H, d, Jˆ11.8 Hz, CH2Ph), 4.77
(1H, d, Jˆ10.8 Hz, CH2Ph), 4.80 (1H, d, Jˆ11.1 Hz,
CH2Ph), 4.83 (1H, d, Jˆ11.1 Hz, CH2Ph), 4.87 (1H, d, Jˆ
11.1 Hz, CH2Ph), 5.56 (1H, d, Jˆ3.6 Hz, H-10), 7.16±7.42
(25H, m, Ph); 13C (75 MHz, CDCl3), d 9.6 (CH3), 20.3
(CH3), 20.6 (CH3), 26.9 (CH2), 29.8 (CH2), 44.8 (CH2),
45.1 (CH), 47.9 (Cq), 51.5 (Cq), 62.7 (C-20), 69.4 (C-60),
69.5 (C-50), 72.4 (C-40), 72.5 (CH2Ph), 73.3 (CH2Ph), 73.8
(C-1), 74.7 (CH2Ph), 74.8 (CH2Ph), 75.1 (CH2Ph), 76.0
(C-6), 76.9 (C-2), 77.8 (C-5), 79.2 (C-30), 80.6 (C-3), 80.7
(C-4), 95.5 (C-10), 118.0 (OCO), 127.6±129.0 (Ph), 137.9±
138.4 (Ph); Anal. Calcd for C57H65N3O10: C, 71.9; H, 6.9
Found: C, 71.7; H 7.0.
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