Synthesis of a tetrasaccharide phosphate from the linkage region of the arabinogalactan-peptidoglycan complex in the mycobacterial cell wall

Article abstract of DOI:10.1016/j.carres.2008.05.009

The synthesis of dibenzyl 6-O-naphthylmethyl-2,3,5-tri-O-benzoyl-β-d-galactofuranosyl-(1→5)-2,3-di-O-benzoyl-6-O-benzyl-β-d-galactofuranosyl-(1→4)-3-O-benzyl-2-O-pivaloyl-α-l-rhamnopyranosyl-(1→3)-2-acetamido-2-deoxy-4,6-di-O-benzoyl-α-d-glucopyranosyl phosphate (1), a protected form of the tetrasaccharide phosphate of the linkage region of the arabinogalactan-peptidoglycan complex in the mycobacterial cell wall, has been accomplished. Key steps include the coupling of four monosaccharide building blocks with complete stereoselectivity by glycosylations employing thioglycosides, 2′-carboxybenzyl glycosides, and glycosyl fluorides as glycosyl donors. The α-glycosyl phosphate linkage was also stereoselectively elaborated by reaction of a tetrasaccharide hemiacetal with tetrabenzyl pyrophosphate in the presence of a base.

Full text of DOI:10.1016/j.carres.2008.05.009

Available online at www.sciencedirect.com
Carbohydrate Research 343 (2008) 1574–1584
Synthesis of a tetrasaccharide phosphate from the linkage
region of the arabinogalactan–peptidoglycan complex
in the mycobacterial cell wall
Yong Joo Lee, Dinanath Baburao Fulse and Kwan Soo Kim*
Center for Bioactive Molecular Hybrids and Department of Chemistry Yonsei University,
Seodaemun-gu Sinchon-dong 134, Seoul 120-749, Republic of Korea
Received 20 March 2008; received in revised form 5 May 2008; accepted 6 May 2008
Available online 13 May 2008
Abstract—The synthesis of dibenzyl 6-O-naphthylmethyl-2,3,5-tri-O-benzoyl-b-D-galactofuranosyl-(1?5)-2,3-di-O-benzoyl-6-O-
benzyl- b-D-galactofuranosyl-(1?4)-3-O-benzyl-2-O-pivaloyl-a-L-rhamnopyranosyl-(1?3)-2-acetamido-2-deoxy-4,6-di-O-benzoyl-a-
D-glucopyranosyl phosphate (1), a protected form of the tetrasaccharide phosphate of the linkage region of the arabinogalactan–
peptidoglycan complex in the mycobacterial cell wall, has been accomplished. Key steps include the coupling of four monosaccha-
ride building blocks with complete stereoselectivity by glycosylations employing thioglycosides, 20-carboxybenzyl glycosides, and
glycosyl fluorides as glycosyl donors. The a-glycosyl phosphate linkage was also stereoselectively elaborated by reaction of a
tetrasaccharide hemiacetal with tetrabenzyl pyrophosphate in the presence of a base.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords: Oligosaccharides; Glycosylation; Glycosyl phosphate; CB glycosides; Mycobacterial cell wall
1. Introduction
peptidoglycan via a linkage unit, ?4)-a-L-Rhap-(1?3)-
a-D-GlcNAc-1-P3b as shown in Figure 1.
Mycobacterial infections have attracted a great deal of
attention in recent years mainly due to the emergence
of multi-drug resistant strains1 of Mycobacterium tuber-
culosis, the causative agent of tuberculosis, one of the
most threatening of human infectious diseases. The
resistance of M. tuberculosis to many therapeutic agents
is partly attributable to its extremely robust and largely
impermeable cell wall envelope.2 One of the major struc-
tural components of the cell wall of M. tuberculosis is
composed of a covalently linked complex of mycolic
acid, D-arabinan, D-galactan, and peptidoglycan and is
often referred to as the mAGP complex, which plays a
crucial role for the survival and pathogenicity of M.
tuberculosis.3 Within the mAGP complex, the D-galac-
tan, composed of about 30 alternating b-(1?5)-, and
b-(1?6)-galactofuranose units,3a is attached to the
Ethambutol, an effective anti-TB drug, inhibits the
polymerization step of D-arabinan biosynthesis4 while
the D-galactan moiety was suggested to be essential for
the growth and viability of mycobacteria5 and the bio-
synthetic pathway for the linkage unit has been eluci-
dated.6 Very recently, it has also been reported that
the biosynthesis of the D-galactan is catalyzed by two
galactofuranosyltransferase enzymes.7
Because of their biological importance as substrates
for enzymes involved in the biosynthesis of mycobacte-
rial cell wall, as well as their potential as anti-TB agents,
several motifs of the mAGP complex have been synthe-
sized. For example, Lowary and co-workers succeeded
in the synthesis of a highly complex 22 unit arabinan
domain containing the b-D-arabinofuranosyl linkages
of D-arabinogalactan.8 Arabinosyl–galactosyl disaccha-
rides,9 trisaccharides,10 and tetrasaccharides11 have also
been synthesized. Galactosyl trisaccharides12 and link-
age di-13 and oligosaccharides7 have also been prepared.
*
Corresponding author. Tel.: +82 2 2123 2640; fax: +82 2 365 7608;
e-mail: kwan@yonsei.ac.kr
0008-6215/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2008.05.009

Y. J. Lee et al. / Carbohydrate Research 343 (2008) 1574–1584
1575
HO
HO
Peptidoglycan
O
O
O
O
BzO
BzO
AcHN
O
O
P
O
O
O
O
HO
OH
OH
O
AcHN
HO
O P OBn
OBn
OH
O
O
BzO
O
O
HO
OH
BnO
O
OPiv
O
BzO
OBz
HO
OH
O
OBn
OBz
O
BzO
1
ONAP
Arabinogalactan
Figure 1. Structure of the linkage region of the arabinogalactan–peptidoglycan complex of the mycobacterial cell wall and target tetrasaccharide
phosphate 1.
Herein we report for the first time the synthesis of
compound 1 (Fig. 1) a protected form of the tetrasac-
charide phosphate, b-D-Galf-(1?5)-b-D-Galf-(1?4)-a-
L-Rhap-(1?3)-a-D-GlcNAc-1-P, of the linkage region
of mAGP complex in the mycobacterial cell wall. The
naphthylmethyl (NAP) protective group of the target
molecule 1 was chosen after consideration of the future
connection of the linkage region with the arabinogalac-
tan moiety.
sequence: (i) protection of 6 with a levulinyl group, (ii)
debenzylidenation of resulting 7 with camphorsulfonic
acid, (iii) benzoylation of resulting diol to give dibenzo-
ate 8, and (iv) conversion of levulinyl ester 8 with hydra-
zine acetate into desired glucosamine derivative 9.
Glycosylation of 9 with 5 was carried out by activa-
tion of the donor 5 with 1-benzenesulfinyl piperidine
(BSP)18 and Tf2O in the presence of tri-t-butylpyrimi-
dine (TTBP) at ꢀ40 °C followed by addition of the
acceptor 9 at ꢀ40 °C to afford exclusively the a-L-
rhamnosyl disaccharide 10 in 85% yield as shown in
Scheme 2. It is worth commenting that the efficiency
of the glycosylation was quite sensitive to the protecting
groups on the glycosyl donor 5. Thus, the glycosylation
of 9 with a donor having an acetyl or levulinyl group
instead of the NAP group at O-4 of the compound 5 pro-
vided the desired disaccharide 10 in a much lower yield.
The glycosyl donor having a benzoyl group in place of
the pivaloyl group at O-2 of 5 was not satisfactory in
the glycosylation of 9. Deprotection of the NAP group
of disaccharide 10 with DDQ gave disaccharide acceptor
11 in 84% yield. The stereochemistry of the newly gener-
ated anomeric center of the disaccharide was unequivo-
cally determined to be of the a-configuration on the
2. Results and discussion
The synthesis of the rhamnose building block started
with a selective benzylation of known thio-L-rhamnoside
214 by using the dibutyltin oxide method15 to afford
exclusively monobenzyl ether 3 in 76% yield as shown
in Scheme 1. Selective protection of the diol 3 employing
bis(tributyltin) oxide16 and pivaloyl chloride followed by
naphthylmethylation of resulting 2-O-pivaloyl sugar 4
provided the fully protected rhamnosyl donor 5.
Because the glycosylation of the known glucosamine
derivative 617 with donor 5 gave the desired disaccharide
in poor yield, compound 6 was converted into a pro-
perly protected glycosyl acceptor by the following
SPh
SPh
SPh
SPh
a
b
c
O
O
O
O
HO
HO
HO
NAPO
BnO
HO
BnO
BnO
OH
OH
OPiv
OPiv
2
4
3
5
BzO
BzO
LevO
BzO
BzO
HO
O
O
Ph
Ph
O
O
O
e
O
f
d
O
O
LevO
HO
AcHN
AcHN
AcHN
AcHN
OAll
OAll
OAll
OAll
7
9
8
6
Scheme 1. Reagents and conditions: (a) (i) n-Bu2SnO, benzene, reflux, 10 h; (ii) BnBr, n-Bu4NI, DMF, 50 °C, 3 h, 76% in two steps; (b) (i) (n-
Bu3Sn)2O, benzene, reflux, 10 h; (ii) PivCl, benzene, 60 °C, 3 h, 79% in two steps; (c) NAPBr, NaH, n-Bu4NI, DMF, 0 °C to rt, 2 h, 86%; (d) levulinic
acid, EDC, DMAP, CH2Cl2, DMF, rt, 3 h, 83%; (e) (i) CSA, CH2Cl2, MeOH, rt, 2 h; (ii) BzCl, DMAP, pyridine, rt, 5 h, 62% in two steps; (f)
NH2NH2, AcOH, THF, MeOH, rt, 30 min, 95%.

1576
Y. J. Lee et al. / Carbohydrate Research 343 (2008) 1574–1584
BzO
BzO
BzO
BzO
O
O
O
O
a
b
AcHN
AcHN
OAll
OAll
5
+
9
O
O
NAPO
HO
BnO
BnO
OPiv
10
OPiv
11
˚
Scheme 2. Reagents and conditions: (a) BSP, Tf2O, TTBP, 4 A MS, CH2Cl2, ꢀ40 °C?0 °C, 2 h, 85%; (b) DDQ, CH2Cl2, MeOH, rt, 2 h, 84%.
OBCB
BzO
OBCB
OBCB
OCB
BzO
BzO
OH
BzO
O
b
O
a
O
O
c
HO
BzO
HO
BzO
OBz
OBz
OBz
OBz
ONAP
ONAP
14
ONAP
15
12
13
d
OBCB
BzO
CH2 O
CH2 O
BCB =
O
CB =
OBn
OH
HO
OBz
OBn
16
OCB
OBz
OBCB
F
BzO
O
BzO
BzO
O
O
O
15
g
e
f
+
O
O
BzO
BzO
BzO
OBz
OBz
O
O
O
16
OBn
OBz
OBn
OBz
OBn
OBz
BzO
BzO
BzO
ONAP
ONAP
ONAP
17
18
19
Scheme 3. Reagent and conditions: (a) (i) n-Bu2SnO, benzene, reflux, 10 h; (ii) NAPBr, NaH, n-Bu4NI, DMF, 60 °C, 3 h, 82% in two steps; (b) BzCl,
Et3N, DMAP, CH2Cl2, 0 °C to rt, 30 min, 96%; (c) H2, Pd–C, NH4OAc, MeOH, EtOAc, rt, 1 h, 89%; (d) (i) n-Bu2SnO, benzene, reflux, 10 h; (ii)
˚
BnCl, NaH, n-Bu4NI, DMF, 60 °C, 3 h, 86% in two steps; (e) DTBMP, Tf2O, CH2Cl2, 4 A MS, ꢀ78 °C to 0 °C, 2 h, 88%; (f) H2, Pd(OH)2, NH4OAc,
˚
MeOH, EtOAc, rt, 5 h, 89%; (g) 4A MS, DTBMP, Tf2O, CH2Cl2, Deoxofluor, HF–pyridine, 2 h, 84%.
basis of the one-bond C10-H10 coupling constant of com-
charide donor 18 did not provide a desired tetrasaccha-
ride because of the generation of an undesired self-
condensed ester of the CB glycoside 18.22 This result
led us to examine another glycosyl donor in place of
18, such as a glycosyl fluoride. We have previously
shown that CB glycosides could be readily converted
into glycosyl fluorides by treatment with Tf2O followed
by HF–pyridine20 or by (diethylamino)sulfur trifluoride
(DAST).23 However, neither HF–pyridine nor DAST
with Tf2O, was quite satisfactory for the conversion of
the CB disaccharide 18 into fluoride 19, but a combina-
tion of Tf2O, bis(2-methoxyethyl)aminosulfur trifluoride
(Deoxofluor),24 and HF–pyridine cleanly converted 18
into 19. Thus, sequential addition of Tf2O, Deoxofluor,
and HF–pyridine to a solution of 18 in CH2Cl2 in the
presence of DTBMP at ꢀ78 °C provided desired disac-
charide fluoride 19 in 84% yield. The anomeric carbon
chemical shifts at dC 105.3 of 17, dC 105.5 or 105.6 of
18, and dC 105.3 of 19 clearly indicated that the newly
generated galactosyl linkage of the disaccharides is in
the b-configuration.20,25
pound 11, JC1 ꢀH1 ¼ 170 Hz at dC 100.4.19
0
0
The synthesis of a galactose disaccharide started with
selective naphthylmethylation of the known 20-(benzyl-
oxycarbonyl)benzyl (BCB) galactoside 1220 using n-
Bu2SnO and subsequent benzoylation of the resulting
NAP ether 13 to give the fully protected galactoside 14
as shown in Scheme 3. The BCB galactoside 14 was con-
verted into 20-carboxybenzyl (CB) galactoside 15 by
selective hydrogenolysis of the benzyl ester functionality
of the BCB moiety of 14 in the presence of ammonium
acetate.21 On the other hand, selective benzylation of
12 afforded compound 16 as a glycosyl acceptor. Glyco-
sylation of 16 with 15 was performed by sequential addi-
tion of Tf2O and the donor 15 to a solution of the
acceptor 16 and DTBMP in CH2Cl2 at ꢀ78 °C to give
exclusively the b-D-galactosyl disaccharide 17 in 88%
yield.
The BCB disaccharide 17 was transformed to CB
disaccharide 18 by selective hydrogenolysis. However,
coupling of the disaccharide acceptor 11 and the disac-

Y. J. Lee et al. / Carbohydrate Research 343 (2008) 1574–1584
1577
BzO
BzO
BzO
BzO
O
O
O
P
O
O
AcHN
AcHN
OBn
O
OR
O
O
11
+
O
BzO
O
BzO
OBn
a
c
O
O
BnO
BnO
OPiv
OPiv
O
19
O
BzO
BzO
OBz
OBz
O
O
OBn
OBz
OBn
OBz
ONAP
BzO
BzO
20 R = allyl
21 R = H
ONAP
b
Scheme 4. Reagents and conditions: (a) SnCl2, AgClO4, Et2O/CH2Cl2, 0 °C to rt, 30 min, 90%; (b) PdCl2, NaOAc, 95% aq AcOH, rt, 12 h, 71%; (c)
LDA, [(BnO)2P(O)]2O, THF, ꢀ78 °C to 0 °C, 2 h, 92%.
A proposed mechanism of the conversion of 18 into 19
could be as follows: Addition of Tf2O to 18 would give a
highly reactive mixed anhydride intermediate, a glycosyl
acyl triflate. Then, upon addition of Deoxofluor, the tri-
flate would be displaced by the fluoride anion from Deo-
xofluor to provide a glycosyl acyl fluoride intermediate.
Finally, HF–pyridine would facilitate the lactonization
of the acyl fluoride to generate a glycosyl oxocarbenium
ion, which would readily react with a fluoride ion to
afford the glycosyl fluoride 19. In fact, we were able to
isolate the glycosyl acyl fluoride intermediate.
The stage was set now for the construction of the tet-
rasaccharide by coupling of the pyranose disaccharide
acceptor 11 and the furanose disaccharide donor 19.
Glycosylation of 11 with 19 employing SnCl2 and Ag-
ClO4 as promoters in Et2O and CH2Cl2 at 0 °C gave
exclusively b-tetrasaccharide 20 in 90% yield (see
Scheme 4). The anomeric allyl group of 20 was removed
by PdCl2 and sodium acetate in aqueous acetic acid to
afford tetrasaccharide hemiacetal 21 in 71% yield. Phos-
phorylation of 21 with tetrabenzyl pyrophosphate in the
presence of LDA26 provided exclusively the a-glycosyl
dibenzyl phosphate 1 in 92% yield. The stereochemistry
at the newly generated anomeric center of the tetrasac-
charide was determined to be the b-configuration on
the basis of their anomeric carbon chemical shifts at
dC 105.2 for all three tetrasaccharides, 20, 21, and 1.
The stereochemistry at all other anomeric centers in
the tetrasaccharide was confirmed by 13C NMR spectral
of more complex oligosaccharide phosphates and
biological evaluation of their deprotected forms are
currently underway.
3. Experimental
3.1. General methods
All reactions were conducted under a positive pressure of
dry argon with dry, freshly distilled solvents unless other-
wise noted. All reagents were purchased from commer-
cial suppliers and used without further purification
unless otherwise noted. Optical rotations were deter-
mined at 20 °C with an automatic polarimeter. 1H
NMR and 13C NMR spectra were recorded on a
1
400 MHz spectrometer (400 MHz for H, 100 MHz for
13C). Chemical shifts are given in ppm downfield from
internal tetramethylsilane for spectra recorded in CDCl3.
Flash column chromatography was performed employ-
ing 230–400 mesh silica gel. Thin-layer chromatography
was performed using Silica Gel 60 F254 precoated plates
(0.25 mm thickness) with a fluorescent indicator. Visual-
ization on TLC was achieved by UV light (254 nm) and a
typical TLC indication solution (cerium sulfate–molyb-
dic acid solution). Solutions were concentrated at below
40 °C under reduced pressure.
3.2. Phenyl 3-O-benzyl-1-thio-a-L-rhamnopyranose (3)
data. One-bond C1–H1 coupling constants of 1, JC1–H1
=
A solution of phenyl 1-thio-a-L-rhamnopyranose14
(9.65 g, 37.7 mmol) and n-Bu2SnO (11.25 g, 45.2 mmol)
in benzene (100 mL) was stirred under reflux using a
Dean–Stark trap for 10 h. After removal of the solvent
in vacuo, the residue was dissolved in DMF (50 mL)
and then benzyl chloride (5.2 mL, 45.2 mmol) and n-
Bu4NI (16.7 g, 45.2 mmol) were added to the DMF
solution. After being stirred at 50 °C for 3 h, the reac-
tion mixture was diluted with EtOAc (100 mL). The or-
ganic layer was washed with satd aq NH4Cl (2 ꢁ 50 mL)
and brine (50 mL), dried (MgSO4), and concentrated in
vacuo. The residue was purified by silica gel flash
0
0
179 Hz and JC1 ꢀH1 ¼ 172 Hz, indicated that the ano-
meric linkages of both pyranose rings of 1 were in a-con-
figuration26 while the presence of another anomeric
carbon chemical shift at dC 106.6 of 1 indicated that
the galactofuranosyl linkage formed in the coupling of
11 and 19 was also in the b-configuration.20,25
In summary, the synthesis of compound 1, a protected
form of the tetrasaccharide phosphate, b-D-Galf-(1?5)-
b-D-Galf-(1?4)-a-L-Rhap-(1?3)-a-D-GlcNAc-1-P, of
the linkage region of the mAGP complex in the myco-
bacterial cell wall has been accomplished. The synthesis

1578
Y. J. Lee et al. / Carbohydrate Research 343 (2008) 1574–1584
column chromatography (hexane–EtOAc 2:1, v/v) to
afford compound 3 (9.91 g, 28.6 mmol, 76%) as a color-
less oil, Rf 0.20 (hexane–EtOAc 2:1, v/v); IR (CHCl3
concentrated in vacuo. The residue was purified by silica
gel flash column chromatography (hexane–EtOAc 9:1,
v/v) to afford compound 5 (2.48 g, 4.34 mmol, 86%) as
a colorless oil, Rf 0.38 (hexane–EtOAc 9:1, v/v); IR
20
film) 3424, 1103, 1070 cmꢀ1; ½aꢂD ꢀ184.3 (c 0.3, CHCl3);
20
1H NMR (400 MHz, CDCl3) dH 1.31 (d, J = 6 Hz, 3H,
CH3), 2.28 (d, J = 1.6 Hz, 1H, OH), 2.60 (d, J = 2.4 Hz,
1H, OH), 3.60–3.67 (m, 2H, H-3,4), 4.11–4.18 (m, 1H,
H-5), 4.25 (d, J = 1.2 Hz, 1H, H-2), 4.61 and 4.73
(ABq, J = 11.2 Hz, 2H, PhCH2), 5.53 (d, J = 1.2 Hz,
1H, H-1), 7.25–7.46 (m, 10H, Ph-H); 13C NMR
(100 MHz, CDCl3) dC 17.7, 69.2, 69.6, 71.98, 71.99,
80.0, 87.4 (C-1), 127.5, 128.2, 128.5, 129.0, 129.2,
131.5, 134.2, 137.5. Anal. Calcd for C19H22O4S: C,
65.87; H, 6.40; S, 9.26. Found: C, 65.80; H, 6.39; S, 9.17.
(CHCl3 film) 1728, 1160, 1103 cmꢀ1; ½aꢂD ꢀ98.3 (c 0.3,
1
CHCl3); H NMR (400 MHz, CDCl3) dH 1.21 (s, 9H,
3 ꢁ CH3C), 1.34 (d, J = 6 Hz, 3H, CH3), 3.54 (t, J =
9.2 Hz, 1H, H-4), 3.97 (dd, J = 3.2, 9.2 Hz, 1H, H-3),
4.28–4.32 (m, 1H, H-5), 4.49 and 4.69 (ABq, J =
11.2 Hz, 2H, PhCH2), 4.79 and 5.04 (ABq, J =
11.2 Hz, 2H, PhCH2), 5.42 (d, J = 1.6 Hz, 1H, H-1),
5.67 (dd, J = 1.6, 2.8 Hz, 1H, H-2), 7.04–7.76 (m, 17H,
Ph-H); 13C NMR (100 MHz, CDCl3) dC 18.1, 27.1,
38.9, 68.9, 70.0, 71.5, 75.3, 78.7, 79.8, 86.2 (C-1),
125.9, 126.0, 126.2, 126.9, 127.6, 127.7, 127.9, 128.0,
128.3, 129.0, 131.9, 133.0, 133.2, 133.9, 135.7, 137.9,
177.3 (CO). Anal. Calcd for C35H38O5S: C, 73.65; H,
6.71; S, 5.62. Found: C, 73.61; H, 6.58; S, 5.53.
3.3. Phenyl 3-O-benzyl-2-O-pivaloyl-1-thio-a-L-rhamno-
pyranose (4)
A solution of diol 3 (5.0 g, 14.43 mmol) and (n-Bu3Sn)2O
(3.67 mL, 7.22 mmol) in benzene (50 mL) was stirred
under reflux using a Dean–Stark trap for 10 h and cooled
to room temperature. After addition of PivCl (1.95 mL,
15.83 mmol) to the above solution, the reaction mixture
was stirred at 60 °C for 3 h, cooled to room temperature,
and diluted with EtOAc (100 mL). The combined organ-
ic layer was washed with brine (50 mL), dried (MgSO4),
and concentrated in vacuo. The residue was purified by
silica gel flash column chromatography (hexane–EtOAc
7:1, v/v) to afford compound 4 (4.92 g, 11.43 mmol,
79%) as a colorless amorphous solid, Rf 0.60 (hexane–
EtOAc 2:1, v/v); IR (CHCl3 film) 3473, 1728, 1483,
3.5. Allyl 2-acetamido-2-deoxy-3-O-levulinyl-4,6-O-benz-
ylidene-a-D-glucopyranoside (7)
A solution of allyl 2-acetamido-2-deoxy-4,6-O-benzyli-
dene-a-D-glucopyranoside (6)13 (4.15 g, 11.88 mmol),
levulinic acid (2.07 g, 17.83 mmol), 1-ethyl-3-(3-dimeth-
ylaminopropyl)carbodiimide hydrochloride (3.42 g,
17.84 mmol),
4-(dimethylamino)pyridine
(436 mg,
3.57 mmol) in CH2Cl2 (20 mL) and DMF (20 mL) was
stirred at room temperature for 3 h. The reaction mixture
was diluted with CHCl3 (100 mL) and washed with satd
aq NH4Cl (2 ꢁ 50 mL) and brine (50 mL). The organic
layer was dried over MgSO4 and concentrated in vacuo.
The residue was purified by silica gel flash column chro-
matography (CH2Cl2–MeOH 9:1, v/v) to afford com-
pound 7 (4.40 g, 9.83 mmol, 83%) as a colorless oil, Rf
0.53 (CH2Cl2–MeOH 9:1, v/v); IR (CHCl3 film) 3273,
20
1160, 1111, 1074 cmꢀ1; ½aꢂD ꢀ43.2 (c 1.5, CHCl3); H
NMR (400 MHz, CDCl3) dH 1.21 (s, 9H, 3 ꢁ CH3C),
1.34 (d, J = 6 Hz, 3H, CH3), 2.39 (d, J = 6.8 Hz, 1H,
OH), 3.61 (t, J = 9.2 Hz, 1H, H-4), 3.71 (dd, J = 2.8,
9.2 Hz, 1H, H-3), 4.18–4.22 (m, 1H, H-5), 4.43 and
4.71 (ABq, J = 10.8 Hz, 2H, PhCH2), 5.40 (br s, 1H,
H-1), 5.59 (t, J = 1.4 Hz, 1H, H-2), 7.25–7.49 (m, 10H,
Ar); 13C NMR (100 MHz, CDCl3) dC 17.9, 27.3, 39.1,
69.3, 69.4, 71.4, 72.3, 78.2, 86.6 (C-1), 127.9, 128.2,
128.4, 128.7, 129.3, 132.1, 134.0, 137.5, 177.7 (CO). Anal.
Calcd for C24H30O5S: C, 66.95; H, 7.02; S, 7.45. Found:
C, 67.05; H, 7.01; S, 7.33.
1
20
1740, 1716, 1659, 1548, 1377, 1095 cmꢀ1; ½aꢂD +50.5 (c
1
0.6, CHCl3); H NMR (400 MHz, CDCl3) dH 1.98 (s,
3H, COCH3), 2.09 (s, 3H, COCH3), 2.50–2.68 (m, 4H),
3.68–3.77 (m, 2H), 3.87–3.99 (m, 2H), 4.16 (dd,
J = 5.2, 12.8 Hz, 1H), 4.25 (dd, J = 4.4, 10.0 Hz, 1H),
4.34–4.40 (m, 1H), 4.87 (d, J = 3.2 Hz, 1H, H-1), 5.18–
5.36 (m, 3H), 5.49 (s, 1H), 5.80–5.90 (m, 1H, allyl CH),
6.13 (d, J = 9.2 Hz, 1H), 7.31–7.44 (m, 5H, Ar); 13C
NMR (100 MHz, CDCl3) dC 22.8, 27.8, 29.4, 37.6,
52.0, 62.8, 68.4, 68.5, 70.1, 78.9, 97.0 (C-1), 101.1
(PhCH), 117.9, 126.0, 127.9, 128.8, 133.2, 136.9, 170.2
(CO), 172.6 (CO), 205.89 (CO). Anal. Calcd for
C23H29NO8: C, 61.73; H, 6.53; N, 3.13. Found: C,
61.93; H, 6.50; N, 3.09.
3.4. Phenyl 3-O-benzyl-4-O-naphthylmethyl-2-O-piva-
loyl-1-thio-a-L-rhamnopyranose (5)
To a solution of compound 4 (2.18 g, 5.06 mmol) in
DMF (20 mL) were added NaH (60%, 243 mg,
6.08 mmol) and 2-bromomethyl naphthalene (1.34 g,
6.06 mmol) at 0 °C and then the ice bath was removed.
After being stirred at room temperature for 2 h, the
reaction mixture was quenched by the addition of water
(10 mL) and extracted with EtOAc (2 ꢁ 50 mL). The
combined organic layer was washed with satd aq NH4Cl
(3 ꢁ 50 mL) and brine (50 mL), dried (MgSO4), and
3.6. Allyl 2-acetamido-2-deoxy-4,6-di-O-benzoyl-3-O-
levulinyl-a-D-glucopyranoside (8)
A solution of compound 7 (4.40 g, 9.83 mmol) and
camphorsulfonic acid (457 mg, 1.97 mmol) in CH2Cl2

Y. J. Lee et al. / Carbohydrate Research 343 (2008) 1574–1584
1579
(20 mL) and MeOH (20 mL) was stirred at room tem-
perature for 2 h. The reaction mixture was concentrated
in vacuo, diluted with CH2Cl2, and washed with satd aq
NaHCO3 (2 ꢁ 50 mL) and brine (50 mL). The organic
phase was dried over MgSO4 and concentrated in vacuo.
The residue was dissolved in pyridine (20 mL). After
addition of BzCl (2.78 mL, 23.93 mmol) and DMAP
(293 mg, 2.61 mmol) to the above solution, the reaction
mixture was stirred at room temperature for 5 h, diluted
with CHCl3 (100 mL), and washed with 1 N HCl
(2 ꢁ 50 mL) and brine (50 mL). The organic layer was
dried over MgSO4 and concentrated in vacuo. The resi-
due was purified by silica gel flash column chromato-
graphy (CH2Cl2–MeOH 20:1, v/v) to afford compound
8 (3.45 g, 6.08 mmol, 62% in two steps) as a colorless
amorphous solid, Rf 0.53 (CH2Cl2–MeOH 20:1, v/v);
NMR (100 MHz, CDCl3) dC 23.1, 54.1, 63.4, 68.1,
68.7, 71.5, 72.6, 96.5 (C-1), 118.3, 128.4, 128.42, 129.5,
129.7, 129.73, 130.0, 133.1, 133.3, 133.4, 166.0 (CO),
166.3 (CO), 171.7 (CO). Anal. Calcd for C25H27NO8:
C, 63.96; H, 5.80; N, 2.98. Found: C, 63.70; H, 5.72;
N, 3.23.
3.8. Allyl 3-O-benzyl-4-O-naphthylmethyl-2-O-pivaloyl-
a-L-rhamnopyranosyl-(1?3)-2-acetamido-2-deoxy-4,6-
di-O-benzoyl-a-D-glucopyranoside (10)
To a solution of thioglycoside 9 (133 mg, 0.23 mmol), 1-
benzenesulfinyl piperidine (73 mg, 0.34 mmol), and tri-t-
butylpyrimidine (174 mg, 0.70 mmol) in the presence of
˚
activated 4 A powdered molecular sieves in CH2Cl2
(10 mL) at ꢀ40 °C under an argon atmosphere was
added Tf2O (59 lL, 0.35 mmol). After 5 min, a solution
of the glycosyl acceptor 5 (164 mg, 0.35 mmol) in
CH2Cl2 (2 mL) was added to the above solution at
ꢀ40 °C. The reaction mixture was stirred for 1 h at
ꢀ40 °C, then warmed to 0 °C, diluted with CH2Cl2
(50 mL), and filtered. The filtrate was washed with satd
aq NaHCO3 (50 mL) and brine (50 mL), dried over
MgSO4, and concentrated in vacuo. The residue was
purified by silica gel flash column chromatography (hex-
ane–EtOAc 2:1, v/v) to afford disaccharide 10 (185 mg,
0.12 mmol, 85%) as a white foam, Rf 0.25 (hexane–
EtOAc 2:1, v/v); IR (CHCl3 film) 3264, 1727, 1274,
20
IR (CHCl3 film) 3371, 1728, 1279, 1034 cmꢀ1; ½aꢂD
1
+73.4 (c 1.2, CHCl3); H NMR (400 MHz, CDCl3) dH
2.02 (s, 3H, COCH3), 2.04 (s, 3H, COCH3), 2.31–2.62
(m, 4H), 4.05 (dd, J = 6.0, 12.4 Hz, 1H), 4.22–4.27 (m,
2H), 4.38 (dd, J = 5.2, 12.0 Hz, 1H), 4.44–4.50 (m,
1H), 4.53 (dd, J = 2.4, 12.0 Hz, 1H), 4.97 (d,
J = 3.6 Hz, 1H, H-1), 5.23 (d, J = 10.4 Hz, 1H), 5.30
(dd, J = 1.4, 17.2 Hz, 1H), 5.46–5.53 (m, 2H), 5.83 (d,
J = 9.6 Hz, 1H), 5.87–5.97 (m, 1H, allyl CH), 7.40–
7.58 (m, 6H, Ar), 7.98 (d, J = 7.6 Hz, 2H, Ar), 8.02 (d,
J = 7.6 Hz, 2H, Ar); 13C NMR (100 MHz, CDCl3) dC
23.3, 28.2, 29.6, 37.8, 51.9, 63.0, 68.2, 68.9, 69.4, 71.2,
96.6 (C-1), 118.6, 128.5, 128.6, 129.0, 129.7, 129.8,
130.0, 133.19, 133.21, 133.6, 165.2 (CO), 166.2 (CO),
170.5 (CO), 172.9 (CO), 206.0 (CO). HRMS calcd for
[M+Na]+: 590.2002. Found: 590.2006.
20
1122 cmꢀ1; ½aꢂD +22.6 (c 0.5, CHCl3); 1H NMR
(400 MHz, CDCl3) dH 0.62 (d, J = 6.0 Hz, 3H, L-Rha
CH3), 1.15 (s, 9H, Piv (CH3)3C), 2.12 (s, 3H, acetyl
CH3), 3.26 (t, J = 9.6 Hz, 1H), 3.55–3.60 (m, 1H), 3.94
(dd, J = 3.2, 9.6 Hz, 1H), 4.00–4.08 (m, 2H), 4.19–4.23
(m, 2H), 4.34 (dd, J = 4.8, 12.0 Hz, 1H), 5.00–4.63 (m,
5H), 4.87–4.89 (m, 3H), 5.13 (br s, 1H), 5.22–5.31 (m,
2H), 5.49 (t, J = 9.6 Hz, 1H), 5.86–5.96 (m, 2H), 7.22–
8.04 (m, 22H, Ar); 13C NMR (100 MHz, CDCl3) dC
17.7, 23.6, 27.1, 39.0, 52.9, 63.1, 68.4, 68.6, 68.8, 69.4,
70.2, 71.3, 74.5, 77.6, 79.4, 79.9, 96.9 (C-1), 100.1 (C-
10), 118.7, 125.7, 125.9, 126.1, 126.5, 127.4, 127.7,
127.8, 127.86, 127.9, 128.2, 128.4, 128.44, 129.5, 129.7,
129.8, 130.1, 132.9, 133.2, 133.22, 133.3, 136.1, 138.5,
165.1 (CO), 166.3 (CO), 170.5 (CO), 178.0 (CO). Anal.
Calcd for C54H59NO13: C, 69.74; H, 6.39; N, 1.51.
Found: C, 69.72; H, 6.14; N, 1.49.
3.7. Allyl 2-acetamido-2-deoxy-4,6-di-O-benzoyl-a-D-
glucopyranoside (9)
To
a stirred solution of compound 8 (238 mg,
0.42 mmol) in THF–MeOH (10:1 v/v, 10 mL) was
added 80% hydrazine–acetic acid (1:2 v/v, 3 mL) in
THF–MeOH (5:1 v/v, 2 mL) at room temperature.
After being stirred at room temperature for 30 min,
the reaction mixture was concentrated in vacuo. The
resulting oil was dissolved in CHCl3 (50 mL), washed
with sat. NaHCO3 (2 ꢁ 50 mL) and brine (50 mL).
The organic phase was dried (MgSO4) and concentrated
in vacuo. The residue was purified by silica gel flash
column chromatography (CH2Cl2–MeOH 20:1, v/v) to
afford compound 9 (188 mg, 0.40 mmol, 95%) as a col-
orless amorphous solid, Rf 0.25 (CH2Cl2–MeOH 20:1,
v/v); IR (CHCl3 film) 3375, 3305, 1728, 1654, 1552,
3.9. Allyl 3-O-benzyl-2-O-pivaloyl-a-L-rhamnopyranosyl-
(1?3)-2-acetamido-2-deoxy-4,6-di-O-benzoyl-a-D-gluco-
pyranoside (11)
20
1
1274, 1123, 1029 cmꢀ1; ½aꢂD +79.6 (c 0.8, CHCl3); H
NMR (400 MHz, CDCl3) dH 2.04 (s, 3H, COCH3),
3.33 (br s, 1H), 3.97–4.07 (m, 2H), 4.20–4.33 (m, 3H),
4.39 (dd, J = 5.6, 12.0 Hz, 1H), 4.56 (dd, J = 2.8,
12.0 Hz, 1H), 4.95 (d, J = 4.0 Hz, 1H), 5.22–5.35 (m,
3H), 5.88–5.96 (m, 2H), 7.39–8.06 (m, 10H, Ar); 13C
To a solution of compound 10 (220 mg, 0.24 mmol) was
added dichlorodicyanobenzoquinone (161 mg, 0.71
mmol) in CH2Cl2 (4.5 mL) and MeOH (0.25 mL) in
two portions over 20 min at 0 °C. After being stirred
at room temperature for 2 h, the reaction mixture was

1580
Y. J. Lee et al. / Carbohydrate Research 343 (2008) 1574–1584
diluted with CH2Cl2 (50 mL), washed with satd aq
NaHCO3 (2 ꢁ 50 mL) and brine (50 mL), dried
(MgSO4), and concentrated in vacuo. The residue was
purified by silica gel flash column chromatography (hex-
ane–EtOAc 1:1, v/v) to afford compound 11 (156 mg,
0.20 mmol, 84%) as a white foam, Rf 0.43 (hexane–
EtOAc, 1:1, v/v); IR (CHCl3 film) 3273, 1728, 1663,
for C46H40O10: C, 73.39; H, 5.36. Found: C, 73.39; H,
5.31.
3.11. 20-(Benzyloxycarbonyl)benzyl 6-O-naphthylmethyl-
2,3,5-tri-O-benzoyl-b-D-galactofuranoside (14)
A solution of compound 13 (1.57 g, 2.09 mmol), benzoyl
chloride (291 lL, 2.51 mmol), and 4-(dimethyl-
amino)pyridine (77 mg, 0.63 mmol) in Et3N (2 mL)
and CH2Cl2 (10 mL) was stirred at room temperature
for 30 min. The reaction mixture was quenched by the
addition of satd aq NH4Cl (2 mL) and extracted with
CH2Cl2 (2 ꢁ 50 mL). The combined organic layer was
washed with brine (30 mL), dried (MgSO4), and concen-
trated in vacuo. The residue was purified by silica gel
flash column chromatography (hexane–EtOAc 2:1, v/v)
to afford compound 14 (1.71 g, 1.99 mmol, 96%) as a
colorless oil, Rf 0.5 (hexane–EtOAc, 2:1, v/v); IR
20
1279, 1140, 1050 cmꢀ1; ½aꢂD +55 (c 0.5, CHCl3); 1H
NMR (400 MHz, CDCl3) dH 0.62 (d, J = 6.0 Hz, 3H,
L-Rha CH3), 1.15 (s, 9H, Piv (CH3)3C), 2.10 (s, 3H, acet-
yl CH3), 2.16 (br s, 1H), 3.37 (t, J = 9.6 Hz, 1H), 3.46–
3.50 (m, 1H), 3.69 (dd, J = 3.2, 9.6 Hz, 1H), 4.01–4.07
(m, 2H), 4.18–4.24 (m, 2H), 4.34 (dd, J = 4.8, 12.0 Hz,
1H), 4.39 (d, J = 11.2 Hz, 1H), 4.50–4.60 (m, 3H),
4.88–4.89 (m, 2H), 5.09 (d, J = 2.4 Hz, 1H), 5.24–5.32
(m, 2H), 5.49 (t, J = 9.6 Hz, 1H), 5.86–5.93 (m, 2H),
7.22–8.04 (m, 15H, Ar); 13C NMR (100 MHz, CDCl3)
dC 17.4, 23.6, 27.1, 38.9, 52.9, 63.1, 68.4, 68.5, 68.7,
69.2, 70.2, 71.1, 71.7, 80.2, 96.9 (JC–H = 172 Hz), 100.4
(JC–H = 170 Hz), 118.8, 127.8, 128.0, 128.4, 128.43,
128.5, 129.4, 129.7, 129.8, 130.1, 133.1, 133.15, 133.5,
138.0, 165.2 (CO), 166.2 (CO), 170.5 (CO), 177.9
(CO). Anal. Calcd for C43H51NO13: C, 65.39; H, 6.51;
N, 1.77. Found: C, 65.50; H, 6.46; N, 1.79.
20
(CHCl3 film) 1728, 1270, 1119 cmꢀ1; ½aꢂD ꢀ22.1 (c 0.8,
CHCl3); 1H NMR (400 MHz, CDCl3) dH 3.90 (dd,
J = 6.0, 10.0 Hz, 1H), 3.96 (dd, J = 6.0, 10.0 Hz, 1H),
4.67 and 4.72 (ABq, J = 12.0 Hz, 2H), 4.79 (t, J =
4.4 Hz, 1H), 5.14 and 5.31 (ABq, J = 14.4 Hz, 2H),
5.27 (br s, 2H), 5.48 (br s, 1H), 5.64 (br s, 1H), 5.71
(d, J = 5.2 Hz, 1H), 5.92–5.94 (m, 1H), 7.24–8.11 (m,
31H, Ar); 13C NMR (100 MHz, CDCl3) dC 66.7, 67.1,
68.6, 71.4, 73.4, 77.7, 81.7, 82.2, 105.4 (C-1), 125.6,
125.8, 126.0, 126.4, 127.1, 127.6, 127.7, 127.9, 128.13,
128.15, 128.2, 128.36, 128.4, 128.6, 129.0, 129.2, 129.8,
129.9, 130.0, 130.7, 132.5, 132.9, 133.1, 133.2, 133.3,
133.4, 135.3, 135.9, 140.2, 165.4 (CO), 165.6 (CO),
165.9 (CO), 166.5 (CO). Anal. Calcd for C53H44O11:
C, 74.29; H, 5.18. Found: C, 74.31; H, 5.05.
3.10. 20-(Benzyloxycarbonyl)benzyl 6-O-naphthylmethyl-
2,3-di-O-benzoyl-b-D-galactofuranoside (13)
A solution of compound 12 (1.91 g, 3.12 mmol) and n-
Bu2SnO (931 mg, 3.74 mmol) in benzene (100 mL) was
stirred under reflux using a Dean–Stark trap for 10 h.
After removal of the solvent in vacuo, the residue was
dissolved in DMF (50 mL) and then 2-bromomethyl
naphthalene (828 mg, 3.74 mmol) and n-Bu4NI (1.38 g,
3.74 mmol) were added to the reaction mixture. After
being stirred at 60 °C for 3 h, the reaction mixture was
diluted with EtOAc (100 mL), washed with satd aq
NH4Cl (2 ꢁ 50 mL) and brine (50 mL), dried (MgSO4),
and concentrated in vacuo. The residue was purified by
silica gel flash column chromatography (hexane–EtOAc
2:1, v/v) to afford compound 13 (1.93 g, 2.56 mmol,
82%) as a colorless oil, Rf 0.35 (hexane–EtOAc 2:1, v/
3.12. 20-Carboxybenzyl 6-O-naphthylmethyl-2,3,5-tri-O-
benzoyl-b-D-galactofuranoside (15)
Compound 14 (1.71 g, 1.99 mmol) was stirred under
hydrogen atmosphere using a balloon in the presence
of Pd–C (10%, 212 mg) and ammonium acetate
(154 mg, 2.00 mmol) as an additive in MeOH–EtOAc
(1:1 v/v, 20 mL) at room temperature for 1 h. The reac-
tion mixture was filtered through Celite and the filtrate
was concentrated in vacuo. The residue was purified
by silica gel flash column chromatography (hexane–
EtOAc 1:1, v/v) to afford compound 15 (1.35 g,
1.77 mmol, 89%) as a colorless oil, Rf 0.23 (hexane–
EtOAc 2:1, v/v); IR (CHCl3 film) 1724, 1691, 1274,
20
v); IR (CHCl3 film) 3501, 1720, 1262, 1115 cmꢀ1; ½aꢂD
1
ꢀ11.5 (c 0.6, CHCl3); H NMR (400 MHz, CDCl3) dH
2.76 (d, J = 7.2 Hz, 1H), 3.64 (dd, J = 5.2, 9.6 Hz,
1H), 3.70 (dd, J = 6.8, 9.6 Hz, 1H), 4.29–4.31 (m, 1H),
4.42 (t, J = 3.6 Hz, 1H), 4.64 and 4.68 (ABq,
J = 12.0 Hz, 2H), 5.09 and 5.24 (ABq, J = 14.4 Hz,
2H), 5.27 (br s, 2H), 5.41 (br s, 1H), 5.64 (br s, 1H),
5.72 (d, J = 4.4 Hz, 1H), 7.24–8.11 (m, 26H, Ar); 13C
NMR (100 MHz, CDCl3) dC 66.7, 67.2, 69.8, 71.4,
73.5, 77.9, 81.6, 83.5, 105.5 (C-1), 125.7, 125.8, 126.1,
126.4, 127.1, 127.7, 127.8, 127.9, 128.1, 128.2, 128.3,
128.46, 128.5, 128.6, 129.2, 129.3, 129.9, 130.0, 130.7,
132.5, 133.0, 133.2, 133.4, 133.5, 135.4, 135.9, 140.3,
165.4 (CO), 165.9 (CO), 166.5 (CO). Anal. Calcd
20
1115 cmꢀ1; ½aꢂD ꢀ30.6 (c 0.5, CHCl3); 1H NMR
(400 MHz, CDCl3) dH 3.89 (dd, J = 6.0, 10.0 Hz, 1H),
3.94 (dd, J = 6.0, 10.0 Hz, 1H), 4.68 and 4.72 (ABq,
J = 12.0 Hz, 2H), 4.77 (dd, J = 1.2, 3.6 Hz, 1H), 5.08
and 5.28 (ABq, J = 14.8 Hz, 2H), 5.49 (br s, 1H), 5.61
(d, J = 1.2 Hz, 1H), 5.67 (d, J = 5.2 Hz, 1H), 5.87–
5.91 (m, 1H), 7.24–8.11 (m, 26H, Ar); 13C NMR

Y. J. Lee et al. / Carbohydrate Research 343 (2008) 1574–1584
1581
(100 MHz, CDCl3) dC 67.4, 68.5, 71.4, 73.5, 77.7, 81.7,
82.4, 105.6 (C-1), 125.7, 125.9, 126.1, 126.5, 126.9,
127.3, 127.7, 128.0, 128.2, 128.4, 128.5, 129.1, 129.3,
129.9, 129.91, 130.0, 130.1, 131.6, 133.0, 133.2, 133.24,
133.4, 133.5, 135.3, 141.0, 165.6 (CO), 165.8 (CO),
166.0 (CO), 172.2 (CO). Anal. Calcd for C46H38O11:
C, 72.05; H, 5.00. Found: C, 72.04; H, 4.95.
(50 mL). The organic phase was washed with satd aq
NaHCO3 (2 ꢁ 50 mL) and brine (50 mL), dried over
MgSO4, and concentrated in vacuo. The residue was
purified by flash column chromatography (hexanes–
EtOAc–CH2Cl2 5:1:1, v/v) to afford compound 17
(1.21 g, 0.92 mmol, 88%) as a colorless oil, Rf 0.53 (hex-
anes–EtOAc–CH2Cl2, 3:1:1, v/v); IR (CHCl3 film) 1723,
20
1270, 1114 cmꢀ1; ½aꢂD ꢀ23.2 (c 0.5, CHCl3); H NMR
(400 MHz, CDCl3) dH 3.82–3.85 (m, 1H), 3.91–3.95
(m, 3H), 4.51–4.61 (m, 4H), 4.63 (t, J = 4.8 Hz, 1H),
4.67 (d, J = 12.8 Hz, 1H), 5.03–5.07 (m, 2H), 5.21–5.29
(m, 3H), 5.38 (br s, 1H), 5.66–5.67 (m, 2H), 5.71 (d,
J = 1.2 Hz, 1H), 5.81 (br s, 1H), 5.89 (d, J = 4.0 Hz,
1H), 5.95–5.99 (m, 1H), 7.14–8.10 (m, 46H, Ar); 13C
NMR (100 MHz, CDCl3) dC 66.6, 67.1, 68.7, 69.5,
70.2, 71.3, 72.9, 73.4, 74.0, 77.7, 81.5, 81.7, 82.1, 82.5,
105.3 (C-1 ꢁ 2), 122.0, 125.39, 125.4, 125.5, 125.6,
125.8,126.1,126.7, 127.4,127.5, 127.6, 127.7, 127.9,
128.07, 128.14, 128.2, 128.23, 128.3, 128.4, 128.5,
128.8, 128.9, 129.0, 129.1, 129.68,129.7, 129.73, 129.8,
129.9, 130.5,132.4, 132.7, 132.95, 133.0,133.04, 133.2,
133.3, 133.8, 135.3, 135.8, 137.8, 140.2, 146.4, 165.2,
165.3, 165.5 (CO ꢁ 2), 165.8 (CO), 166.3 (CO). HRMS
calcd for [M+Na]+: 1339.4303. Found: 1339.4307.
1
3.13. 20-(Benzyloxycarbonyl)benzyl 2,3-di-O-benzoyl-6-
O-benzyl-b-D-galactofuranoside (16)
A solution of compound 12 (1.74 g, 2.85 mmol) and n-
Bu2SnO (851 mg, 3.42 mmol) in benzene (100 mL) was
stirred under reflux using a Dean–Stark trap for 10 h.
After removal of the solvent in vacuo, the residue was
dissolved in DMF (50 mL) and then benzyl chloride
(394 lL, 3.42 mmol) and n-Bu4NI (1.26 g, 3.41 mmol)
were added to the reaction mixture. After being stirred
at 60 °C for 3 h, the reaction mixture was diluted
with EtOAc (100 mL), washed with satd aq NH4Cl
(2 ꢁ 50 mL) and brine (50 mL), dried (MgSO4), and
concentrated in vacuo. The residue was purified by silica
gel flash column chromatography (hexane–EtOAc 2:1,
v/v) to afford compound 16 (1.72 g, 2.45 mmol, 86%)
as a colorless oil, Rf 0.35 (hexane–EtOAc 2:1, v/v); IR
20
(CHCl3 film), 1106, 1251, 1654, 1718, 3428 cmꢀ1; ½aꢂD
3.15. 20-Carboxybenzyl 6-O-naphthylmethyl-2,3,5-tri-O-
benzoyl-b-D-galactofuranosyl-(1?5)-2,3-di-O-benzoyl-6-
O-benzyl-b-D-galactofuranoside (18)
1
+5.0 (c 0.2, CHCl3); H NMR (400 MHz, CDCl3) dH
2.53 (d, J = 7.2 Hz, 1H, OH), 3.60 (dd, J = 5.2,
9.6 Hz, 1H, H-6), 3.66 (dd, J = 6.8, 9.6 Hz, 1H, H-60),
4.23–4.26 (m, 1H, H-5), 4.38 (dd, J = 3.2, 4.4 Hz, 1H,
H-4), 4.51 and 4.55 (ABq, J = 12.0 Hz, 2H, PhCH2),
5.08 and 5.23 (ABq, J = 14.4 Hz, 2H, PhCH2), 5.31
(br s, 2H, PhCH2), 5.41 (br s, 1H, H-1), 5.61 (d,
J = 1.2 Hz, 1H, H-2), 5.67 (d, J = 4.8 Hz, 1H, H-3),
7.28–8.08 (m, 24H, Ph-H); 13C NMR (100 MHz,
CDCl3) dC 66.9, 67.3, 69.9, 71.4, 73.6, 78.0, 81.7, 83.5,
105.6 (C-1), 127.2, 127.75, 127.79, 127.9, 128.3, 128.4,
128.5, 128.6, 128.7, 128.8, 130.0, 130.1, 130.8, 132.6,
133.6, 133.7, 136.1, 138.1, 140.5, 165.5 (CO), 166.0
(CO), 166.8 (CO). Anal. Calcd for C42H38O10: C,
71.78; H, 5.45. Found: C, 71.84; H, 5.33.
Compound 17 (570 mg, 0.43 mmol) was stirred under
hydrogen atmosphere using a balloon in the presence
of Pd(OH)2 (20%, 30 mg) and ammonium acetate
(17 mg, 0.22 mmol) as an additive in MeOH–EtOAc
(1:1 v/v, 20 mL) at room temperature for 5 h. The reac-
tion mixture was filtered through Celite and the filtrate
was concentrated in vacuo. The residue was purified
by silica gel flash column chromatography (hexane–
EtOAc 1:1, v/v) to afford compound 18 (473 mg,
0.38 mmol, 89%) as a colorless oil, Rf 0.45 (hexane–
EtOAc 1:1, v/v); IR (CHCl3 film) 1724, 1274,
20
1115 cmꢀ1; ½aꢂD ꢀ19.2 (c 0.3, CHCl3); 1H NMR
(400 MHz, CDCl3) dH 3.80–3.88 (m, 4H), 4.49–4.55
(m, 4H), 4.60 (t, J = 4.8 Hz, 1H), 4.65 (d, J = 12.8 Hz,
1H), 4.90 and 5.20 (ABq, J = 14.0 Hz, 2H), 4.97 (t,
J = 4.4 Hz, 1H), 5.33 (br s, 1H), 5.57–6.00 (m, 2H),
5.62 (br s, 1H), 5.69 (br s, 1H), 5.81 (d, J = 4.8 Hz,
1H), 5.85–5.89 (m, 1H), 7.13–8.05 (m, 41H, Ar); 13C
NMR (100 MHz, CDCl3) dC 67.5, 68.8, 70.1, 71.4,
73.2, 73.6, 74.3, 77.3, 77.8, 81.6, 82.0, 82.4, 82.6, 105.5
(C-1), 105.6 (C-1), 127.0,127.3, 127.59,127.6, 127.7,
127.8, 127.9, 128.1, 128.2, 128.4, 128.5, 128.54, 129.1,
129.15, 129.2,129.3, 129.86, 129.88, 129.9, 130.0, 130.1,
131.6, 133.0, 133.1, 133.2, 133.22, 133.3, 133.4, 135.4,
138.0, 140.9, 165.4 (CO), 165.55 (CO), 165.66 (CO),
165.7 (CO), 166.0 (CO), 171.4 (CO). Anal. Calcd for
C73H62O18: C, 71.44; H, 5.09. Found: C, 71.53; H, 4.93.
3.14. 20-(Benzyloxycarbonyl)benzyl 6-O-naphthylmethyl-
2,3,5-tri-O-benzoyl-b-D-galactofuranosyl-(1?5)-2,3-di-
O-benzoyl-6-O-benzyl-b-D-galactofuranoside (17)
A solution of compound 16 (734 mg, 1.04 mmol) and
DTBMP (641 mg, 3.12 mmol) in CH2Cl2 (40 mL) in
˚
the presence of 4 A molecular sieves was stirred for
10 min at room temperature and cooled to ꢀ78 °C.
After addition of Tf2O (350 lL, 2.08 mmol) to the above
solution, compound 15 (877 mg, 1.14 mmol) in CH2Cl2
(10 mL) was added drop-wise. After being stirred at
ꢀ78 °C for a further 1 h, the reaction mixture was
warmed to 0 °C over 1 h, quenched by the addition of
satd aq NaHCO3 (1 mL), and diluted with CH2Cl2

1582
Y. J. Lee et al. / Carbohydrate Research 343 (2008) 1574–1584
3.16. 6-O-Naphthylmethyl-2,3,5-tri-O-benzoyl-b-D-galac-
tofuranosyl-(1?5)-2,3-di-O-benzoyl-6-O-benzyl-b-D-
galactofuranosyl fluoride (19)
MgSO4, and concentrated in vacuo. The residue was
purified by silica gel flash column chromatography (hex-
ane–EtOAc 1:1, v/v) to afford compound 20 (286 mg,
0.15 mmol, 90%) as a white foam, Rf 0.3 (hexane–
EtOAc 1:1, v/v); IR (CHCl3 film) 3301, 1728, 1458,
A solution of compound 18 (304 mg, 0.25 mmol) and
20
1
DTBMP (153 mg, 0.74 mmol) in CH2Cl2 (20 mL) in
1270, 1119 cmꢀ1; ½aꢂD þ19:8 (c 0.4, CHCl3); H NMR
(400 MHz, CDCl3) dH 0.64 (d, J = 6.0 Hz, 3H, L-Rha
CH3), 1.11 (s, 9H, Piv (CH3)3C), 2.12 (s, 3H, acetyl
CH3), 3.55–3.60 (m, 1H), 3.64–3.68 (m, 2H), 3.74–3.80
(m, 3H), 3.98–4.06 (m, 3H), 4.16–4.30 (m, 3H), 4.35–
4.47 (m, 5H), 4.50–4.59 (m, 5H), 4.82–4.84 (m, 2H),
4.92 (d, J = 3.2 Hz, 1H), 5.11 (m, 1H), 5.25–5.33 (m,
2H), 5.52–5.57 (m, 4H), 5.64 (br s, 1H), 5.69 (br s,
1H), 5.70–5.78 (m, 2H), 5.85 (d, J = 10.0 Hz, 1H),
5.87–5.99 (m, 1H, allyl CH), 6.89–8.08 (m, 52H); 13C
NMR (100 MHz, CDCl3) dC 17.9, 23.7, 27.2, 39.0,
52.8, 63.1, 68.1,68.4, 68.9, 69.0, 69.1, 70.2, 70.3, 71.47,
71.5, 73.0, 73.5, 73.6, 75.8, 77.4, 77.7, 77.8, 81.5, 81.6,
82.1, 83.0, 97.0 (C-1), 101.0 (C-10), 105.2, 106.6, 118.9,
125.6, 125.7, 125.9, 126.2, 127.3, 127.5, 127.60, 127.65,
127.7, 127.90, 127.98, 128.00, 128.04, 128.10, 128.13,
128.26, 128.32, 128.35, 128.40, 128.48, 128.5, 128.7,
128.8, 129.10, 129.18, 129.2, 129.4, 129.5, 129.80,
129.84, 129.90, 129.99, 130.1, 132.9, 133.0, 133.18,
133.23, 133.4, 133.5, 135.6, 137.9, 138.0, 165.0 (CO),
165.1 (CO), 165.3 (CO), 165.6 (CO), 165.7 (CO), 165.9
(CO), 166.3 (CO), 170.4 (CO), 178.3 (CO). Anal. Calcd
for C108H105NO28: C, 69.55; H, 5.67; N, 0.75. Found: C,
69.45; H, 5.64; N, 0.78.
˚
the presence of 4 A molecular sieves was stirred for
10 min at room temperature and cooled to ꢀ78 °C.
After sequential addition of Tf2O (63 lL, 0.37 mmol),
Deoxofluor (69 lL, 0.37 mmol), and hydrogen fluoride
(70% in pyridine, 10 lL, 0.385 mmol) to the above solu-
tion, the reaction mixture was stirred at ꢀ78 °C for
further 1 h, allowed to warm to 0 °C over 1 h, quenched
by the addition of satd aq NaHCO3 (1 mL), and diluted
with CH2Cl2 (50 mL). The organic phase was washed
with satd aq NaHCO3 (2 ꢁ 30 mL) and brine (50 mL),
dried over MgSO4, and concentrated in vacuo. The res-
idue was purified by flash column chromatography (hex-
ane–EtOAc 2:1, v/v) to afford compound 19 (228 mg,
0.21 mmol, 84%) as a colorless oil, Rf 0.45 (hexane–
EtOAc 2:1, v/v); IR (CHCl3 film) 1724, 1270,
20
1115 cmꢀ1; ½aꢂD ꢀ3.5 (c 0.6, CHCl3); 1H NMR
(400 MHz, CDCl3) dH 3.82–3.90 (m, 4H), 4.49–4.55
(m, 3H), 4.58 and 4.68 (ABq, J = 12.4 Hz, 2H), 4.78
(t, J = 4.0 Hz, 1H), 4.97 (dd, J = 3.6, 5.2 Hz, 1H),
5.62–5.63 (m, 3H), 5.72 (br s, 1H), 5.89 (d, J =
58.4 Hz, 1H, H-1), 5.84–5.88 (m, 2H), 7.15–8.08 (m,
37H); 13C NMR (100 MHz, CDCl3) dC 68.6, 69.6,
71.4, 73.3, 73.5, 73.8, 76.0, 77.6, 80.9 (d, J = 40 Hz,
C-2), 81.5, 82.2, 85.8, 105.1 (C-10), 112.4 (d,
J = 225 Hz, C-1), 125.6, 125.8, 126.0, 126.4, 127.6,
127.7, 127.9, 128.1, 128.2, 128.4, 128.5, 128.58, 128.6,
128.9,129.0, 129.1, 129.9, 129.94, 130.0, 132.9, 133.1,
133.19, 133.24, 133.3, 133.6, 133.7, 135.3, 137.8, 165.1
(CO), 165.4 (CO), 165.55 (CO), 165.6 (CO), 165.9
(CO). Anal. Calcd for C65H55FO15: C, 71.29; H, 5.06.
Found: C, 71.33; H, 5.01.
3.18. 6-O-Naphthylmethyl-2,3,5-tri-O-benzoyl-b-D-galac-
tofuranosyl-(1?5)-2,3-di-O-benzoyl-6-O-benzyl-b-D-
galactofuranosyl-(1?4)-3-O-benzyl-2-O-pivaloyl-a-L-
rhamnopyranosyl-(1?3)-2-acetamido-2-deoxy-4,6-di-O-
benzoyl-a-D-glucopyranose (21)
A solution of compound 20 (78 mg, 0.04 mmol), NaOAc
(14 mg, 0.17 mmol), and PdCl2 (15 mg, 0.08 mmol) in
95% aq HOAc (1 mL) was stirred for 12 h at room tem-
perature. The reaction mixture was filtrated through a
Celite pad, diluted with EtOAc (50 mL), washed with
satd aq NaHCO3 (2 ꢁ 50 mL) and brine (50 mL), dried
(MgSO4), and concentrated in vacuo. The residue was
purified by silica gel flash column chromatography
(CH2Cl2–MeOH 20:1, v/v) to afford compound 21
(54 mg, 0.03 mmol, 71%) as a white foam, Rf 0.33
(CH2Cl2–MeOH 20:1, v/v); 1H NMR (400 MHz,
CDCl3) dH 0.64 (d, J = 5.6 Hz, 3H, L-Rha CH3), 1.11
(s, 9H, Piv (CH3)3C), 2.06 (s, 3H, acetyl CH3), 3.57 (t,
J = 9.2 Hz, 1H), 3.65–3.68 (m, 2H), 3.76–3.82 (m, 3H),
3.93–4.09 (m, 2H), 4.28–4.60 (m, 12H), 4.76–4.87 (m,
3H), 5.12 (br s, 1H), 5.25 (br s, 1H), 5.55–5.75 (m,
8H), 6.10 (d, J = 9.6 Hz, 1H), 6.90–8.07 (m, 52H, Ar);
13C NMR (100 MHz, CDCl3) dC 18.0, 23.5, 27.2, 39.0,
53.4, 68.0, 68.1, 69.0, 69.1, 70.2, 70.3, 71.5, 71.54, 73.0
(2), 73.5 (2), 73.6, 75.8, 77.7, 77.8, 81.1, 81.6, 81.7,
3.17. Allyl 6-O-naphthylmethyl-2,3,5-tri-O-benzoyl-b-D-
galactofuranosyl-(1?5)-2,3-di-O-benzoyl-6-O-benzyl-b-
D-galactofuranosyl-(1?4)-3-O-benzyl-2-O-pivaloyl-a-L-
rhamnopyranosyl-(1?3)-2-acetamido-2-deoxy-4,6-di-O-
benzoyl-a-D-glucopyranoside (20)
A solution of compound 11 (134 mg, 0.17 mmol), SnCl2
(71 mg, 0.37 mmol), and AgClO4 (78 mg, 0.37 mmol) in
Et2O (10 mL) and CH2Cl2 (10 mL) in the presence of
˚
4 A molecular sieves was stirred for 30 min at room
temperature and cooled down to 0 °C. After drop-wise
addition of a solution of glycosyl fluoride (205 mg,
0.19 mmol) in Et2O (5 mL) and CH2Cl2 (5 mL) to the
above solution at 0 °C, the reaction mixture was stirred
for a further 30 min and concentrated to half its volume.
After dilution of the concentrated solution with CH2Cl2
(50 mL), the organic solution was washed with satd aq
NaHCO3 (2 ꢁ 30 mL) and brine (30 mL), dried over

Y. J. Lee et al. / Carbohydrate Research 343 (2008) 1574–1584
1583
82.1, 83.0, 92.2 (C-1), 100.9 (C-10), 105.2, 106.6, 128.0,
Acknowledgments
128.1, 128.20, 128.28, 128.33, 128.37, 128.4, 128.5,
128.56, 128.7, 129.1, 129.2, 129.4, 129.6, 129.80,
129.88, 129.92, 129.95, 130.0, 130.1, 132.9, 133.0,
133.2, 133.3, 133.5, 135.5, 137.9, 138.0, 165.1(CO ꢁ 2),
165.3 (CO), 165.7 (CO ꢁ 2), 166.0 (CO), 166.5 (CO),
This work was supported by a grant from the Korea
Science and Engineering Foundation through Center
for Bioactive Molecular Hybrids (CBMH). Y.J.L. and
D.B.F. thank the fellowship of the BK 21 program
from the Ministry of Education and Human Resources
Development.
171.0 (CO). MALDI-TOFMS calcd for C105H101
NNaO28 [M+Na]+: 1846.6408. Found: 1846.6321.
-
3.19. Dibenzyl 6-O-naphthylmethyl-2,3,5-tri-O-benzoyl-
b-D-galactofuranosyl-(1?5)-2,3-di-O-benzoyl-6-O-benz-
yl-b-D-galactofuranosyl-(1?4)-3-O-benzyl-2-O-pivaloyl-
a-L-rhamnopyranosyl-(1?3)-2-acetamido-2-deoxy-4,6-
di-O-benzoyl-a-D-glucopyranosyl phosphate (1)
References
1. (a) Nettleman, M. D. JAMA 2005, 293, 2788–2790; (b)
Long, R. CMAJ 2000, 163, 425–428; (c) Pablos-Mendez,
A.; Raviglione, M. C.; Laszlo, A.; Binkin, N.; Rieder, H.
L.; Bustreo, F.; Cohn, D. L.; Weezenbeek, C. S. B. L.;
Kim, S. J.; Chaulet, P.; Nunn, P. N. Eng. J. Med. 1998,
338, 1641–1649.
2. (a) Brennan, P. J. Tuberculosis 2003, 83, 91–97; (b)
Lowary, T. L. In Glycoscience: Chemistry and Chemical
Biology; Springer: Berlin, 2001; pp 2005–2080; (c) Chat-
terjee, D. Curr. Opin. Chem. Biol. 1997, 1, 579–588; (d)
Brennan, P. J.; Nikaido, H. Annu. Rev. Biochem. 1995, 64,
29–63; (e) Jarlier, V.; Nikaido, H. FEMS Microbiol. Lett.
1994, 123, 11–18.
3. (a) Daffe, M.; Brennan, P. J.; McNeil, M. J. Biol. Chem.
1990, 265, 6734–6743; (b) McNeil, M.; Daffe, M.; Bren-
nan, P. J. J. Biol. Chem. 1990, 265, 18200–18206; (c) Bersa,
G. S.; Khoo, K.-H.; McNeil, M. R.; Dell, A.; Morris, H.
R.; Brennan, P. J. Biochem. 1995, 34, 4257–4266; (d) Lee,
R. E. B.; Li, W.; Chatterjee, D.; Lee, R. E. Glycobiology
2005, 15, 139–151.
4. (a) Takayama, K.; Kilburn, J. O. Antimicrob. Agents
Chemother. 1989, 33, 1493–1499; (b) Mikusov, K.; Slay-
den, R. A.; Bersa, G. S.; Brennan, P. J. Antimicrob.
Chemother. 1995, 39, 2484–2489.
5. (a) Kremer, L.; Dover, L. G.; Morehouse, C.; Hitchin, P.;
Everett, M.; Morris, H. R.; Dell, A.; Brennan, P. J.;
McNeil, M. R.; Flaherty, C.; Ducan, K.; Besra, G. S. J.
Biol. Chem. 2001, 276, 26430–26440; (b) Pan, F.; Jackson,
M.; Ma, Y.; McNeil, M. J. Bacteriol. 2001, 183, 3991–
3998.
6. (a) Crick, D. C.; Mahapatra, S.; Brennan, P. Glycobiology
2001, 11, 107R–118R; (b) Mikusova, K.; Mikus, M.;
Besra, G. S.; Hancock, I.; Brennan, P. J. J. Biol. Chem.
1996, 271, 7820–7828; (c) Mikusova, K.; Yagi, T.; Stern,
R.; McNeil, M. R.; Besra, G. S.; Crick, D. C.; Brennan,P.
J. J. Biol. Chem. 2000, 275, 33890–33897.
7. Belanova, M.; Dianiskova, P.; Brennan, P. J.; Completo,
G. C.; Rose, N. L.; Lowary, T. L.; Mikusova, K. J.
Bacteriol. 2008, 190, 1141–1145.
8. Joe, M.; Bai, Y.; Nacario, R. C.; Lowary, T. L. J. Am.
Chem. Soc. 2007, 129, 9885–9901.
To a stirred solution of compound 21 (100 mg,
0.05 mmol) in THF (3 mL) was added 2.0 M LDA in
THF (55 lL, 0.11 mmol) at ꢀ78 °C under an argon
atmosphere. The solution was stirred for 30 min and
then a solution of tetrabenzyl pyrophosphate (35 mg,
0.06 mmol) in THF (1 mL) was added. After being stir-
red at ꢀ78 °C for further 1 h, the reaction mixture was
allowed to warm to 0 °C over 30 min, diluted with
EtOAc (50 mL), washed with satd aq NaHCO3
(2 ꢁ 50 mL) and brine (50 mL), dried over MgSO4,
and concentrated in vacuo. The residue was purified
by flash column chromatography (CH2Cl2–MeOH
20:1, v/v) to afford compound 1 (105 mg, 0.05 mmol,
92%) as a white foam, Rf 0.48 (CH2Cl2–MeOH 20:1,
v/v); IR (CHCl3 film) 3210, 2953, 2923, 2854, 1725,
20
1688, 1451, 1270, 1109, 1046 cmꢀ1 ½aꢂD +8.5 (c 0.5,
1
CHCl3); H NMR (400 MHz, CDCl3) dH 0.64 (d, J =
5.6 Hz, 3H, L-Rha CH3), 1.13 (s, 9H, Piv (CH3)3C),
1.89 (s, 3H, acetyl CH3), 3.54–3.59 (m, 2H), 3.66–3.69
(m, 1H), 3.72–3.81 (m, 3H), 3.82–3.90 (m, 2H), 4.22–
4.29 (m, 3H), 4.36–4.47 (m, 7H), 4.49–4.59 (m, 2H),
4.75 (d, J = 1.6 Hz, 1H), 4.83 (dd, J = 4.0, 4.8 Hz,
1H), 5.02–5.13 (m, 5H), 5.49 (d, J = 1.6 Hz, 1H), 5.53–
5.56 (m, 3H), 5.63–5.68 (m, 3H), 5.71–5.77 (m, 3H),
6.89–8.06 (m, 62H, Ar); 13C NMR (100 MHz, CDCl3)
dC 17.9, 23.2, 27.2, 39.0, 52.8, 52.9, 62.3, 68.2, 68.9,
69.0, 69.3, 70.1, 70.2 (2), 70.3, 71.4, 71.5, 72.0, 73.5,
75.7, 77.4, 77.67, 77.7, 79.7, 81.6, 81.7, 82.1, 82.9, 97.2
(d, J = 6.0 Hz; JC–H = 179 Hz), 100.7 (JC–H = 172 Hz),
105.2 (JC–H = 181 Hz), 106.6 (JC–H = 181 Hz), 125.7,
125.9, 126.2, 127.4, 127.5, 127.64, 127.66, 127.7, 127.9,
128.0, 128.04, 128.06, 128.1, 128.2, 128.3, 128.4, 128.4,
128.5, 128.7, 128.9, 129.10, 129.14, 129.2, 129.3, 129.4,
129.6, 129.7, 129.8, 129.90, 129.99, 130.00, 130.05,
130.1, 132.9, 133.0, 133.2, 133.2, 133.5, 135.3 (d,
J = 6.0 Hz), 135.5 (d, J = 6.0 Hz), 135.6, 137.8, 137.9,
164.9 (CO), 165.1 (CO), 165.3 (CO), 165.6 (CO ꢁ 2),
166.0 (CO), 166.2 (CO), 170.8 (CO), 178.1 (CO). MAL-
DI-TOFMS calcd for C119H114NNaO31P [M+Na]+:
2106.7010. Found: 2106.6941.
9. (a) Pathak, A. K.; Pathak, V.; Suling, W. J.; Gurcha, S. S.;
Morehouse, C. B.; Besra, G. S.; Maddry, J. A.; Reynolds,
R. C. Bioorg. Med. Chem. 2002, 10, 923–928; (b) Gandolfi-
Donadio, L.; Gallo-Rodriguez, C.; de Lederkremer, R. M.
Can. J. Chem. 2006, 84, 486–491.
10. (a) Gurjar, M. K.; Reddy, L. K.; Hotha, S. J. Org. Chem.
2001, 66, 4657–4660; (b) Wang, H.; Ning, J. J. Org. Chem.
2003, 68, 2521–2524.
11. Gandolfi-Donadio, L.; Gallo-Rodriguez, C.; de Leder-
kremer, R. M. Carbohydr. Res. doi:10.1016/j.carres.2008.
01.024. Available online January 29, 2008.

1584
Y. J. Lee et al. / Carbohydrate Research 343 (2008) 1574–1584
12. Gandolfi-Donadio, L.; Gallo-Rodriguez, C.; de Leder-
kremer, R. M. J. Org. Chem. 2003, 68, 6928–6934.
13. Wen, X.; Crick, D. C.; Brennan, P. J.; Hultin, P. G.
Bioorg. Med. Chem. 2003, 11, 3579–3587.
20. Lee, Y. J.; Lee, B-. Y.; Jeon, H. B.; Kim, K. S. Org. Lett.
2006, 8, 3971–3974.
21. Kim, K. S.; Kim, J. H.; Lee, Y. J.; Lee, Y. J.; Park, J. J.
Am. Chem. Soc. 2001, 123, 8477–8481.
14. Groneberg, R. D.; Miyazaki, T.; Stylianides, N. A.;
Schulze, T. J.; Stahl, W.; Schreiner, E. P.; Suzuki, T.;
Iwabuchi, Y.; Smith, A. L.; Nicolaou, K. C. J. Am. Chem.
Soc. 1993, 115, 7593–7611.
15. Grindley, T. B. Adv. Carbohydr. Chem. Biochem. 1998, 53,
117–142.
16. David, S.; Hanessian, S. Tetrahedron 1985, 41, 643–663.
17. Feng, F.; Okuyama, K.; Niikura, K.; Ohta, T.; Sadamoto,
R.; Monde, K.; Noguchi, T.; Nishimura, S. I. Org. Biomol.
Chem. 2004, 2, 1617–1623.
18. Crich, D.; Smith, M. J. Am. Chem. Soc. 2001, 123, 9015–
9020.
22. Kim, K. S.; Kang, S. S.; Seo, Y. S.; Kim, H. J.; Lee, Y. J.;
Jeong, K.-S. Synlett 2003, 1311–1314.
23. Lee, Y. J.; Baek, J. Y.; Lee, B.-Y.; Kang, S. S.; Park, H.-
S.; Jeon, H. B.; Kim, K. S. Carbohydr. Res. 2006, 341,
1708–1716.
24. Lal, G. S.; Pez, G. P.; Pesaresi, R. J.; Prozonic, F. M.;
Cheng, H. J. Org. Chem. 1999, 64, 7048–7054.
´
25. Gelin, M.; Ferrieres, V.; Plusquellec, D. Eur. J. Org.
Chem. 2000, 1423–1431.
26. (a) Yuko, N.; Tomoharu, N.; Hironobu, H.; Yoshiaki, N.
Biosci. Biotechnol. Biochem. 2003, 67, 1761–1766; (b)
Muller, T.; Danac, R.; Ball, L.; Gurr, S. J.; Fairbanks, A.
Tetrahedron: Asymmetry 2007, 18, 1299–1307.
19. Bock, K.; Pedersen, C. J. Chem. Soc., Perkin Trans. 2
1974, 293–297.