Dimethylthexylsilyl 2-acetamido-3-O-allyl-2-deoxy-6-O-(4-methoxybenzyl)-β-d-glucopyrano side, dimethylthexylsilyl 3,4,6-tri-O-benzyl-β-d-mannopyranosyl-(1→4)-2-acetamido-3-O-al lyl-2-deoxy-6-O-(4-methoxybenzyl)-β-d-glucopyranoside, and dimethylthexylsilyl

Article abstract of DOI:10.1016/j.carres.2008.10.007

Full title: Dimethylthexylsilyl 2-acetamido-3-O-allyl-2-deoxy-6-O-(4-methoxybenzyl)-β-d-glucopyrano side, dimethylthexylsilyl 3,4,6-tri-O-benzyl-β-d-mannopyranosyl-(1→4)-2-acetamido-3-O-al lyl-2-deoxy-6-O-(4-methoxybenzyl)-β-d-glucopyranoside, and dimethy

Full text of DOI:10.1016/j.carres.2008.10.007

Carbohydrate Research 344 (2009) 140–144
Contents lists available at ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Note
Dimethylthexylsilyl 2-acetamido-3-O-allyl-2-deoxy-6-O-(4-methoxybenzyl)-
b-D-glucopyranoside, dimethylthexylsilyl 3,4,6-tri-O-benzyl-b-D-
mannopyranosyl-(1?4)-2-acetamido-3-O-allyl-2-deoxy-6-O-(4-methoxy-
benzyl)-b-D-glucopyranoside, and dimethylthexylsilyl 2-O-(benzylsulfonyl)-
3,4,6-tri-O-benzyl-b-D-mannopyranosyl-(1?4)-2-acetamido-3-O-allyl-2-deoxy-
6-O-(4-methoxybenzyl)-b-D-glucopyranoside: synthesis of authentic samples q
a
b
David Crich a,b, , Ming Li , Prasanna Jayalath
*
a Department of Chemistry, Wayne State University, 5101 Cass Avenue, Detroit, MI 48202, USA
b Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street, Chicago, IL 60607-7061, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
Dimethylthexylsilyl 2-acetamido-3-O-allyl-2-deoxy-6-O-(4-methoxybenzyl)-b-D-glucopyranoside was
Received 25 August 2008
Received in revised form 3 October 2008
Accepted 7 October 2008
prepared by reduction of the corresponding 4,6-O-(4-methoxybenzylidene) acetal with sodium cyano-
borohydride and trifluoroacetic acid. This alcohol was coupled to 2-O-benzoyl-3,4,6-tri-O-benzyl-
glucopyranosyl trichloroacetimidate to give a b-glucoside that was converted to dimethylthexylsilyl
3,4,6-tri-O-benzyl-b- -mannopyranosyl-(1?4)-2-acetamido-3-O-allyl-2-deoxy-6-O-(4-methoxybenzyl)-
b- -glucopyranoside by saponification, Dess–Martin oxidation, and sodium borohydride reduction.
Sulfonylation then gave dimethylthexylsilyl 2-O-(benzylsulfonyl)-3,4,6-tri-O-benzyl-b- -mannopyrano-
syl-(1?4)-2-acetamido-3-O-allyl-2-deoxy-6-O-(4-methoxybenzyl)-b- -glucopyranoside.
a-D-
Available online 14 October 2008
D
D
Keywords:
Glycosylation
Uloside
D
D
Ó 2008 Elsevier Ltd. All rights reserved.
Mannoside
The NMR spectral data for dimethylthexylsilyl 2-acetamido-3-O-
4-methoxybenzylidene acetal with sodium cyanoborohydride and
trifluoroacetic acid5 finally gave the acceptor 4 in 70% yield to-
gether with 6% of the 4-O-(4-methoxybenzyl) ether 5 (Scheme 1).
The regioselectivity of the reductive ring opening reaction is sup-
ported by the chemical shift (d 70.7) of C-6 in the 6-O-(4-methoxy-
benzyl) isomer 4, which is consistent to that of C-6 in a closely
allyl-2-deoxy-6-O-(4-methoxybenzyl)-b-
D-glucopyranoside
(4)
and dimethylthexylsilyl 3,4,6-tri-O-benzyl-b-
D
-mannopyranosyl-
(1?4)-2-acetamido-3-O-allyl-2-deoxy-6-O-(4-methoxybenzyl)-b-
D
-glucopyranoside (11), as described by Schmidt and co-workers,1
are incorrect.2,3 We describe unambiguous syntheses of authentic
samples of both compounds and of the 2-benzylsulfonyl derivative
(12) of 11, and provide full characterization data for all three
compounds.
related compound, allyl 3-O-benzyl-2-deoxy-2-acetamido-b-D-
glucopyranoside, which was accessed by a different route.6 Addi-
tional confirmation was obtained by acetylation of both 4 and 5,
giving 6 and 7, respectively, when the anticipated chemical shift
changes were observed in the NMR spectra.
Synthesis of the glycosyl acceptor 4 began with the known dim-
ethylthexylsilyl glycoside 14 from which the esters were removed
with catalytic sodium methoxide to give a triol that was immedi-
ately converted to the 4-methoxybenzylidene acetal 2 (Scheme
1). The 3-O-allyl ether 6 was then obtained by treatment with
sodium hydride and allyl bromide. Reductive cleavage of the
Adapting the classical Lindberg approach to b-mannosides,7,8
2-O-benzoyl-3,4,6-tri-O-benzyl-a-D-glucopyranosyl trichloroace-
timidate (8)9 was activated with trimethylsilyl triflate10 in the
presence of 4, leading to the isolation of the b-glucoside 9 in 51%
yield (Scheme 2). Saponification gave the alcohol 10, Dess–Martin
oxidation11 of which then provided a uloside that was immediately
reduced with sodium borohydride to give the b-mannoside 11 in
84% yield along with 4.5% of the gluco-isomer 10. Finally, sulfonyl-
ation of 11 with benzylsulfonyl chloride in pyridine gave 12 in 97%
yield (Scheme 2).
q
Supplementary data is available for this Note.
* Corresponding author. Tel.: +1 313 577 1915; fax: +1 313 577 8822.
E-mail address: dcrich@chem.wayne.edu (D. Crich).
0008-6215/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2008.10.007

D. Crich et al. / Carbohydrate Research 344 (2009) 140–144
141
OAc
O
i) NaOMe (cat),
PMP
O
NaH, CH2=CHCH2Br
O
AcO
AcO
O
OTDS
OTDS
NHAc
2, 67%
HO
ii) MeOC6H4CH(OMe)2, PPTS
NHAc
1
OH
O
OPMB
O
PMP
O
NaBH3CN, TFA, DMF
O
+
O
PMBO
AllO
HO
AllO
OTDS
NHAc
OTDS
OTDS
AllO
NHAc
NHAc
5, 6%
4, 70%
3
Ac2O, pyridine
Ac2O, pyridine
OAc
OPMB
O
+
O
PMBO
AllO
AcO
AllO
OTDS
NHAc
7, 83%
OTDS
NHAc
6, 91%
Scheme 1. Synthesis of acceptor 4.
OPMB
O
BnO
TMSOTf, CH2Cl2
BnO
PMBO
O
O
O
BnO
BnO
HO
AllO
O
NH
OTDS
NHAc
OTDS
BnO
AllO
BnO
51%
+
BzO
NHAc
OR
9: R = Bz
10: R = H
O
CCl3
4
8
NaOMe,
77%
SO2Bn
OPMB
O
OPMB
O
O
OH
O
i) Dess-Martin
ii) NaBH4
BnCH2SO2Cl,
pyridine
BnO
BnO
BnO
BnO
O
BnO
O
O
OTDS
OTDS
AllO
BnO
AllO
NHAc
NHAc
12, 97%
11, 84% (+ 4.5% 10)
Scheme 2. Unambiguous synthesis of the b-mannosides 11 and 12.
1H NMR (400 MHz) d 7.40 (d, 2H, J = 8.8 Hz, Ar-H), 6.86 (d, 2H,
J = 8.0 Hz, Ar-H), 5.83 (d, 1H, J = 6.7 Hz, CH3CONH), 5.47 (s, 1H,
PhCHO2), 4.87 (d, 1H, J = 8.0 Hz, H-1), 4.23 (dd, 1H, J = 3.2,
10.0 Hz, H-6a), 4.18 (br s, 1H, OH), 4.02 (t, 1H, J = 9.9 Hz, H-3),
3.77 (s, 3H, OCH3), 3.73 (t, 1H, J = 10.2 Hz, H-6b), 3.52 (t, 1H, J =
9.2 Hz, H-4), 3.48–3.40 (m, 2H, H-5, H-2), 1.99 (s, 3H, CH3CONH),
1.65–1.58 (m, 1H, SiC(CH3)2CH(CH3)2), 0.88–0.84 (m, 12H,
SiC(CH3)2CH(CH3)2), 0.15 (s, 3H, SiCH3), 0.14 (s, 3H, SiCH3); 13C
NMR (100 MHz) d 171.8, 160.4, 129.9, 127.9, 113.8, 102.0, 96.2,
81.9, 71.4, 68.8, 66.6, 61.0, 55.5, 34.2, 25.0, 23.8, 20.3, 20.2, 18.8,
18.7, ꢁ1.5, ꢁ3.2. ESIMS m/z calcd for C24H39NO7SiNa [M+Na+]:
504.2394. Found: 504.2407.
1. Experimental
1.1. General methods
Optical rotations were determined with an Autopol III polarim-
eter for solutions in CHCl3. NMR spectra were recorded for CDCl3
solutions with a Varian 400 or 500 MHz spectrometer. Chemical
shifts are in ppm downfield from tetramethylsilane. High resolu-
tion mass spectra were recorded with a Waters Micromass-LCT-
Premier-XE instrument.
1.2. Dimethylthexylsilyl 2-acetamido-4,6-di-O-(4-
methoxybenzylidene)-2-deoxy-b-D-glucopyranoside (2)
1.3. Dimethylthexylsilyl 2-acetamido-3-O-allyl-4,6-di-O-(4-
To a solution of 14 (3.38 g, 6.89 mmol) in MeOH–CH2Cl2 (1:1
v:v, 30 mL) was added a solution of NaOMe in MeOH (25 wt %,
0.2 mL, 0.88 mmol). The resulting mixture was stirred for 2.5 h at
ambient temp under N2 atmosphere. Monitoring by TLC (MeOH–
CH2Cl2 1:4) indicated that the reaction went to completion. The
reaction mixture was neutralized with Amberlist-15 resin (H+), fil-
tered, and the filtrate was concentrated to furnish a white foam,
which was dissolved in DMF (20 mL). PPTS (184 mg, 0.73 mmol)
and p-methoxybenzaldehyde dimethyl acetal (1.40 mL, 8.26
mmol) were added. The mixture was evaporated on a rotary evap-
orator at 50 °C to remove the methanol produced during the reac-
tion. After 2 h, TLC (EtOAc–hexane 1:3) showed that the reactant
was completely consumed. The mixture was poured into 1 N aq
NaHCO3 and extracted with CH2Cl2. The organic phase was washed
with brine, dried over Na2SO4, and concentrated. The residue was
subjected to silica gel column chromatography (EtOAc–CH2Cl2
methoxybenzylidene)-2-deoxy-b-D-glucopyranoside (3)
To a solution of alcohol 2 (2.15 g, 4.46 mmol) in anhydr DMF
(15 mL) was added 60% NaH in mineral oil (284 mg, 7.10 mmol)
at 0 °C under N2 atmosphere. After stirring for 10 min, allyl bro-
mide (0.50 mL, 5.91 mmol) was added. The resulting mixture was
stirred for 30 min at 0 °C, then was allowed to warm to ambient
temperature, and stirred for another 1.5 h. The mixture was poured
into satd aq NH4Cl and extracted with CH2Cl2. The organic phase
was washed with brine, dried over Na2SO4, and concentrated.
The residue was subjected to silica gel column chromatography
to furnish 3 (1.59 g, 3.04 mmol, 68%). ½a D22
ꢀ
ꢁ14.6 (c 1.0); 1H NMR
(400 MHz) d 7.38 (d, 2H, J = 8.0 Hz, Ar-H), 6.87 (d, 2H, J = 8.0 Hz,
Ar-H), 5.93 (br s, 1H, CH3CONH), 5.89–5.81 (m, 1H, CH2CH@CH2),
5.46 (s, 1H, ArCHO2), 5.23–5.16 (m, 2H, H-1, CH2CH@CH2), 5.10
(d, 1H, J = 10.4 Hz, CH2CH@CH2), 4.31 (dd, 1H, J = 5.6, 13.2 Hz,
CH2CH@CH2), 4.24 (dd, 1H, J = 4.8, 10.8 Hz, H-6a), 4.14–4.07 (m,
3:2?2:1) to give 2 (2.22 g, 4.62 mmol, 67%). ½a D22
ꢁ49.7 (c 1.1);
ꢀ

142
D. Crich et al. / Carbohydrate Research 344 (2009) 140–144
2H, CH2CH@CH2, H-3), 3.78 (s, 3H, OCH3), 3.72 (t, 1H, J = 10.6 Hz,
H-6b), 3.58 (t, 1H, J = 9.0 Hz, H-4), 3.50–3.44 (m, 1H, H-5), 3.24–
3.21 (m, 1H, H-2), 1.95 (s, 3H, CH3CONH), 1.62–1.57 (m, 1H,
SiC(CH3)2CH(CH3)2), 0.86 (s, 3H, SiC(CH3)2CH(CH3)2), 0.85 (s, 3H,
SiC(CH3)2CH(CH3)2), 0.83 (s, 6H, SiC(CH3)2CH(CH3)2), 0.13 (s, 3H,
SiCH3), 0.12 (s, 3H, SiCH3); 13C NMR (100 MHz) d 170.4, 160.2,
135.3, 130.2, 127.6, 117.1, 113.8, 101.3, 95.5, 82.7, 76.8, 73.5,
69.0, 66.2, 60.2, 55.5, 34.2, 25.0, 23.8, 20.2, 18.8, ꢁ1.6, ꢁ3.2. ESIMS
m/z calcd for C27H43NO7SiNa [M+Na+]: 544.2693. Found: 544.2693.
reaction mixture was quenched with MeOH and the volatiles were
removed under reduced pressure. The residue was dissolved in
CH2Cl2 and washed with 0.1 N HCl, satd aq NaHCO3, and brine.
The organic phase was dried over Na2SO4 and concentrated. The
residue was subjected to silica gel column chromatography
(EtOAc–hexane 2:3) to afford acetate 6 (63.9 mg, 113
l
mol, 91%)
as a syrup. ½a 2D2
ꢀ
+15.1 (c 1.1); 1H NMR (500 MHz) d 7.22 (d, 2H,
J = 8.5 Hz, Ar-H), 6.84 (d, 2H, J = 9.0 Hz, Ar-H), 5.82–5.74 (m, 2H,
CH3CONH, CH2CH@CH2), 5.21–5.15 (m, 2H, H-1, CH2CH@CH2),
5.10 (dd, 1H, J = 1.5, 10.5 Hz, CH2CH@CH2), 4.89 (t, 1H, J = 9.5 Hz,
H-4), 4.43 (s, 2H, Ar-CH2), 4.17 (t, 1H, J = 9.5 Hz, H-3), 4.06–4.04
(m, 2H, CH2CH@CH2), 3.78 (s, 3H, OCH3), 3.63–3.59 (m, 1H, H-5),
3.49–3.48 (m, 2H, H-6a, H-6b), 3.14–3.09 (m, 1H, H-2), 1.96 (s,
3H, CH3COO), 1.94 (s, 3H, CH3CONH), 1.64–1.58 (m, 1H,
SiC(CH3)2CH(CH3)2), 0.86 (d, 3H, J = 2.0 Hz, SiC(CH3)2CH(CH3)2),
0.85 (d, 3H, J = 2.0 Hz, SiC(CH3)2CH(CH3)2), 0.83 (s, 3H, SiC(CH3)2-
CH(CH3)2), 0.82 (s, 3H, SiC(CH3)2CH(CH3)2), 0.16 (s, 3H, SiCH3),
0.12 (s, 3H, SiCH3); 13C NMR (125 MHz) d 170.5, 170.0, 159.4,
134.9, 130.4, 129.5, 116.9, 113.9, 94.6, 77.8, 73.3, 72.8, 72.1,
69.9, 60.2, 55.5, 34.3, 25.0, 23.8, 21.2, 20.3, 18.8, ꢁ1.6, ꢁ3.3. ESIMS
1.4. Dimethylthexylsilyl 2-acetamido-3-O-allyl-2-deoxy-6-
O-(4-methoxybenzyl)-b-
dimethylthexylsilyl 2-acetamido-3-O-allyl-2-deoxy-4-
O-(4-methoxybenzyl)-b- -glucopyranoside (5)
D-glucopyranoside (4) and
D
To a solution of 3 (1.59 g, 3.04 mmol), in anhyd DMF (22 mL) in
the presence of 4 Å MS was added NaBH3CN (1.91 g, 30.4 mmol)
followed by a solution of TFA (4.70 mL, 61 mmol) in anhydr DMF
(24 mL) at 0 °C over 25 min. After 1 h at 0 °C, the reaction mixture
was warmed to room temperature and stirred for another 4 h. At
this point, the reaction mixture was poured into H2O (500 mL)
and solid NaHCO3 was slowly added to neutralize the mixture to
pH 7.0. The water phase was extracted with CH2Cl2 (3 ꢂ 100 mL).
The collected organic phase was washed with brine, dried over
Na2SO4, and concentrated. The resulting residue was purified by
flash chromatography on silica gel to afford 4 (1.11 g, 2.12 mmol,
70%) and 5 (90.5 mg, 0.17 mmol, 6%).
m/z calcd for C29H47NO8SiNa [M
+
Na+]: 588.2969. Found:
588.2970.
1.6. Dimethylthexylsilyl 2-acetamido-6-O-acetyl-3-O-allyl-2-
deoxy-4-O-(4-methoxybenzyl)-b- -glucopyranoside (7)
D
Following a similar protocol for 6, 5 (87.2 mg, 166 lmol) was al-
For 4 ½a 2D1
ꢀ
ꢁ20.5 (c 0.8); 1H NMR (400 MHz) d 7.23 (d, 2H,
lowed to react with Ac2O (100 lL, 1.1 mmol) in pyridine (1 mL) to
J = 8.0 Hz, Ar-H), 6.85 (d, 1H, J = 8.8 Hz, Ar-H), 5.92–5.83 (m, 1H,
CH2CH@CH2), 5.72 (d, 1H, J = 7.2 Hz, CH3CONH), 5.24 (d, 1H,
J = 17.2 Hz, CH2CH@CH2), 5.13 (d, 1H, J = 9.6 Hz, CH2CH@CH2),
5.02 (d, 1H, J = 7.2 Hz, H-1), 4.53–4.46 (m, 2H, ArCH2O), 4.24 (dd,
1H, J = 5.6, 13.2 Hz, CH2CH@CH2), 4.15 (dd, 1H, J = 6.0, 13.2 Hz,
CH2CH@CH2), 3.85 (t, 1H, J = 10.0 Hz, H-3), 3.79 (s, 3H, OCH3),
3.69 (d, 2H, J = 4.8 Hz, H-6a, H-6b), 3.56 (t, 1H, J = 8.8 Hz, H-4),
3.51–3.46 (m, 1H, H-5), 3.25–3.20 (m, 1H, H-2), 3.08 (br s, 1H,
OH), 1.94 (s, 3H, CH3CONH), 1.63–1.56 (m, 1H, SiC(CH3)2CH(CH3)2),
0.86 (s, 3H, SiC(CH3)2CH(CH3)2), 0.84 (s, 3H SiC(CH3)2CH(CH3)2),
0.82 (s, 6H, SiC(CH3)2CH(CH3)2), 0.14 (s, 3H, SiCH3), 0.11 (s, 3H,
SiCH3); 13C NMR (100 MHz) d 170.4, 159.5, 135.4, 130.2, 129.5,
117.2, 114.0, 95.2, 80.6, 74.0, 73.5, 73.2, 59.2, 55.5, 34.1, 25.0,
23.8, 20.1, 18.7, ꢁ1.6, ꢁ3.3. ESIMS m/z calcd for C27H45NO7SiNa
[M+Na+]: 546.2851. Found: 546.2863.
furnish 7 (78.0 mg, 138
l
mol, 83%) as a syrup. ½a D22
ꢀ
+20.8 (c 1.1); 1H
NMR (500 MHz) d 7.22 (d, 2H, J = 8.5 Hz, Ar-H), 6.85 (d, 2H,
J = 8.5 Hz, Ar-H), 5.94–5.86 (m, 1H, CH2CH@CH2), 5.80–5.76 (m,
1H, CH3CONH), 5.25 (dd, 1H, J = 1.5, 17.5 Hz, CH2CH@CH2), 5.14
(d, 1H, J = 10.5 Hz, CH2CH@CH2), 4.97 (d, 1H, J = 8.0 Hz, H-1), 4.73
(d, 1H, J = 10.5 Hz, Ar-CH2), 4.48 (d, 1H, J = 10.5 Hz, ArCH2), 4.30–
4.25 (m, 2H, CH2CH@CH2, H-6a), 4.17–4.10 (m, 2H, CH2CH@CH2,
H-6b), 3.95 (t, 1H, J = 9.5 Hz, H-3), 3.78 (s, 3H, OCH3), 3.54–3.51
(m, 1H, H-5), 3.38 (t, 1H, J = 9.0 Hz, H-4), 3.31–3.26 (m, 1H, H-2),
2.01 (s, 3 H, CH3COO), 1.94 (s, 3H, CH3CONH), 1.61–1.56 (m, 1H,
SiC(CH3)2CH(CH3)2), 0.85 (d, 3H, J = 1.5 Hz, SiC(CH3)2CH(CH3)2),
0.83 (d, 3H, 1.0 Hz, SiC(CH3)2CH(CH3)2), 0.81 (s, 3H, SiC(CH3)2-
CH(CH3)2), 0.80 (s, 3H, SiC(CH3)2CH(CH3)2), 0.11 (s, 3H, SiCH3),
0.10 (s, 3H, SiCH3); 13C NMR (125 MHz) d 171.0, 170.3, 159.6,
135.2, 130.1, 130.0, 117.1, 114.1, 95.0, 80.8, 78.2, 74.4, 73.7, 73.0,
63.6, 59.5, 55.5, 34.3, 25.0, 23.8, 21.0, 20.3, 20.2, 18.7, ꢁ1.7, ꢁ3.3.
ESIMS m/z calcd for C29H47NO8SiNa [M + Na+]: 588.2969. Found:
588.2967.
For 5 ½a 2D1
ꢀ
+5.2 (c 0.6); 1H NMR (500 MHz) d 7.23 (d, 2H,
J = 8.5 Hz, Ar-H), 6.85 (d, 1H, J = 8.0 Hz, Ar-H), 5.92–5.86 (m, 1H,
CH2CH@CH2), 5.84 (d, 1H, J = 8.5 Hz, CH3CONH), 5.24 (d, 1H,
J = 17.0 Hz, CH2CH@CH2), 5.14 (d, 1H, J = 10.5 Hz, CH2CH@CH2),
5.02 (d, 1H, J = 7.5 Hz, H-1), 4.73 (d, 1H, J = 10.5 Hz, ArCH2O), 4.54
(d, 1H, J = 11.0 Hz, ArCH2O), 4.28 (dd, 1H, J = 5.0, 12.5 Hz,
CH2CH@CH2), 4.14 (dd, 1H, J = 6.0, 13.0 Hz, CH2CH@CH2), 3.93 (t,
1H, J = 10.0 Hz, H-3), 3.78 (s, 4H, OCH3, H-6a), 3.64–3.62 (m, 1H,
H-6b), 3.45 (t, 1H, J = 9.5 Hz, H-4), 3.42–3.38 (m, 1H, H-5), 3.30–
3.25 (m, 1H, H-2), 1.98 (s, 3H, CH3CONH), 1.63–1.56 (m, 1H,
SiC(CH3)2CH(CH3)2), 0.86 (s, 3H, SiC(CH3)2CH(CH3)2), 0.84 (s, 3H,
SiC(CH3)2CH(CH3)2), 0.82 (s, 6H, SiC(CH3)2CH(CH3)2), 0.14 (s, 3H,
SiCH3), 0.10 (s, 3H, SiCH3); 13C NMR (125 MHz) d 170.4, 159.6,
135.3, 130.4, 129.9, 117.0, 114.1, 95.2, 80.8, 78.3, 75.2, 74.6, 73.7,
62.5, 59.6, 55.5, 34.2, 25.0, 23.8, 20.2, 18.7, ꢁ1.5, ꢁ3.2. ESIMS m/z
calcd for C27H45NO7SiNa [M + Na+]: 546.2863. Found: 546.2863.
1.7. Dimethylthexylsilyl 2-O-benzoyl-3,4,6-tri-O-benzyl-b-
glucopyranosyl-(1?4)-2-acetamido-3-O-allyl-2-deoxy-6-O-(4-
methoxybenzyl)-b- -glucopyranoside (9)
D-
D
A solution of 4 (253 mg, 483
red for 2 h in the presence of 5 Å MS (820 mg) at ambient temper-
ature under N2 atmosphere after which TMSOTf (48 L, 265 mol)
lmol) in CH2Cl2 (15 mL) was stir-
l
l
was added followed by a solution of 89 (605.8 mg, 867 mmol) in
CH2Cl2 (8 mL) over 1.5 h. The mixture was stirred for another
2.5 h until TLC (EtOAc–hexane 2:3) showed that the reactant was
completely consumed. The reaction mixture was diluted with
CH2Cl2 and the solid was filtered off. The filtrate was washed with
satd aq NaHCO3 and brine. The collected organic phase was dried
over Na2SO4 and concentrated. The resulting residue was purified
by flash chromatography (EtOAc–hexane 2:5) on silica gel to afford
1.5. Dimethylthexylsilyl 2-acetamido-4-O-acetyl-3-O-allyl-2-
deoxy-6-O-(4-methoxybenzyl)-b-D-glucopyranoside (6)
disaccharide 9 (260.0 mg, 245
l
mol, 51%). ½a 2D1
ꢀ
+13.1 (c 0.8); 1H
To a solution of 4 (65.0 mg, 124
(1 mL) was added Ac2O (80.0 L, 846
was stirred for 4 h at room temperature under N2 atmosphere. The
lmol) in anhydrous pyridine
NMR (500 MHz) d 7.97 (d, 2H, J = 7.5 Hz, Ar-H), 7.58 (t, 1H,
J = 7.5 Hz, Ar-H), 7.46–7.57 (t, 2H, J = 8.0 Hz, Ar-H), 7.38–7.11 (m,
17H, Ar-H), 6.88 (d, 2H, J = 8.5 Hz, Ar-H), 5.88–5.82 (m, 2H,
l
lmol). The resulting mixture

D. Crich et al. / Carbohydrate Research 344 (2009) 140–144
143
CH3CONH, CH2CH@CH2), 5.24–5.18 (m, 2H, H00-2, CH2CH@CH2),
5.05 (d, 1H, J = 10.5 Hz, CH2CH@CH2), 4.81 (d, 1H, J = 10.5 Hz,
ArCH2), 4.76 (d, 1H, J = 6.5 Hz, H0-1), 4.74 (d, 1H, J = 11.5 Hz, ArCH2),
4.66–4.52 (m, 6H, H00-1, ArCH2), 4.31 (d, 1H, J = 11.5 Hz, ArCH2),
4.28 (dd, 1H, J = 5.0, 13.0 Hz, CH2CH@CH2), 4.11 (dd, 1H, J = 5.5,
13.0 Hz, CH2CH@CH2) 3.96 (t, 1H, J = 7.0 Hz, H0-3), 3.83–3.69 (m,
8 H, OCH3, H0-4, H0-6a, H0-6b, H00-6a, H00-6b), 3.58–3.53 (m, 3H, H00-
3, H00-4, H0-5), 3.46–3.42 (m, 1 H, H00-5), 3.41–3.38 (m, 1H, H0-2),
1.99 (s, 3H, CH3CONH), 1.59–1.54 (m, 1H, SiC(CH3)2CH(CH3)2),
0.84 (d, 3H, J = 2.5 Hz, SiC(CH3)2CH(CH3)2), 0.82 (d, 3H, J = 2.5 Hz,
SiC(CH3)2CH(CH3)2), 0.78 (s, 3H, SiC(CH3)2CH(CH3)2), 0.77 (s, 3H,
SiC(CH3)2CH(CH3)2), 0.03 (s, 3H, SiCH3), ꢁ0.02 (s, 3H, SiCH3); 13C
NMR (125 MHz, CDCl3) d 170.1, 165.6, 159.5, 138.4, 138.3, 138.1,
135.6, 133.5, 130.6, 130.0, 129.8, 128.7, 128.6, 128.5, 128.2,
ing residue was dissolved in MeOH–CH2Cl2 (1:1, v:v, 6 mL). The
solution was cooled to 0 °C, and NaBH4 (58 mg, 1.5 mmol) was
added. The resulting mixture was stirred for 12 h, while the tem-
perature was elevated to the ambient. TLC (EtOAc–CH2Cl2 1:1)
showed that the reaction went to completion. The reaction mixture
was quenched with AcOH and concentrated. The residue was di-
luted with CH2Cl2 and washed with brine. The organic phase was
dried over Na2SO4 and concentrated. The residue was applied to
silica gel column (EtOAc–CH2Cl2 1:2) to afford 11 (92.3 mg,
97
l
mol, 84%) and 10 (5.0 mg, 5.2
l
mol, 4.5%).
Compound 11: ½a 2D1
ꢀ
+2.8 (c 1.0); 1H NMR (500 MHz) d 7.36–7.20
(m, 17H, Ar-H), 6.85 (d, 2H, J = 8.5 Hz, Ar-H), 5.94 (d, 1H, J = 8.0 Hz,
CH3CONH), 5.87–5.81 (m, 1H, CH2@CHCH2), 5.19 (d, 1H, J = 12.5 Hz,
CH2@CHCH2), 5.05 (d, 1H, J = 10.0 Hz, CH2@CHCH2), 5.02 (d, 1H,
J = 6.5 Hz, H0-1), 4.86 (d, 1H, J = 11.0 Hz, ArCH2), 4.67 (d, 1H,
J = 12.0 Hz, ArCH2), 4.61 (s, 1H, H00-1), 4.58–4.51 (m, 5H, ArCH2),
4.43 (d, 1H, J = 11.5 Hz, ArCH2), 4.28 (dd, 1H, J = 5.5, 12.5 Hz,
CH2@CHCH2), 4.10 (dd, 1H, J = 6.0, 12.5 Hz, CH2@CHCH2), 4.03 (d,
1H, J = 3.0 Hz, H00-2), 3.99 (t, 1H, J = 8.0 Hz, H0-3), 3.93 (t, 1H,
J = 8.0 Hz, H0-4), 3.87 (t, 1H, J = 9.5 Hz, H00-4), 3.77–3.69 (m, 7H,
OCH3, H0-6a, H0-6b, H00-6a, H00-6b), 3.60–3.57 (m, 1H, H0-5), 3.47–
3.42 (m, 2H, H0-2, H00-3), 3.36–3.33 (m, 1H, H00-5), 2.60 (br s, 1H,
OH), 1.94 (s, 3H, CH3CONH), 1.66–1.60 (m, 1H, SiC(CH3)2CH(CH3)2),
0.87 (d, 3H, J = 2.5 Hz, SiC(CH3)2CH(CH3)2), 0.86 (d, 3H, J = 2.5 Hz,
SiC(CH3)2CH(CH3)2), 0.84 (s, 6H, SiC(CH3)2CH(CH3)2), 0.15 (s, 3H,
SiCH3), 0.13 (s, 3H, SiCH3); 13C NMR (125 MHz) d 170.2, 159.4,
138.5, 138.4, 135.6, 130.4, 129.6, 128.7, 128.6, 128.5, 128.3,
00
00
00
128.1, 128.0, 127.8, 116.5, 114.1, 99.9 (C1 , JC1 –H1 = 163.4), 95.2
0
0
0
(C1 , JC1 –H1 = 164.2), 83.1, 78.3, 78.2, 75.4, 75.2, 74.6, 74.4, 73.8,
73.3, 72.6, 68.9, 68.8, 56.5, 55.4, 34.2, 25.0, 23.7, 20.3, 18.8, ꢁ1.8,
ꢁ3.4. ESIMS m/z calcd for C61H77NO13SiNa [M+Na+]: 1082.5062.
Found: 1082.5066.
1.8. Dimethylthexylsilyl 3,4,6-tri-O-benzyl-b-D-glucopyranosyl-
(1?4)-2-acetamido-3-O-allyl-2-deoxy-6-O-(4-methoxybenzyl)-
b-
D-glucopyranoside (10)
To a solution of 9 (160.0 mg, 151
6 mL) was added a solution of NaOMe in MeOH (25 wt %, 150
l
mol) in MeOH–THF (1:1, v:v,
L,
mol). The resultant mixture was stirred for 18 h at ambient
l
656
l
00
00
00
temperature under N2 atmosphere. Monitoring by TLC (MeOH–
CH2Cl2 1:4) indicated that the reaction went to completion. The
reaction mixture was neutralized with Amberlite IR-120 resin
(H+), filtered, and the filtrate was concentrated. The residue was
purified by flash chromatography on silica gel (EtOAc–CH2Cl2
128.1, 127.9, 127.7, 116.6, 114.1, 100.0 (C1 , JC1 –H1 = 160.6), 95.0
0
0
0
(C1 , JC1 –H1 = 165.0), 81.9, 78.6, 76.0, 75.6, 75.4, 74.7, 74.3, 73.7,
73.4, 73.0, 71.6, 69.4, 68.1, 57.8, 55.4, 34.3, 25.0, 23.8, 20.3, 18.8,
ꢁ1.7, ꢁ3.2. ESIMS m/z calcd for C54H73NO12SiNa [M + Na+]:
978.4800. Found: 978.4818.
1:5) to furnish alcohol 10 (110.5 mg, 116
l
mol, 77%). ½a 2D1
ꢀ
+17.5
(c 1.3); 1H NMR (500 MHz) d 7.39–7.27 (m, 15H, Ar-H), 7.17 (d,
2H, J = 7.5 Hz, Ar-H), 6.87 (d, 2H, J = 9.0 Hz, Ar-H), 5.88–5.81 (m,
1H, CH2CH@CH2), 5.75 (d, 1H, J = 7.5 Hz, CH3CONH), 5.19 (d, 1H,
J = 12.5 Hz, CH2CH@CH2), 5.06–5.03 (m, 2H, CH2CH@CH2, H0-1),
4.94 (d, 1H, J = 11.5 Hz, ArCH2), 4.84–4.80 (m, 2H, ArCH2), 4.62 (d,
1H, J = 12.0 Hz, ArCH2), 4.58–4.47 (m, 5H, ArCH2, H00-1), 4.45 (dd,
1H, J = 5.0, 12.5 Hz, CH2CH@CH2), 4.08–4.02 (m, 2H, CH2CH@CH2,
H0-3), 3.96–3.91 (m, 2H, H0-4, H0-6a), 3.76 (s, 3H, OCH3), 3.70–
3.66 (m, 3H, H0-6b, H00-6a, H00-6b), 3.63–3.59 (m, 2H, H00-4, OH),
3.52–3.45 (m, 3H, H00-2, H00-3, H0-5), 3.42–3.39 (m, 1H, H00-5),
3.25–3.20 (m, 1H, H0-2), 1.94 (s, 3H, CH3CONH), 1.65–160 (m, 1H,
SiC(CH3)2CH(CH3)2), 0.88 (d, 3H, J = 2.5 Hz, SiC(CH3)2CH(CH3)2),
0.87 (d, 3H, J = 2.5 Hz, SiC(CH3)2CH(CH3)2), 0.84 (s, 3H, SiC(CH3)2-
CH(CH3)2), 0.83 (s, 3H, SiC(CH3)2CH(CH3)2), 0.16 (s, 3H, SiCH3),
0.12 (s, 3H, SiCH3); 13C NMR (125 MHz) d 170.3, 159.5, 139.1,
138.5, 138.4, 135.7, 129.9, 128.6, 128.5, 128.2, 128.1, 128.0,
1.10. Dimethylthexylsilyl 2-O-(benzylsulfonyl)-3,4,6-tri-O-
benzyl-b-
deoxy-6-O-(4-methoxybenzyl)-b-
D
-mannopyranosyl-(1?4)-2-acetamido-3-O-allyl-O-2-
-glucopyranoside (12)
D
To a solution of 11 (89.0 mg, 93
lmol) in pyridine (2 mL) was
added benzylsulfonyl chloride (31.0 mg, 162
lmol) at 0 °C under
N2 atmosphere. After stirring 7 h, TLC (EtOAc–hexane 1:1) showed
that the reaction went to completion. The reaction mixture was di-
luted with CH2Cl2, washed with 0.1 N HCl, satd aq NaHCO3, and
brine. The combined organic phase was dried over Na2SO4 and con-
centrated. The residue was purified by flash chromatography on
silica gel (EtOAc–hexane 2:3) to afford sulfonate 12 (100 mg,
90
l
mol, 97%) as a syrup. ½a D22
ꢀ
ꢁ43.6 (c 0.8); 1H NMR (500 MHz)
d 7.42–7.26 (m, 22H, Ar-H), 6.85 (d, 2H, J = 9.0 Hz, Ar-H), 5.93 (d,
1H, J = 8.5 Hz, CH3CONH), 5.84–5.78 (m, 1H, CH2@CHCH2), 5.17
(d, 1H, J = 17.0 Hz, CH2@CHCH2), 5.11 (d, 1H, J = 2.0 Hz, H00-2),
5.03 (d, 1H, J = 10.5 Hz, CH2@CHCH2), 4.93 (d, 1H, J = 7.5 Hz, H0-
1), 4.90 (d, 1H, J = 10.5 Hz, ArCH2), 4.76 (d, 1H, J = 11.0 Hz, ArCH2),
4.63–4.49 (m, 6H, ArCH2, H00-1), 4.43 (d, 1H, J = 12.0 Hz, ArCH2),
4.38 (s, 2H, ArCH2SO2), 4.22 (dd, 1H, J = 5.0, 13.0 Hz, CH2@CHCH2),
4.13 (dd, 1H, J = 5.5, 13.0 Hz, CH2@CHCH2), 3.97 (t, 1H, J = 6.0 Hz,
H0-3), 3.81–3.65 (m, 11H, OCH3, H0-2, H0-4, H0-5, H0-6a, H0-6b, H00-
4, H00-6a, H00-6b), 3.53–3.50 (dd, 1H, J = 3.0, 9.5 Hz, H00-3), 3.34–
3.32 (m, 1H, H00-5) 1.80 (s, 3H, CH3CONH), 1.64–1.60 (m, 1H,
SiC(CH3)2CH(CH3)2), 0.88–0.84 (m, 12H, SiC(CH3)2CH(CH3)2), 0.15
(s, 3H, SiCH3), 0.14 (s, 3H, SiCH3); 13C NMR (125 MHz) d 170.1,
159.5, 138.5, 138.3, 137.4, 135.7, 131.1, 130.5, 129.7, 129.0,
128.9, 128.8, 128.7, 128.6, 128.5, 128.4, 128.3, 128.2, 128.1,
00
00
00
0
127.9, 127.8, 116.2, 114.0, 103.4 (C1 , JC1 –H1 = 165.7), 95.0 (C1 ,
0
0
JC1 –H1 = 164.1), 84.8, 79.5, 77.7, 76.1, 75.3, 75.2, 74.4, 73.7, 73.6,
73.3, 69.1, 68.9, 59.1, 55.4, 34.3, 25.0, 23.8, 20.3, 18.8, ꢁ1.6, ꢁ3.2.
ESIMS m/z calcd for C54H73NO12SiNa [M + Na+]: 978.4800. Found:
978.4823.
1.9. Dimethylthexylsilyl 3,4,6-tri-O-benzyl-b-
mannopyranosyl-(1?4)-2-acetamido-3-O-allyl-2-deoxy-6-O-(4-
methoxybenzyl)-b- -glucopyranoside (11)
D-
D
To a solution of 10 (110.5 mg, 116
lmol) in CH2Cl2 (6 mL) was
added Dess–Martin periodinane (97 mg, 229
lmol). The resulting
00
00
00
0
mixture was stirred for 2 h at ambient temperature under N2 tem-
perature. Monitoring by TLC (EtOAc–hexane 1:1) showed the reac-
tion went to completion. The mixture was diluted with CH2Cl2,
washed with satd aq NaHCO3 containing Na2S2O3 and brine. The
organic phase was dried over Na2SO4 and concentrated. The result-
128.0, 127.8, 116.4, 114.1, 98.3 (C1 , JC1 –H1 = 160.4), 95.3 (C1 ,
0
0
JC1 –H1 = 163.4), 80.3, 79.0, 77.8, 75.9, 75.6, 75.5, 74.3, 73.8, 73.4,
72.8, 72.1, 69.8, 69.1, 57.9, 56.6, 55.4, 34.3, 25.0, 23.4, 20.3, 18.8,
ꢁ1.7, ꢁ3.2. ESIMS m/z calcd for C61H79NO14SiNa [M+Na+]:
1132.4888. Found: 1132.4905.

144
D. Crich et al. / Carbohydrate Research 344 (2009) 140–144
2. Abdel-Rahman, A. A.-H.; Jonke, S.; El Ashry, E. S. H.; Schmidt, R. R. Angew. Chem.,
Acknowledgment
Int. Ed. 2004, 43, 4389.
3. Abdel-Rahman, A. A.-H.; Jonke, S.; El Ashry, E. S. H.; Schmidt, R. R. Angew. Chem.,
Int. Ed. 2008, 47, 5277.
4. Bernardi, A.; Arosio, D.; Manzoni, L.; Monti, D.; Posteri, H.; Potenza, D.; Mari, S.;
Jiménez-Barbero, J. Org. Biomol. Chem. 2003, 785–792.
We thank the NIH (GM62160) for support of this work.
Supplementary data
5. Johansson, R.; Samuelsson, B. J. Chem. Soc., Perkin Trans.
1 1984, 2371–
2374.
6. Pozsgay, V.; Brisson, J.-R.; Jennings, H. J. Carbohydr. Res. 1990, 205, 133–146.
7. Ekborg, G.; Lindberg, B.; Lonngren, J. Acta Chem. Scand. B 1972, 26, 3287–
3292.
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.carres.2008.10.007.
8. Shaban, M. A. E.; Jeanloz, R. W. Carbohydr. Res. 1976, 52, 115–127.
9. Nicolaou, K. C.; Mitchell, H. J.; Jain, N. F.; Bando, T.; Hughes, R.; Winssinger, N.;
Natarajan, S.; Koumbis, A. E. Chem. Eur. J. 1999, 5, 2648–2667.
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