Selective deprotection of terminal isopropylidene acetals and trityl ethers using HClO4 supported on silica gel

Article abstract of DOI:10.1016/j.carres.2005.04.005

Terminal isopropylidene acetals are selectively cleaved to the corresponding 1,2-diols in good to excellent yields in 6-24 h at room temperature by using the 'HClO₄?SiO₂' reagent system. Likewise, trityl ethers are readily cleaved to the corresponding alcohols in good to excellent yields within 2-3 h at room temperature. Work-up involves merely filtration of the reagent followed by purification of the crude product.

Full text of DOI:10.1016/j.carres.2005.04.005

Carbohydrate
RESEARCH
Carbohydrate Research 340 (2005) 1661–1667
Note
Selective deprotection of terminal isopropylidene acetals and
trityl ethers using HClO4 supported on silica gelI
Aditi Agarwal and Yashwant D. Vankar*
Department of Chemistry, Indian Institute of Technology, Kanpur 208 016, India
Received 10 February 2005; received in revised form 8 April 2005; accepted 8 April 2005
Available online 10 May 2005
Abstract—Terminal isopropylidene acetals are selectively cleaved to the corresponding 1,2-diols in good to excellent yields in 6–24 h
at room temperature by using the ꢀHClO4ÆSiO2ꢁ reagent system. Likewise, trityl ethers are readily cleaved to the corresponding alco-
hols in good to excellent yields within 2–3 h at room temperature. Work-up involves merely filtration of the reagent followed by
purification of the crude product.
ꢀ 2005 Elsevier Ltd. All rights reserved.
Keywords: Isopropylidene acetals; Trityl ether; HClO4–SiO2
Selective protection and deprotection of functional
groups is extremely useful in organic synthesis. Isopro-
pylidene acetals (acetonides) have been widely used for
the protection of 1,2- and 1,3-diols in carbohydrate
and nucleoside chemistry.1 Hydrolysis of terminal iso-
propylidene acetals in the presence of internal ones is
often needed in a synthetic sequence. There are various
types of protic and Lewis acids that have been used
for the deprotection of isopropylidene acetals such as
aq H2SO4,2a Dowex acidic ion-exchange resin in
CH3OH–H2O (9:1),2b trifluoroacetic acid,2c Zn(NO3)2Æ
6H2O,3a and BiCl3.3b Clearly, some of the protic acids
are strongly acidic, and because water is invariably used
along with many of these reagents, sometimes nonselec-
tive hydrolysis is also observed leading to decreased
yields of the desired products. Interestingly, thiourea4
has been reported as a reagent for this purpose and this
can be considered as a somewhat neutral reagent. Iden-
tification of these various reagents was the result of
investigations aimed at improving the efficiency of
deprotections of terminal isopropylidene groups in
terms of cost, ease of handling of the reagent, mildness,
and duration of the reactions, and also ease of work-up.
There have also been attempts to introduce supported
5a
reagents like FeCl3Æ6H2O/SiO2 and NaHSO4ÆSiO2,5b
due to ease of work-up and environmental factors.
Likewise, trityl ethers have also served as excellent
protecting groups in organic synthesis, especially in car-
bohydrate chemistry,1 and consequently their deprotec-
tion is also reported using different reagents. As
applicable for isopropylidene deprotections, both protic
and Lewis acids such as formic acid,6a trifluoroacetic
7b
acid,6b BCl3,7a and Yb(OTf)3 have been reported for
the deprotection of trityl ethers. Recently, deprotection
of trityl ethers has been reported8a by using column
chromatography where the silica gel was saturated with
5% trifluoroacetic acid. More recently, deprotection of
trityl ethers has been reported8b by using NaHSO4ÆSiO2.
Clearly, the last two procedures fall in the category of
supported reagents.
Recently we have reported9a that HClO4 supported on
silica gel (HClO4ÆSiO2)10 acts as an efficient and mild re-
agent for both the Ferrier reaction of tri-O-acetyl glucal,
and the conversion of D-glucose and D-galactose into a
chiral furan diol. In these cases, the yields are excellent.
In continuation of these studies,9 we now report that
HClO4ÆSiO2 effectively deprotects terminal isopropylid-
ene groups and trityl ethers to form the desired products
q Transformations in Carbohydrate Chemistry. Part 11. For part 10,
see Ref. 9a.
*
Corresponding author. Tel.: +91 5122597169; fax: +91 5122597436;
e-mail: vankar@iitk.ac.in
0008-6215/$ - see front matter ꢀ 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2005.04.005

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A. Agarwal, Y. D. Vankar / Carbohydrate Research 340 (2005) 1661–1667
Table 1. Deprotection of isopropylidene acetals by HClO4ÆSiO2
a
in good to excellent yields. Deprotection of the isopro-
pylidene group is based on transacetalization, as
CH3OH is used as a solvent. The reactions were also
performed in other solvents such as CH2Cl2 and
CH3CN; however, they were found to be extremely slug-
gish in CH3CN whereas no reaction was observed in
CH2Cl2. Likewise, during the deprotection of trityl
ethers, CH3OH acts as a nucleophile to trap the gener-
ated trityl cation. Under these conditions, several func-
tional groups such as benzoyl, p-nitrobenzoyl, tosyl,
tert-butyldimethylsilyl, allyl, p-methoxyphenyl, thiophe-
nyl, and p-methoxybenzyl all remain unaffected. The
work-up simply involves filtration of the reagent fol-
lowed by evaporation of the solvent and purification
of the product by chromatography. Further, the reac-
tions could also be performed at relatively larger scale
(30–40 mmol) with practically no change in yields or
the reaction time. Thus, compound 16, which is needed
for other purposes, is routinely prepared in our labora-
tory by deprotecting acetonide 2 on a large scale using
HClO4ÆSiO2 and we find it very convenient because the
method avoids any aqueous work-up. Stirring a solution
of the substrate (a trityl ether or an acetonide) in
CH3OH with silica gel for several days did not permit
any appreciable cleavage indicating that HClO4 is neces-
sary to be used along with silica gel for the efficient
deprotections. Our results are summarized in Tables 1
Diisopropylidene
Product 1,2-diol
Time Yield
(%)
(h)
HO
O
O
O
HO
O
O
O
O
O
RO
RO
1: R = H11
2: R = Bn13
3: R = Allyl14
4: R = Ms15
5: R = Ts15
6: R = Bz
1512
1613
1714
1816
195b
1017
21
10
10
6
95
90
85
90
85
90
85
85
86
12
20
8
7: R = PNB
8: R =TBDMS5a
9: R = PMB18
10
24
10
223b
2318
O
HO
HO
O
O
O
OR
OR
O
O
O
O
10: R = Bn19
11: R = Bz20
2419
2521
20
20
88
85
O
O
HO
O
O
O
HO
O
OMe
OMe
O
OR
O
OR
12: R = H22
13: R = Bz
14: R = Ts
263a
27
24
24
24
87
85
85
1
and 2. All products were characterized by H NMR,
13C NMR, and mass spectral data and compared with
the literature data where available.
This supported reagent system is very cheap, environ-
mentally friendly and easy to handle. Furthermore, be-
cause the work-up involves merely filtration of the
reagent followed by purification, it is expected that these
methods will find application in organic synthesis.
28
a For compounds 1–11 the amount of reagent was 100 mg per 100 mg
of substrate; for 12–14, 200 mg of the reagent was used per 100 mg of
substrate.
1.2. Preparation of the HClO4ÆSiO2 reagent system
HClO4 (0.061 mL, as a 70% aqueous solution) was
added to a suspension of silica gel (2 g, 200–400 mesh)
in Et2O (20 mL) while swirling. The mixture was con-
centrated on a rotary evaporator under vacuum. The
residue so obtained was heated for 6 h at 100 ꢁC under
vacuum, while being magnetically stirred, to obtain
HClO4ÆSiO2 as a free flowing powder.
1. Experimental
1.1. General methods
1H NMR (400 MHz) and 13C NMR (100 MHz) were re-
corded on JEOL JNM-LA 400 FT NMR spectrometer
in a solution of CDCl3 as a solvent using Me3Si as an
internal standard. Infrared spectra were recorded on a
Bruker Vector 22 FT-IR spectrometer. Elemental analy-
ses were determined using Themoquest CE-instruments
EA-1110 automatic elemental analyzer. Mass spectra
were recorded on Microscopic II Triple Quadrupole
mass spectrometer using the electrospray technique.
Optical rotation values were recorded on Autopol II
automatic polarimeter at the wavelength of sodium
d-line (589 nm) at 25 ꢁC. Thin-layer chromatography
was performed on precoated silica gel plates (E-Merck,
Germany). Solvents and liquid reagents were purified
and dried according to recommended procedures.
1.3. Deprotection of isopropylidene acetals
To a solution of an isopropylidene acetal protected com-
pound (100 mg) in CH3OH (1.5 mL) was added HClO4Æ
SiO2 (amount according to Table 1). The heterogeneous
mixture was stirred at room temperature for the appro-
priate time (Table 1). After completion of the reaction
(TLC monitoring), the mixture was filtered and washed
with CH3OH. The combined filtrate was concentrated
under vacuum and the residue was purified by column
chromatography to obtain the pure 1,2-diol.

A. Agarwal, Y. D. Vankar / Carbohydrate Research 340 (2005) 1661–1667
1663
a
Table 2. Deprotection of trityl ethers by HClO4ÆSiO2
1.4. Deprotection of trityl ethers
Trityl ether
Time
(h)
Product
Yield
(%)
To a solution of a trityl ether (100 mg) in CH3OH
(1.5 mL) was added HClO4ÆSiO2 (100 mg) and the reac-
tion mixture was stirred at room temperature for the re-
quired time (see Table 2). After completion of the
reaction (TLC monitoring), the solution was filtered
and the filtered solid was washed with CH3OH. The
combined organic solution was concentrated under vac-
uum and the crude product was purified by column
chromatography to obtain the pure detritylated
product.
OTr
OH
O
O
2
92
BnO
BnO
BnO
BnO
BnO
BnO
OMe
OMe
2923
4024
OTr
OH
O
O
2
2
2
HO
90
90
85
HO
BnO
BnO
BnO
BnO
OMe
OMe
3025
4126
OTr
OH
1.5. 3-O-Benzoyl-1,2:5,6-di-O-isopropylidene-a-D-gluco-
furanose (6)
O
O
AllO
BnO
AllO
BnO
BnO
OH
BnO
OMe
OMe
OMe
OMe
To a solution of 1,2:5,6-di-O-isopropylidiene-a-D-gluco-
furanose (1, 260 mg, 1 mmol) in dry pyridine (3 mL) was
added benzoyl chloride (0.13 mL, 1.1 mmol) and the
reaction mixture was stirred at room temperature for
48 h. After completion of the reaction (TLC monitor-
ing), the solution was diluted with CH2Cl2, washed with
water and brine, dried over Na2SO4, and then concen-
trated under vacuum. The product was purified by col-
umn chromatography on silica gel, yielding 6 in 92%
yield; [a]D ꢀ3.5 (c 4.2, CHCl3); 1H NMR (400 MHz,
CDCl3): dH 1.28 (s, 3H, CH3), 1.32 (s, 3H, CH3), 1.43
(s, 3H, CH3), 1.56 (s, 3H, CH3), 4.09–4.15 (m, 2H, H-
6, H-60), 4.33–4.41 (m, 2H, H-4, H-5), 4.64 (d, 1H, J
3.7 Hz, H-2), 5.51 (d, 1H, J 2.7 Hz, H-3), 5.96 (d, 1H,
J 3.6 Hz, H-1), 7.43–7.69 (m, 3H, OCOC6H5), 8.02–
8.17 (m, 2H, OCOC6H5); 13C NMR (100 MHz, CDCl3):
dC 25.1, 26.1, 26.6, 26.7, 67.1, 72.5, 76.5, 79.8, 83.3,
105.0, 109.3, 112.3, 128.4, 128.8, 129.6, 130.5, 133.4,
134.5, 165.1; IR (CH2Cl2) 3022, 1742 cmꢀ1; ESIMS
(m/z): 387 [M+Na]+, 281 [(Mꢀ84)+1]+. Anal. Calcd
for C19H24O7 (364.15): C, 62.63; H, 6.64. Found: C,
62.66; H, 6.61.
3125
42
OTr
O
O
BzO
BnO
BzO
BnO
BnO
BnO
OMe
OMe
32
43
OTr
O
OH
O
2
MsO
BnO
85
89
MsO
BnO
BnO
BnO
33
34
44
OH
OTr
O
O
SPh
SPh
2.5
BnO
BnO
BnO
BnO
OBn
OBn
4527
OH
OTr
O
O
BnO
BnO
BnO
BnO
2
2
86
85
BnO
BnO
OMp
OMp
35
46
TrO
TrO
TrO
HO
O
O
O
O
O
O
AllO
AllO
1.6. 1,2:5,6-Di-O-isopropylidene-3-O-p-nitrobenzoyl-a-D-
glucofuranose (7)
3628
4728
HO
O
O
2
3
O
O
90
85
O
To a solution of 1,2:5,6-di-O-isopropylidiene-a-D-gluco-
furanose (1, 260 mg, 1 mmol) in dry CH2Cl2 (3 mL) was
added p-nitrobenzoyl chloride (204 mg, 1 mmol) and tri-
ethylamine (0.15 mL, 1 mmol). The reaction mixture
was stirred at room temperature for 48 h. After comple-
tion of the reaction (TLC monitoring) the solution was
diluted with CH2Cl2 and washed with water and brine,
dried over Na2SO4 and then concentrated under vac-
uum. The crude product was purified by column chro-
matography on silica gel to give the product in 72%
O
BnO
BnO
3729
4829
HO
O
O
O
O
O
O
TsO
TsO
3828
4928
TrO
HO
O
O
O
2.5
O
O
87
1
O
yield as a syrup; [a]D ꢀ50.7 (c 0.8, CHCl3); H NMR
MsO
MsO
(400 MHz, CDCl3): dH 1.26 (s, 3H, CH3), 1.34 (s, 3H,
CH3), 1.41 (s, 3H, CH3), 1.57 (s, 3H, CH3), 4.07–4.09
(dd, 1H, J 4.2, 8.6 Hz, H-6), 4.09–4.14 (dd, 1H, J 5.1,
3930
5031
a 100 mg of HClO4ÆSiO2 was used per 100 mg of substrate.

1664
A. Agarwal, Y. D. Vankar / Carbohydrate Research 340 (2005) 1661–1667
8.5 Hz, H-60), 4.30–4.36 (m, 2H, H-4, H-5), 4.65 (d, 1H,
J 3.9 Hz, H-2), 5.53 (d, 1H, J 2.4 Hz, H-3), 5.97 (d, 1H,
J 3.6 Hz, H-1), 8.19–8.22 (m, 2H, OCOC6H5), 8.31–8.33
(2H, m, OCOC6H5); 13C NMR (100 MHz, CDCl3): dC
25.1, 25.2, 26.2, 26.7, 28.9, 67.5, 72.5, 76.1, 77.6, 79.9,
83.3, 105.1, 109.6, 112.5, 123.7, 130.8, 134.9, 150.8,
1.9. 1,2-O-Isopropylidene-3-O-p-nitrobenzoyl-a-D-gluco-
furanose (21)
The product was obtained in 85% yield as a syrup;
[a]D ꢀ14.9 (c 0.9, CH2Cl2); 1H NMR (400 MHz,
CDCl3): dH 1.34 (s, 3H, CH3), 1.56 (s, 3H, CH3),
3.74–3.89 (m, 3H, H-5, H-6, H-60), 4.31 (dd, 1H, J 2.7,
8.8 Hz, H-4), 4.70 (d, 1H, J 3.6 Hz, H-2), 5.56 (d, 1H,
J 2.7 Hz, H-3), 5.99 (d, 1H, J 3.7 Hz, H-1), 8.20–8.31
(m, 4H, OCOC6H5); 13C NMR (100 MHz, CDCl3): dC
26.1, 26.5, 29.6, 63.9, 68.4, 76.7, 78.9, 82.9, 104.9,
112.5, 123.7, 134.6, 150.9, 164.2; IR (CH2Cl2) 3428,
163.4; IR (CH2Cl2): 2988, 1734, 1607, 1531 cmꢀ1
;
ESIMS (m/z): 432 [M+Na]+, 325 [Mꢀ84]+. Anal. Calcd
for C19H23NO9 (409.14): C, 55.74; H, 5.66; N, 3.42.
Found: C, 55.67, H, 5.61; N, 3.39.
1.7. 2-O-Benzoyl-3,4:5,6-di-O-isopropylidene-D-gluconate
(13)
2993, 1729, 1609, 1530 cmꢀ1
; ESIMS (m/z): 756
[2M+18]+, 387 [M+18]+, 370 [M+H]+. Anal. Calcd for
C16H19NO9 (369.11): C, 52.03; H, 5.19; N, 3.79. Found:
C, 52.00; H, 5.15; N, 3.69.
Benzoate 13 was synthesized from 12 following the pro-
cedure used for the preparation of 6. The product was
obtained in 92% yield as a yellow syrup; [a]D +2.0 (c
1
0.5, CH2Cl2); H NMR (400 MHz, CDCl3): dH 1.29 (s,
1.10. 2-O-Benzoyl 3,4-O-isopropylidene-D-gluconate (27)
3H, CH3), 1.33 (s, 3H, CH3), 1.43 (s, 3H, CH3), 1.53
(s, 3H, CH3), 3.81 (s, 3H, OCH3), 3.92–3.99 (m, 2H,
H-4, H-6), 4.13 (m, 2H, H-5, H-60), 4.60 (dd, 1H, J
2.2, 7.8 Hz, H-3), 5.62 (d, 1H, J 2.0 Hz, H-2), 7.45–
7.49 (m, 1H, OCOC6H5), 7.58–7.62 (m, 2H, OCOC6H5),
8.10–8.12 (m, 2H, OCOC6H5); 13C NMR (100 MHz,
CDCl3): dC 25.1, 26.6, 26.8, 27.2, 52.7, 67.6, 71.2, 76.6,
77.1, 79.4, 109.9, 110.5, 128.5, 129.2, 129.9, 133.5,
The product was obtained in 85% yield as a yellow syrup;
1
[a]D +7.8 (c 1.4, CHCl3); H NMR (400 MHz, CDCl3):
dH 1.39 (s, 3H, CH3), 1.48 (s, 3H, CH3), 3.63 (m, 1H,
H-6), 3.78 (s, 3H, CO2CH3), 3.80–3.85 (m, 2H, H-5,
H-60), 3.96–3.99 (dd, 1H, J 7.6, 7.3 Hz, H-4), 4.67 (dd,
1H, J 2.2, 7.3 Hz, H-3), 5.61 (d, 1H, J 2.2 Hz, H-2),
7.41–7.45 (m, 2H, OCOC6H5), 7.52–7.58 (m, 1H,
OCOC6H5), 8.10 (m, 2H, OCOC6H5); 13C NMR
(100 MHz, CDCl3): dC: 26.8, 27.3, 52.7, 63.8, 71.7,
72.9, 76.1, 78.6, 110.4, 128.5, 129.1, 130.0, 133.6, 166.0,
168.3; IR (CH2Cl2) 3530, 1747, 1714 cmꢀ1; ESIMS
(m/z): 377 [M+Na]+. Anal. Calcd for C17H22O8 (354.13):
C, 57.62; H, 6.26. Found: C, 57.55; H, 6.23.
165.7, 168.1; IR (CH2Cl2): 3025, 1747, 1730 cmꢀ1
;
ESIMS (m/z): 417 [M+Na]+. Anal. Calcd for
C20H26O8 (394.16): C, 60.90; H, 6.64. Found: C, 60.83;
H, 6.61.
1.8. 3,4:5,6-Di-O-isopropylidene-2-O-p-toluenesulfonyl-
D-gluconate (14)
1.11. 3,4-O-Isopropylidene-2-O-p-toluenesulfonyl-D-
gluconate (28)
To a solution of compound 12 (289 mg, 1 mmol) in pyr-
idine (3 mL), was added p-toluenesulfonyl chloride
(209.72 mg, 1.1 mmol). The reaction mixture was stirred
for 24 h at room temperature. After completion (TLC
monitoring) the solution was diluted with CH2Cl2,
washed with water and brine, dried over Na2SO4, and
concentrated under vacuum. The product was purified
by silica gel column chromatography to yield 14 in
91% yield as a yellow syrup; [a]D +2.0 (c 0.1, CHCl3);
1H NMR (400 MHz, CDCl3): dH 1.33, (s, 3H, CH3),
1.35 (s, 3H, CH3), 1.42 (s, 3H, CH3), 1.46 (s, 3H,
CH3), 2.44 (s, 3H, OCOC6H4–pCH3), 3.69 (s, 3H,
CO2CH3), 3.83–4.01 (m, 2H, H-4, H-6), 4.04–4.19 (m,
2H, H-5, H-60), 4.44–4.46 (dd, 1H, J 2.0, 7.1 Hz, H-3),
5.16 (d, 1H, J 2.0 Hz, H-1), 7.31–7.36 (m, 2H,
OCOC6H4–pCH3), 7.82–7.87 (m, 2H, OCOC6H4–pCH3);
13C NMR (100 MHz, CDCl3): dC 21.5, 25.2, 25.4,
26.3, 27.2, 52.6, 57.9, 58.1, 63.5, 75.6, 78.5, 109.6,
110.2, 128.2, 129.6, 132.8, 145.2, 167.3; IR (CH2Cl2)
1745 cmꢀ1; ESIMS (m/z): 467 [M+Na]+. Anal. Calcd
for C20H28O9S (444.15): C, 54.04; H, 6.35; S, 7.85.
Found: C, 54.00; H, 6.21; S, 7.87.
The product was obtained in 85% yield as a syrup;
1
[a]D +6.7 (c 0.2, CHCl3); H NMR (400 MHz, CDCl3):
dH 1.34 (s, 3H, CH3), 1.36 (s, 3H, CH3), 2.45 (s, 3H,
OCOC6H4–pCH3), 3.64 (m, 1H, H-6), 3.68 (s, 3H,
CO2CH3), 3.75–3.79 (m, 1H, H-5), 3.82 (dd, 1H, J 3.4,
11.5 Hz, H-60), 4.00 (dd, 1H, J 7.3, 7.1 Hz, H-4), 4.53
(dd, 1H, J 2.2, 7.8 Hz, H-3), 5.27 (d, 1H, J 2.0 Hz, H-
2), 7.35 (d, 2H, J 8.3 Hz, OCOC6H4–pCH3), 7.85 (d,
2H, J 8.0 Hz, OCOC6H4–pCH3); 13C NMR (100 MHz,
CDCl3): dC 21.6, 26.2, 27.1, 52.7, 57.9, 58.2, 63.4, 75.6,
78.5, 110.3, 128.1, 129.7, 132.8, 145.3, 167.2; IR
(CH2Cl2) 3540, 1746, 1341 cmꢀ1; ESIMS (m/z): 427
[M+Na]+. Anal. Calcd for C17H24O9S (404.11): C,
50.49; H, 5.98; S, 7.93. Found: C, 50.37; H, 5.89; S, 7.88.
1.12. Methyl 4-O-benzoyl-2,3-di-O-benzyl-6-O-trityl-
a-D-glucopyranoside (32)
This compound was synthesized from 30 by the same
procedure used for the preparation of 6. The product

A. Agarwal, Y. D. Vankar / Carbohydrate Research 340 (2005) 1661–1667
1665
was obtained in 92% yield as a syrup; [a]D +8.0 (c 0.3,
CHCl3); 1H NMR (400 MHz, CDCl3): dH 3.26–
3.36 (m, 2H, H-6, H-60), 3.42 (s, 3H, OCH3), 3.52–3.57
(m, 2H, H-2, H-5), 3.67–3.79 (m, 2H, H-3, H-4), 4.66
(d, 1H, J 3.7 Hz, H-1), 4.69 (d, 1H, J 11.0 Hz,
OCH2C6H5), 4.73 (d, 1H, J 11.2 Hz, OCH2C6H5), 4.77
(d, 1H, J 11.5 Hz, OCH2C6H5), 4.95 (d, 1H, J 11.5 Hz,
OCH2C6H5), 7.13–7.99 (m, 30H, 3 · OC(C6H5), 2 ·
OCH2C6H5, COC6H5); 13C NMR (100 MHz, CDCl3):
dC 55.1, 63.8, 71.5, 73.1, 75.6, 78.8, 79.4, 97.9, 127.0,
127.8, 127.9, 128.0, 128.4, 128.5, 128.7, 138.1, 143.8;
IR (CH2Cl2) 1735 cmꢀ1; ESIMS (m/z): 738 [M+18]+.
Anal. Calcd for C47H44O7 (720.31): C, 78.31; H, 6.15.
Found: C, 78.35; H, 6.10.
and NaH (172 mg, 7.15 mmol) in DMF (4 mL) was
added benzyl bromide (0.44 mL, 3.72 mmol) at 0 ꢁC
and the resulting mixture was stirred at room tempera-
ture for 5 h. Excess NaH was destroyed by CH3OH
and the reaction mixture was poured into water and ex-
tracted with CH2Cl2. The combined organic layers were
washed with brine, dried, and concentrated. The crude
product was purified by silica gel column chromatogra-
phy to give 34 in 70% yield as a yellow paste; [a]D ꢀ12.9
1
(c, 0.9, CHCl3); H NMR (400 MHz, CDCl3): dH 3.26
(m, 1H, H-5), 3.45 (dd, 1H, J 9.5 Hz, H-2), 3.58–
3.69 (m, 3H, H-6, H-60,H-4), 3.74 (dd, 1H, J 9.5 Hz,
H-3), 4.31 (d, 1H, J 10.2 Hz, H-1), 4.56–4.93 (m, 6H,
OCH2C6H5), 7.16–7.52 (m, 35H, 3 · OC(C6H5), 3 ·
OCH2C6H5, SC6H5); 13C NMR (100 MHz, CDCl3): dC
62.4, 72.1, 75.0, 75.4, 76.0, 76.7, 78.8, 80.8, 86.5, 86.8,
87.3, 126.9, 127.4, 127.6, 127.8, 128.1, 128.2, 128.4,
128.5, 128.8, 128.9, 131.9, 133.8, 137.6, 138.1, 138.3;
IR (CH2Cl2) 1122 cmꢀ1; ESIMS (m/z): 803 [M+18]+.
Anal. Calcd for C52H48O5S (784.32): C, 79.56; H, 6.16;
S, 4.08. Found: C, 78.93; H, 6.12; S, 4.12.
1.13. Methyl 2,3-di-O-benzyl-4-O-methanesulfonyl-6-
O-trityl-a-D-glucopyranoside (33)
To a solution of compound 30 (616 mg, 1 mmol) in dry
CH2Cl2 at 0 ꢁC, was added triethylamine (0.15 mL,
1.5 mmol) and methanesulfonyl chloride (0.09 mL,
1.2 mmol). The reaction mixture was stirred for 1 h
and after completion of reaction (TLC monitoring) aq
NaHCO3 was added. The organic layer was separated,
washed with water, brine, dried over Na2SO4, and con-
centrated under vacuum. The product was purified by
silica gel column chromatography to give 33 in 82%
1.15. p-Methoxyphenyl 2,3,4-tri-O-benzyl-6-O-trityl-
a-D-glucopyranoside (35)
p-Methoxyphenyl 2,3,4,6-tetra-O-acetyl-a-D-glucopyr-
anoside was prepared according to the literature proce-
dure.33 To a solution of this compound (465 mg,
1 mmol) in CH3OH (4 mL) was added NaOCH3 to
maintain the pH of the solution at 10. After stirring
the solution for 6 h at room temperature, it was neutral-
ized by addition of Dowex-50 (H+). The mixture was fil-
tered and concentrated under vacuum. The residue was
selectively tritylated and benzylated using the same pro-
cedure employed for the synthesis of 34. Compound 35
was obtained in 72% yield as a yellow syrup; [a]D +63.3
1
yield as a syrup; [a]D +35.5 (c 0.7, CHCl3); H NMR
(400 MHz, CDCl3): dH 2.79 (s, 3H, SO2CH3), 3.17 (dd,
1H, J 7.6, 7.3 Hz, H-6), 3.38 (s, 3H, OCH3), 3.44 (dd,
1H, J 7.3 Hz, H-60) 3.58 (dd, 1H, J 3.4, 9.8 Hz, H-2),
3.71–3.75 (m, 1H, H-5), 3.91–4.06 (dd, 1H, J 9.3 Hz,
H-4), 4.45–4.50 (t, 1H, J 8.8 Hz, H-3), 4.65 (d, 1H, J
3.4 Hz, H-1), 4.61–4.64 (m, 2H, OCH2C6H5), 4.74 (d,
1H, J 12.0 Hz, OCH2C6H5), 5.08 (d, 1H, J 11.2 Hz,
OCH2C6H5), 7.26–7.33 (m, 25H, 2 · OCH2C6H5,
OC(C6H5)3); 13C NMR (100 MHz, CDCl3): dC 38.2,
55.5, 60.3, 69.6, 73.3, 75.7, 76.7, 77.6, 78.5, 80.1, 97.7,
127.2, 127.8, 127.9, 128.3, 128.5, 128.6, 137.8, 146.8;
IR (CH2Cl2) 1125 cmꢀ1; ESIMS (m/z): 712 [M+18]+,
695 [M+1]+. Anal. Calcd for C41H42O8S (694.26):
C, 70.87; H, 6.09; S, 4.61. Found: C, 70.77; H, 5.99; S,
4.59.
1
(c, 0.4, CHCl3); H NMR (400 MHz, CDCl3): dH 3.14
(m, 1H, H-5), 3.45 (dd, 1H, J 10.2 Hz, H-2), 3.55 (m,
2H, H-3, H-6), 3.77 (s, 3H, OCH3), 3.95 (m, 1H, H-
60), 4.23 (t, 1H, J 9.3 Hz, H-4), 4.35 (dd, 1H, J
11.0 Hz, OCH2C6H5), 4.69–4.74 (m, 5H, OCH2C6H5),
5.48 (d, 1H, J 3.4 Hz, H-1), 6.83–7.45 (m, 34H, 3 ·
OCH2C6H5, OC6H4–pOCH3); 13C NMR (100 MHz,
CDCl3): dC 55.6, 62.7, 65.4, 70.6, 73.5, 74.6, 76.7, 79.5,
86.3, 95.5, 114.5, 118.2, 126.9, 127.0, 127.7, 127.9,
128.0, 128.3, 128.6, 128.8, 143.9; IR (CH2Cl2)
1132 cmꢀ1; ESIMS (m/z): 816 [M+18]+. Anal. Calcd
for C53H50O7 (798.36): C, 79.67; H, 6.31. Found: C,
79.31; H, 6.18.
1.14. Phenyl 2,3,4-tri-O-benzyl-1-thio-6-O-trityl-b-D-
glucopyranoside (34)
Phenyl 1-thio-b-D-glucopyranoside was prepared
according to the literature procedure.32 A solution of
this compound (400 mg, 1.48 mmol) and trityl chloride
(380 mg, 1.35 mmol) in pyridine was stirred at room
temperature for 24 h. The mixture was poured into
water and extracted with CH2Cl2. The combined extract
was washed with water, dried, and concentrated in vac-
uum to give crude phenyl 1-thio-6-O-trityl-b-D-gluco-
pyranoside (637 mg). To a mixture of this intermediate
1.16. Methyl 4-O-allyl-2,3-di-O-benzyl-a-D-gluco-
pyranoside (42)
The product was obtained in 90% yield as a white solid;
mp 77–78 ꢁC; [a]D +40.9 (c 1, CHCl3); lit.26 mp 76–
79 ꢁC; [a]D +39.2 (c 1, CHCl3); 1H NMR (400 MHz,

1666
A. Agarwal, Y. D. Vankar / Carbohydrate Research 340 (2005) 1661–1667
CDCl3): dH 3.37 (s, 3H, OCH3), 3.35–3.40 (m, 1H,
H-4), 3.45 (dd, 1H, J 3.6, 9.5 Hz, H-2), 3.60–3.64 (m,
1H, H-5), 3.71 (dd, 1H, J 4.2, 11.7 Hz, H-6), 3.80 (dd,
1H, J 2.9, 11.7 Hz, H-60), 3.93 (dd, 1H, J 9.0, 9.5 Hz,
H-3), 4.11–4.15 (m, 1H, @CH–CH2), 4.31–4.35 (m,
1H, @CH–CH2), 4.56 (d, 1H, J 3.6 Hz, H-1), 4.64 (d,
1H, J 12.2 Hz, OCH2C6H5), 4.78 (d, 1H, J 11.0 Hz,
OCH2C6H5), 4.79 (d, 1H, J 12.2 Hz, OCH2C6H5), 4.93
(d, 1H, J 11.0 Hz, OCH2C6H5), 5.14–5.29 (m, 2H,
–CH@CH2), 5.86–5.93 (m, 1H, –CH@CH2), 7.25–7.39
(m, 10H, 2 · OCH2C6H5); 13C NMR (100 MHz,
CDCl3): dC 55.2, 61.9, 70.6, 73.4, 73.7, 75.7, 77.5,
79.8, 81.7, 98.2, 117.1, 127.6, 127.9, 128.0, 128.3,
1.19. p-Methoxyphenyl 2,3,4-tri-O-benzyl-a-D-gluco-
pyranoside (46)
The product was obtained in 87% yield as a foam; [a]D
+
64 (c 0.5, CHCl3); 1H NMR (400 MHz, CDCl3): dH
3.62–3.72 (m, 3H, H-2, H-3, H-6), 3.78–3.86 (m, 1H,
H-5, H-60), 4.18 (t, 1H, J 9.3 Hz, H-4), 4.66–4.71 (m,
2H, OCH2C6H5), 4.79 (d, 1H, J 11.9 Hz, OCH2C6H5),
4.89–4.93 (m, 2H, OCH2C6H5), 5.29 (d, 1H, J 3.6 Hz,
H-1), 6.81 (d, 2H, J 9.3 Hz, OC6H4–pOCH3), 6.96 (d,
2H, J 9.0 Hz, OC6H4–pOCH3), 7.28–7.40 (m, 15H,
OCH2C6H5); 13C NMR (100 MHz, CDCl3): dC 55.6,
61.6, 71.5, 73.3, 75.1, 75.8, 76.7, 79.9, 81.8, 96.5, 114.5,
118.3, 127.7, 127.9, 128.0, 128.4, 128.5, 138.1, 138.7,
150.6, 155.1; IR (CH2Cl2) 3429 cmꢀ1; ESIMS (m/z):
574 [M+18]+. Anal. Calcd for C34H36O7 (556.25): C,
73.36; H, 6.52. Found: C, 72.93; H, 6.45.
128.4, 134.7, 138.1, 138.7; IR (CH2Cl2) 3423 cmꢀ1
;
ESIMS (m/z): 437 [M+Na]+. Anal. Calcd for
C24H30O6 (414.20): C, 69.54; H, 7.30. Found: C, 69.51;
H, 7.24.
1.17. Methyl 4-O-benzoyl-2,3-di-O-benzyl-a-D-gluco-
pyranoside (43)
Acknowledgements
We thankthe Department of Science and Technology,
New Delhi for financial support (project SP/S1/G21/
2001). A.A. thanks the Council of Scientific and Indus-
trial Research, New Delhi for a Senior Research
Fellowship.
The product was obtained in 85% yield as a syrup;
[a]D +77.5 (c 0.4, CH2Cl2); 1H NMR (400 MHz,
CDCl3): dH 2.67 (br s, 1H, OH), 3.42 (s, 3H, OCH3),
3.57–3.77 (m, 4H, H-2, H-5, H-6, H-60), 4.12 (t, 1H, J
9.3 Hz, H-3), 4.66 (d, 1H, J 3.2 Hz, H-1), 4.69 (d, 2H,
J
11.0 Hz, OCH2C6H5), 4.81(d, 1H, J 12.2 Hz,
OCH2C6H5), 4.85 (d, 1H, J 11.2 Hz, OCH2C6H5), 5.14
(t, 1H, J 9.5 Hz, H-4), 7.13–7.99 (m, 15H, OCH2C6H5,
OCOC6H5); 13C NMR (100 MHz, CDCl3): dC 55.4,
61.1, 69.7, 71.1, 73.6, 75.5, 78.8, 79.4, 98.3, 127.5,
127.9, 128.0, 128.2, 129.1, 129.9, 133.5, 137.9, 138.1,
Supplementary data
Supplementary data associated with this article can be
found, in the online version at doi:10.1016/j.carres.
2005.04.005.
166.6; IR (CH2Cl2) 3502, 2917, 1732, 1557, 1450 cmꢀ1
;
ESIMS (m/z): 496 [M+18]+, 479 [M+1]+, 447 [Mꢀ31]+.
Anal. Calcd for C28H30O7 (478.20): C, 70.28; H, 6.32.
Found: C, 70.31; H, 6.32.
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[a]D +6.9 (c 0.7, CH2Cl2); 1H NMR (400 MHz, CDCl3):
dH 2.79 (s, 3H, SO2CH3), 3.39 (s, 3H, OCH3), 3.58 (dd,
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H, 6.21; S, 6.98.

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