Synthesis of aryl-2-deoxy-d-lyxo/arabino-hexopyranosides from 2-deoxy-1-thioglycosides

Article abstract of DOI:10.1016/j.carres.2007.02.030

The synthesis of either anomers of aryl 2-deoxy-d-glycopyranosides from 2-deoxy-1-thioglycosides is reported. The α-anomers form as the major product when thioglycosides react with differently substituted phenols and naphthols, in the presence of N-iodosu

Full text of DOI:10.1016/j.carres.2007.02.030

Carbohydrate Research 342 (2007) 1305–1314
Synthesis of aryl-2-deoxy-D-lyxo/arabino-hexopyranosides
from 2-deoxy-1-thioglycosides
Somak Paul and Narayanaswamy Jayaraman*
Department of Organic Chemistry, Indian Institute of Science, Bangalore 560 012, India
Received 16 December 2006; received in revised form 21 February 2007; accepted 25 February 2007
Available online 1 March 2007
Abstract—The synthesis of either anomers of aryl 2-deoxy-D-glycopyranosides from 2-deoxy-1-thioglycosides is reported. The
a-anomers form as the major product when thioglycosides react with differently substituted phenols and naphthols, in the presence
of N-iodosuccinimide/triflic acid. On the other hand, reaction of the thioglycosides with bromine initially, followed by reaction with
aryloxy anions lead to aryl 2-deoxy-b-D-glycosides with high specificities.
Ó 2007 Elsevier Ltd. All rights reserved.
Keywords: Aryl glycosides; Deoxysugars; Glycosylations; Thioglycosides
1. Introduction
1-thioglycosides, in the presence of thiophilic activators,
provided the a-anomeric glycosylated products. In
continuing the efforts to involve the newly formed
2-deoxy-1-thioglycosides in glycosylations, the prepara-
tion of aryl 2-deoxy-D-glycosides was undertaken.
b-Anomeric configuration is seen commonly in the aryl
2-deoxy-glycosides present in naturally occurring com-
pounds. Known synthetic methods to prepare the aryl
2-deoxy-glycosides are (i) acid catalyzed reaction of a
glycal with phenol;15 (ii) [4+2] cycloaddition of a glycal
with ortho-thioquinones, followed by a desulfuriza-
tion;16 (iii) an SN2-like displacement of 2-deoxy-
glycopyranosyl iodide sugar derivatives with aryloxy
anion;17 (iv) Lewis acid catalyzed reaction of anomeric
fluorides and acetates of 2-deoxy sugar donor with
phenols;18 (v) 2-deoxygenations of an arylglycoside;19
and (vi) a Mitsunobu glycosylation protocol.20 We
herein present the synthesis of aryl 2-deoxy-D-glyco-
sides, initiated from a 2-deoxy-1-thioglycoside as the
sugar donor.
Many naturally-occurring antibiotic and antitumor
drugs contain 2-deoxy glycosides as important struc-
tural components.1 The synthesis of these biologically
important 2-deoxy glycosides encounters difficulties
due to the absence of stereoelectronic influences at C-2
carbon of 2-deoxy glycosyl derivatives.2 Various meth-
odologies have been developed to synthesize 2-deoxy
glycosides. Prominent among them are the radical-med-
iated or reductive cleavage of a halo-3 or a sulfur4 or an
oxygen5 or a nitrogen6 or a selenium7 functionality at
C-2 of the glycosides. Direct methods of activating
2-deoxy sugars with phosphates,8 phosphoroamidites,9
phosphites,10 phosphorodithioates,11 phenylthioglyco-
sides,12 and (20-carboxyl)benzyl glycosides13 are also
known.
We have developed previously an efficient method to
synthesize activated 2-deoxy-1-thio sugar derivatives
that result from the reaction of glycals with a thiol
reagent in the presence of catalytic amount of ceric
ammonium nitrate.14 The 2-deoxy-1-thioglycosides
being an activated glycosyl donor, could be subjected
to glycosylation reactions directly. Glycosylation of
few aglycosyl and glycosyl acceptors with the 2-deoxy-
2. Results and discussion
2.1. Synthesis of aryl 2-deoxy-a-D-glycosides
Direct glycosylation of phenols with 2-deoxy-1-thio glyco-
sides was targeted initially, by employing commonly
*
Corresponding author. E-mail: jayaraman@orgchem.iisc.ernet.in
0008-6215/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2007.02.030

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S. Paul, N. Jayaraman / Carbohydrate Research 342 (2007) 1305–1314
R3
R5
OAc
OH
(i) ArOH, NIS, TfOH, CH2Cl2 or
MeCN, 30 min.
R4
AcO
O
R6
HO
O
R2
(ii) NaOMe/MeOH, 2 h, rt
R1
OAr
1: R1 = SEt (or H), R2 = H (or SEt), R3 = OAc, R4 = H
2: R1 = H, R2 = SEt, R3 = H, R4 = OAc
3-9: R5 = OH, R6 = H (from 1)
10-16: R5 = H, R6 = OH (from 2)
Scheme 1. Synthesis of aryl-2-deoxy-a-D-lyxo/arabino-hexopyranosides 3–16.
used thiophilic activator N-iodosuccinimide/triflic acid
and naphthols with thioglycosides 1 and 2 afforded the
(NIS/TfOH). Reaction of various substituted phenols
glycosylated product in a nearly quantitative yield.
Table 1. Synthesis of different aryl-2-deoxy-a-D-lyxo/arabino-hexopyranoside 3–16a
Entry
1
Glycosyl donor
Acceptor
Product from 1
Product from 2
OH
OH
OH
OH
HO
HO
HO
OH
O
O
1, 2
HO
O
O
10
3
OH
HO
HO
HO
OH
OH
O
O
O
CH3
H3C
H C
2
3
4
5
1, 2
1, 2
1, 2
1, 2
3
HO
O
11
O
4
OH
HO
HO
O
HO
HO
O
CH3
O
CH
3
12
CH3
OH
5
OH
OH
OH
HO
HO
O
O
O
HO
HO
O
OCH3
O
OCH
3
13
OCH3
OH
6
OH
HO
HO
O
HO
HO
OH
OH
HO
HO
O
O
14
7
OH
OH
HO
HO
O
O
HO
6
7
1, 2
HO
O
O
O
O
15
8
OH
OH
HO
HO
HO
O
O
OH
HO
1, 2
16
9
a Isolated yields after two steps were between 85% and 90%.

S. Paul, N. Jayaraman / Carbohydrate Research 342 (2007) 1305–1314
1307
The a-anomeric configuration of the glycosides was
1
ascertained by H and 13C NMR spectroscopies. The
anomeric proton appeared as an apparent doublet in
the range of 5.5–5.9 ppm, with coupling constant
approximately 3.0 ppm. The H-2 protons resonated
between 2.15 and 1.85 ppm, with the exception of
mono-O-glycosyated catechol 7, which showed the H-2
1
protons at 2.90 and 2.65 ppm. The H and 13C NMR
chemical shift values of all the products are presented
in Tables 2–5.
2.2. Synthesis of aryl 2-deoxy-b-D-glycosides
Figure 1. The HPLC trace for the reaction leading to the formation of
o-tolyl 2-deoxy-D-lyxo-hexopyranoside.
In the absence of formation of the b-anomeric product in
significant amounts in glycosylation involving 2-deoxy-
1-thioglycosides, formation of aryloxy anion intermedi-
ates as glycosyl acceptors and the reaction of such inter-
mediates with the glycosyl component to provide the
b-anomer was conducted. Preparation of aryl glycosides
using aryloxy anions is known previously.21 Lam and
Gervey-Hague have reported the reaction of 2-deoxy-
glycopyranosyl iodide with aryl anions,17 to obtain aryl
Analysis of the reaction mixtures by HPLC technique
showed that a-anomers formed as the major product
(Scheme 1, Table 1). A HPLC trace of the reaction mix-
ture resulting from glycosylation of 1 with o-cresol is
presented in Figure 1.
Table 2. 1H NMR chemical shifts (in ppm), multiplicities and coupling constants of 3–9 in acetone-d6/D2Oa
3
4
5
6
7
8
9
H-1
5.66 (d)
(3.0)
5.69 (d)
(2.7)
5.55 (d)
(2.7)
5.59 (d)
(3.0)
5.60 (d)
(2.9)
5.89 (d)
(2.7)
5.89 (d)
(3.0)
H-2a
H-2e
2.11 (ddd)
2.15 (ddd)
2.07 (ddd)
2.16 (ddd)
2.90–2.65f (m) 2.24 (ddd)
2.25 (ddd)
(3.1, 11.7, 12.5) (2.9, 8.1, 12.0) (3.0, 11.7, 12.0)
1.95 (app.dd)
(5.1, 12.5)
(3.0, 11.5, 12.5)
2.02 (app.dd)
(5.1, 12.5)
(2.7, 11.9, 12.5) (3.6, 12.0, 12.5)
2.15 (app.dd)
(5.5, 12.5)
2.03 (app.dd) 1.89 (app.dd)
(5.1, 12.1)
2.08 (app.dd)
(4.9, 12.5)
(5.1, 12.3)
H-3
4.15 (ddd)
4.23 (ddd)
(3.0, 5.1, 8.1)
3.99 (app.s)
4.10–4.04c (band) 4.19 (ddd)
(3.0, 5.1, 11.7)
3.98–3.94d
4.23 (ddd)
4.38 (ddd)
4.08–4.03h
(band)
(3.1, 5.1, 11.9)
3.94 (app.s)
3.84–3.63b (m) 3.87 (app.t)
(3.1, 5.4, 10.0) (2.7, 5.4, 11.9)
H-4
H-5
3.89 (app.s)
3.80 (app.t)
(6.0)
3.94–3.61g
(band)
3.99 (app.s)
3.88 (app.t)
(5.9)
3.81–3.61e (m)
(band)
3.95 (app.t)
(6.3)
3.77 (dd)
(6.2, 11.2)
3.66 (dd)
(6.1, 11.2)
(6.4)
H-6a
H-6b
3.74 (dd)
(6.3, 11.1)
3.63 (dd)
(6.0, 11.0)
3.65 (dd)
(6.0, 10.5)
3.54 (dd)
(6.3, 10.8)
3.74–3.63e (m)
Ph-H
Other signals
7.33–6.94 (m)
7.19–6.86 (m) 7.01 (d), 6.92 (d) 7.09 (dd), 6.90 (dd) 7.27–7.20 (m) 8.26–7.26 (m)
2.21 (s) 2.17 (s) 3.78 (br s)
7.89–7.29 (m)
a 1H NMR recorded in 300 MHz instrument.
f
Signals for b H-4, H-5, H-6a,b; c H-3 with residual H2O peak; d H-4, H-5; e H-6a, H-6b; H-2a, H-2e; g H-4, H-5, H-6a,b; h H-3, H-4 overlap.
Table 3. 13C NMR chemical shift assignments of 3–9 in acetone-d6/D2Oa
Compound
C-1
C-2
C-3b
C-4b
C-5
C-6
Other signals
3
4
5
6
7
8
9
97.5
96.9
97.4
96.4
98.8
97.5
97.5
33.8
33.1
32.9
34.9
33.6
33.9
33.1
69.1
68.2
68.1
70.3
69.1
69.1
68.4
65.9
65.8
65.6
67.8
65.7
66.1
65.8
72.6
72.4
72.1
74.4
72.8
73.0
72.7
62.7
61.7
61.6
61.6
62.7
62.7
61.9
156.0, 130.1, 122.5, 117.6,
155.6, 131.2, 127.7, 127.4, 122.1, 115.4, 16.1
155.4, 131.6, 130.3, 117.5, 117.4, 20.3
157.5, 153.7, 121.5, 117.4, 58.1
148.2, 145.9, 123.3, 120.4, 117.6, 116.5
135.6, 128.4, 127.0, 126.9, 126.1, 122.6, 121.8, 109.5
155.5, 130.4, 130.1, 128.4, 127.9, 127.2, 124.9, 120.0
a 13C NMR recorded in 75 MHz instrument.
b Assignments interchangeable.

1308
S. Paul, N. Jayaraman / Carbohydrate Research 342 (2007) 1305–1314
2-deoxy-b-D-glycopyranoside. The 2-deoxy-1-thioglyco-
sides were converted first to 2-deoxy glycopyranosyl
halides. The in situ formed 2-deoxy glycopyranosyl
halide was reacted with aryloxy acceptors using LHMDS
as the base. Analysis of the product formed, following
the deprotection, had shown the formation of the b-ano-
meric product 17–30, in excellent yields (Scheme 2 and
Table 6). Figure 2 presents the HPLC trace of the reac-
tion mixture corresponding to the reaction of 1 with
o-cresol under the above reaction conditions.
The b-anomers of the aryl 2-deoxy-D-glycosides were
1
characterized by H and 13C NMR spectroscopies and
mass spectrometry. Consistent up-field chemical shifts
with detectable double-doublet splitting pattern in the
1H NMR spectra and down-field chemical shifts in the
13C NMR spectra of the anomeric proton and carbon
nuclei, respectively, were observed for all the b-anomers,
in comparison to that for the a-anomer.
1H and 13C NMR chemical shifts for various aryl
2-deoxy-b-D-glycosides are presented in Tables 7–10.
The coupling constants J1,2a of 9.8 Hz and J1,2e of
2.0 Hz indicate the b-configuration of the substituent
at C-1. The chemical shift of the anomeric carbon in
the b-anomer resonated at ꢀ98–101 ppm. The 13C reso-
nances corresponding to C-2 appeared in the range of
34–39 ppm for the b-anomers. High resolution mass
spectrometry further confirmed the constitutions of the
glycosides. A single crystal X-ray structure of the aryl
glycoside 18 is presented in Figure 3.22
The fact that NIS/TfOH mediated glycosylation,
using thioglycoside donor, led to formation of a-glycos-
ylated product as the major product and b-glycosylated
product as the minor product, indicate that an
oxocarbenium ion forms as the intermediate. The a-ano-
mer product formation may be compared analogous to
such a-anomer formation in non-neighboring group
participating glycosylations. Further, when the glycosyl-
ation reaction was performed in the coordinating
solvent MeCN, the a:b ratio was observed to change
significantly. In studying the glycosylation of o-cresol
with ethyl 2-deoxy-3,4,6-tri-O-acetyl-1-thio-arabino-
hexopyranoside, in NIS/TfOH, in MeCN solution, the
HPLC analysis of the reaction mixture had shown an
a:b ratio of 60:40, as opposed to the ratio of 90:10 for
the same reaction performed in CH2Cl2 solution. The
increase in the b-anomer in this reaction is likely to be
due to the effect of MeCN coordinating the a-face of
the intermediate oxocarbenium ion.
The glycosylation via the bromide route, involving a
phenoxide as the glycosyl acceptor, led to the b-glyco-
sylated product in more than 90% specificity, presum-
ably due to an SN2 type of mechanism.
In conclusion, the methodology presented herein
allows a facile preparation of each of the anomers of
aryl 2-deoxy-D-glycosides from a common precursor,
namely, 2-deoxy-1-thioglycoside.

S. Paul, N. Jayaraman / Carbohydrate Research 342 (2007) 1305–1314
Table 5. 13C NMR chemical shift assignments of 10–16 in acetone-d6/D2O
1309
Compound
C-1
C-2
C-3c
C-4c
C-5
C-6
Other signals
10a
11b
12a
13a
14b
15a
16a
97.7
96.0
97.7
97.6
97.5
96.4
96.1
37.2
37.5
38.6
37.4
37.3
37.0
37.1
73.4
73.5
73.4
73.4
71.1
72.0
71.8
70.8
70.9
70.8
70.9
71.0
69.6
69.6
76.7
76.8
76.6
76.7
73.4
75.0
75.1
61.3
61.5
60.9
61.7
60.8
59.7
59.8
138.7, 130.0, 123.2, 116.8
155.4, 131.1, 127.7, 127.3, 122.7, 115.0, 15.9
153.4, 130.4, 123.2, 116.9, 14.7
157.8, 154.1, 119.0, 115.2, 55.9
146.6, 144.6, 123.6, 120.8, 117.8, 116.5
133.0, 126.1, 125.0, 124.6, 120.5, 120.5, 120.1, 107.7, 107.5
152.8, 132.9, 127.9, 126.0, 125.6, 122.9, 117.2, 109.4
13C NMR recorded in a100 MHz, b75 MHz instrument.
c Assignments interchangeable.
R3
(i) Br2, CH2Cl2, 0 oC, 10 min.
(ii) ArOH, LHMDS, THF, 0 oC-rt, 30 min.-2 h
R5
OAc
OH
R4
AcO
O
R6
HO
O
R2
OAr
R1
(iii) NaOMe (cat.), MeOH, rt, 2 h.
1: R1 = SEt (or H), R2 = H (or SEt), R3 = OAc, R4 = H
2: R1 = H, R2 = SEt, R3 = H, R4 = OAc
17-23: R5 = OH, R6 = H (from 1)
24-30: R5 = H, R6 = OH (from 2)
Scheme 2. Synthesis of aryl-2-deoxy-b-D-lyxo/arabino-hexopyranosides 17–30.
3. Experimental
in CH2Cl2 or MeCN (1 mL) was added and stirred at
0 °C for 15–30 min. The reaction mixture was diluted
with CH2Cl2 (50 mL), washed with aqueous Na2S2O3
(50 mL), brine (50 mL), dried (Na2SO4) and concen-
trated. De-O-acetylation was performed by dissolving
the crude reaction mixture in MeOH, addition of
NaOMe (1 M in MeOH) and stirring for 2 h at room
temperature. The reaction mixture was then neutralized
(AcOH–MeOH 1:9 v/v), concentrated, and purified
(SiO2, CHCl3–MeOH eluant mixture), to afford the
desired product.
3.1. General methods
Chemicals were purchased from commercial sources and
were used without further purification. Solvents were
dried and distilled according literature procedures. Ana-
lytical TLC was performed on commercial Merck plates
coated with silica gel GF254 (0.25 mm). Silica gel (100–
200 mesh) was used for column chromatography. Opti-
cal rotations were recorded on a Jasco Model P-1020
polarimeter at the sodium D line at 24 °C. Microanaly-
ses were performed on an automated C, H, N analyzer.
High-resolution mass spectra were obtained from
Q-TOF instrument by electron spray ionization (ESI)
technique. 1H and 13C NMR spectral analysis were
performed on a 300/400 MHz and 75/100 MHz spec-
trometer, respectively, with residual solvent signal acting
as the internal standard. The following abbreviations
were used to explain the multiplicities: s, singlet; d, dou-
blet; t, triplet; m, multiplet; band, several overlapping
signals; br, broad.
3.3. General procedure for synthesis of aryl-2-deoxy-b-D-
lyxo/arabino-hexopyranoside (17–30)
Bromine (1.2 mmol) was added at 0 °C to a solution
of ethyl 2-deoxy-3,4,6-tri-O-acetyl-1-thio-lyxo/arabino-
hexopyranoside (1, 2)14 (1 mmol) in CH2Cl2 (3 mL).
After 10 min, reaction mixture was concentrated and
co-evaporated twice with PhMe to afford bromide,
which was used in the next step without purification.
A solution of the acceptor phenol (1.2 mmol) in THF
(2 mL) was admixed with LHMDS in THF (1 M)
(1.2 mmol) at 0 °C and stirred for 30 min. A solution
of the bromide in THF (2 mL) was added to the reaction
mixture dropwise at 0 °C and stirred for 2.5 h. The
reaction mixture was diluted with EtOAc, washed with
aq Na2S2O3 solution, followed by brine and concen-
trated in vacuo. De-O-acetylation and product isola-
tion were performed, as detailed in the previous
paragraph.
3.2. General procedure for synthesis of aryl-2-deoxy-a-D-
lyxo/arabino-hexopyranoside (3–16)
Ethyl 2-deoxy-3,4,6-tri-O-acetyl-1-thio-lyxo/arabino-hexo-
pyranoside (1, 2)14 (1 mmol), molecular sieves 4 A
˚
(ꢀ0.7 g), NIS (1.2 mmol), and acceptor phenol (1.2–
2 mmol) was dissolved in CH2Cl2 or MeCN (3 mL)
and stirred for 1 h at rt. A solution of TfOH (0.1 mmol)

1310
S. Paul, N. Jayaraman / Carbohydrate Research 342 (2007) 1305–1314
Table 6. Synthesis of different aryl-2-deoxy-b-D-hexopyranosides 17–30a
Entry
1
Glycosyl donor
Acceptor
Product from 1
Product from 2
OH
OH
OH
HO
HO
O
O
O
O
O
1, 2
O
O
HO
HO
24
17
OH
OH
OH
OH
OH
OH
HO
HO
CH3
CH3
O
O
CH3
2
3
4
5
6
7
1, 2
1, 2
1, 2
1, 2
1, 2
1, 2
HO
HO
25
18
OH
HO
HO
HO
O
O
O
O
O
O
HO
26
CH3
CH3
CH3
OH
19
OH
HO
HO
HO
O
O
HO
OCH3
27
OCH3
OCH3
OH
20
OH
OH
OH
HO
HO
OH
OH
O
OH
OH
O
O
O
O
HO
HO
28
21
OH
HO
HO
O
O
HO
HO
29
22
OH
OH
HO
HO
HO
O
O
OH
O
O
HO
30
23
a Isolated yields after two steps were above 90%.
3.4. Phenyl 2-deoxy-a-D-lyxo-hexopyranoside (3)
Mp 127–129 °C, lit.23 mp 126–127 °C, lit.24 mp 125 °C;
24
20
½aꢁD +159.0 (c 1.0, MeOH), lit.23 ½aꢁD +154 (H2O),
24
lit.24 ½aꢁD +150 (c 2.02, H2O). ESIMS m/z calcd
for C12H16O5: 263.0895 [M+Na]+. Found: 263.0889.
Anal. Calcd: C, 60.00; H, 6.71. Found: C, 59.75; H,
7.03.
3.5. o-Tolyl 2-deoxy-a-D-lyxo-hexopyranoside (4)
24
Mp 128–129 °C; ½aꢁD +154.3 (c 1.0, MeOH). ESIMS
m/z calcd for C13H18O5: 277.1052 [M+Na]+. Found:
277.1060. Anal. Calcd: C, 61.40; H, 7.14. Found: C,
61.12; H, 7.48.
Figure 2. The HPLC trace for the reaction leading to the formation of
o-tolyl 2-deoxy-D-lyxo-hexopyranoside.

S. Paul, N. Jayaraman / Carbohydrate Research 342 (2007) 1305–1314
1311
Table 7. 1H NMR chemical shifts, multiplicities, and coupling constants of 17–23 in acetone-d6/D2Oa
17
18
19
20
21
22
23
H-1
5.25 (dd)
(1.9, 9.7)
1.94 (ddd)
(9.8, 11.7, 12.5)
2.11 (ddd)
(2.1, 3.0, 12.5)
3.93 (ddd)
(3.3, 4.5, 11.9)
3.83–3.65b (band)
5.17 (dd)
(2.1, 7.0)
2.14–2.07c
(band)
5.17 (dd)
(1.8, 7.2)
2.14–2.00c (m)
5.03 (dd)
(3.1, 8.8)
2.05–1.94c (m)
5.93 (dd)
(3.1, 9.0)
5.32 (dd)
(3.9, 7.8)
5.25 (dd)
(2.4, 9.3)
2.05–1.90c
H-2a
H-2e
H-3
2.21–2.02c (m) 2.14 (ddd)
(8.0, 11.4, 12.5) (band)
2.03 (ddd)
(3.3, 3.9, 12.5)
3.93–3.84d
(band)
3.96–3.88d
(band)
3.92 (ddd)
3.85–3.79d (band) 4.59–4.50d
(band)
3.86 (ddd)
(2.4, 3.3, 11.7)
3.88 (app.s)
3.48 (app.t)
(6.1)
(3.0, 5.0, 11.4)
3.80 (app.s)
3.70–3.62g
(band)
H-4
H-5
3.66 (app.t)
(6.3)
3.84–3.73e
(band)
3.71–3.67f (band) 4.39 (app.t)
3.73–3.66g
(band)
(5.7)
H-6a
H-6b
3.79–3.74e (band)
4.59–4.50e
(band)
Ph-H
Other signals
7.33–7.03 (m)
7.14–6.88 (m) 7.10 (d), 6.97 (d) 6.95 (d), 6.79 (d) 7.95–7.53 (m) 8.13–7.14 (m)
2.20 (s) 2.17 (s)
3.71–3.67f (band)
7.15–7.12 (m)
a 1H NMR recorded in 300 MHz instrument.
Signals for b H-4, H-5, H-6a,b; c H-2a, H-2e with residual H2O peak; d H-3, H-4, e H-6a, H-6b; f H-5, H-6a,b, and benzylic proton; g H-5, H-6a,b
overlap.
Table 8. 13C NMR chemical shift assignment of 17–23 in acetone-d6/D2Oa
Compound
C-1
C-2
C-3b
C-4b
C-5
C-6
Other signals
17
18
19
20
21
22
23
101.3
98.9
98.7
99.4
103.2
98.8
98.8
36.9
34.9
34.8
34.8
35.0
34.5
34.6
71.3
68.7
68.7
68.7
71.4
68.5
68.7
70.1
67.3
67.3
67.3
70.2
67.2
67.5
79.0
76.1
76.1
76.1
79.1
76.1
76.4
64.5
61.6
61.6
61.6
64.4
61.5
61.8
159.9, 133.3, 126.3, 119.9
156.1, 131.0, 127.5, 122.4, 114.5, 114.5, 16.1
155.8, 131.7, 130.3, 117.0, 116.9, 20.3
155.3, 131.9, 118.4, 115.0, 55.7
151.1, 148.4, 126.8, 123.0, 121.4, 119.5
153.1, 134.9, 128.0, 126.9, 126.0, 122.0, 109.4
155.5, 135.1, 130.4, 128.4, 128.0, 127.5, 125.2, 119.5
a 13C NMR recorded in 75 MHz instrument.
b Assignments interchangeable.
Table 9. 1H NMR chemical shifts, multiplicities, and coupling constants of 24–30 in acetone-d6/D2Oa
24
25
26
27
28
29
30
H-1
H-2a
H-2e
H-3
H-4
5.21 (dd)
(2.1, 9.6)
5.10 (dd)
(1.9, 9.7)
5.15 (dd)
(1.8, 9.9)
5.09 (dd)
(1.9, 9.9)
5.23 (dd)
(1.9, 9.7)
5.30 (dd)
(2.3, 8.7)
5.39 (dd)
(1.9, 9.4)
1.69 (app.ddd) 1.68 (app.ddd) 1.65 (app.ddd) 1.65 (app.ddd)
(9.6, 11.1, 12.3) (9.7, 11.1, 12.3) (9.9, 11.7, 12.3) (9.9, 12.0, 12.3)
2.26 (ddd)
(2.1, 5.1, 12.3)
3.41–3.26b
(band)
1.97 (app.ddd) 2.03 (app.ddd) 1.78 (app.ddd)
(9.7, 11.8, 12.3) (8.7, 11.1, 12.0) (9.4, 11.8, 12.2)
2.25 (ddd)
(2.1, 5.2, 11.1)
3.37–3.29 (m)
2.24 (ddd)
(1.8, 4.8, 12.3)
3.39–3.32 (m)
2.24 (ddd)
(1.9, 5.4, 12.3)
3.39–3.23b
(band)
2.11 (ddd)
(2.0, 4.9, 12.3)
3.90 (ddd)
(4.9, 9.0, 11.8)
3.81–3.58e
(band)
2.14 (ddd)
(2.1, 5.1, 12.0)
3.73–3.66b
(band)
2.33 (ddd)
(2.1, 5.4, 12.2)
3.60–3.55 (m)
3.23 (t)
(9.1)
3.26 (t)
(8.7)
3.23 (t)
(9.1)
H-5
H-6a
3.84–3.62c
(band)
3.77–3.58c
(band)
3.80–3.58c
(band)
3.81–3.59d
(band)
3.93–3.84c
(band)
3.88–3.66c
(band)
H-6b
Ph-H
7.25–6.90
(band)
7.01–6.78
(band)
2.04 (br s)
6.99 (d),
6.84 (d)
2.13 (br s)
6.94 (d),
6.78 (d)
3.81–3.59d (band)
7.33–7.00 (m)
7.90–7.45
(band)
7.78–7.16
(band)
Other signals
a 1H NMR recorded in 300 MHz instrument.
c
e
Signal for bH-3, H-4; H-5, H-6a,b; dH-5, H-6a, H-6b and benzylic proton; H-4, H-5, H-6a,b overlap.
3.6. p-Tolyl 2-deoxy-a-D-lyxo-hexopyranoside (5)
3.7. 4-Methoxylphenyl 2-deoxy-a-D-lyxo-hexopyranoside
(6)
24
Mp 123–125 °C; ½aꢁD +178.5 (c 1.0, MeOH). ESIMS m/z
24
calcd for C13H18O5: 277.1052 [M+Na]+. Found: 277.1042.
Anal. Calcd: C, 61.40; H, 7.14. Found: C, 61.50; H, 7.21.
Mp 127–130 °C; ½aꢁD +167.0 (c 1.0, MeOH). ESIMS
m/z calcd for C13H18O6: 293.1001 [M+Na]+. Found:

1312
S. Paul, N. Jayaraman / Carbohydrate Research 342 (2007) 1305–1314
Table 10. 13C NMR chemical shift assignments of 24–30 in acetone-d6/D2Oa
Compound
C-1
98.1
C-2
C-3b
C-4b
C-5
C-6
Other signals
25
26
27
28
29
30
31
39.7
39.1
39.4
39.3
37.0
39.0
39.3
72.3
71.5
71.9
71.7
71.3
71.5
71.9
71.6
70.9
71.3
71.1
70.0
70.2
71.2
77.6
76.9
77.3
77.0
79.1
79.0
77.2
62.2
61.6
61.9
61.8
64.4
64.0
61.9
130.3, 122.9, 117.2
155.6, 131.0, 127.5, 127.4, 122.7, 115.4, 15.9
132.7, 130.8, 117.8, 117.2, 20.6
155.3, 151.6, 118.8, 114.9, 101.0, 55.7
160.0, 130.2, 122.4, 117.0
155.2, 130.4, 130.0, 128.4, 127.3, 124.8, 120.1
155.4, 135.0, 130.1, 129.9, 128.0, 127.7, 126.9, 124.7, 119.2, 111.1
98.2
98.3
98.7
101.3
98.8
97.9
a 13C NMR recorded in 75 MHz instrument.
b Assignments interchangeable.
Figure 3. Single crystal X-ray structure of o-tolyl 2-deoxy-b-D-lyxo-hexopyranoside (18).
293.1017. Anal. Calcd: C, 57.77; H, 6.71. Found: C,
57.23; H, 6.69.
263.0899. Anal. Calcd: C, 60.00; H, 6.71. Found: C,
59.90; H, 7.29.
3.12. o-Tolyl 2-deoxy-a-D-arabino-hexopyranoside (11)
3.8. 2-Hydroxy-phenyl 2-deoxy-a-D-lyxo-hexopyranoside
(7)
24
Mp 117–119 °C; ½aꢁD +113.8 (c 1.1, MeOH). ESIMS
m/z calcd for C13H18O5: 277.1052 [M+Na]+. Found:
277.1049. Anal. Calcd: C, 61.40; H, 7.14. Found: C,
61.74; H, 7.39.
24
Mp 130–131 °C; ½aꢁD +164.6 (c 0.9, MeOH). ESIMS
m/z calcd for C12H16O6: 279.0845 [M+Na]+. Found:
279.0833. Anal. Calcd: C, 56.24; H, 6.29. Found: C,
56.23; H, 6.26.
3.13. p-Tolyl 2-deoxy-a-D-arabino-hexopyranoside
(12)
3.9. 1-Naphthyl 2-deoxy-a-D-lyxo-hexopyranoside (8)
24
Mp 168–170 °C, lit.26 mp 170 °C; ½aꢁD +165.1 (c 1.0,
24
Mp 192–194 °C; ½aꢁD +76.0 (c 1.1, MeOH). ESIMS m/z
MeOH), lit.26 [a]D +166 (MeOH). ESIMS m/z calcd
for C13H18O5: 277.1052 [M+Na]+. Found: 277.1039.
Anal. Calcd: C, 61.40; H, 7.14. Found: C, 61.70; H,
6.93.
calcd for C16H18O5: 313.1052 [M+Na]+. Found:
313.1064. Anal. Calcd: C, 66.19; H, 6.25. Found: C,
66.43; H, 6.16.
3.10. 2-Naphthyl 2-deoxy-a-D-lyxo-hexopyranoside (9)
3.14. 4-Methoxylphenyl 2-deoxy-a-D-arabino-hexo-
pyranoside (13)
24
Mp 198–201 °C; ½aꢁD +164.8 (c 2.1, MeOH). ESIMS
m/z calcd for C16H18O5: 313.1052 [M+Na]+. Found:
313.1056. Anal. Calcd: C, 66.19; H, 6.25. Found: C,
66.55; H, 6.28.
24
Mp 157–160 °C; ½aꢁD +135.9 (c 0.3, MeOH). ESIMS
m/z calcd for C13H18O6: 293.1001 [M+Na]+. Found:
293.1006. Anal. Calcd: C, 57.77; H, 6.71. Found: C,
57.54; H, 6.81.
3.11. Phenyl 2-deoxy-a-D-arabino-hexopyranoside (10)
Mp 159–161 °C, lit.25 mp 162–163 °C, lit.26 mp
3.15. 2-Hydroxy-phenyl 2-deoxy-a-D-arabino-hexo-
pyranoside (14)
24
163.5 °C; ½aꢁD +162.2 (c 1.1, MeOH) , lit.25 [a]D +159
20
24
(H2O), lit.26 ½aꢁD +161 (c 0.5, MeOH). ESIMS m/z
Mp 150–152 °C; ½aꢁD +161.5 (c 1.0, MeOH). ESIMS
calcd for C12H16O5: 263.0895 [M+Na]+. Found:
m/z calcd for C12H16O6: 279.0845 [M+Na]+. Found:

S. Paul, N. Jayaraman / Carbohydrate Research 342 (2007) 1305–1314
1313
279.0847. Anal. Calcd: C, 56.24; H, 6.29. Found: C,
3.23. 1-Naphthyl 2-deoxy-b-D-lyxo-hexopyranoside (22)
55.75; H, 6.03.
24
Mp 227–228 °C; ½aꢁD ꢂ36.1 (c 0.9, MeOH). ESIMS m/z
3.16. 1-Naphthyl 2-deoxy-a-D-arabino-hexopyranoside
(15)
calcd for C16H18O5: 313.1052 [M+Na]+. Found:
313.1051. Anal. Calcd: C, 66.19; H, 6.25. Found: C,
66.48; H, 6.65.
24
Mp 154–156 °C, lit.26 mp 157 °C; ½aꢁD +57.6 (c 1.0,
MeOH), lit.26 [a]D +53.6 (MeOH). ESIMS m/z calcd
for C16H18O5: 313.1052 [M+Na]+. Found: 313.1060.
Anal. Calcd: C, 66.19; H, 6.25. Found: C, 66.65; H,
6.44.
3.24. 2-Naphthyl 2-deoxy-b-D-lyxo-hexopyranoside (23)
24
Mp 224–226 °C; ½aꢁD ꢂ43.3 (c 2.1, MeOH). ESIMS m/z
calcd for C16H18O5: 313.1052 [M+Na]+. Found: 313.1040.
Anal. Calcd: C, 66.19; H, 6.25. Found: C, 66.25; H, 5.96.
3.17. 2-Naphthyl 2-deoxy-a-D-arabino-hexopyranoside
(16)
3.25. Phenyl 2-deoxy-b-D-arabino-hexopyranoside (24)
24
Mp 163–165 °C; ½aꢁ2D4 +160.6 (c 1.0, MeOH). ESIMS m/z
calcd for C16H18O5: 313.1052 [M+Na]+. Found: 313.1051.
Anal. Calcd: C, 66.19; H, 6.25. Found: C, 66.54; H,
6.39.
Mp 179–181 °C, lit.27 mp 143–146 °C; ½aꢁD ꢂ65.0 (c 1.0,
20
MeOH), lit.27 ½aꢁD ꢂ75.0 (c 0.5, H2O). ESIMS m/z calcd
for C12H16O5: 263.0895 [M+Na]+. Found: 263.0893.
Anal. Calcd: C, 60.00; H, 6.71. Found: C, 59.78; H, 7.32.
3.18. Phenyl 2-deoxy-b-D-lyxo-hexopyranoside (17)
3.26. o-Tolyl 2-deoxy-b-D-arabino-hexopyranoside (25)
24
24
Mp 147–149 °C; ½aꢁD ꢂ31.0 (c 0.9, MeOH). ESIMS m/z
Mp 137–139 °C; ½aꢁD ꢂ47.6 (c 1.1, MeOH). ESIMS m/z
calcd for C12H16O5: 263.0895 [M+Na]+. Found:
263.0893. Anal. Calcd: C, 60.00; H, 6.71. Found: C,
59.63; H, 6.29.
calcd for C13H18O5: 277.1052 [M+Na]+. Found:
277.1062. Anal. Calcd: C, 61.40; H, 7.14. Found: C,
61.26; H, 7.20.
3.19. o-Tolyl 2-deoxy-b-D-lyxo-hexopyranoside (18)
3.27. p-Tolyl 2-deoxy-b-D-arabino-hexopyranoside (26)
24
24
Mp 161–163 °C; ½aꢁD ꢂ35.0 (c 1.0, MeOH). ESIMS m/z
Mp 182–184 °C; ½aꢁD ꢂ65.0 (c 0.7, MeOH). ESIMS m/z
calcd for C13H18O5: 277.1052 [M+Na]+. Found:
277.1037. Anal. Calcd: C, 61.40; H, 7.14. Found: C,
61.15; H, 7.19.
calcd for C13H18O5: 277.1052 [M+Na]+. Found:
277.1065. Anal. Calcd: C, 61.40; H, 7.14. Found: C,
61.11; H, 7.56.
3.20. p-Tolyl 2-deoxy-b-D-lyxo-hexopyranoside (19)
3.28. 4-Methoxyphenyl 2-deoxy-b-D-arabino-hexo-
pyranoside (27)
24
Mp 161–162 °C; ½aꢁD ꢂ38.1 (c 0.9, MeOH). ESIMS m/z
24
calcd for C13H18O5: 277.1052 [M+Na]+. Found:
277.1061. Anal. Calcd: C, 61.40; H, 7.14. Found: C,
61.68; H, 6.78.
Mp 185–187 °C; ½aꢁD ꢂ55.3 (c 1.2, MeOH). ESIMS m/z
calcd for C13H18O6: 293.1001 [M+Na]+. Found: 293.1018.
Anal. Calcd: C, 57.77; H, 6.71. Found: C, 57.44; H, 7.03.
3.21. 4-Methoxyphenyl 2-deoxy-b-D-lyxo-hexopyranoside
(20)
3.29. 2-Hydroxy-phenyl 2-deoxy-b-D-arabino-hexo-
pyranoside (28)
24
24
Mp 169–172 °C; ½aꢁD ꢂ40.0 (c 1.1, MeOH). ESIMS m/z
Mp 186–188 °C; ½aꢁD ꢂ33.7 (c 0.4, MeOH). ESIMS m/z
calcd for C13H18O6: 293.1001 [M+Na]+. Found:
293.1001. Anal. Calcd: C, 57.77; H, 6.71. Found: C,
57.68; H, 6.96.
calcd for C12H16O6: 279.0845 [M+Na]+. Found:
279.0855. Anal. Calcd: C, 56.24; H, 6.29. Found: C,
56.02; H, 6.21.
3.22. 2-Hydroxy-phenyl 2-deoxy-b-D-lyxo-hexopyran-
oside (21)
3.30. 1-Naphthyl 2-deoxy-b-D-arabino-hexopyranoside
(29)
24
24
Mp 157–160 °C; ½aꢁD ꢂ26.4 (c 0.9, MeOH). ESIMS m/z
Mp 193–195 °C; ½aꢁD ꢂ29.0 (c 1.0, MeOH). ESIMS m/z
calcd for C12H16O6: 279.0845 [M+Na]+. Found:
279.0848. Anal. Calcd: C, 56.24; H, 6.29. Found: C,
55.77; H, 6.31.
calcd for C16H18O5: 313.1052 [M+Na]+. Found:
313.1061. Anal. Calcd: C, 66.19; H, 6.25. Found: C,
65.93; H, 6.37.

1314
S. Paul, N. Jayaraman / Carbohydrate Research 342 (2007) 1305–1314
7. (a) Perez, M.; Beau, J.-M. Tetrahedron Lett. 1989, 30, 75–
78; (b) Nicolaou, K. C.; Mitchell, H. J.; Fylaktakidou, K.
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8. Koch, A.; Lamberth, C.; Wetterich, F.; Giese, B. J. Org.
Chem. 1993, 58, 1083–1089.
3.31. 2-Naphthyl 2-deoxy-b-D-arabino-hexopyranoside
(30)
24
Mp 191–193 °C; ½aꢁD ꢂ76.2 (c 1.2, MeOH). ESIMS m/z
calcd for C16H18O5: 313.1052 [M+Na]+. Found:
313.1044. Anal. Calcd: C, 66.19; H, 6.25. Found: C,
66.07; H, 6.45.
9. Li, H.; Chen, M.; Zhao, K. Tetrahedron Lett. 1997, 38,
6143–6144.
10. Hashimoto, S.-I.; Sano, A.; Sakamoto, H.; Nakajima, Y.;
Yanagiya, Y.; Ikegami, S. Synlett 1995, 1271–1273.
11. (a) Bielawska, H.; Michalska, M. J. Carbohydr. Chem.
1991, 10, 107–112; (b) Laupichler, L.; Sajus, H.; Thiem, J.
Synthesis 1992, 1133–1136.
12. (a) Sun, L.; Li, P.; Zhao, K. Tetrahedron Lett. 1994, 35,
7147–7150; (b) Jaunzems, J.; Sourkouni-Argirusi, G.;
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44, 637–639; (c) Lear, M. J.; Yoshimura, F.; Hirama, M.
Angew. Chem., Int. Ed. 2001, 40, 946–949.
3.32. HPLC analysis
HPLC analysis of reaction mixtures was carried out on a
˚
Phenogel (5 l silica gel, 100 A) semi preparative column
attached to a Shimadzu HPLC system and eluted with
3% MeOH/ EtOAc (flow rate: 0.8 mL/min) and detected
with a UV detector (k = 272 nm).
13. Kim, K. S.; Park, J.; Lee, Y. J.; Seo, Y. S. Angew. Chem.,
Int. Ed. 2003, 42, 459–462.
Acknowledgments
14. Paul, S.; Jayaraman, N. Carbohydr. Res. 2004, 339, 2197–
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We are grateful to Department of Science and Technol-
ogy, New Delhi, for a financial support. We thank Pro-
fessor T. N. Guru Row and Mr. Diptikanta Swain,
Solid State and Structural Chemistry Unit, Indian Insti-
tute of Science, Bangalore, for their assistance to deter-
mine the single crystal X-ray structure. S.P. thanks
Council of Scientific and Industrial Research, New Del-
hi, for a research fellowship.
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