Synthesis, the crystal structure, and high-resolution NMR spectroscopy of methyl 4-O-acetyl-3-azido-2,3,6-trideoxy-6-iodo-α-D-arabino-hexopyranoside

Article abstract of DOI:10.1016/S0008-6215(01)00302-0

Selective tosylation followed by acetylation of methyl 3-azido-2,3-dideoxy-α-D-arabino-hexopyranoside (1) in pyridine at room temperature affords a mixture of methyl 4-O-acetyl-3-azido-2,3-dideoxy-6-di-O-p-tolylsulfonyl-α-D-arabino- hexopyranoside (4) and methyl 3-azido-2,3-dideoxy-4,6-di-O-p-tolylsulfonyl-α-D-arabino-hexopyranoside (3). Compound 4 undergoes nucleophilic displacement with sodium iodide in acetic anhydride to give methyl 4-O-acetyl-3-azido-2,3,6-trideoxy-6-iodo-α-D-arabino-hexopyranoside (7), whose crystal structure and ¹H and ¹³C NMR data are reported. This compound adopts the ⁴C₁ conformation.

Full text of DOI:10.1016/S0008-6215(01)00302-0

Carbohydrate Research 337 (2002) 175–181
www.elsevier.com/locate/carres
Note
Synthesis, the crystal structure, and high-resolution NMR
spectroscopy of methyl 4-O-acetyl-3-azido-2,3,6-
trideoxy-6-iodo-a- -arabino-hexopyranoside
D
Aleksandra Da˛browska,a,* Antoni Konitz,b Zygfryd Smiatacza
aDepartment of Chemistry, Uni6ersity of Gdan´sk, 18/19 Sobieski Strasse, PL-80-952 Gdan´sk, Poland
bDepartment of Inorganic Chemistry, Technical Uni6ersity of Gdan´sk, 11/12 Narutowicz Strasse, PL-80-952 Gdan´sk, Poland
Received 14 August 2001; received in revised form 24 September 2001; accepted 1 November 2001
Abstract
Selective tosylation followed by acetylation of methyl 3-azido-2,3-dideoxy-a-
temperature affords a mixture of methyl 4-O-acetyl-3-azido-2,3-dideoxy-6-di-O-p-tolylsulfonyl-a-
and methyl 3-azido-2,3-dideoxy-4,6-di-O-p-tolylsulfonyl-a- -arabino-hexopyranoside (3). Compound 4 undergoes nucleophilic
D
-arabino-hexopyranoside (1) in pyridine at room
D
-arabino-hexopyranoside (4)
D
displacement with sodium iodide in acetic anhydride to give methyl 4-O-acetyl-3-azido-2,3,6-trideoxy-6-iodo-h-D-arabino-hexopy-
ranoside (7), whose crystal structure and 1H and 13C NMR data are reported. This compound adopts the 4C1 conformation.
© 2002 Elsevier Science Ltd. All rights reserved.
Keywords: Methyl 4-O-acetyl-3-azido-2,3,6-trideoxy-6-iodo-a-D
-arabino-hexopyranoside; Synthesis, X-ray diffraction; 1H and 13C NMR spec-
troscopy
acetylsporaciridine.2
component of a number of important anthracycline
antibiotics that exhibit impressive activity against a
broad range of solid tumors and soft tissue sarcomas.2
L-Daunosamine is the glycosidic
1. Introduction
In a previous paper, we reported on the synthesis of
1, a useful intermediate for synthesis of 3-amino deriva-
tives of 2,3-dideoxy sugars.1 Here we show that this
compound can be converted into methyl 3-azido-2,3,6-
trideoxy-6-iodo-a-
methyl 4-O-acetyl-3-azido-6-iodo-2,3,6-trideoxy-a-
Changing L-daunosamine to its 4-epimer, L-acosamine,
was reported to suppress the cardiotoxicity of semisyn-
thetic anthracycline antibiotics while retaining antitu-
mor activity.3
D
-arabino-hexopyranoside (5) or
D
-
arabino-hexopyranoside (7) in good yields. Both 5 and
7 can serve as useful intermediates in the synthesis of
the diastereoisomers of 3-amino-2,3,6-trideoxy-hexose
derivatives—glycoside-type antibiotics useful in clinical
practice. Acosamine, with the arabino configuration,
2. Results and discussion
Methyl 3-azido-2,3-dideoxy-a-D-arabino-hexopyra-
noside1 (1) was treated with 3 mol of p-toluenesulfonyl
chloride in pyridine at room temperature to gave a
mixture of methyl 3-azido-2,3-dideoxy-6-O-p-tolylsul-
has been found both in
L and D forms. L-Acosamine
was isolated from the antibiotic actinodine and their
D
enantiomer was obtained from the basic antibiotic N-
fonyl-a-
product and methyl 3-azido-2,3-dideoxy-4,6-di-O-p-
-arabino-hexopyranoside (3) as a mi-
D
-arabino-hexopyranoside (2) as the major
* Corresponding author: Tel.: +48-58-3450395; fax: +48-
tolylsulfonyl-a-
D
58-3410357.
E-mail
nor product (Scheme 1). The reason for the lower
address:
alex@chemik.chem.univ.gda.pl
(A.
Da˛browska).
susceptibility for tosylation at O-4 is thought to be due
0008-6215/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0008-6215(01)00302-0

176
A. Da˛browska et al. / Carbohydrate Research 337 (2002) 175–181
to the steric effect of the equatorial azide group at C-3
preventing the access of the reagent from the other side.
The conformation and configuration of 2 and 3 was
ascertained on the basis of IR and 1H NMR spec-
troscopy. In the IR spectrum of 2, the broad band
centered at 3500 cm−1 indicated that the hydroxyl
3 into 3-azido-2,3-dideoxy-6-iodo-4-O-p-tolylsulfonyl-
a- -arabino-hexopyranoside (6) in 65% yield, and 4
into 7 in 47% yield. The H-6 signal in the H NMR
spectrum of 6 was shifted to a higher field by 0.88 ppm
as compared to that of compound 3, indicating replace-
ment of the OTs group.
The reaction of 4 with sodium iodide in acetic anhy-
dride gave improved yields of the 6-iodo derivative: 4
was converted into 7 in 83% yield, and methyl 4,6-di-
D
1
1
group is present. The values of the H NMR coupling
constants (J2a,3=J3,4=J4,5 ꢀ10 Hz) indicate that these
4
6-O-sulfonyl derivatives 2 and 3 adopt the C1 confor-
mation and the coupling values clearly indicated the
arabino configuration. The positive sign of optical rota-
tion additionally confirmed that both compounds are
the a anomers.
O-acetyl-3-azido-2,3-dideoxy-a-D-arabino-hexopyra-
noside1 (8) was obtained as a minor byproduct in 2%
yield.
Acetylation of the unseparated mixture of 2 and 3
obtained in an optimized run afforded 4 with 90% yield
and unchanged 3 in 6% yield. After extraction of 3+4
with dichloromethane and removing solvents, this mix-
ture was subjected to reaction with sodium iodide in
acetic anhydride. After chromatographic separation,
pure 6, 7, and 8 were obtained with yields of 4, 63, and
5%, respectively.
Acetylation of 2 using acetic anhydride in pyridine
gave methyl 4-O-acetyl-3-azido-2,3-dideoxy-6-O-p-
tolylsulfonyl-a- -arabino-hexopyranoside (4) in 85%
D
yield.
Compounds 2, 3, and 4 underwent selective nucle-
ophilic displacement4 at C-6, when refluxed for 24 h
with sodium iodide in acetone. Under these conditions,
2 was converted into methyl 3-azido-6-iodo-2,3,6-
Comparison of coupling constants calculated for hy-
drogen atoms of sugar moiety in the crystal of 7 with
trideoxy-a- -arabino-hexopyranoside (5) in 52% yield,
D
Scheme 1.

A. Da˛browska et al. / Carbohydrate Research 337 (2002) 175–181
177
Table 1
field-desorption ionization mode. Progress of the reac-
tion was monitored by thin-layer chromatography
(TLC) using aluminum plates precoated with Silica Gel
60 (0.08 mm, E. Merck, Darmstadt, Germany) using
the following eluent systems (v/v): (A) 20:1 CCl4–ace-
tone; (B) 2:1 CCl4–ether; (C) 10:1 CCl4–ether; (D) 2:1
heptane–EtOAc; (E) 4:1 CCl4–ether; (F) 20:1
petroleum ether–EtOAc; (G) 3:1 heptane–EtOAc;
components were detected by heating at ca 200 °C.
Flash chromatography was performed on Silica Gel 60
(0.08 mm, E. Merck). Evaporations were carried out
under diminished pressure at 35–40 °C. Some elemen-
tary analyses for the syrupy products are not satisfac-
tory within accepted limits, but all other spectral data
confirms unambiguously the structures of obtained
compounds.
1
Selected torsion angles and their coupling constants in the H
NMR spectrum of compound 7
[ (°)
−78 J1,2e 0.07 J1,2e 1.47
39 J1,2a 4.83 J1,2a 3.66 −1.17
Jcalc
Jfound
DJ
H-1AꢀC-1ꢀC-
2ꢀH-2A(e)
H-1AꢀC-1ꢀC-
2ꢀH-2B(a)
H-2A(e)ꢀC-2ꢀC-
3ꢀH-3A
H-2B(a)ꢀC-2ꢀC- −159 J2a,3 7.98 J2a,3 8.78
3ꢀH-3A
H-3AꢀC-3ꢀC-
4ꢀH-4A
H-4AꢀC-4ꢀC-
5ꢀH-5A
H-5AꢀC-5ꢀC-
6ꢀH-6A(a)
H-5AꢀC-5ꢀC-
6ꢀH-6B(e)
1.4
−41 J2e,3 4.54 J2e,3 4.94
0.40
0.80
0.65
0.71
0.00
1.57
173 J3,4 9.06
J3,4 9.71
−177 J4,5 9.17
J4,5 9.88
Methyl 3-azido-2,3-dideoxy-6-O-p-tolylsulfonyl-h-
arabino-hexopyranoside (2) and methyl 3-azido-2,3-
dideoxy-4,6-di-O-p-tolylsulfonyl-h- -arabino-hexopyran
oside (3).—To a solution of methyl 3-azido-2,3-
D-
176 J5,6a 9.15 J5,6a 9.15
67 J5,6e 0.99 J5,6e 2.56
D
dideoxy-a-
-arabino-hexopyranoside1 (1) (0.2 g, 0.98
D
Table 2
1
Crystal data and structure refinement for 7
those found in the H NMR spectrum (Table 1) shows
that conformations in the crystal, as well as in the
solution are very similar.
Empirical formula
Formula weight
Temperature (K)
Wavelength (A)
Crystal system
Space group
C9H14IN3O4
355.13
293(2)
0.71073
orthorhombic
P212121
The crystal structure of 7 was solved by the SHELXS
program and refined by SHELXL-97.5,6 A summary of
crystallographic data, data collection, and structure
refinement is presented in Table 2. A view of 7 and
molecular packing in the crystal are presented in Figs. 1
and 2, respectively.7,8 The coordinates of atoms and
their isotropic temperature factors are presented in
Table 3, and a selection of important geometric
parameters of 7 is tabulated in Table 4.
,
Unit cell dimensions
,
a (A)
7.331(1)
8.928(2)
20.652(4)
1351.7(4)
4
1.745
2.377
696
0.4×0.4×0.5
,
b (A)
,
c (A)
3
,
V (A )
In the crystal, 7 adopts a 4C1 chair conformation
with puckering parameters Q=0.046(7) and [=
4.6(7)°. The values of bond lengths and angles deter-
mined in this work for 7 agree well with the expected
ones.9 An interesting, nearby linear contact of 4.691(7)
Z
Dcalcd (Mg m−3
)
Absorption coefficient (mm−1
F(000)
)
Crystal size (mm)
[ Range for data collection (°) 1.97–30.13
Limiting indices
,
A between the iodine atom and the outer N atom of the
05h510, 05k512,
05l528
2194/2192
[Rint=0.6977]
azido group of neighboring molecules was not found in
the Cambridge Structural Database (CSD).10
Reflections collected/unique
Completeness to 2[=60.26 (%) 95.3
Refinement method
full-matrix least-squares
3. Experimental
on F2
Data/restraints/parameters
Goodness-of-fit on F2
Final R indices [I\2|(I)]
2192/0/156
1.016
General methods.—Melting points were uncorrected.
Optical rotations were determined with a Hilger–Watt
polarimeter in 1-dm tubes at the D line of sodium and
rt. Infrared spectra were recorded in Nujol mulls with a
Perkin–Elmer 257 spectrophotometer. NMR spectra
were measured with a Varian XL-100 spectrometer at
500 MHz in CDCl3 (unless otherwise stated) with
Me4Si as the internal standard. Mass spectra were
recorded with a Varian Mat 711 spectrometer with the
R1=0.0484
wR2=0.1158
R1=0.1097
wR2=0.1447
−0.05(6)
R indices (all data)
Absolute structure parameter
Largest difference peak and hole 0.862 and −1.103
−3
,
(e A
)

178
A. Da˛browska et al. / Carbohydrate Research 337 (2002) 175–181
Table 3
Atomic coordinates (×104) and equivalent isotropic displace-
2
3
,
ment parameters (A ×10 ) for 7
Atom
x
y
z
Ueq
86(1)
I-21
O-1
O-4
O-5
O-1
N-1
N-2
N-3
C-1
C-2
C-3
C-4
C-5
C-6
C-7
C-17
C-19
H-1A
H-2A
H-2B
H-3A
H-4A
H-5A
H-6A
H-6B
H-7A
H-7B
H-7C
−725(1)
6147(1)
2448(6)
4997(5)
5047(6)
7462(6)
4014(10)
4033(9)
4030(19)
3816(10)
3798(10)
3816(8)
5114(7)
5000(8)
6275(9)
2241(13)
6260(9)
5961(12)
3969
2813
4513
2889
6069
4077
7154
6420
1202
2027(1)
1571(3)
−162(2)
519(2)
−351(3)
−293(3)
−817(3)
−5059(10)
−3111(7)
−4717(7)
−3313(10)
−6940(10)
−6274(11)
−5832(15)
−5959(10)
−7010(10)
−5750(9)
−4401(10)
−3400(10)
−2105(10)
−4267(16)
−2698(11)
−1423(17)
−6813
−7534
−7986
−5098
−5004
−2731
−2859
−1234
−3978
61(2)
47(1)
51(1)
70(2)
71(2)
67(2)
154(6)
53(2)
55(2)
44(1)
42(1)
43(2)
55(2)
86(3)
53(2)
85(3)
63
65
65
53
50
52
66
66
129
Fig. 1. Structure of methyl 4-O-acetyl-3-azido-2,3,6-trideoxy-
6-iodo-a-D-arabino-hexopyranoside (7) showing 50% proba-
bility displacements for ellipsoids.
−1315(5)
1502(3)
877(3)
292(3)
363(3)
1015(3)
1107(4)
2207(4)
−495(4)
−1031(5)
1848
mmol) in CH2Cl2 (5 mL), dry pyridine (0.5 mL) and
p-toluenesulfonyl chloride (0.57 g, 3 mmol) were added.
After stirring at rt for 20 h the mixture was diluted with
CH2Cl2 (10 mL), washed with aq NaHCO3 and water.
The resulting solution was dried with Na2SO4, concen-
trated to a syrup (0.5 g), and then submitted to column
chromatography (A) to give 2 as a syrup (0.22 g, 62%);
[h]2D0 +90° (c 0.9, CHCl3); Rf 0.32 (B); IR (Nujol); w
3280–3140, 2960–2840, 2100, 1600, 1370, 1170, 815
875
851
250
351
1034
1117
765
2269
1
cm−1; H NMR (CDCl3): l 7.69 (dd, 4 H, J 8 Hz,
CH3C6H4SO3), 4.82 (d, 1 H, J1,2a 4, J1,2e 1.5 Hz, H-1),
4.5 (dd, 1 H, J6,6% 12 Hz, H-6), 4.28 (dd, 1 H, J5,6% 4 Hz,
H-6%), 4.23 (t, 1 H, J4,5 10 Hz, H-4), 3.86 (m, 1 H, J3,4
10 Hz, H-3), 3.64 (m, 1 H, J5,6 2 Hz, H-5), 3.35 (s, 3 H,
OCH3), 2.84 (ps. 1 H, OH), 2.5 (s, 3 H, CH3C6H4), 2.19
(m, 1 H, J2a,2e 13 Hz, H-2e), 1.7 (m, 1 H, J3,2a 13, J3,2e
5 Hz, H-2a); FDMS: m/z 357 [M+]. Anal. Calcd for
C14H19N3O6S (357.38): C, 47.05; H, 5.36; N, 11.76; S,
8.97. Found: C, 46.18; H, 5.50, N, 11.20; S,
9.02.Compound 3 was isolated as a syrup (0.1 g, 20%);
[h]2D0 +105° (c 1.1, CHCl3); Rf 0.44 (B); IR (Nujol); w
2960–2840, 2100, 1600, 1450, 1375, 1175, 1000, 820
−5123
−3174
2556
2828
2531
2242
129
129
H-19A −1179
6875
5246
5566
−1259
−1322
−860
127
127
127
H-9B
H-9C
−1955
−304
Ueq is defined as one third of the trace of the orthogonalized
Uij tensor.
1
cm−1; H NMR (CDCl3): l 7.65 (dd, 8 H, J 8 Hz,
Fig. 2. Molecular packing of 7 (view along x axis).

A. Da˛browska et al. / Carbohydrate Research 337 (2002) 175–181
179
Table 4
dropwise for 15 min. The mixture was then stored at rt
overnight and the resulting solution was then extracted
with CH2Cl2. The organic layer was washed with aq
NaHCO3 and water, dried over Na2SO4, and concen-
trated to a syrup yielding 1.3 g of a mixture of 2 and 3.
This mixture was then diluted with CH2Cl2 (70 mL),
and acetylated in pyridine (10 mL), using Ac2O (10 mL)
at rt to the point when all the starting compounds
(TLC, D) had disappeared (about 2 h). In this way,
0.52 g of the crude syrupy product was obtained, which
after chromatographic separation with the eluent sys-
tem (A) gave two syrupy products 3 (0.10 g, 20%) and
4 (0.25 g, 63%).
,
Selected bond lengths (A), valence angles (°) and torsion
angles (°) for 7
Bond lengths
I-21ꢀC-6
O-1ꢀC-1
O-1ꢀC-7
O-4ꢀC-17
O-4ꢀC-4
O-5ꢀC-5
O-5ꢀC-1
N-1ꢀN-2
N-1ꢀC-3
N-2ꢀN-3
C-1ꢀC-2
C-2ꢀC-3
C-3ꢀC-4
C-4ꢀC-5
C-5ꢀC-6
2.156(7)
1.396(10)
1.448(11)
1.356(9)
1.442(8)
1.421(8)
1.428(9)
1.186(10)
1.502(9)
1.079(11)
1.504(10)
1.521(9)
1.531(9)
1.537(10)
1.495(10)
Method B. To a solution of 11 (0.2 g, 1 mmol) in
CH2Cl2 (6 mL), a solution of p-toluenesulfonyl chloride
(0.58 g, 3 mmol) in pyridine (0.6 mL) was added
dropwise for 15 min. The mixture was then stored at rt
overnight. The resulting solution was then acetylated in
pyridine (2 mL), using Ac2O (2 mL) at rt for 2 h,
whereupon TLC (D) indicated that all the starting
compound had disappeared. The mixture was then
diluted with Et2O (5 mL) and the supernatant layer
decanted. The filtrate was concentrated to dryness, and
the syrupy residue was dissolved in CHCl3 (100 mL).
The solution was washed with aq NaHCO3 and water,
dried over Na2SO4, and evaporated to dryness to give
0.6 g of crude syrupy product containing a mixture of 3
and 4 [TLC, Rf 0.44 and 0.52 (B)]. Column chromatog-
raphy with the eluent system (A) gave 3 as a syrup (0.03
g, 6%) and 4 as a syrup (0.36 g, 91%).
Valence angles
C-1ꢀO-1ꢀC-7
C-17ꢀO-4ꢀC-4
C-5ꢀO-5ꢀC-1
N-2ꢀN-1ꢀC-3
N-3ꢀN-2ꢀN-1
C-1ꢀC-2ꢀC-3
N-1ꢀC-3ꢀC-2
N-1ꢀC-3ꢀC-4
C-2ꢀC-3ꢀC-4
C-3ꢀC-4ꢀC-5
C-6ꢀC-5ꢀC-4
C-5ꢀC-6ꢀI-21
113.1(7)
117.9(5)
113.1(5)
119.8(7)
173.1(10)
111.7(6)
106.7(6)
111.3(6)
108.9(6)
110.0(5)
111.3(6)
111.7(5)
Methyl 4-O-acetyl-3-azido-2,3-dideoxy-6-O-p-tolyl-
sulfonyl-h- -arabino-hexopyranoside (4).—To a solu-
D
Torsion angles
tion of 2 (0.22 g, 0.6 mmol) in CH2Cl2 (20 mL),
pyridine (2 mL), Ac2O (2 mL) and catalytic amount of
DMAP was added. The mixture was kept at rt for 2 h
(TLC, C), and then poured on to ice–water and ex-
tracted with CH2Cl2. The organic layer was washed
with aq NaHCO3 and water, dried over Na2SO4, and
concentrated to a syrup yielding 4 (0.21 g, 85%); [h]D20
+118° (c 0.9, CHCl3); Rf 0.52 (B); IR (Nujol); w
2960–2880, 2110, 1770, 1620, 1385, 1245, 1200, 850
C-5ꢀO-5ꢀC-1ꢀC-2
O-5ꢀC-1ꢀC-2ꢀC-3
C-1ꢀC-2ꢀC-3ꢀC-4
C-2ꢀC-3ꢀC-4ꢀC-5
C-3ꢀC-4ꢀC-5ꢀO-5
C-1ꢀO-5ꢀC-5ꢀC-4
−60.6(8)
54.2(9)
−52.0(9)
54.4(7)
−59.4(7)
62.8(7)
CH3C6H4SO3), 4.74 (d, 1 H, J1,2a 4, J1,2e 1.5 Hz, H-1),
4.45 (dd, 1 H, J6,6% 12 Hz, H-6), 4.41 (t, 1 H, J4,5 10 Hz,
H-4), 4.21 (dd, 1 H, J5,6% 10 Hz, H-6%), 4.12 (m, 1 H, J5,6
3 Hz, H-5), 3.79 (m, 1 H, J3,4 10 Hz, H-3), 3.3 (s, 3 H,
OCH3), 2.5 (s, 6 H, CH3C6H4), 2.17 (m, 1 H, J2a,2e 13
Hz, H-2e), 1.69 (m, 1 H, J3,2a 13, J3,2e 5 Hz, H-2a);
FDMS: m/z 511 [M+]. Anal. Calcd for C21H25N3O8S2
(511.56): C, 49.31; H, 4.93; N, 8.21; S, 12.53. Found: C,
48.90; H, 4.94, N, 7.61; S, 11.25.
1
cm−1; H NMR (CDCl3): l 7.63 (dd, 4 H, J 8 Hz,
CH3C6H4SO3), 4.78 (t, 1 H, J4,5 10 Hz, H-4), 4.77 (d, 1
H, J1,2a 4, J1,2e 1.5 Hz, H-1), 4.03 (dd, 1 H, J6,6% 13 Hz,
H-6), 3.98 (m, 1 H, J3,4 10 Hz, H-3), 3.93 (m, 1 H, J5,6
2 Hz, H-5), 3.81 (dd, 1 H, J5,6% 5 Hz, H-6%), 3.375 (s, 3
H, OCH3), 2.47 (s, 3 H, CH3C6H4), 2.15 (m, 1 H, J2a,2e
13 Hz, H-2e), 2.12 (s, 3 H, CH3CO), 1.67 (m, 1 H, J3,2a
13, J3,2e 5 Hz, H-2a); FDMS: m/z 399 [M+]. Anal.
Calcd for C16H21N3O7S (399.42): C, 48.11; H, 5.30; N,
10.52; S, 8.03. Found: C, 48.01; H, 5.02, N, 9.12; S,
9.02.
Methyl 3-azido-2,3-dideoxy-4,6-di-O-p-tolylsulfonyl-
h- -arabino-hexopyranoside (3) and methyl 4-O-
D
acetylo-3-azido-2,3-dideoxy-6-O-p-tolylsulfonyl-h-
D-ara
bino-hexopyranoside (4)
Methyl 3-azido-6-iodo-2,3,6-trideoxy-h-D-arabino-
Method A. To a solution of 11 (0.2 g, 0.98 mmol) in
CH2Cl2 (6 mL), a solution of p-toluenesulfonyl chloride
(0.58 g, 3 mmol) in pyridine (0.6 mL) was added
hexopyranoside (5).—A solution of the 6-sulfonate 2
(0.22 g, 0.6 mmol) in acetone (5.5 mL) containing NaI
(0.55 g, 0.01 mol) was refluxed for 10 h. TLC (E)

180
A. Da˛browska et al. / Carbohydrate Research 337 (2002) 175–181
indicated a fast-moving product. The mixture was then
cooled, precipitated sodium p-toluenesulfonate was
filtered off, and the filtrate concentrated to dryness. The
residue was partitioned between water and CHCl3, and
the organic layer washed with aq Na2S2O3 and water,
dried over Na2SO4, and concentrated to give the crude
product (0.13 g) which, after column chromatography
(C), gave the 6-iodo derivative 5 as a syrup (0.1 g,
52%); [h]2D0 +83° (c 1.1, CHCl3); Rf 0.45 (E); IR
(Nujol); w 3280–3160, 2960-2840, 2100, 1725, 1430,
H, CH3CO), 1.748 (m, 1 H, J3,2a 8.78, J3,2e 4.94 Hz,
H-2a); 13C NMR: l 170.1 (CH3CO), 97.716 (C-1),
74.472 (C-4), 70.01 (C-5), 57.668 (C-3), 55.501 (OCH3),
35.272 (C-2), 21.052 (CH3CO), 4.46 (C-6); FDMS: m/z
355 [M+]. Anal. Calcd for C9H14IN3O4 (355.13): C,
30.40; H, 3.97; N, 11.80. Found: C, 30.59; H, 4.00; N,
11.80.
The byproduct 8 was a syrup (0.01 g, 2.3%); [h]2D0+
81° (c 1.0, CHCl3); Rf 0.26 (G); IR (Nujol); w 2960–
2840, 2100, 1735, 1440, 1370, 1260–1220, 1130, 1050,
970 cm−1; 1H NMR (CDCl3): l 4.95 (t, 1 H, J4,5 10 Hz,
H-4), 4.87 (dd, 1 H, J1,2a 4, J1,2e 1.5 Hz, H-1), 4.28 (dd,
1 H, J6,6% 12 Hz, H-6), 4.04 (dd, 1 H, J5,6% 2 Hz, H-6%),
3.95 (m, 1 H, J3,4 10 Hz, H-3), 3.88 (m, 1 H, J5,6 5 Hz,
H-5), 3.37 (s, 3 H, OCH3), 2.33 (m, 1 H, J2a,2e 13 Hz,
H-2e), 2.02 (s, 3 H, CH3CO), 2.01 (s, 3 H, CH3CO),
1.77 (m, 1 H, J3,2a 12, J3,2e 5 Hz, H-2a); FDMS: m/z
287 [M+]. Anal. Calcd for C11H17N3O6 (287.27): C,
45.99; H, 5.96; N, 14.62. Found: C, 45.83; H, 5.99; N,
14.69.
1
1230, 1040, 930, 820, 760 cm−1; H NMR (CDCl3): l
4.9 (d, 1 H, J1,2a 3.5, J1,2e 1.5 Hz, H-1), 4.13 (t, 1 H, J4,5
12 Hz, H-4), 3.85 (dd, 1 H, J6,6% 13 Hz, H-6), 3.74 (dd,
1 H, J5,6% 10 Hz, H-6%), 3.57 (m, 1 H, J3,4 10 Hz, H-3),
3.24 (m, 1 H, J5,6 5 Hz, H-5), 3.44 (s, 3 H, OCH3), 2.72
(ps, 1 H, OH), 2.22 (m, 1 H, J2a,2e 14 Hz, H-2e), 1.74
(m, 1 H, J3,2a 8, J3,2e 5 Hz, H-2a); FDMS: m/z 313
[M+]. Anal. Calcd for C7H12IN3O3 (313.10): C, 26.85;
H, 3.86; N, 13.42. Found: C, 27.01; H, 3.54, N, 12.7.
Methyl 3-azido-6-iodo-2,3,6-trideoxy-4-O-p-tolylsul-
fonyl-h-
D
-arabino-hexopyranoside (6).—A solution of
Methyl 3-azido-6-iodo-2,3,6-trideoxy-4-O-p-tolylsul-
the 4,6-disulfonate 3 (0.1 g, 0.2 mmol) in acetone (2
mL) containing NaI (0.2 g, 1.3 mmol) was refluxed for
24 h. The reaction was processed as described previ-
ously to give 6 as a syrup (0.06 g, 65%); [h]2D0 +168° (c
1.0, CHCl3); Rf 0.64 (E); IR (Nujol); w 2960–2840,
2100, 1600, 1370, 1180, 1130, 1050, 1000, 885. 830, 770
fonyl-h-
tyl-3-azido-6-iodo-2,3,6-trideoxy-h-
pyranoside (7), and methyl 4,6-di-O-acetyl-3-azido-2,3-
dideoxy-h- -arabino-hexopyranoside (8).—The crude
D
-arabino-hexopyranoside (6), methyl 4-O-ace-
D
-arabino-hexo-
D
mixture of compounds of 3 and 4 (0.6 g) (obtained by
method B without final chromatography) in Ac2O (6.1
mL) containing NaI (0.61 g, 4.1 mmol) was refluxed for
6 h. TLC with solvent (G) showed three spots (Rf 0.54,
0.43, and 0.27). After conventional processing, the
crude product (0.4 g) was separated by a column chro-
matography with solvent (F). Three compounds were
obtained: 6 (0.02 g, 4.3%), 7 (0.22 g, 63%), and 8 (0.015
g, 5.3%), identical with those obtained earlier, on the
1
cm−1; H NMR (CDCl3): l 7.68 (dd, 4 H, J 8 Hz,
CH3C6H4SO3), 4.86 (d, 1 H, J1,2a 3.5, J1,2e 1.5 Hz, H-1),
4.3 (t, 1 H, J4,5 12 Hz, H-4), 3.85 (dd, 1 H, J6,6% 13 Hz,
H-6), 3.79 (m, 1 H, J3,4 10 Hz, H-3), 3.74 (dd, 1 H, J5,6%
10 Hz, H-6%), 3.44 (s, 3 H, OCH3), 3.24 (m, 1 H, J5,6
5
Hz, H-5), 2.48 (s, 3 H, CH3C6H4), 2.22 (m, 1 H, J2a,2e
14 Hz, H-2e), 1.74 (m, 1 H, J3,2a 8, J3,2e 5 Hz, H-2a);
FDMS: m/z 467 [M+]. Anal. Calcd for C14H18IN3O5S
(467.28): C, 35.99; H, 3.88; N, 8.99; S, 6.86. Found: C,
36.68; H, 4.23, N, 8.7; S, 6.04.
1
basis of their H NMR spectra. (The yields of these
compounds were calculated in regards to the starting
substrate 1.)
Methyl 4-O-acetyl-3-azido-6-iodo-2,3,6-trideoxy-h-
D
-arabino-hexopyranoside (7) and methyl 4,6-di-O-ace-
tyl-3-azido-2,3-dideoxy-h- -arabino-hexopyranoside
D
4. Supplementary material
(8).—A solution of 4 (0.61 g, 1.5 mmol) in Ac2O (6.2
mL) containing NaI (0.62 g, 4.1 mmol) was refluxed for
6 h. After cooling, precipitated sodium p-toluenesul-
fonate was filtered off, washed with CHCl3 and the
filtrate concentrated to dryness. The residue was parti-
tioned between water and ether, and worked up as just
described to give 0.54 g of a mixture of products.
Column chromatography (F) gave the main product 7
(0.45 g, 83%); mp 77–78 °C; [h]2D0 +96° (c 1.1, CHCl3);
Rf 0.54 (G); IR (Nujol); w 2960–2840, 2100, 1725, 1430,
Full crystallographic details, excluding structure fea-
tures, have been deposited (deposition no. CCDC
168192) with the Cambridge Crystallographic Data
Centre. These data may be obtained, on request, from
The Director, CCDC, 12 Union Road, Cambridge
CB2 1EZ, UK (Tel.: +44-1223-336408; fax: +44-
1223-336033; e-mail: deposit@ccdc.cam.ac.uk or
www: http://www.ccdc.cam.ac.uk).
1
1230, 1040 cm−1; H NMR (CDCl3): l 4.841 (d, 1 H,
J1,2a 3.66, J1,2e 1.47 Hz, H-1), 4.701 (t, 1 H, J4,5 9.88 Hz,
H-4), 3.883 (m, 1 H, J3,4 9.71 Hz, H-3), 3.727 (m, 1 H,
J5,6 2.56 Hz, H-5), 3.438 (s, 3 H, OCH3), 3.283 (dd, 1
H, J6,6% 10.98 Hz, H-6), 3.11 (dd, 1 H, J5,6% 9.15 Hz,
H-6%), 2.173 (m, 1 H, J2a,2e 13.36 Hz, H-2e), 2.154 (s, 3
Acknowledgements
This study was supported by The Polish Research
Council under grant BW-8000-5-0243-0.

A. Da˛browska et al. / Carbohydrate Research 337 (2002) 175–181
181
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7. Johnson, C. K. ORTEP II; Report ORNL-5138; Oak
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8. Motherwell, S.; Clegg, S. PLUTO-78; Program for Draw-
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9. Cambridge Structural Database (CSD) System, Version
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10. Allen, F. H.; Kennard, O.; Watson, D. G.; Brammer, L.;
Orpen, A. G.; Taylor, R. J. Chem. Soc. Perkin Trans. 2
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