Synthesis of novel N-carbohydrate-derived heterocyclic compounds by nucleophilic substitution reaction of carbohydrate imidazole-1-sulfonates

Article abstract of DOI:10.1080/07328303.2011.605193

The nucleophilic substitution reaction of carbohydrate imidazole-1- sulfonates with pyrrole and other nitrogen heterocyclic compounds is reported for the first time. Several novel N-carbohydrate-derived heterocyclic compounds have been prepared by this displacement reaction. The desired carbon-nitrogen bond formation proceeds under mild conditions to generate the coupling products in good yields with readily available and inexpensive reagents. This method is particularly suitable for carbohydrate imidazole-1-sulfonates of primary alcohols. Supplemental materials are available for this article. Go to the publisher's online edition of Journal of Carbohydrate Chemistry to view the free supplemental file. Taylor & Francis Group, LLC.

Full text of DOI:10.1080/07328303.2011.605193

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Synthesis of Novel N-carbohydrate-
derived Heterocyclic Compounds by
Nucleophilic Substitution Reaction of
Carbohydrate Imidazole-1-sulfonates
a
a
a
a
Shiyong Huo , Yueqing Li , Chaoyan Liang , Jihong Liu & Weijie
a
Zhao
a
School of Pharmaceutical Science and Technology , Dalian
University of Technology , 2 Linggong Road, Dalian, 116024, China
Published online: 21 Sep 2011.
To cite this article: Shiyong Huo , Yueqing Li , Chaoyan Liang , Jihong Liu & Weijie Zhao (2011)
Synthesis of Novel N-carbohydrate-derived Heterocyclic Compounds by Nucleophilic Substitution
Reaction of Carbohydrate Imidazole-1-sulfonates, Journal of Carbohydrate Chemistry, 30:2, 75-84,
DOI: 10.1080/07328303.2011.605193
To link to this article: http://dx.doi.org/10.1080/07328303.2011.605193
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Journal of Carbohydrate Chemistry, 30:75–84, 2011
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 0732-8303 print / 1532-2327 online
DOI: 10.1080/07328303.2011.605193
Synthesis of Novel
N-carbohydrate-derived
Heterocyclic Compounds
by Nucleophilic Substitution
Reaction of Carbohydrate
Imidazole-1-sulfonates
Shiyong Huo, Yueqing Li, Chaoyan Liang, Jihong Liu,
and Weijie Zhao
School of Pharmaceutical Science and Technology, Dalian University of Technology,
2
Linggong Road, Dalian 116024, China
The nucleophilic substitution reaction of carbohydrate imidazole-1-sulfonates with pyr-
role and other nitrogen heterocyclic compounds is reported for the first time. Several
novel N-carbohydrate-derived heterocyclic compounds have been prepared by this dis-
placement reaction. The desired carbon-nitrogen bond formation proceeds under mild
conditions to generate the coupling products in good yields with readily available and
inexpensive reagents. This method is particularly suitable for carbohydrate imidazole-
1
-sulfonates of primary alcohols. Supplemental materials are available for this article.
Go to the publisher’s online edition of Journal of Carbohydrate Chemistry to view the
free supplemental file.
Keywords Carbohydrates; Heterocycles; Nucleophilic substitution; Imidazole-1-
sulfonates
INTRODUCTION
Since the pioneering work of Karl Freudenberg on displacements of car-
[
1–4]
bohydrate p-toluenesulfonates,
bimolecular nucleophilic substitution has
Received October 24, 2010; accepted July 11, 2011.
Address correspondence to Weijie Zhao, School of Pharmaceutical Science and Tech-
nology, Dalian University of Technology, 2 Linggong Road, Dalian 116024, P. R. China.
E-mail: zyzhao@dlut.edu.cn
7
5

S. Huo et al.
7
6
become one of the most employed and useful reactions in carbohydrate chem-
istry. Indeed, SN2-type reactions have allowed the introduction of a variety of
heteroatoms (halogens, nitrogen, oxygen, sulfur) into carbohydrates, and the
resulting compounds have been used in many synthetic and biological fields.[
Sulfonic esters of sugar derivatives provide a versatile and simple method
for activating hydroxy groups for bimolecular displacement reactions with nu-
cleophiles. Until the late 1970s, the most common sulfonate leaving groups
consisted of either tosylates (4-toluenesulfonates) or mesylates (methanesul-
5]
[
6–8]
fonates).
The introduction of the triflate (trifluoromethanesulfonate) group
in the field of carbohydrate chemistry greatly improved the efficiency of dis-
placement, which was sluggish or impossible when other sulfonic ester was
used.[
9–11]
The imidazylate (imidazole-1-sulfonate) moiety was introduced by the
[
12,13]
Hanessian group as a superb leaving group for sugar compounds.
The
imidazylate group is a complement to the triflate leaving group for “difficult”
substitution reactions of carbohydrate derivatives. Imidazylates have signifi-
cant advantages over triflates, such as a longer shelf life, crystallinity, and be-
ing compatible with chromatographic purification. And they can be prepared
from readily available and inexpensive reagents. This group has been reported
primarily in carbohydrate- and nucleoside-related literature as a useful elec-
trophile in several total syntheses of carbohydrate-containing natural prod-
ucts.[
14–18]
Furthermore, imidazylate azide hydrochloride has been introduced
as a useful and practical diazo donor reagent that mimics trifluoromethane-
[
19]
sulfonyl azide in reactivity.
More recently, imidazylates have also been used
as effective electrophilic coupling partners in metal-catalyzed coupling reac-
tions.[
20]
RESULTS AND DISCUSSION
We report herein the reactions of sugar imidazole sulfonates with pyrrole and
related heterocyclic compounds. Even though substitution of sugar tosylates
and mesylates by potassium succinimide was described,[ there was no re-
port about the substitution of sugar imidazylates by metal salts of pyrrole and
related heterocyclic compounds. Generally, alkylation at the nitrogen atoms
of pyrrole and related heterocyclic compounds could be easily achieved via
their conjugate bases. The electrophiles can be alkyl halides, mesylates, or
tosylates. However, in the carbohydrate field, these electrophiles have been
found to be difficult to undergo the SN2 displacement reaction. The reaction of
21]
1
-bromo-1-deoxy-2,3:4,5-di-O-isopropylidene-β-D-froctopyranose with sodium
◦
salt of pyrrole-2-carboxaldehyde in DMF at 150 C for 50 h only afforded com-
pound 10 in a yield of 10%. Given the versatile properties of the imidazylate
group, we reasoned that imidazylates would participate as electrophiles in SN2

Synthesis of Novel N-carbohydrate-derived Heterocyclic Compounds
7
7
displacement reactions with pyrrole or other N-heterocyclic anions. We antici-
pated that imidazylates would provide enough increased activity.
As shown in Scheme 1, 6-imidazylate ester of 1,2:3,4-di-O-isopropylidene-
α-D-galactopyranose (2) could be prepared by the reaction of compound 1 with
◦
sulfuryl chloride in DMF at −40 C in the presence of 6 equiv. of imidazole
according to the method reported by the Hanessian group.[ Treatment of
12]
compound 2 with sodium salts of pyrrole and pyrrole-2-carboxaldehyde in DMF
◦
at 120 C led to compounds 5 and 6 in the yields of 71% and 80%, respectively.
O
O
6
OH
O
S
N
R
N
SO2Cl2, DMF
Imidazole
O
O
O
NaH, DMF
120 o
8
O
4
5
O
O
2
O
+
RH
O
1
-40 o
C
O
O
C
O
O
3
O
O
7
O
, R=R1
, R=R2
5, R=R1 71%
6, R=R2 80%
3
4
1
2
7
6
6
SO2Cl2, DMF
Imidazole
O
O
2
O
O
5
O
O
O
3
2
1
O
O
5
4
O
1'
NaH, DMF
O
4
O
S
+
R'H
R'
3
OH
O
1
O
O
o
2'
120 o
C
-
40 C
O
N
O
O
5
'
N
3'
8
9, R'=R1 74%
3
, R'=R1
4'
8
2
0, R'=R2 83%
7
4, R'=R
1
3
3
1
1
1
1, R'=R
12, R'=R 81%
14, R'=R4 80%
16, R'=R5 47%
3, R'=R4
5, R'=R5
O
S
N
O
O
SO Cl , DMF
Imidazole
O
N
O
O
2
2
OH
O
O
O
NaH, DMF
r.t.
O
O
O
o
+
RH
-
40 C
O
O
O
O
O
O
, R=R1
, R=R2
3
19
1
7
18
4
O
O
5
'
2'
2'
1'
2
'
3'
3'
O
7'
S
1'
3
'
1'
4'
3'
1'
N
N
1'
R3
N
2'
3'
R1
R2
N
=
R4 =
N
R5
N
=
N
=
9'
=
8'
4
'
4'
8
'
4'
'
5'
2'
5'
OHC
9'
4'
7
'
5
6'
6
'
5
'
Scheme 1: Synthesis of N-carbohydrate-derived heterocyclic compounds.
◦
Treatment of compound 8 with excess pyrrole and NaH in DMF at 120 C
led to the corresponding compound 9 in a yield of 74%. Compound 8 was pre-
pared on a 0.2 mol scale with a yield of 80%. It is worth noting that when
the displacement reaction was carried out in toluene or THF under reflux, no
product of compound 9 was generated. We also used the sodium salts of pyrrole-
2-carboxaldehyde, imidazole, and benzimidazole as nucleophiles to react with

S. Huo et al.
7
8
Figure 1: The X-ray crystal structure of compound 9.
compound 8 in the same way, and obtained corresponding products 10, 12, and
1
4 in high yields.
The structures of the products were determined by H, 13C, 2D NMR, and
1
HRMS. X-ray crystallographic of compound 9 is shown in Figure 1.[
Sodium salt of indole failed in imidazylate displacement of compound 8 and
the unexpected product 16 was isolated in 47% yield. The molecular formula
22]
+
was established as C20H25NO8S by HRMS at m/z 462.1207 [M+Na] (calcd
462.1199). The structure of compound 16 was also confirmed by the fact that
HMBC interactions of H-1a/C-2’, H-1b/C-2’, and H-2’/C-1 were not observed;
in contrast, corresponding HMBC interactions were clearly observed in com-
pounds 9, 10, 12, and 14. In all cases of sodium salts of pyrrole, indole, imida-
zole, and benzimidazole, the negative charge on N-atom is delocalized. Among
them, the negative charge at the indole N-atom is the lowest, calculated by the
Gasteiger-H u¨ ckel method on Sybyl-X 1.1 (The data is supplied in the Support-
ing Information). We proposed it was the weak nucleophilicity of indole sodium
salt that led to the formation of compound 16.
As shown in Scheme 1, in the reaction of 3-imidazylates of 1,2:5,6-di-O-
isopropylidene-α-D-glucofuranose (18) with sodium salt of pyrrole and pyrrole-
2-carboxaldehyde in DMF even at rt, the β-elimination products were isolated
in the yields of 71% and 73%. That is, the imidazylates of primary alcohols
favor the SN2 displacement reaction to generate N-substituent pyrroles, while
the imidazylats of secondary alcohols are more likely to favor β-elimination
reaction by an antielimination process.

Synthesis of Novel N-carbohydrate-derived Heterocyclic Compounds
7
9
CONCLUSION
In summary, we have developed the first example for nucleophilic substitution
of carbohydrate imidazylates with pyrrole and other N-heterocyclic compounds
and prepared several novel N-carbohydrate-derived heterocyclic compounds.
The desired carbon-nitrogen bond formation proceeds under mild conditions to
generate the coupling products in good yields. N-heterocyclic compounds with
more acidity and less steric hindrance are advantageous for this displacement
reaction. This method is particularly suitable for carbohydrate imidazylates of
primary alcohols.
EXPERIMENTAL
General
DMF was dried by distillation over CaH2. Other chemicals were used as
received, and all reactions conducted under standard conditions were moni-
tored by thin-layer chromatography (TLC) on gel F254 plates. The silica gel
(
200–300 meshes) was used for column chromatography. Compounds 2 and 18
[
12]
were prepared according to the method reported by the Hanessian group.
Melting points were determined with a SGW X-6 melt instrument and un-
corrected. Optical rotations were measured on a DIP-370 polarimeter at the
◦
1
13
1
1
sodium D line (λ = 589 nm) at 28 C. H NMR, C NMR, H- H COSY, HSQC,
and HMBC spectra were recorded on Bruker Avance 400 MHz instruments,
and spectral data were reported in ppm relative to tetramethylsilane (TMS) as
internal standard. HRMS data were determined on a TOF-ESI-MS spectrom-
eter.
6-Deoxy-6-(1H-pyrrol-1-yl)-1,2:3,4-di-O-isopropylidene-α-D-
galactopyranose (5)
A solution of compound 3 (0.24 g, 3.58 mmol) in 3 mL DMF was added
◦
dropwise at 0 C to a suspension of sodium hydride (0.14 g, 60% suspension
in mineral oil, 3.5 mmol) in 10 mL DMF. After stirring 1 h at rt, compound 2
(
0.69 g, 1.77 mmol) in 5 mL DMF was added. The reaction mixture was heated
◦
at 120 C for 6 h. While compound 2 disappeared detected by TLC, the mix-
ture was cooled to rt. Then water (20 mL) and ether (20 mL) were added.
The aqueous layer was extracted with ether (5 × 20 mL) and the combined
organic extracts were washed with water (2 × 20mL), dried over anhydrous
Na2SO4, and evaporated. Purification of the residue by flash chromatogra-
2
8
◦
phy (ethyl acetate/petroleum ether: 1/5) afforded 5 (0.39 g, 71%), [α]D –42.4
1
(
c 1.0, MeOH). H NMR (400 MHz, CDCl3): δ 1.31 (3H, s, CH3), 1.35 (3H, s,
CH3), 1.47 (3H, s, CH3), 1.50 (3H, s, CH3), 4.00 (1H, m, H-4), 4.03 (1H, m, H-5),

S. Huo et al.
8
0
4
.05 (1H, dd, J = 13.6 and 6.2 Hz, H-6a), 4.15 (1H, dd, J = 13.6 and 7.4 Hz,
H-6b), 4.30 (1H, dd, J = 5.0 and 2.4 Hz, H-2), 4.56 (1H, dd, J = 7.9 and 2.4
ꢁ
ꢁ
Hz, H-3) 5.53 (1H, d, J = 5.0 Hz, H-1), 6.14 (2H, t, J = 2.1 Hz, H-3 and H-4 ),
ꢁ
ꢁ
13
6
.73 (2H, t, J = 2.1 Hz, H-2 and H-5 ). C NMR (100 MHz, CDCl3): δ 24.39
(
CH3), 24.88 (CH3), 26.00 (CH3), 26.04 (CH3), 49.08 (C-6), 67.76 (C-4), 70.58 (C-
ꢁ
ꢁ
2, C-3), 70.75 (C-5), 96.44 (C-1), 108.23 (C-3 , C-4 ), 108.67 (C-7), 109.39 (C-8),
ꢁ
ꢁ
+
1
21.09 (C-2 , C-5 ). HRMS (ESI): Calcd for C16H23NO5Na [M+Na] 332.1474,
found 332.1477.
6
-Deoxy-6-(2-formyl-1H-pyrrol-1-yl)-1,2:3,4-di-O-isopropylidene-
α-D-galactopyranose (6)
Compound 6 (0.45 g, 80% yield) was prepared from compounds 2 (0.65 g,
1
.66 mmol) and 4 (0.32 g, 2.0 equiv) according to the procedure for the prepara-
2
8
◦
1
tion of compound 5. [α]D –37 (c 0.33, MeOH). H NMR (400 MHz, CDCl3): δ
1
.26 (3H, s, CH3), 1.35 (6H, s, 2CH3), 1.50 (3H, s, CH3), 4.10 (1H, ddd, J = 8.2,
4
.0 and 1.5 Hz, H-5), 4.20 (1H, m, H-4), 4.22 (1H, m, H-6a), 4.27 (1H, dd, J = 4.8
and 2.4 Hz, H-2), 4.59 (1H, dd, J = 8.0 and 2.4 Hz, H-3), 4.68 (1H, dd, J = 13.7
and 4.0 Hz, H-6b), 5.47 (1H, d, J = 4.9 Hz, H-1), 6.22 (1H, dd, J = 4.0 and 2.4
ꢁ
ꢁ
ꢁ
Hz, H-4 ), 6.96 (1H, dd, J = 4.0 and 1.7 Hz, H-3 ), 7.08 (1H, s, H-5 ), 9.52 (1H,
s, CHO). 13C NMR (100 MHz, CDCl3): δ 24.31 (CH3), 24.97 (CH3), 25.75 (CH3),
2
5.98 (CH3), 49.49 (C-6), 67.42 (C-5), 70.56 (C-2),70.81 (C-3), 71.27 (C-4), 96.27
ꢁ
ꢁ
ꢁ
(C-1), 108.73 (C-7), 109.41 (C-8), 109.45 (C-4 ), 125.38 (C-3 ), 131.08 (C-2 ),
ꢁ
+
1
33.33 (C-5 ), 179.18 (CHO). HRMS (ESI): Calcd for C17H23NO6Na [M+Na]
360.1423, found 360.1423.
2
,3:4,5-di-O-isopropylidene-1-O-(N-imidazole-1-sulfonyl)-β-D-
fructopyranose (8)
To a solution of compound 7 (52.0 g, 0.2 mol) and imidazole (82.0 g,
◦
1
0
.2 mol) in 1,000 mL DMF, cooled to –40 C, was added sulfuryl chloride (40.5 g,
◦
.3 mol) under nitrogen. The solution was stirred for 1 h at –40 C and 1 h
at rt. Then water (1,000 mL) and ether (1,000 mL) were added. The aqueous
layer was extracted with ether (3 × 500 mL) and the combined organic ex-
tracts were washed with water (2 × 500 mL), dried over anhydrous Na2SO4,
and evaporated. Purification of the residue by flash chromatography (ethyl ac-
◦
etate/petroleum ether: 1/3) afforded compound 8 (62.5 g, 80%), mp 75–76 C
◦
1
(
(
ether-hexane), [α]D28 –27 (c 7.4, MeOH). H NMR (400 MHz, CDCl3): δ 1.33
6H, s, 2CH ), 1.42 (3H, s, CH ), 1.51 (3H, s, CH ), 3.73 (1H, d, J = 13.0 Hz,
3
3
3
H-6a), 3.85 (1H, dd, J = 13.0 and 1.7 Hz, H-6b), 4.16 (1H, d, J = 10.4 Hz,
H-1a), 4.18 (1H, d, J = 2.8 Hz, H-3), 4.22 (1H, dd, J = 7.9, 0.7 Hz, H-5), 4.25
(
1H, d, J = 10.4 Hz, H-1b), 4.58 (1H, dd, J = 7.9 and 2.8 Hz, H-4), 7.19 (1H, s,
ꢁ
ꢁ
ꢁ
13
H-4 ), 7.36 (1H, s, H-5 ), 8.03 (1H, s, H-2 ). C NMR (100 MHz, CDCl3): δ 23.86

Synthesis of Novel N-carbohydrate-derived Heterocyclic Compounds
8
1
(
(
(
[
CH3), 24.94 (CH3), 25.71(CH3), 26.36 (CH3), 61.40 (C-6), 69.59 (C-4), 70.27
C-3), 70.32 (C-5), 72.91 (C-1), 99.79 (C-2), 109.21 (C-8), 109.55 (C-7), 118.13
ꢁ
ꢁ
ꢁ
C-5 ), 130.86 (C-4 ), 137.06 (C-2 ). HRMS (ESI): Calcd for C15H22N2O8SNa
+
M+Na] 413.0995, found 413.1016.
1-Deoxy-1-(1H-pyrrol-1-yl)-2,3:4,5-di-O-isopropylidene-β-D-
fructopyranose (9)
A solution of compound 3 (1.34 g, 20 mmol) in 10 mL DMF was added
◦
dropwise at 0 C to a suspension of sodium hydride (0.80 g, 60% suspension
in mineral oil, 20 mmol) in 50 mL DMF. After stirring 1 h at rt, compound 8
(
3.9 g, 10 mmol) in 40 mL DMF was added. The reaction mixture was heated
◦
at 120 C for 8 h. While compound 8 disappeared detected by TLC, the mixture
was cooled to rt. Then water (100 mL) and ether (100 mL) were added. The
aqueous layer was extracted with ether (5 × 100 mL) and the combined organic
extracts were washed with water (2 × 100mL), dried over anhydrous Na2SO4,
and evaporated. Purification of the residue by flash chromatography (ethyl
◦
acetate/petroleum ether: 1/5) afforded compound 9 (2.3 g, 74%), mp 79–80 C
ether-hexane), [α]D28 –45.8 (c 10.1, MeOH). H NMR (400 MHz, CDCl3): δ
◦
1
(
0
.76 (3H, s, CH ), 1.38 (3H, s, CH ), 1.48 (3H, s, CH ), 1.55 (3H, s, CH ), 3.79
3 3 3 3
(
1H, d, J = 12.9 Hz, H-6a), 3.95 (1H, dd, J = 12.9 and 1.8 Hz, H-6b), 4.08 (1H,
d, J = 14.8 Hz, H-1a), 4.21 (1H, d, J = 14.8 Hz, H-1b), 4.25 (1H, dd, J = 7.9
Hz and 1.8 Hz, H-5), 4.30 (1H, d, J = 2.7 Hz, H-3), 4.63 (1H, dd, J = 7.9 and
ꢁ
ꢁ
ꢁ
2
.7 Hz, H-4), 6.11 (2H, t, J = 2.1 Hz, H-3 , H-4 ), 6.71 (2H, t, J = 2.1 Hz, H-2 ,
ꢁ
13
H-5 ). C NMR (100 MHz, CDCl3): δ 23.99 (CH3), 24.15 (CH3), 25.95 (CH3),
2
6.62 (CH3), 54.23 (C-1), 61.49 (C-6), 70.02 (C-3), 70.15 (C-4), 70.93 (C-5),
ꢁ
ꢁ
ꢁ
101.75 (C-2), 108.25 (C-3 and C-4 ), 109.18 (C-8), 109.30 (C-7), 122.98 (C-2
ꢁ
+
and C-5 ). HRMS (ESI): Calcd for C16H23NO5Na [M+ Na] 332.1474, found
32.1483.
3
1
-Deoxy-1-(2-formyl-1H-pyrrol-1-yl)-2,3:4,5-di-O-isopropylidene-
β-D-fructopyranose (10)
The compound 10 (2.81 g, 83% yield) was prepared from compounds 8
(
3.9 g, 10 mmol) and 4 (1.9 g, 2.0 equiv) according to the procedure for the
2
8
◦
1
preparation of compound 9. [α]D –30.6 (c 9.4, MeOH). H NMR (400 MHz,
CDCl3): δ 1.13 (3H, s, CH ), 1.33 (3H, s, CH ), 1.41 (3H, s, CH ), 1.48 (3H, s,
3
3
3
CH ), 3.76 (1H, d, J = 13.0 Hz, H-6a), 3.88 (1H, dd, J = 13.0 and 1.8 Hz, H-6b),
3
4
.20 (1H, dd, J = 7.9 and 1.8 Hz, H-5), 4.36 (1H, d, J = 2.5 Hz, H-3), 4.56 (1H,
dd, J = 7.9 and 2.5 Hz, H-4), 4.69 (1H, d, J = 14.4 Hz, H-1a), 4.80 (1H, d, J =
ꢁ
1
1
4.4 Hz, H-1b), 6.24 (1H, dd, J = 4.0 and 2.6 Hz, H-4 ), 6.92 (1H, dd, J = 4.0 and
ꢁ
ꢁ
13
.5 Hz, H-3 ), 7.11 (1H, s, H-5 ), 9.59 (1H, s, CHO). C NMR (100 MHz, CDCl3):
δ 23.84 (CH3), 24.52 (CH3), 25.87 (CH3), 26.34 (CH3), 52.95 (C-1), 61.40 (C-6),

S. Huo et al.
8
2
7
0.23 (C-4), 70.53 (C-5), 71.21 (C-3), 102.05 (C-2), 108.86 (C-7), 108.92 (C-8),
ꢁ
ꢁ
ꢁ
ꢁ
110.06 (C-4 ), 123.96 (C-3 ), 132.24 (C-2 ), 133.60 (C-5 ), 179.65 (CHO). HRMS
+
(ESI): Calcd for C17H23NO6Na [M+Na] 360.1423, found 360.1431.
1
-Deoxy-1-(1H-imidazol-1-yl)-2,3:4,5-di-O-isopropylidene-β-D-
fructopyranose (12)
The compound 12 (0.61 g, 81% yield) was prepared from compounds 8
(
0.95 g, 2.4 mmol) and 11 (0.33 g, 2.0 equiv) according to the procedure for the
2
8
◦
1
preparation of compound 9. [α]D –31.6 (c 6.1, MeOH). H NMR (400 MHz,
CDCl3): δ 0.23 (3H, s, CH3), 0.78 (3H, s, CH3), 0.88 (3H, s, CH3), 0.93 (3H, s,
CH ), 3.17 (1H, d, J = 12.9 Hz, H-6a), 3.32 (1H, d, J = 12.9 Hz, H-6b), 3.54
3
(
1H, d, J = 14.8 Hz, H-1a), 3.58 (1H, d, J = 2.0 Hz, H-3), 3.65 (1H, d, J = 14.8
Hz, H-1b), 3.68 (1H, d, J = 7.8 Hz, H-5), 4.04 (1H, dd, J = 7.8 and 2.0 Hz, H-4),
ꢁ
ꢁ
ꢁ
13
6
2
6
1
.41 (2H, m, H-4 and H-5 ), 6.94 (1H, s, H-2 ). C NMR (100 MHz, CDCl3): δ
3.70 (CH3), 23.96 (CH3), 25.62 (CH3), 26.17 (CH3), 51.45 (C-1), 61.29 (C-6),
9.63 (C-4), 69.94 (C-5), 70.41 (C-3), 100.72 (C-2), 108.78 (C-8), 108.93 (C-7),
ꢁ
ꢁ
ꢁ
20.80 (C-5 ), 128.45 (C-4 ), 138.63 (C-2 ). HRMS (ESI): Calcd for C15H23N2O5
+
[
M+H] 311.1607, found 311.1346.
1
-Deoxy-1-(1H-benzimidazol-1-yl)-2,3:4,5-di-O-isopropylidene-β-
D-fructopyranose (14)
The compound 14 (0.70 g, 80% yield) was prepared from compound 8
(
0.95 g, 2.4 mmol) and 13 (0.57 g, 2.0 equiv) according to the procedure for the
◦
28
◦
preparation of compound 9. mp 164–165 C (ether), [α]D –36.6 (c 2.0, MeOH).
1
H NMR (400 MHz, CDCl3): δ 0.78 (3H, s, CH ), 1.40 (3H, s, CH ), 1.48 (3H,
3
3
s, CH ), 1.53 (3H, s, CH ), 3.81 (1H, d, J = 13.0 Hz, H-6a), 3.93 (1H, d, J =
3
3
1
4
3.0 Hz, H-6b), 4.26 (2H, m, H-3 and H-5), 4.50 (1H, d, J = 14.9 Hz, H-1a),
.57 (1H, d, J = 14.9 Hz, H-1b), 4.64 (1H, dd, J = 7.8 and 2.4 Hz, H-4), 7.37
ꢁ
ꢁ
(
1H, t, J = 7.7 Hz, H-5 ), 7.41 (1H, t, J = 7.7 Hz, H-6 ), 7.62 (1H, d, J = 7.9
ꢁ
ꢁ
ꢁ
13
Hz, H-7 ), 7.86 (1H, d, J = 7.9 Hz, H-4 ), 8.44 (1H, s, H-2 ). C NMR (100 MHz,
CDCl3): δ 23.91 (CH3), 24.65 (CH3), 25.97 (CH3), 26.38 (CH3), 50.41 (C-1), 61.71
ꢁ
ꢁ
(C-6), 69.96 (C-4), 70.64 (C-3 and C-5), 101.56 (C-2), 111.18 (C-7 ), 119.01 (C-4 ),
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
123.64 (C-5 ), 124.39 (C-6 ), 133.79 (C-9 ), 139.32 (C-8 ), 143.76 (C-2 ). HRMS
+
(ESI): Calcd for C19H25N2O5 [M+H] 361.1763, found 361.1759.
2
,3:4,5-di-O-isopropylidene-1-O-(N-indole-1-sulfonyl)-β-D-
fructopyranose (16)
The compound 16 (0.50 g, 47% yield) was prepared from compounds 8
(
0.95 g, 2.4 mmol) and 15 (0.57 g, 2.0 equiv) according to the procedure for
2
8
◦
1
the preparation of compound 9. [α]D –29.2 (c 3.3, MeOH). H NMR (400

Synthesis of Novel N-carbohydrate-derived Heterocyclic Compounds
8
3
MHz, CDCl3): δ 1.25 (3H, s, CH ), 1.26 (3H, s, CH ), 1.27 (3H, s, CH ), 1.46
3
3
3
(
3H, s, CH ), 3.66 (1H, d, J = 13.0 Hz, H-6a), 3.81 (1H, dd, J = 13.0 and 1.8
3
Hz, H-6b), 3.95 (1H, d, J = 10.0 Hz, H-1a), 4.07 (1H, d, J = 10.0 Hz, H-1b),
4
.15 (2H, m, H-3 and H-5), 4.48 (1H, dd, J = 7.9 and 2.6 Hz, H-4), 6.68 (1H,
ꢁ
ꢁ
ꢁ
d, J = 4.0 Hz, H-3 ), 7.29 (1H, m, H-5 ), 7.36 (1H, m, H-6 ), 7.44 (1H, d, J =
ꢁ
ꢁ
ꢁ
4
.0 Hz, H-2 ), 7.59 (1H, d, J = 7.8 Hz, H-4 ), 7.89 (1H, d, J = 8.3 Hz, H-7 ).
1
3
C NMR (100 MHz, CDCl3): δ 23.89 (CH3), 24.96 (CH3), 25.59 (CH3), 26.41
(
2
(
CH3), 61.33 (C-6), 69.67 (C-4), 69.94 (C-5),70.44 (C-3), 71.13 (C-1), 100.13 (C-
ꢁ
ꢁ
ꢁ
), 108.54 (C-3 ), 109.05 (C-8), 109.36 (C-7), 113.51 (C-7 ), 121.47 (C-4 ), 123.63
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
C-5 ), 124.94 (C-6 ), 126.67 (C-2 ), 130.86 (C-9 ), 137.06 (C-8 ). HRMS (ESI):
+
Calcd for C20H25NO8SNa [M+Na] 462.1199, found 462.1207.
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2. CCDC-793557 contains the supplementary crystallographic data for this paper.
The data can be obtained free of charge at www.ccdc.cam.ac.uk/deposit or can be ordered
from the following address: Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK: fax +44(1223)336033; e-mail: deposit@ccdc.cam.ac.uk.