Towards the synthesis of new benzimidazolone derivatives with surfactant properties

Article abstract of DOI:10.1016/j.carres.2007.11.028

New water-soluble benzimidazolone derivatives were synthesized. In the first approach, di-N-glycosyl and mono-N-alkyl-N-glycosyl compounds were obtained by grafting C-6-activated glycosides onto benzimidazolone. In the second approach, benzimidazolone der

Full text of DOI:10.1016/j.carres.2007.11.028

Available online at www.sciencedirect.com
Carbohydrate Research 343 (2008) 421–433
Towards the synthesis of new benzimidazolone derivatives
with surfactant properties
Brahim Lakhrissi,a Abdelhafid Benksim,b Mohamed Massoui,a,c El Mokhtar Essassi,c
d
b
b
Vincent Lequart,d, Nicolas Joly, Daniel Beaupere, Anne Wadouachi and
*
`
Patrick Martind
aLaboratoire de Chimie des Agroressources, Universite´ Ibn Tofaı¨l, Ke´nitra, Morocco
bLaboratoire des Glucides UMR CNRS 6219, Universite´ de Picardie Jules Verne, 33 Rue Saint-Leu 80039 Amiens Cedex, France
c
ˆ
´
Pole de Competence Pharmacochimie, Laboratoire de Chimie Organique Heterocyclique,
´ ´
Universite´ Mohammed V-Agdal, Rabat, Morocco
dLaboratoire de Physico-Chimie des Interfaces et Applications FRE CNRS 2485, Fe´de´ration Chevreul FR CNRS 2638,
Site de Be´thune, IUT de Be´thune BP819, 62408 Be´thune, France
Received 18 July 2007; received in revised form 22 November 2007; accepted 27 November 2007
Available online 5 December 2007
Abstract—New water-soluble benzimidazolone derivatives were synthesized. In the first approach, di-N-glycosyl and mono-N-alkyl-
N-glycosyl compounds were obtained by grafting C-6-activated glycosides onto benzimidazolone. In the second approach, benzimi-
dazolone derivatives bearing a glucosyl unit were synthesized using an efficient glycosylation method. Every compound structure
was confirmed by means of NMR spectroscopy and elemental analysis. The preliminary surfactant properties of some compounds
were evaluated.
Ó 2007 Elsevier Ltd. All rights reserved.
Keywords: Benzimidazolones; N-Glycosylation; Water solubility; Surface tension
1. Introduction
created a great deal of interest because of the direct
activation of the potassium (K+) cation channels.
Taking into account a number of applications of
benzimidazolone derivatives, this study focuses on the
synthesis of benzimidazolone bearing glucosidic units.
We first dedicated ourselves to the synthesis of two
Benzimidazolone is well known for its large range of
biological activities1–5 and industrial applications.6
Thus, some benzimidazolone derivatives such as
1-ethyl-2-benzimidazolone7 (EBIO, Scheme 1) have
Glucosyl-R
N
R'
N
H
N
O
O
O
R,R' = CnH2n+1
N
N
N
C2H5
Glucosyl-R
Glucosyl-R
EBIO
Type I
Type II
Scheme 1.
*
Corresponding author. Tel.: +33 (0)321632325; fax: +33 (0)321630294; e-mail: vincent.lequart@univ-artois.fr
0008-6215/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2007.11.028

422
B. Lakhrissi et al. / Carbohydrate Research 343 (2008) 421–433
new benzimidazolones of series type I and II (Scheme 1)
bearing either one or two sugar units on the nitrogen
atoms. The presence of the sugar moiety should enhance
the water solubility of these heterocyclic compounds,
and the alkyl chain should modulate the hydrophilic–
lipophilic balance (HLB). Functionalization of glucose
to create glucobenzimidazolones was performed on the
primary alcohol. So we used a method previously devel-
oped in our laboratory by using anhydroglucose.8 More-
over, the anomeric position could be considered as
another possibility to be functionalized considering that
this method could be generalized for all carbohydrates.
In the second part of this work, we present an efficient
glycosylation method.
derivatives 8–10 (type I) in good yields (70–95%). All
these structures were confirmed by NMR spectroscopic
analyses. The 13C NMR spectra of these compounds
showed two anomeric carbons at 96 ppm (C-1b) and
92 ppm (C-1a), which confirmed that the glucosidic parts
were in pyranose forms.
2.2. Synthesis of 3-N-alkyl-1-N-(6-deoxy-3-O-methyl-D-
glucopyranos-6-yl)benzimidazol-2-one derivatives
A second glucobenzimidazolone series (type II) was then
investigated, and its synthesis is shown in Scheme 3.
The strategy followed in this part was to partially pro-
tect the benzimidazolone unit leaving only one NH
group available for an alkylation reaction with an alkyl
bromide (step ii). For this purpose, the first step was per-
formed by using the method of Meth-Cohen and
Smith.11 The condensation of o-phenylenediamine with
ethyl acetoacetate afforded the expected benzimidazo-
lone derivative 11 in 72% yield. To modulate the HLB,
an alkyl chain (R = n-CnH2n+1; n = 1, 4, 6, 8, 10 and
12) was introduced (step i, 90–95% yield), and the pro-
tecting isopropenyl group was then removed by using
1:1 water–H2SO4 at room temperature. Addition of
the glucose derivative 4b to benzimidazolones 13a–e
using the same procedure as previously reported8
for 5–7 mainly provided the desired 3-N-alkyl-1-
N-(6-deoxy-1,2-O-isopropylidene-3-O-methyl-a-D-gluco-
furanos-6-yl)-benzimidazol-2-one derivatives 14a–e
(step iii, 93–97% yield). Subsequent deprotection of
14a–e was performed by using Amberlyst-15 (H+) in
4:1 dioxane–water to lead benzimidazolone derivatives
15a–e in 72–89% yield (step iv).
2. Results and discussion
2.1. Synthesis of 1,3-N,N0-bis-(6-deoxy-D-glucopyranos-
6-yl)benzimidazol-2-one derivatives
The starting benzimidazolones 1–3 (Scheme 2) were
prepared according to the method described by Town-
send et al.9 o-Phenylenediamine was reacted with 1 equiv
of urea in dry n-butanol at 120 °C. After 10 h,
benzimidazolones derivatives 1–3 were obtained by the
filtration of the crude product in 80–94% yield.
The glucopyranosyl benzimidazolone derivatives 5–7
(type I) were obtained by the regiospecific condensation
of benzimidazolones 1–3 on the anhydroglucosyl sub-
strates 4a–g8 in the presence of K2CO3 at 110 °C, and
by using 4:1 toluene–DMSO as solvent. Under these con-
ditions we obtained the desired products 5–7 with 70–93%
yield. Taking advantage of the convergent synthesis and
with the aim of modulating hydrophilic–lipophilic bal-
ance, we replaced 4a by homologues 5,6-anhydro-3-O-al-
kyl-1,2-O-isopropylidene-a-D-glucofuranose 4b–g (R2 =
n-CnH2n+1; n = 1, 4, 6, 8, 10 and 12). Deprotection of
the isopropylidene groups with 9:1 CF3CO2H–H2O10
afforded the expected glucopyranosyl benzimidazolone
2.3. Glycosylation of benzimidazolone
Efficient glycosylation methods are of particular interest
in the synthesis of biologically important glycomole-
cules.12 For example, the benzimidazolone bearing a
glucose moiety on the aromatic nitrogen strongly
R1
R1
H
R1
O
N
O
OR2
i
ii
+
O
O
N
N
N
N
N
H
CMe2
O
CH2
CH2
O
O
O
O
HO
O
OR2
HO
O
OR2
OR2
OR2
1-3
4
OH
OH
O
O
CMe2
HO
HO
R1
CMe2
O
OH
OH
O
1, 5, 8
2, 6, 9
3, 7, 10 Cl
H
5, 6, 7
R2: H, CH3, CnH2n+1 (n = 4, 6, 8, 10, 12)
Scheme 2. Reagents and conditions: (i) K2CO3, 4:1 toluene–DMSO, 110 °C, 2 h; (ii) 9:1 CF3COOH–H2O, rt, 30 min.
8, 9, 10
CH3

B. Lakhrissi et al. / Carbohydrate Research 343 (2008) 421–433
423
H
N
R
N
R
N
i
ii
R-Br
+
O
O
O
N
N
N
H
H3C
CH2
H3C
CH2
O
12
13
11
O
OMe
iii
O
R
N
R
CMe2
O
N
iv
O
O
4
N
N
CH2
R : CnH2n+1 (n = 4, 6, 8, 10, 12)
O
HO
O
OH
OMe
OMe
O
HO
OH
15
14
CMe2
O
Scheme 3. Reagents and conditions: (i) K2CO3, DMF, 110 °C, 12 h; (ii) H2SO4 (50%), DMF, rt, 12 h; (iii) K2CO3, DMSO, 110 °C, 4–12 h; (iv)
Amberlyst 15 (H+), 4:1 dioxane–H2O, 80 °C, 1–2 h.
inhibits the growth of bacteria such as Bacillus cereus,
Streptomyces chartreusis and Escherichia coli.13 Glycosyl-
ation of benzimidazolone has been described from
glycosyl bromide donors,13,14 with mercuric acetate in
the presence of pyridine. These conditions used very
toxic reagents. In the previous work we had shown that
o-sulfinyl monosaccharides are useful substrates for
stereoselective N-glycosylation reactions to form glycosyl
azides and 1,2-cyclic carbamates.15 The nucleophilic
opening of cyclic sulfites has also proven to be a useful
method for the synthesis of chiral molecules and natural
products.16 We chose this alternative glycosylation using
cyclic sulfite derivatives as glycosyl donors.
diols 16a and 16b, respectively, by sulfinylation reaction
with N,N0-sulfinyldiimidazole.15a,17
The nucleophilic opening of the cyclic sulfites was
realized by the potassium form of the benzimidazoli-
none anion, preliminary formed with K2CO3 in DMF.
The 1,2-trans compounds 18a and 18b were obtained
in 61% and 62% yields, respectively. The latter com-
pounds were characterized by NMR spectroscopy show-
ing the anomeric protons at 5.82 ppm with a coupling
constant J1,2 0 Hz for the glucofuranosyl compound
18a and 5.25 ppm with J1,2 9.8 Hz for the arabinopyr-
anoside 18b.
Our glycosylation conditions were applied to benzimi-
dazolone 11 and studied with 3,4,6-tri-O-benzyl-1,2-O-
sulfinyl-a-D-glucofuranose 17a and 3,4-O-isopropyl-
idene-1,2-O-sulfinyl-b-D-arabinopyranose 17b (Scheme
4).17 These latter compounds were obtained from 1,2-
2.4. Surfactant properties
Preliminary study on surfactant properties was per-
formed to determine water solubility and surface tension
of this new range of benzimidazolones. The purpose was
H2C
CH3
N
N
O
O
BnO
BnO
BnO
BnO
BnO
O
BnO
O
ii
i
OH
OBn
OBn
OBn
O
OH
16
OH
O
S
O
17
18
O
OO
O
O
ii
i
S
OH
O
HO
HO
O
Me C
O
Me C
O
Me C
N
N
O
2
O
O
2
2
O
18
17
16
H3C CH2
Scheme 4. Reagents and conditions: (i) SOIm2, THF, rt; (ii) K2CO3, DMF, 11, 90 °C, 3 h.

424
B. Lakhrissi et al. / Carbohydrate Research 343 (2008) 421–433
Table 1. Water solubility (10ꢀ3 mol Lꢀ1) and surface tension (c, mN mꢀ1) of benzimidazolone derivatives (type I) at 25 °C
Product
1
2
3
8a
8b
8c
8d
8e
8f
8g
R2 = CnH2n+1
Water solubility
c
—
<0.075
—
—
<0.067
—
—
<0.059
—
H
>200
52.2a
CH3
>200
46.6a
n = 4
3.5
41.5b
n = 6
0.48
44.9b
n = 8
<0.015
—
n = 10
<0.014
—
n = 12
<0.013
—
9a
9b
9e
9f
9g
10a
10b
10e
10f
10g
R = CnH2n+1
Water solubility
c
n = 4
>200
54.0a
n = 6
>200
55.1a
n = 8
<0.014
—
n = 10
<0.013
—
n = 12
<0.012
—
n = 4
>200
55.8a
n = 6
>200
56.0a
n = 8
<0.014
—
n = 10
<0.013
—
n = 12
<0.012
—
a 1 g Lꢀ1 solution.
b At water solubility value.
Table 2. Water solubility (10ꢀ3 mol Lꢀ1) and surface tension (c, mN mꢀ1) of benzimidazolone derivatives 13 and 15 at 25 °C
Product
13a
13b
13c
13d
13e
15a
15b
15c
15d
15e
R = CnH2n+1
Water solubility
c
n = 4
<0.053
—
n = 6
<0.046
—
n = 8
<0.041
—
n = 10
<0.036
—
n = 12
<0.033
—
n = 4
13.1
39.6a
n = 6
2.69
35.2a
n = 8
0.47
43.8a
n = 10
0.02
43.0a
n = 12
0.006
—
a 1 g Lꢀ1 solution.
also to evaluate the influence of substituents on these
properties. The compounds (type I and II) were evalu-
ated for their amphiphilic characteristics and were com-
pared to native benzimidazolones 1–3. The results are
summarized in Tables 1 and 2.
Data provided in Table 1 indicate that benzimidazol-
ones 1–3 have water solubility (Sw) lower than
10ꢀ4 mol Lꢀ1 at 25 °C. On one hand, benzimidazolone
derivatives 8–10a,b (type I) have a water solubility higher
than 200 ꢁ 10ꢀ3 mol Lꢀ1, while on the other hand, the
water solubility of analogues 8–10c,d bearing an
alkyl chain (R2 = C4H9 to C6H13) decreases abruptly
for analogues 8–10c,d (R2 = C8H17 to C16H33) until
becoming close to the values of benzimidazolones 1–3.
Moreover no critical micelle concentration (cmc) was
observed.
As shown in Table 2, N-alkylbenzimidazolones 13a–e
have water solubility lower than 10ꢀ4 mol Lꢀ1, whereas
the graft of 6-deoxy-3-O-methyl-D-glucopyranos-6-yl
15a–e allows a partial water solubility that decreases
with the alkyl chain length. As previously observed with
the first series of benzimidazolone derivatives 8–10, we
observed a strong reduction of water solubility when
n > 6 (15b, CnH2n+1). Moreover, compounds 15a–d have
shown a lower surface tension than water (c = 35–
44 mN mꢀ1 vs 72 mN mꢀ1 for pure water), but these
compounds have not shown any cmc.
In summary, two new series of benzimidazolone deriv-
atives were synthesized. Grafting of one or two mono-
saccharides on benzimidazolone led to new
compounds with a strongly increased water solubility.
Therefore, the addition of an alkyl chain on the sugar
moiety has a strong influence on the amphiphilic charac-
teristics. We have also shown that glycosylated benzimi-
dazolone derivatives could be obtained by cyclic sulfite
derivatives as glycosyl donors. Biological evaluations
(blood–brain barrier delivery) of the glycosyl benzimi-
dazolone derivatives are currently underway.
3. Experimental
3.1. General methods
All chemicals were purchased from Aldrich or Acros
(France). All solvents were distilled before use. THF
was distilled from LiAlH4, and thionyl chloride from
triphenylphosphite (10% v/v). Thin-layer chromato-
graphy (TLC) was performed on Silica Gel 60 F254 (E.
Merck) plates with visualization by UV light (254 nm)
and/or charring with the vanillin–H2SO4 reagent.
Column chromatography was performed using 230–
400 mesh E. Merck silica gel. Melting points were deter-
mined on an automatic electrothermal apparatus and
are uncorrected. Optical rotations were determined with
a Jasco Dip 370 electronic micropolarimeter (10-cm
1
cell). H NMR spectra were recorded on a Bruker 300
WB spectrometer at 300 MHz, and 13C NMR spectra
were recorded at 75 MHz. Chemical shifts are given as
d values with reference to tetramethylsilane (TMS) as
internal standard. Low-resolution electrospray-ioniza-
tion mass spectra (ESIMS) in the positive-ion mode
were obtained on a Waters-Micromass ZQ quadrupole
instrument, equipped with an electrospray (Z-spray)

B. Lakhrissi et al. / Carbohydrate Research 343 (2008) 421–433
425
ion source (Waters-Micromass, Manchester, UK). High-
resolution electrospray-ionization experiments (HRE-
Harom); 13C NMR (CDCl3) dglucose 111.6 (Ciso),
104.9 (C-1), 83.0 (C-3), 82.1 (C-2), 81.5 (C-4),
SIMS) were performed on
a
Waters-Micromass
68.9 (C-5), 58.4 (OCH3), 45.4 (C-6), 26.8–26.5 (CH3iso)
Q-TOF Ultima Global hybrid quadrupole time-of-flight
instrument, equipped with an electrospray (Z-spray)
ion source (Waters-Micromass, Manchester, UK). Ele-
dbenzimidazolone 157.3 (CO), 129.7 (C-8, C-9), 121.8 (C-5,
C-6), 108.6 (C-4, C-7); Anal. Calcd for C27H38N2O11:
C, 57.23; H, 6.75; N, 4.94. Found: C, 57.21; H, 6.72;
N, 4.87.
´
mental analyses were performed by the IUT de Bethune,
´
´
Departement de Chimie (Bethune, France). The water
solubility was determined for each sample at 25 °C.
For cmc studies, an initial aqueous solution (C0) of each
compound was prepared at 25 °C. Several samples were
obtained by diluting S0 in the concentration range C0:
C0/2, C0/4, C0/8, C0/16, C0/32, C0/64, C0/128 and
C0/256. The surface tension (c) of each sample was mea-
sured by the Wilhelmy plate method (Prolabo TD 2000
tensiometer) after a period of more than 6 h in the
thermostated cell (25 °C).
3.2.3. 1,3-N,N0-Bis-(3-O-butyl-6-deoxy-1,2-O-isopropyl-
idene-a-D-glucofuranos-6-yl)benzimidazol-2-one
(5c).
27
White solid (93%): mp 114–116 °C; ½aꢂD ꢀ75.2 (c 0.6,
CHCl3); 1H NMR (CDCl3) dglucose 5.85 (d, 2H, J1,2
3.6 Hz, H-1), 4.50 (d, 2H, J2,3 0 Hz, H-2), 4.27, 4.05
(m, 4H, J6a,6b 14.4 Hz, H-6), 4.20 (m, 2H, J5,6a 2.5 Hz,
J5,6b 5.4 Hz, H-5), 3.95 (dd, 2H, J4,5 8.2 Hz, H-4), 3.85
(d, 2H, J3,4 3.0 Hz, H-3), 3.54, 3.42, (2dt, 4H, O–CHa),
2
1.49 (m, 4H, CHb), 1.40–1.10 (4s, 12H, CH3iso), 1.23
2
(m, 4H, CHc2), 0.80 (t, 6H, CHx) dbenzimidazolone 7.28–
3
3.2. General procedure for condensation step (i)
7.05 (m, 4H, Harom); 13C NMR (CDCl3) dglucose 111.7
(Ciso), 105.1 (C-1), 82.5 (C-3), 82.1 (C-2), 80.1 (C-4),
70.5 (O–CHa2), 68.7 (C-5), 45.5 (C-6), 31.7 (CHb2), 26.6–
To
a solution of benzimidazolone 1–3, K2CO3
(2.0 equiv) in 4:1 toluene–DMSO (100 g Lꢀ1) at 100 °C
were added activated carbohydrate derivatives 4a–g
(2 equiv). When the starting material was no longer
detected by TLC or HPLC, the mixture was concentrated
under reduced pressure. The residue was extracted with
toluene–water, the organic layer was removed, washed
with satd aq NaCl, dried (Na2SO4) and concentrated.
The crude product was purified by silica gel chromato-
graphy (hexane–acetone gradient).
26.3 (CH3iso), 19.2 (CHc2), 13.8 (CHx) dbenzimidazolone
3
157.4 (CO), 129.7 (C-8, C-9), 121.8 (C-5, C-6), 108.8
(C-4, C-7); Anal. Calcd for C33H50N2O11: C, 60.91; H,
7.75; N, 4.30. Found: C, 60.87; H, 7.72; N, 4.33.
3.2.4. 1,3-N,N0-Bis-(6-deoxy-3-O-hexyl-1,2-O-isopropyl-
idene-a-D-glucofuranos-6-yl)benzimidazol-2-one
(5d).
27
White solid (80%): mp 92–95 °C; ½aꢂD ꢀ68.1 (c 0.6,
CHCl3); 1H NMR (CDCl3) dglucose 5.85 (d, 2H, J1,2
3.6 Hz, H-1), 4.51 (d, 2H, J2,3 0 Hz, H-2), 4.27, 4.05
(m, 4H, J6a,6b 14.4 Hz, H-6), 4.20 (m, 2H, J5,6a 2.5 Hz,
J5,6b 5.4 Hz, H-5), 3.95 (dd, 2H, J4,5 8.2 Hz, H-4), 3.85
(d, 2H, J3,4 3.2 Hz, H-3), 3.53, 3.42, (2dt, 4H,
O–CHa2), 1.48 (m, 4H, CHb2), 1.40–1.10 (4s, 12H,
CH3iso), 1.30–1.24 (m, 12H, CH2), 0.82 (t, 6H, CH3)
dbenzimidazolone 7.30–7.05 (m, 4H, Harom); 13C NMR
(CDCl3) dglucose 111.7 (Ciso), 105.1 (C-1), 82.4 (C-3),
82.0 (C-2), 80.1 (C-4), 70.8 (O–CHa2), 68.7 (C-5), 45.5
3.2.1. 1,3-N,N0-Bis-(6-deoxy-1,2-O-isopropylidene-a-D-
glucofuranos-6-yl)benzimidazol-2-one (5a). White solid
(97%): mp 121–123 °C; ½aꢂD ꢀ66.7 (c 0.6, CHCl3); H
NMR (CDCl3) dglucose 5.88 (d, 2H, J1,2 3.5 Hz, H-1),
4.45 (d, 2H, J2,3 0 Hz, H-2), 4.05 (d, 2H, J3,4 2.2 Hz,
H-3), 3.95 (m, 2H, J5,6a 3.1 Hz, J5,6b 5.6 Hz, H-5), 3.85
(dd, 2H, J4,5 8.5 Hz, H-4), 3.81 (m, 2H, J6a,6b 12.0 Hz,
27
1
H-6a), 3.75 (dd, 2H, H-6b), 1.45–1.15 (4s, 12H, CH3iso
)
dbenzimidazolone 7.41–7.05 (m, 4H, Harom); 13C NMR
(CDCl3) dglucose 110.5 (Ciso), 104.6 (C-1), 84.6 (C-2),
81.5 (C-4), 73.0 (C-3), 65.8 (C-5), 45.1 (C-6), 26.9–26.5
(CH3iso) dbenzimidazolone 154.1 (CO), 130.0 (C-8, C-9),
120.3 (C-5, C-6), 108.3 (C-4, C-7); Anal. Calcd for
C25H34N2O11: C, 55.75; H, 6.36; N, 5.20. Found: C,
55.63; H, 6.29; N, 5.23.
(C-6), 31.4 (CHb), 29.6, 25.6, 22.4 (CH2), 26.6–26.2
2
(CH3iso), 13.9 (CH3) dbenzimidazolone 157.4 (CO), 129.7
(C-8, C-9), 121.8 (C-5, C-6), 108.8 (C-4, C-7); Anal.
Calcd for C37H58N2O11: C, 62.87; H, 8.27; N, 3.96.
Found: C, 62.82; H, 8.25; N, 4.01.
3.2.5. 1,3-N,N0-Bis-(6-deoxy-1,2-O-isopropylidene-3-O-
octyl-a-D-glucofuranos-6-yl)benzimidazol-2-one
(5e).
27
3.2.2. 1,3-N,N0-Bis-(6-deoxy-1,2-O-isopropylidene-3-O-
methyl-a-D-glucofuranos-6-yl)benzimidazol-2-one (5b).
White solid (93%): mp 73–75 °C; ½aꢂD ꢀ80.3 (c 0.6,
CHCl3); 1H NMR (CDCl3) dglucose 5.85 (d, 2H, J1,2
3.6 Hz, H-1), 4.51 (d, 2H, J2,3 0 Hz, H-2), 4.27, 4.05
(m, 4H, J6a,6b 14.4 Hz, H-6), 4.20 (m, 2H, J5,6a 2.5 Hz,
J5,6b 5.4 Hz, H-5), 3.95 (dd, 2H, J4,5 8.2 Hz, H-4), 3.85
(d, 2H, J3,4 3.2 Hz, H-3), 3.54, 3.42 (2dt, 4H, O–CHa2),
27
White solid (78%): mp 159–161 °C; ½aꢂD ꢀ93.1 (c 0.6,
CHCl3); 1H NMR (CDCl3) dglucose 5.90 (d, 2H, J1,2
3.6 Hz, H-1), 4.51 (d, 2H, J2,3 0 Hz, H-2), 4.27, 4.05
(m, 4H, J6a,6b 14.4 Hz, H-6), 4.19 (m, 2H, J5,6a 2.5 Hz,
J5,6b 5.8 Hz, H-5), 3.96 (dd, 2H, J4,5 8.5 Hz, H-4), 3.84
(d, 2H, J3,4 3.0 Hz, H-3), 3.45 (s, 6H, OCH3), 1.42–
1.29 (4s, 12H, CH3iso) dbenzimidazolone 7.47–7.05 (m, 4H,
1.54 (m, 4H, CHb), 1.32–1.18 (m, 20H, CH2), 1.40–
2
1.10 (4s, 12H, CH3iso), 0.80 (t, 6H, CH3) dbenzimidazolone
7.32–7.05 (m, 4H, Harom); 13C NMR (CDCl3) dglucose

426
B. Lakhrissi et al. / Carbohydrate Research 343 (2008) 421–433
111.7 (Ciso), 105.1 (C-1), 82.5 (C-3), 82.1 (C-2),
80.1 (C-4), 70.9 (O–CHa2), 68.8 (C-5), 45.5 (C-6), 31.7–
29.1, 25.9, 22.5 (CH2), 26.6–26.2 (CH3iso), 14.0 (CH3)
dbenzimidazolone 157.4 (CO), 129.7 (C-8, C-9), 121.7 (C-5,
C-6), 108.7 (C-4, C-7); Anal. Calcd for C41H66N2O11:
C, 64.54; H, 8.72; N, 3.67. Found: C, 64.50; H, 8.69;
N, 3.70.
(C-3), 67.7 (C-5), 45.9, 45.1 (C-6), 26.7–26.1 (CH3iso)
dbenzimidazolone 156.6 (CO), 131.7 (C-5), 129.5, 127.2 (C-
8, C-9), 122.5 (C-6), 109.2, 109.1 (C-4, C-7), 21.4
(CH3); Anal. Calcd for C26H36N2O11: C, 56.51; H,
6.57; N, 5.07. Found: C, 56.45; H, 6.56; N, 5.12.
3.2.9.
1,3-N,N0-Bis-(6-deoxy-1,2-O-isopropylidene-3-
O-methyl-a-D-glucofuranos-6-yl)-5-methylbenzimidazol-
27
3.2.6. 1,3-N,N0-Bis-(3-O-decyl-6-deoxy-1,2-O-isopropyl-
2-one (6b). White solid (70%): mp 190–192 °C; ½aꢂD
1
idene-a-D-glucofuranos-6-yl)benzimidazol-2-one
(5f).
1
ꢀ104.0 (c 0.6, CHCl3); H NMR (CDCl3) dglucose 5.90
27
Colourless syrup (79%): ½aꢂD ꢀ76.4 (c 0.6, CHCl3); H
NMR (CDCl3) dglucose 5.90 (d, 2H, J1,2 3.6 Hz, H-1),
4.50 (d, 2H, J2,3 0 Hz, H-2), 4.25, 4.05 (m, 4H, J6a,6b
14.4 Hz, H-6), 4.20 (m, 2H, J5,6a 2.5 Hz, J5,6b 5.4 Hz,
H-5), 3.95 (dd, 2H, J4,5 8.2 Hz, H-4), 3.85 (d, 2H, J3,4
3.2 Hz, H-3), 3.54, 3.42 (2dt, 4H, O–CHa2), 1.49 (m,
(d, 2H, J1,2 3.7 Hz, H-1), 4.52 (d, 2H, J2,3 0 Hz, H-2),
4.25 (dd, 2H, J6a,6b 14.6 Hz, H-6a), 4.20 (m, 2H, J5,6a
2.5 Hz, J5,6b 5.4 Hz, H-5), 4.05 (dd, 2H, H-6b), 3.96
(dd, 2H, J4,5 8.2 Hz, H-4), 3.75 (d, 2H, J3,4 2.5 Hz, H-
3), 3.45 (2s, 6H, OCH3), 1.40–1.30 (4s, 12H, CH3iso
)
dbenzimidazolone 7.50–6.91 (m, 3H, Harom), 2.35 (s, 3H,
CH3); 13C NMR (CDCl3) dglucose 111.7 (Ciso), 105.2
(C-1), 83.9 (C-3), 81.8 (C-2), 80.0 (C-4), 68.7 (C-5),
4H, CHb), 1.32–1.22 (m, 28H, CH2), 1.40–1.10 (4s,
2
12H, CH3iso), 0.82 (t, 6H, CH3) dbenzimidazolone 7.28–
7.02 (m, 4H, Harom); 13C NMR (CDCl3) dglucose 111.7
(Ciso), 105.1 (C-1), 82.4 (C-3), 82.1 (C-2), 80.2 (C-4),
70.8 (O–CHa2), 68.7 (C-5), 45.5 (C-6), 31.6–29.1, 26.0,
22.5 (CH2), 26.6–26.2 (CH3iso), 13.9 (CH3) dbenzimidazolone
157.4 (CO), 129.9 (C-8, C-9), 121.8 (C-5, C-6), 108.7
(C-4, C-7); Anal. Calcd for C45H74N2O11: C, 65.99; H,
9.10; N, 3.42. Found: C, 65.85; H, 8.99; N, 3.45.
58.2 (OCH3), 45.7 (C-6), 26.6–26.2 (CH3iso
)
dbenzimidazolone 157.7 (CO), 131.7 (C-5), 129.5, 127.5
(C-8, C-9), 122.5 (C-6), 109.2, 108.4 (C-4, C-7), 21.4
(CH3); Anal. Calcd for C28H40N2O11: C, 57.92; H,
6.94; N, 4.82. Found: C, 57.86; H, 6.89; N, 4.93.
3.2.10. 1,3-N,N0-Bis-(6-deoxy-1,2-O-isopropylidene-3-O-
octyl-a-D-glucofuranos-6-yl)-5-methylbenzimidazol-2-one
27
3.2.7. 1,3-N,N0-Bis-(6-deoxy-3-O-dodecyl-1,2-O-isopro-
pylidene-a-D-glucofuranos-6-yl)benzimidazol-2-one (5g).
(6e). Colourless syrup (80%): ½aꢂD ꢀ80.5 (c 0.6,
CHCl3); 1H NMR (CDCl3) dglucose 5.94 (d, 2H, J1,2
3.5 Hz, H-1), 4.54 (d, 2H, J2,3 0 Hz, H-2), 4.31 (dd,
2H, J6a,6b 14.2 Hz, H-6a), 4.25 (m, 2H, J5,6a 2.5 Hz,
J5,6b 5.2 Hz, H-5), 4.08 (dd, 2H, H-6b), 4.02 (dd, 2H,
J4,5 8.2 Hz, H-4), 3.98 (d, 2H, J3,4 3.2 Hz, H-3), 3.58–
3.52 (2dt, 4H, O–CH2a), 1.54 (m, 4H, CHb2), 1.32–1.24
(m, 20H, CH2), 0.82 (s, 6H, CH3), 1.40–1.15 (4s, 12H,
CH3iso) dbenzimidazolone 7.12–6.88 (m, 3H, Harom), 2.39
(s, 3H, CH3); 13C NMR (CDCl3) dglucose 111.7 (Ciso),
105.1 (C-1), 82.5 (C-3), 82.1 (C-2), 80.1 (C-4), 70.9
(O–CHa2), 69.1 (C-5), 45.5 (C-6), 31.5–29.3, 25.9, 22.6
(CH2), 26.6–26.3 (CH3iso), 14.0 (CH3) dbenzimidazolone
157.6 (CO), 131.6 (C-5), 129.7, 127.5 (C-8, C-9), 122.4
(C-6), 109.3, 108.4 (C-4, C-7), 21.4 (CH3); Anal. Calcd
for C42H68N2O11: C, 64.92; H, 8.82; N, 3.60. Found:
C, 64.90; H, 8.81; N, 3.61.
27
White solid (90%): mp 61–62 °C; ½aꢂD ꢀ69.7 (c 0.6,
CHCl3); 1H NMR (CDCl3) dglucose 5.90 (d, 2H, J1,2
3.6 Hz, H-1), 4.50 (d, 2H, J2,3 0 Hz, H-2), 4.25, 4.05
(m, 4H, J6a,6b 14.4 Hz, H-6), 4.20 (m, 2H, J5,6a 2.5 Hz,
J5,6b 5.4 Hz, H-5), 3.95 (dd, 2H, J4,5 8.2 Hz, H-4), 3.85
(d, 2H, J3,4 3.2 Hz, H-3), 3.58, 3.52 (2dt, 4H, O–CHa2),
1.54 (m, 4H, CHb), 1.40–1.10 (4s, 12H, CH3iso), 1.32–
2
1.23 (m, 36H, CH2), 0.84 (t, 6H, CH3) dbenzimidazolone
7.28–7.02 (m, 4H, Harom); 13C NMR (CDCl3) dglucose
111.7 (Ciso), 105.2 (C-1), 82.4 (C-3), 82.1 (C-2),
80.0 (C-4), 70.7 (O–CHa2), 68.7 (C-5), 45.6 (C-6), 31.8–
29.2, 25.9, 22.6 (CH2), 26.6–26.3 (CH3iso), 14.0 (CH3)
dbenzimidazolone 157.4 (CO), 129.7 (C-8, C-9), 121.6 (C-5,
C-6), 108.7 (C-4, C-7); Anal. Calcd for C49H82N2O11:
C, 67.25; H, 9.44; N, 3.20. Found: C, 67.21; H, 9.43;
N, 3.18.
3.2.11. 1,3-N,N0-Bis-(3-O-decyl-6-deoxy-1,2-O-isopropyl-
idene-a-D-glucofuranos-6-yl)-5-methylbenzimidazol-2-one
3.2.8. 1,3-N,N0-Bis-(6-deoxy-1,2-O-isopropylidene-a-D-
27
glucofuranos-6-yl)-5-methylbenzimidazol-2-one
(6a).
(6f). Colourless syrup (75%): ½aꢂD ꢀ80.2 (c 0.6,
27
White solid (90%): mp 120–122 °C; ½aꢂD ꢀ60.6 (c 0.6,
CHCl3); 1H NMR (CDCl3) dglucose 5.90 (d, 2H, J1,2
3.5 Hz, H-1), 4.50 (d, 2H, J2,3 0 Hz, H-2), 4.25 (dd,
2H, J6a,6b 14.4 Hz, H-6a), 4.20 (m, 2H, J5,6a 2.5 Hz,
J5,6b 5.4 Hz, H-5), 4.05 (dd, 2H, H-6b), 4.02 (dd, 2H,
J4,5 8.2 Hz, H-4), 3.98 (d, 2H, J3,4 3.2 Hz, H-3), 3.57–
3.51 (2dt, 4H, O–CH2a), 1.50 (m, 4H, CHb2), 1.32–1.23
(m, 28H, CH2), 0.84 (s, 6H, CH3), 1.40–1.15 (4s, 12H,
CH3iso) dbenzimidazolone 7.12–6.88 (m, 3H, Harom), 2.35
(s, 3H, CH3); 13C NMR (CDCl3): dglucose 111.7 (Ciso),
1
CHCl3); H NMR (CDCl3) dglucose 5.88, 5.84 (2d, 2H,
J1,2 3.5 Hz, H-1), 4.50 (2d, 2H, J2,3 0 Hz, H-2), 4.22
(d, 2H, J3,4 2.7 Hz, H-3), 4.13 (m, 2H, H-5), 4.05 (dd,
2H, J4,5 6.8 Hz, H-4), 3.80–3.74 (m, 2H, J6a,6b 12.4 Hz,
H-6), 1.42–1.26 (4s, 12H, CH3iso) dbenzimidazolone 7.00
(s, 1H, H-4), 6.94 (d, 1H, H-7), 6.83 (d, 1H, H-6), 2.35
(s, 3H, CH3); 13C NMR (CDCl3) dglucose 111.6, 111.5
(Ciso), 105.3, 105.2 (C-1), 84.8 (C-2), 80.6 (C-4), 74.2

B. Lakhrissi et al. / Carbohydrate Research 343 (2008) 421–433
427
105.1 (C-1), 82.5 (C-3), 82.2 (C-2), 80.1 (C-4), 70.8
(O–CHa2), 69.8 (C-5), 45.6 (C-6), 31.8–29.3, 25.9, 22.6
(CH2), 26.6–26.3 (CH3iso), 14.0 (CH3) dbenzimidazolone
157.6 (CO), 131.7 (C-5), 129.8, 127.5 (C-8, C-9), 122.4
(C-6), 109.3, 108.4 (C-4, C-7), 21.4 (CH3); Anal. Calcd
for C46H76N2O11: C, 66.32; H, 9.19; N, 3.36. Found:
C, 66.21; H, 8.99; N, 3.43.
(C-6), 26.6–26.2 (CH3iso) dbenzimidazolone 157.7 (CO),
130.5 (C-5), 129.3, 127.5 (C-8, C-9), 121.8 (C-6), 109.6,
109.2 (C-4, C-7); Anal. Calcd for C27H37ClN2O11: C,
53.96; H, 6.20; N, 4.66; Cl, 5.90. Found: C, 53.95; H,
6.18; N, 4.73; Cl, 5.79.
3.2.15. 5-Chloro-1,3-N,N0-bis-(6-deoxy-1,2-O-isopropyl-
idene-3-O-octyl-a-D-glucofuranos-6-yl)benzimidazol-2-
27
3.2.12. 1,3-N,N0-Bis-(6-deoxy-3-O-dodecyl-1,2-O-isopro-
pylidene-a-D-glucofuranos-6-yl)-5-methylbenzimidazol-2-
one (7e). Colourless syrup (80%): ½aꢂD ꢀ99.5 (c 0.6,
CHCl3); 1H NMR (CDCl3) dglucose 5.92 (d, 2H, J1,2
3.6 Hz, H-1), 4.52 (d, 2H, J2,3 0 Hz, H-2), 4.30 (dd,
2H, J6a,6b 14.4 Hz, H-6a), 4.24 (m, 2H, J5,6a 2.5 Hz,
J5,6b 5.2 Hz, H-5), 4.05 (dd, 2H, H-6b), 4.02 (dd, 2H,
J4,5 8.2 Hz, H-4), 3.98 (d, 2H, J3,4 3.2 Hz, H-3), 3.58,
3.51 (2dt, 4H, O–CH2a), 1.54 (m, 4H, CHb2), 1.40–1.15
(4s, 12H, CH3iso), 1.32–1.23 (m, 20H, CH2), 0.85 (s,
6H, CH3) dbenzimidazolone 7.27–7.02 (m, 3H, Harom); 13C
NMR (CDCl3) dglucose 111.6 (Ciso), 105.2 (C-1), 82.4
(C-3), 82.2 (C-2), 80.0 (C-4), 70.8 (O–CHa2), 68.7 (C-5),
45.5 (C-6), 31.8–29.2, 26.0, 22.6 (CH2), 26.6–26.2
(CH3iso), 14.1 (CH3) dbenzimidazolone 157.4 (CO), 130.6
(C-5), 128.4, 127.4 (C-8, C-9), 121.8 (C-6), 109.6, 109.3
(C-4, C-7); Anal. Calcd for C41H65ClN2O11: C, 61.75;
H, 8.21; N, 3.51; Cl, 4.44. Found: C, 61.54; H, 8.06;
N, 3.58; Cl, 4.41.
27
one (6g). White solid (82%): mp 56–57 °C; ½aꢂD ꢀ72.0 (c
1
0.6, CHCl3); H NMR (CDCl3) dglucose 5.90 (d, 2H, J1,2
3.5 Hz, H-1), 4.50 (d, 2H, J2,3 0 Hz, H-2), 4.28 (dd, 2H,
J6a,6b 14.2 Hz, H-6a), 4.21 (m, 2H, J5,6a 2.5 Hz, J5,6b
5.2 Hz, H-5), 4.06 (dd, 2H, H-6b), 4.02 (dd, 2H, J4,5
8.2 Hz, H-4), 3.98 (d, 2H, J3,4 3.2 Hz, H-3), 3.58–3.52
(2dt, 4H, O–CHa2), 1.54 (m, 4H, CHb2), 1.40–1.15 (4s,
12H, CH3iso), 1.32–1.23 (m, 36H, CH2), 0.84 (s, 6H,
CH3) dbenzimidazolone 7.12–6.88 (m, 3H, Harom), 2.35 (s,
3H, CH3); 13C NMR (CDCl3) dglucose 111.7 (Ciso),
105.1 (C-1), 82.5 (C-3), 82.2 (C-2), 80.0 (C-4), 70.8
(O–CHa2), 69.8 (C-5), 45.6 (C-6), 31.8–29.5, 25.9, 22.6
(CH2), 26.6–26.2 (CH3iso), 14.0 (CH3) dbenzimidazolone
157.6 (CO), 131.7 (C-5), 129.8, 127.5 (C-8, C-9), 122.4
(C-6), 109.2, 108.4 (C-4, C-7), 21.4 (CH3); Anal. Calcd
for C50H84N2O11 C, 67.54; H, 9.52; N, 3.15. Found: C,
67.49; H, 9.48; N, 3.20.
3.2.16. 5-Chloro-1,3-N,N0-bis-(3-O-decyl-6-deoxy-1,2-O-
isopropylidene-a-D-glucofuranos-6-yl)benzimidazol-2-one
27
3.2.13. 5-Chloro-1,3-N,N0-bis-(6-deoxy-1,2-O-isopropyl-
(7f). Colourless syrup (79%): ½aꢂD ꢀ89.9 (c 0.6,
idene-a-D-glucofuranos-6-yl)benzimidazol-2-one
(7a).
CHCl3); 1H NMR (CDCl3) dglucose 5.92 (d, 2H, J1,2
3.6 Hz, H-1), 4.52 (d, 2H, J2,3 0 Hz, H-2), 4.30 (dd,
2H, J6a,6b 14.4 Hz, H-6a), 4.24 (m, 2H, J5,6a 2.5 Hz,
J5,6b 5.2 Hz, H-5), 4.05–4.00 (m, 4H, H-6b, H-4), 3.96
(d, 2H, J3,4 3.2 Hz, H-3), 3.58, 3.51 (2dt, 4H, O–CHa2),
27
White solid (88%): mp 114–116 °C; ½aꢂD ꢀ67.5 (c 0.6,
1
CHCl3); H NMR (CDCl3) dglucose 5.90 (2d, 2H, J1,2
3.2 Hz, H-1), 4.41 (2d, 2H, J2,3 0 Hz, H-2), 4.22 (d,
2H, J3,4 2.8 Hz, H-3), 4.13 (m, 2H, H-5), 4.05 (2dd,
2H, J4,5 7.6 Hz, H-4), 3.90–3.74 (m, 2H, J6a,6b 11.5 Hz,
H-6), 1.40–1.29 (4s, 12H, CH3iso) dbenzimidazolone 7.25–
7.00 (m, 3H, Harom); 13C NMR (CDCl3) dglucose 111.8
(Ciso), 105.2 (C-1), 84.7 (C-2), 80.5 (C-4), 74.2 (C-3),
67.6 (C-5), 45.3 (C-6), 26.6–26.0 (CH3iso) dbenzimidazolone
156.1 (CO), 130.3 (C-5), 129.0, 127.6 (C-8, C-9), 121.0
(C-6), 109.2, 109.1 (C-4, C-7), 21.4 (CH3); Anal. Calcd
for C25H33ClN2O11: C, 52.40; H, 5.80; N, 4.89; Cl,
6.19. Found: C, 52.19; H, 5.75; N, 4.94; Cl, 6.23.
1.54 (m, 4H, CHb), 1.40–1.15 (4s, 12H, CH3iso), 1.32–
2
1.24 (m, 28H, CH2), 0.85 (s, 6H, CH3) dbenzimidazolone
7.35–7.00 (m, 3H, Harom); 13C NMR (CDCl3) dglucose
111.8 (Ciso), 105.1 (C-1), 82.4 (C-3), 82.1 (C-2), 79.9
(C-4), 70.9 (O–CHa2), 68.7 (C-5), 45.6 (C-6), 31.8–29.5,
25.9, 22.6 (CH2), 26.6–26.3 (CH3iso), 14.0 (CH3)
dbenzimidazolone 157.4 (CO), 130.6 (C-5), 128.4, 127.5 (C-
8, C-9), 121.8 (C-6), 109.6, 109.2 (C-4, C-7); Anal. Calcd
for C45H73ClN2O11: C, 63.32; H, 8.62; N, 3.28; Cl, 4.15.
Found: C, 63.24; H, 8.58; N, 3.30; Cl, 4.16.
3.2.14. 5-Chloro-1,3-N,N0-bis-(6-deoxy-1,2-O-isopropyl-
idene-3-O-methyl-a-D-glucofuranos-6-yl)benzimidazol-2-
3.2.17. 5-Chloro-1,3-N,N0-bis-(6-deoxy-3-O-dodecyl-1,2-
O-isopropylidene-a-D-glucofuranos-6-yl)benzimidazol-2-
27
one (7b). White solid (76%): mp 191–193 °C; ½aꢂD
27
1
ꢀ119.9 (c 0.6, CHCl3); H NMR (CDCl3) dglucose 5.87
one (7g). Colourless syrup (88%): ½aꢂD ꢀ82.3 (c 0.6,
(d, 2H, J1,2 3.7 Hz, H-1), 4.51 (d, 2H, J2,3 0 Hz, H-2),
4.27 (dd, 2H, J5,6a 2.7 Hz, J6a,6b 14.4 Hz, H-6a), 4.20
(m, 2H, J4,5 8.5 Hz, J5,6b 5.8 Hz, H-5), 4.05 (dd, 2H,
H-6b), 3.96 (dd, 2H, J3,4 2.9 Hz, H-4), 3.82 (d, 2H, H-
CHCl3); 1H NMR (CDCl3) dglucose 5.92 (d, 2H, J1,2
3.6 Hz, H-1), 4.52 (d, 2H, J2,3 0 Hz, H-2), 4.30 (dd, 2H,
J6a,6b 14.4 Hz, H-6a), 4.24 (m, 2H, J5,6a 2.5 Hz, J5,6b
5.2 Hz, H-5), 4.07–4.00 (m, 4H, H-6b, H-4), 3.98 (d,
2H, J3,4 3.2 Hz, H-3), 3.58, 3.52 (2dt, 4H, O–CHa2),
3), 3.45 (2s, 6H, OCH3), 1.40–1.30 (4s, 12H, CH3iso
)
dbenzimidazolone 7.30–7.00 (m, 3H, Harom); 13C NMR
(CDCl3) dglucose 111.8 (Ciso), 105.1 (C-1), 83.6 (C-3),
81.7 (C-2), 79.9 (C-4), 68.6 (C-5), 58.1 (OCH3), 45.6
1.54 (m, 4H, CHb), 1.40–1.15 (4s, 12H, CH3iso), 1.32–
2
1.23 (m, 36H, CH2), 0.85 (s, 6H, CH3) dbenzimidazolone
7.35–7.00 (m, 3H, Harom); 13C NMR (CDCl3) dglucose

428
B. Lakhrissi et al. / Carbohydrate Research 343 (2008) 421–433
111.8 (Ciso), 105.1 (C-1), 82.4 (C-3), 82.1 (C-2), 79.9
(C-4), 70.8 (O–CHa2), 68.7 (C-5), 45.6 (C-6), 31.8–29.3,
25.8, 22.6 (CH2), 26.6–26.2 (CH3iso), 14.0 (CH3) dbenzim-
idazolone 157.4 (CO), 130.6 (C-5), 128.4, 127.4 (C-8, C-9),
121.8 (C-6), 109.6, 109.3 (C-4, C-7); Anal. Calcd for
C49H81ClN2O11: C, 64.70; H, 8.97; N, 3.07; Cl, 3.90.
Found: C, 64.56; H, 8.92; N, 3.16; Cl, 3.86.
C-6), 109.2 (C-4, C-7); Anal. Calcd for C31H50N2O11:
C, 59.41; H, 8.04; N, 4.47. Found: C, 59.34; H, 7.97;
N, 4.56.
3.3.5. 1,3-N,N0-Bis-(6-deoxy-3-O-octyl-D-glucopyranos-
6-yl)benzimidazol-2-one (8e). White solid (80%, a/b,
27
7:4): mp 86–88 °C; ½aꢂD 92.7 (c 0.6, CHCl3); 13C NMR
(CDCl3) dglucose 96.9 (C-1b), 92.3 (C-1a), 83.3, 81.0 (C-3),
74.7–70.3 (C-2, C-4, C-5), 72.0 (O–CHa2), 42.3 (C-6),
31.8–29.1, 25.9, 22.6 (CH2), 14.0 (CH3) dbenzimidazolone
156.0 (CO), 129.8, 129.5 (C-8, C-9), 121.8 (C-5, C-6),
109.5 (C-4, C-7); Anal. Calcd for C35H58N2O11: C,
61.56; H, 8.56; N, 4.10. Found: C, 61.54; H, 8.53; N,
4.16.
3.3. General procedure for deprotection step (ii)
The protected derivatives 5–7 were added to a stirred
solution of 9:1 CF3COOH–water (100 g Lꢀ1) at room
temperature. When the starting material was no longer
detected by TLC or HPLC, the solution was concen-
trated to dryness under reduced pressure. The crude
product was purified by silica gel chromatography
(hexane–acetone gradient).
3.3.6. 1,3-N,N0-Bis-(3-O-decyl-6-deoxy-D-glucopyranos-
6-yl)benzimidazol-2-one (8f). White solid (83% yield,
27
a/b, 2:0): mp 84–86 °C; ½aꢂD 103.2 (c 0.6, CHCl3); 13C
3.3.1. 1,3-N,N0-Bis-(6-deoxy-D-glucopyranos-6-yl)benz-
imidazol-2-one (8a). White solid (95%, a/b, 3:2): mp
NMR (CDCl3) dglucose 96.9 (C-1b), 92.2 (C-1a), 83.4,
81.0 (C-3), 74.8–70.7 (C-2, C-4, C-5), 72.1 (O–CHa2),
42.3 (C-6), 31.8–29.2, 26.0, 22.6 (CH2), 14.0 (CH3)
dbenzimidazolone 159.9 (CO), 129.8, 129.6 (C-8, C-9),
121.8 (C-5, C-6), 109.5 (C-4, C-7); Anal. Calcd for
C39H66N2O11: C, 63.39; H, 9.00; N, 3.79. Found: C,
63.30; H, 8.94; N, 3.86.
27
202–204 °C; ½aꢂD 31.5–36.8 (c 0.6, MeOH); 13C NMR
(DMSO-d6) dglucose 96.7 (C-1b), 92.1 (C-1a), 76.0, 74.5
(C-3), 73.9–69.3 (C-2, C-4, C-5), 42.9 (C-6) dbenzimidazolone
153.8 (CO), 129.6 (C-8, C-9), 120.6 (C-5, C-6),
108.5 (C-4, C-7); Anal. Calcd for C49H81N2O11: C,
49.78; H, 5.72; N, 6.11. Found: C, 49.74; H, 5.69; N,
6.15.
3.3.7.
1,3-N,N0-Bis-(6-deoxy-3-O-dodecyl-D-glucopyr-
anos-6-yl)benzimidazol-2-one (8g). White solid (84%,
3.3.2.
1,3-N,N0-Bis-(6-deoxy-3-O-methyl-D-glucopyr-
27
a/b, 7:4): mp 84–86 °C; ½aꢂD 80.1 (c 0.6, CHCl3); 13C
anos-6-yl)benzimidazol-2-one (8b). White solid (81%,
27
NMR (CDCl3) dglucose 96.9 (C-1b), 92.2 (C-1a), 83.3,
80.9 (C-3), 74.8–70.7 (C-2, C-4, C-5), 72.0 (O–CHa2),
42.3 (C-6), 31.8–29.1, 26.1, 25.9, 22.6 (CH2), 14.0
(CH3) dbenzimidazolone 156.1 (CO), 129.8, 129.5 (C-8,
C-9), 121.8 (C-5, C-6), 109.5 (C-4, C-7); Anal. Calcd
for C43H74N2O11: C, 64.96; H, 9.38; N, 3.52. Found:
C, 64.92; H, 9.40; N, 3.54.
a/b, 4:3): mp 124–126 °C; ½aꢂD 48.5–50.2 (c 0.6, MeOH);
13C NMR (DMSO-d6) dglucose 96.6 (C-1b), 92.2 (C-1a),
85.6, 82.8 (C-3), 74.1–69.5 (C-2, C-4, C-5), 59.8
(OCH3), 42.7 (C-6) dbenzimidazolone 153.8 (CO), 129.6
(C-8, C-9), 120.7 (C-5, C-6), 108.7, 108.4 (C-4, C-7);
Anal. Calcd for C20H28N2O11: C, 50.84; H, 5.97; N,
5.93. Found: C, 50.80; H, 5.94; N, 5.97.
3.3.8.
1,3-N,N0-Bis-(6-deoxy-D-glucopyranos-6-yl)-5-
3.3.3. 1,3-N,N0-Bis-(3-O-butyl-6-deoxy-D-glucopyranos-
6-yl)benzimidazol-2-one (8c). White solid (90%, a/b,
methylbenzimidazol-2-one (9a). White solid (80%, a/b,
27
27
9:5): mp 104–106 °C; ½aꢂD 103.3 (c 0.6, CHCl3); 13C
5:3): mp 196–198 °C; ½aꢂD 57.7–51.6 (c 0.6, MeOH);
13C NMR (DMSO-d6) dglucose 96.7 (C-1b), 92.1 (C-1a),
76.0, 74.5 (C-3), 73.8–69.4 (C-2, C-4, C-5), 42.9 (C-6)
dbenzimidazolone 153.8 (CO), 129.6 (C-8, C-9), 120.7 (C-5,
C-6), 108.7, 108.4 (C-4, C-7), 21.4 (CH3); Anal. Calcd
for C20H28N2O11: C, 50.84; H, 5.97; N, 5.93. Found:
C, 50.81; H, 5.96; N, 5.97.
NMR (CDCl3) dglucose 96.7 (C-1b), 92.2 (C-1a), 84.3,
81.2 (C-3), 74.3–69.6 (C-2, C-4, C-5), 71.9 (O–CHa2),
42.8 (C-6), 31.9 (CHb), 18.6 (CHc), 13.8 (CH3)
2
2
dbenzimidazolone 156.1 (CO), 129.6 (C-8, C-9), 120.6 (C-5,
C-6), 108.7, 108.4 (C-4, C-7); Anal. Calcd for
C20H28N2O11: C, 56.83; H, 7.42; N, 4.91. Found: C,
56.79; H, 7.28; N, 4.97.
3.3.9.
anos-6-yl)-5-methylbenzimidazol-2-one
1,3-N,N0-Bis-(6-deoxy-3-O-methyl-D-glucopyr-
(9b). White
3.3.4. 1,3-N,N0-Bis-(6-deoxy-3-O-hexyl-D-glucopyranos-
6-yl)benzimidazol-2-one (8d). White solid (88%, a/b,
27
solid (80%, a/b, 9:5): mp 128–130 °C; ½aꢂD 52.3–53.8 (c
0.6, MeOH); 13C NMR (DMSO-d6) dglucose 96.6
(C-1b), 92.2 (C-1a), 83.9, 82.8 (C-3), 74.1–69.5 (C-2,
C-4, C-5), 59.8 (OCH3), 42.7 (C-6) dbenzimidazolone 154.0
(CO), 130.8 (C-5), 129.7, 127.5 (C-8, C-9), 121.1 (C-6),
109.09, 108.7 (C-4, C-7), 21.4 (CH3); Anal. Calcd for
27
9:5): mp 92–94 °C; ½aꢂD 102.1 (c 0.6, CHCl3); 13C
NMR (CDCl3) dglucose 96.7 (C-1b), 92.3 (C-1a), 83.6,
81.1 (C-3), 74.5–69.9 (C-2, C-4, C-5), 72.0 (O–CHa2),
42.4 (C-6), 31.8–29.1, 26.0, 22.6 (CH2), 13.9 (CH3)
dbenzimidazolone 155.8 (CO), 129.6 (C-8, C-9), 120.6 (C-5,

B. Lakhrissi et al. / Carbohydrate Research 343 (2008) 421–433
429
C21H30N2O11: C, 51.85; H, 6.21; N, 5.76. Found: C,
51.81; H, 6.18; N, 5.86.
3.3.15.
glucopyranos-6-yl)benzimidazol-2-one
5-Chloro-1,3-N,N0-bis-(6-deoxy-3-O-octyl-D-
(10e). White
27
solid (83%, a/b, 5:3): mp 88–90 °C; ½aꢂD 109.2 (c 0.6,
CHCl3); 13C NMR (CDCl3) dglucose 96.8 (C-1b), 92.2
(C-1a), 83.4, 81.0 (C-3), 74.7–70.3 (C-2, C-4, C-5), 72.1
3.3.10. 1,3-N,N0-Bis-(6-deoxy-3-O-octyl-D-glucopyranos-
6-yl)-5-methylbenzimidazol-2-one (9e). White solid
27
(84%, a/b, 5:3): mp 87–89 °C; ½aꢂD 106.2 (c 0.6, CHCl3);
(O–CHa), 42.5 (C-6), 31.8–29.3, 25.9, 22.6 (CH2), 14.0
2
13C NMR (CDCl3) dglucose 96.9 (C-1b), 92.3 (C-1a),
(CH3) dbenzimidazolone 156.0 (CO), 130.6 (C-5), 128.2,
127.3 (C-8, C-9), 121.3 (C-6), 110.2, 109.8 (C-4, C-7);
Anal. Calcd for C35H57ClN2O11: C, 58.60; H, 8.01; N,
3.90; Cl, 4.94. Found: C, 58.56; H, 7.93; N, 3.97; Cl,
4.97.
83.5, 81.0 (C-3), 74.7–70.7 (C-2, C-4, C-5), 72.0
(O–CHa), 42.3 (C-6), 31.8–29.2, 25.9, 22.6 (CH2), 14.0
2
(CH3) dbenzimidazolone 156.2 (CO), 131.6 (C-5), 129.9,
129.5 (C-8, C-9), 122.7 (C-6), 109.8, 109.2 (C-4, C-7),
21.4 (CH3); Anal. Calcd for C36H60N2O11: C, 62.05;
H, 8.68; N, 4.02. Found: C, 62.00; H, 8.64; N, 4.04.
3.3.16.
glucopyranos-6-yl)benzimidazol-2-one
5-Chloro-1,3-N,N0-bis-(3-O-decyl-6-deoxy-D-
(10f). White
27
3.3.11. 1,3-N,N0-Bis-(3-O-decyl-6-deoxy-D-glucopyranos-
6-yl)-5-methylbenzimidazol-2-one (9f). White solid
solid (80%, a/b, 2): mp 83–85 °C; ½aꢂD 104.3 (c 0.6,
CHCl3); 13C NMR (CDCl3) dglucose 96.9 (C-1b), 92.3
(C-1a), 83.4, 81.0 (C-3), 74.7–70.6 (C-2, C-4, C-5), 72.1
27
(70%, a/b, 2): mp 90–92 °C; ½aꢂD 99.4 (c 0.6, CHCl3);
13C NMR (CDCl3) dglucose 96.9 (C-1b), 92.3 (C-1a),
(O–CHa), 42.3 (C-6), 31.8–29.2, 25.9, 22.6 (CH2), 14.0
2
83.5, 80.9 (C-3), 74.8–70.8 (C-2, C-4, C-5), 72.1
(CH3) dbenzimidazolone 156.0 (CO), 130.7 (C-5), 128.2,
127.2 (C-8, C-9), 121.4 (C-6), 110.2, 109.8 (C-4, C-7);
Anal. Calcd for C39H65ClN2O11: C, 60.57; H, 8.47; N,
3.62; Cl, 4.58. Found: C, 60.56; H, 8.45; N, 3.64; Cl,
4.54.
(O–CHa), 42.3 (C-6), 31.8–29.3, 25.0, 22.6 (CH2), 14.0
2
(CH3) dbenzimidazolone 156.3 (CO), 131.6 (C-5), 129.9,
129.6 (C-8, C-9), 122.6 (C-6), 109.8, 109.2 (C-4, C-7),
21.4 (CH3); Anal. Calcd for C40H68N2O11: C, 63.80;
H, 9.10; N, 3.72. Found: C, 63.76; H, 9.04; N, 3.78.
3.3.17. 5-Chloro-1,3-N,N0-bis-(6-deoxy-3-O-dodecyl-D-
3.3.12. 1,3-N,N0-Bis-(6-deoxy-3-O-dodecyl-D-glucopyr-
glucopyranos-6-yl)benzimidazol-2-one
(10g). White
27
anos-6-yl)-5-methylbenzimidazol-2-one
(9g). White
solid (88%, a/b, 7:4): mp 90–92 °C; ½aꢂD 90.6 (c 0.6,
CHCl3); 13C NMR (CDCl3) dglucose 96.9 (C-1b), 92.3
(C-1a), 83.4, 81.0 (C-3), 74.7–70.6 (C-2, C-4, C-5), 72.0
27
solid (87%, a/b, 7:4): mp 85–87 °C; ½aꢂD 87.4 (c 0.6,
CHCl3); 13C NMR (CDCl3) dglucose 97.0 (C-1b), 92.3
(C-1a), 83.4, 81.1 (C-3), 74.9–70.7 (C-2, C-4, C-5), 72.0
(O–CHa), 42.3 (C-6), 31.8–29.3, 25.8, 22.6 (CH2), 14.0
2
(O–CHa), 42.3 (C-6), 31.9–29.1, 25.1, 22.6 (CH2), 14.1
(CH3) dbenzimidazolone 156.0 (CO), 130.6 (C-5), 128.5,
128.2 (C-8, C-9), 121.9 (C-6), 110.2, 109.8 (C-4, C-7);
Anal. Calcd for C43H73ClN2O11: C, 62.26; H, 8.87; N,
3.38; Cl, 4.27. Found: C, 62.20; H, 8.84; N, 3.42; Cl, 4.29.
2
(CH3) dbenzimidazolone 156.3 (CO), 131.6 (C-5), 130.0,
129.6 (C-8, C-9), 122.6 (C-6), 109.8, 109.0 (C-4, C-7),
21.4 (CH3); Anal. Calcd for C44H76N2O11: C, 65.32;
H, 9.47; N, 3.46. Found: C, 65.25; H, 9.42; N, 3.50.
3.4. General procedure for alkylation step (i)
3.3.13. 5-Chloro-1,3-N,N0-bis-(6-deoxy-D-glucopyranos-
6-yl)benzimidazol-2-one (10a). The White solid (84%,
To a solution of 1-N-isopropenylbenzimidazolone 11
and K2CO3 (1.5 equiv) in DMF (160 g Lꢀ1) at 110 °C,
was added n-bromoalkyl benzimidazolone (1.1 equiv,
CnH2n+1, n = 4, 6, 8, 10, 12). When starting material
was no longer detected by TLC or HPLC, the mixture
was extracted with toluene–aq NH4Cl, the organic
layer was recovered, washed with satd aq NaCl, dried
(Na2SO4) and concentrated under reduced pressure.
The crude product was purified by silica gel chromato-
graphy (hexane–acetone gradient).
27
a/b, 3:2): mp 170–172 °C; ½aꢂD 38.4–33.5 (c 0.6, MeOH);
13C NMR (DMSO-d6) dglucose 96.6 (C-1b), 92.1 (C-1a),
76.0, 74.5 (C-3), 73.8–69.4 (C-2, C-4, C-5), 43.1 (C-6)
dbenzimidazolone 153.7 (CO), 128.6 (C-8, C-9), 120.3 (C-5,
C-6), 108.8, 108.5 (C-4, C-7); Anal. Calcd for
C19H25ClN2O11: C, 46.30; H, 5.11; N, 5.68; Cl, 7.19.
Found: C, 47.23; H, 5.33; N, 5.60; Cl, 7.05.
3.3.14.
glucopyranos-6-yl)benzimidazol-2-one
5-Chloro-1,3-N,N0-bis-(6-deoxy-3-O-methyl-D-
(10b). White
27
solid (70%, a/b, 5:3): mp 143–146 °C; ½aꢂD 44.8–45.8 (c
0.6, MeOH); 13C NMR (DMSO-d6) dglucose 96.6
(C-1b), 92.2 (C-1a), 85.9, 82.8 (C-3), 74.1–69.4 (C-2,
C-4, C-5), 59.8 (OCH3), 42.9 (C-6) dbenzimidazolone 153.7
(CO), 130.8 (C-5), 128.6, 124.9 (C-8, C-9), 120.3 (C-6),
109.9, 108.5 (C-4, C-7); Anal. Calcd for C20H27ClN2O11:
C, 47.39; H, 5.37; N, 5.53; Cl, 6.99. Found: C, 47.23; H,
5.33; N, 5.60; Cl, 7.05.
3.4.1.
1-N-Butyl-3-N-isopropenylbenzimidazol-2-one
(12a). Colourless syrup (94%): 1H NMR (CDCl3) d
7.10–6.85 (m, 4H, Harom), 5.25, 5.10 (2s, 2H, C@CH2),
3.80 (t, 2H, N–CHa), 2.20 (s, 3H, CH3), 1.70 (m, 2H,
2
CHb2), 1.35 (m, 2H, CH2c), 0.95 (t, 3H, CHx3 ); 13C
NMR (CDCl3) d 152.7 (CO), 138.1 (C@CH2), 129.7,
128.8 (C-8, C-9), 121.3, 121.0 (C-5, C-6), 112.5
(C=CH2), 108.9, 107.6 (C-4, C-7), 40.7 (N–CHa), 30.3
2

430
B. Lakhrissi et al. / Carbohydrate Research 343 (2008) 421–433
(CHb2), 20.1 (CH3), 20.0 (CHc2), 13.7 (CHx); Anal. Calcd
for C14H18N2O: C, 73.01; H, 7.88; N, 12.16. Found: C,
72.56; H, 7.86; N, 12.25.
of 1:1 H2SO4–water. After 12 h the final products 14a–e
were obtained as crystals after diluting the mixture in
cold water and after filtration.
3
3.4.2.
1-N-Hexyl-3-N-isopropenylbenzimidazol-2-one
3.5.1. 1-N-Butylbenzimidazol-2-one (13a). White solid
(75%): mp 98–100 °C; 13C NMR (CDCl3) d 156.3 (CO),
130.8, 128.5 (C-8, C-9), 121.8, 121.5 (C-5, C-6), 110.3,
(12b). Colourless syrup (92%): 1H NMR (CDCl3) d
7.10–6.80 (m, 4H, Harom), 5.25, 5.15 (2s, 2H, C@CH2),
3.75 (t, 2H, N–CHa), 2.20 (s, 3H, CH3), 1.70 (m, 2H,
108.3 (C-4, C-7), 41.1 (N–CHa), 30.9–20.5 (CH2), 14.1
2
2
CHb), 1.40–1.10 (m, 2H, CH2), 0.95 (t, 3H, CH3); 13C
(CH3); Anal. Calcd for C11H14N2O: C, 69.44; H, 7.42;
N, 14.72. Found: C, 69.38; H, 8.35; N, 14.75.
2
NMR (CDCl3): d 152.7 (CO), 138.2 (C@CH2), 129.6,
128.7 (C-8, C-9), 121.3, 120.9 (C-5, C-6), 112.3
(C@CH2), 108.6, 107.6 (C-4, C-7), 40.7 (N–CHa),
31.3–26.4, 22.4 (CH2), 20.1 (CH3), 13.7 (CH3); Anal.
Calcd for C16H22N2O: C, 74,38; H, 8.58; N, 10.84.
Found: C, 74.31; H, 8.54; N, 10.89.
3.5.2. 1-N-Hexylbenzimidazol-2-one (13b). White solid
(83%): mp 56–59 °C; 13C NMR (CDCl3) d 156.3 (CO),
130.8, 128.5 (C-8, C-9), 121.7, 121.5 (C-5, C-6), 110.3,
2
108.3 (C-4, C-7), 41.3 (N–CHa), 31.9–22.9 (CH2), 14.4
2
(CH3); Anal. Calcd for C13H18N2O: C, 71.52; H, 8.21;
N, 12.83. Found: C, 71.49; H, 8.16; N, 12.75.
3.4.3.
3-N-Isopropenyl-1-N-octylbenzimidazol-2-one
(12c). Colourless syrup (95%): 1H NMR (CDCl3) d
7.10–6.80 (m, 4H, Harom), 5.25, 5.15 (2s, 2H, C@CH2),
3.5.3. 1-N-Octylbenzimidazol-2-one (13c). White solid
(94%): mp 68–70 °C; 13C NMR (CDCl3) d 156.1 (CO),
130.7, 128.4 (C-8, C-9), 121.8, 121.6 (C-5, C-6), 110.1,
3.74 (t, 2H, N–CHa), 2.20 (s, 3H, CH3), 1.70 (m, 2H,
2
CHb2), 1.40–1.12 (m, 10H, CH2), 0.95 (t, 3H, CH3); 13C
NMR (CDCl3) d 152.7 (CO), 138.1 (C@CH2), 129.6,
128.9 (C-8, C-9), 121.3, 120.9 (C-5, C-6), 112.4
108.3 (C-4, C-7), 41.3 (N–CHa), 32.2–23.0 (CH2), 14.1
2
(CH3); Anal. Calcd for C15H22N2O: C, 73.13; H, 9.00;
N, 11.37. Found: C, 73.05; H, 8.89; N, 11.48.
(C@CH2), 108.8, 107.7 (C-4, C-7), 40.7 (N–CHa),
2
31.8–26.5, 22.4 (CH2), 20.1 (CH3), 13.8 (CH3); Anal.
Calcd for C18H26N2O: C, 75.48; H, 9.15; N, 9.78.
Found: C, 75.45; H, 9.12; N, 9.85.
3.5.4. 1-N-Decylbenzimidazol-2-one (13d). White solid
(98%): mp 64–66 °C; 13C NMR (CDCl3) d 156.2 (CO),
130.7, 128.3 (C-8, C-9), 121.7, 121.4 (C-5, C-6), 110.0,
3.4.4.
1-N-Decyl-3-N-isopropenylbenzimidazol-2-one
108.3 (C-4, C-7), 41.2 (N–CHa), 32.3–23.0 (CH2), 14.1
2
(12d). Colourless syrup (90%): 1H NMR (CDCl3) d
7.11–6.80 (m, 4H, Harom), 5.25, 5.15 (2s, 2H, C@CH2),
(CH3); Anal. Calcd for C17H26N2O: C, 74.41; H, 9.55;
N, 10.21. Found: C, 74.39; H, 5.79; N, 10.31.
3.75 (t, 2H, N–CHa), 2.20 (s, 3H, CH3), 1.70 (m, 2H,
2
CHb2), 1.40–1.10 (m, 14H, CH2), 0.95 (t, 3H, CH3); 13C
NMR (CDCl3) d 152.7 (CO), 138.0 (C@CH2), 129.7,
128.8 (C-8, C-9), 121.4, 121.0 (C-5, C-6), 112.3
3.5.5. 1-N-Dodecylbenzimidazol-2-one (13e). White
solid (99%): mp 74–76 °C; 13C NMR (CDCl3) d 156.2
(CO), 130.8, 128.5 (C-8, C-9), 121.9, 121.7 (C-5, C-6),
(C@CH2), 108.6, 107.8 (C-4, C-7), 40.9 (N–CHa),
110.0, 108.3 (C-4, C-7), 41.2 (N–CHa), 32.1–22.9 (CH2),
2
2
31.9–26.6, 22.4 (CH2), 20.1 (CH3), 13.9 (CH3). Anal.
Calcd for C20H30N2O: C, 76.39; H, 9.61; N, 8.90.
Found: C, 76.31; H, 9.52; N, 8.84.
14.1 (CH3); Anal. Calcd for C19H30N2O: C, 75.45; H,
10.00; N, 9.26. Found: C, 75.42; H, 9.87; N, 9.32.
3.6. General procedure for condensation step (iii)
3.4.5. 1-N-Dodecyl-3-N-isopropenylbenzimidazol-2-one
(12e). Colourless syrup (90%): 1H NMR (CDCl3) d
7.10–6.80 (m, 4H, Harom), 5.25, 5.15 (2s, 2H, C@CH2),
To a solution of benzimidazolones 13a–e and K2CO3
(1.1 equiv) in DMSO (100 g Lꢀ1) at 110 °C was added
activated carbohydrate derivative 4b (1 equiv). When
the starting material was no longer detected by TLC
or HPLC, the mixture was extracted with toluene–aq
NH4Cl, the organic layer was recovered, washed with
satd aq NaCl, dried (Na2SO4) and concentrated under
diminished pressure. The crude product was purified
by silica gel chromatography (hexane–acetone gradient).
3.74 (t, 2H, N–CHa), 2.20 (s, 3H, CH3), 1.70 (m, 2H,
2
CHb2), 1.40–1.12 (m, 18H, CH2), 0.95 (t, 3H, CH3); 13C
NMR (CDCl3) d 152.7 (CO), 138.1 (C@CH2), 129.7,
128.8 (C-8, C-9), 121.3, 120.9 (C-5, C-6), 112.5
(C@CH2), 108.6, 107.6 (C-4, C-7), 41.0 (N–CHa),
2
31.8–26.8, 22.6 (CH2), 20.1 (CH3), 14.0 (CH3); Anal.
Calcd for C22H34N2O: C, 77.14; H, 10.01; N, 8.18.
Found: C, 77.10; H, 9.89; N, 8.16.
3.6.1. 3-N-Butyl-1-N-(6-deoxy-1,2-O-isopropylidene-3-O-
methyl-a-D-glucofuranos-6-yl)benzimidazol-2-one (14a).
3.5. General procedure for deprotection step (ii)
26
White solid (97%): mp 100–102 °C; ½aꢂD ꢀ76.9 (c 1,
To a solution of protected derivatives 12a–e in DMF
CHCl3); 1H NMR (CDCl3) dglucose 5.93 (d, H, J1,2
3.7 Hz, H-1), 4.52 (d, H, J2,3 0 Hz, H-2), 4.20 (m, H,
(100 g Lꢀ1) at room temperature was added a solution

B. Lakhrissi et al. / Carbohydrate Research 343 (2008) 421–433
431
J5,6a 2.7 Hz, J5,6b 5.7 Hz, H-5), 4.28, 4.05 (2dd, 2H,
J6a,6b 14.6 Hz, H-6), 3.95 (dd, H, J4,5 8.6 Hz, H-4),
3.89 (d, H, J3,4 3.9 Hz, H-3), 3.40 (s, 3H, OCH3), 1.35,
1.23 (2s, 6H, CH3iso) dbenzimidazolone 7.47–7.05 (m, 4H,
3.7 Hz, H-1), 4.57 (d, H, J2,3 0 Hz, H-2), 4.25 (m, H,
J5,6a 2.7 Hz, J5,6b 5.7 Hz, H-5), 4.32, 4.09 (2dd, 2H,
J6a,6b 14.6 Hz, H-6), 3.95 (dd, H, J3,4 3.9 Hz, J4,5
8.6 Hz, H-4), 3.85 (m, 4H, H-3), 3.40 (s, 3H, OCH3),
1.35, 1.23 (2s, 6H, CH3iso) dbenzimidazolone 7.23–6.89 (m,
H
arom), 3.85 (t, 2H, N–CHa), 1.71 (m, 2H, CH2b), 1.30
2
(m, 2H, CHc2), 0.95 (t, 3H, CH3x); 13C NMR (CDCl3)
dglucose 111.6 (Ciso), 105.1 (C-1), 83.6 (C-3), 81.8 (C-2),
80.1 (C-4), 68.8 (C-5), 58.2 (OCH3), 45.6 (C-6), 26.6–
26.2 (CH3iso) dbenzimidazolone 156.0 (CO), 129.7, 129.3
(C-8, C-9), 121.5, 121.3 (C-5, C-6), 108.7, 107.7 (C-4,
C-7), 41.0 (N–CH2a), 30.4 (CH2b), 20.0 (CHc2), 13.7
4H, Harom); 3.80 (t, 2H, N–CHa), 1.70 (m, 2H, CH2b),
2
1.38–1.14 (m, 14H, CH2), 0.95 (t, 3H, CH3); 13C NMR
(CDCl3) dglucose 111.7 (Ciso), 105.1 (C-1), 83.6 (C-3),
81.8 (C-2), 80.1 (C-4), 68.9 (C-5), 58.2 (OCH3), 45.6
(C-6), 26.5, 26.2 (CH3iso) dbenzimidazolone 155.2 (CO),
129.7, 129.3 (C-8, C-9), 121.4, 121.3 (C-5, C-6), 108.7,
107.7 (C-4, C-7), 41.4 (N–CHa2), 31.8–29.4, 26.0, 22.0
(CH2), 13.8 (CH3); Anal. Calcd for C27H42N2O6: C,
66.09; H, 8.63; N, 5.71. Found: C, 65.96; H, 8.57; N,
5.76.
(CHx); Anal. Calcd for C21H30N2O6: C, 62.05; H,
3
7.44; N, 6.89. Found: C, 62.00; H, 7.39; N, 6.96.
3.6.2. 1-N-(6-Deoxy-1,2-O-isopropylidene-3-O-methyl-a-
D-glucofuranos-6-yl)-3-N-hexylbenzimidazol-2-one (14b).
26
White solid (96%): mp 96–98 °C; ½aꢂD ꢀ68.4 (c 1, CHCl3);
3.6.5. 1-N-(6-Deoxy-1,2-O-isopropylidene-3-O-methyl-
a-D-glucofuranos-6-yl)-3-N-dodecylbenzimidazol-2-one
1H NMR (CDCl3) dglucose 5.90 (d, H, J1,2 3.7 Hz, H-1),
4.52 (d, H, J2,3 0 Hz, H-2), 4.20 (m, H, J5,6a 2.7 Hz,
J5,6b 5.7 Hz, H-5), 4.28, 4.06 (2dd, 2H, J6a,6b 14.6 Hz,
H-6), 3.95 (dd, H, J3,4 3.9 Hz, J4,5 8.6 Hz, H-4), 3.85
(m, 2H, H-3), 3.40 (s, 3H, OCH3), 1.34, 1.24 (2s, 6H,
CH3iso) dbenzimidazolone 7.20–6.85 (m, 4H, Harom), 3.75
(t, 2H, N–CHa2), 1.70 (m, 2H, CHb2), 1.40–1.10 (m, 6H,
CH2), 0.95 (t, 3H, CH3); 13C NMR (CDCl3) dglucose
111.6 (Ciso), 105.0 (C-1), 83.5 (C-3), 81.8 (C-2), 80.2
(C-4), 68.3 (C-5), 58.1 (OCH3), 45.4 (C-6), 26.5, 26.1
(CH3iso) dbenzimidazolone 155.8 (CO), 129.7, 129.3 (C-8,
C-9), 121.3, 121.1 (C-5, C-6), 108.6, 107.5 (C-4, C-7),
26
(14e). White solid (91%): mp 50–52 °C; ½aꢂD ꢀ59.6 (c 1,
CHCl3); 1H NMR (CDCl3) dglucose 5.90 (d, H, J1,2
3.7 Hz, H-1), 4.55 (d, H, J2,3 0 Hz, H-2), 4.20 (m, H,
J5,6a 2.7 Hz, J5,6b 5.7 Hz, H-5), 4.28, 4.05 (2dd, 2H,
J6a,6b 14.6 Hz, H-6), 3.95 (dd, H, J3,4 3.9 Hz, J4,5
8.6 Hz, H-4), 3.85 (m, 4H, H-3), 3.35 (s, 3H, OCH3),
1.35, 1.23 (2s, 6H, CH3iso) dbenzimidazolone 7.20–6.85 (m,
4H, Harom); 3.80 (t, 2H, N–CHa), 1.70 (m, 2H, CH2b),
2
1.40–1.10 (m, 18H, CH2), 0.95 (t, 3H, CH3); 13C NMR
(CDCl3) dglucose 111.7 (Ciso), 105.1 (C-1), 83.6 (C-3),
81.9 (C-2), 80.1 (C-4), 68.8 (C-5), 58.2 (OCH3), 45.6
(C-6), 26.5, 26.2 (CH3iso) dbenzimidazolone 155.8 (CO),
129.7, 129.2 (C-8, C-9), 121.4, 121.3 (C-5, C-6), 108.6
41.0 (N–CHa), 31.5, 29.3, 25.7, 22.7 (CH2), 13.7 (CH3);
2
Anal. Calcd for C25H38N2O6: C, 63.58; H, 7.89; N,
6.44. Found: C, 63.53; H, 7.79; N, 6.40.
(C-4, C-7), 41.2 (N–CHa), 31.7–29.6, 25.6, 22.5 (CH2),
2
13.9 (CHx); Anal. Calcd for C29H46N2O6: C, 67.15; H,
3
3.6.3. 1-N-(6-Deoxy-1,2-O-isopropylidene-3-O-methyl-a-
D-glucofuranos-6-yl)-3-N-octylbenzimidazol-2-one (14c).
8.94; N, 5.40. Found: C, 66.98; H, 8.86; N, 5.46.
26
White solid (95%): mp 70–72 °C; ½aꢂD ꢀ68.0 (c 1, CHCl3);
3.7. General procedure for deprotection step (iv)
1H NMR (CDCl3) dglucose 5.94 (d, H, J1,2 3.7 Hz, H-1),
4.55 (d, H, J2,3 0 Hz, H-2), 4.22 (m, H, J5,6a 2.7 Hz,
J5,6b 5.7 Hz, H-5), 4.30, 4.06 (2dd, 2H, J6a,6b 14.6 Hz,
H-6), 3.95 (dd, H, J3,4 3.9 Hz, J4,5 8.6 Hz, H-4), 3.85
(m, 4H, H-3), 3.40 (s, 3H, OCH3), 1.34, 1.24 (2s, 6H,
CH3iso) dbenzimidazolone 7.20–6.85 (m, 4H, Harom), 3.85
The protected derivatives 14a–e and Amberlyst resin 15
(H+) were added to a stirred solution of 4:1 dioxane–
water (100 g Lꢀ1) at 80 °C. When the starting material
was no longer detected by TLC or HPLC, the solution
was concentrated to dryness under reduced pressure.
The crude product was purified by silica gel chromato-
graphy (hexane–acetone gradient).
(N–CHa), 1.70 (m, 2H, CH2b), 1.40–1.10 (m, 10H, CH2),
2
0.95 (t, 3H, CH3); 13C NMR (CDCl3) dglucose 111.6 (Ciso),
105.0 (C-1), 83.5 (C-3), 81.9 (C-2), 80.3 (C-4), 68.7 (C-5),
58.1 (OCH3), 45.2 (C-6), 26.5, 26.1 (CH3iso) dbenzimidazolone
155.8 (CO), 129.7, 129.3 (C-8, C-9), 121.3, 121.1 (C-5,
C-6), 108.6, 107.5 (C-4, C-7), 41.1 (N–CHa2), 31.6–29.3,
25.9, 22.3 (CH2), 13.7 (CH3); Anal. Calcd for
C27H42N2O6: C, 64.91; H, 8.28; N, 6.06. Found: C,
64.86; H, 8.26; N, 6.09.
3.7.1. 3-N-Butyl-1-N-(6-deoxy-3-O-methyl-D-glucopyr-
anos-6-yl)benzimidazol-2-one
(15a). White
solid
26
(83%, a/b, 4:3): mp 67–69 °C; ½aꢂD ꢀ34.9 to 40.6 (c 1,
MeOH); 13C NMR (CDCl3) dglucose 96.7 (C-1b), 92.2
(C-1a), 85.9, 82.8 (C-3), 74.1–69.5 (C-2, C-4, C-5),
59.8 (OCH3), 42.6 (C-6) dbenzimidazolone 153.6 (CO),
129.7, 128.8 (C-8, C-9), 120.6 (C-5, C-6), 108.7,
107.5 (C-4, C-7), 40.5 (N–CHa2), 29.9 (CH2b), 19.3
3.6.4. 3-N-Decyl-1-N-(6-deoxy-1,2-O-isopropylidene-3-
O-methyl-a-D-glucofuranos)-6-ylbenzimidazol-2-one (14d).
(CHc2), 13.5 (CHx); Anal. Calcd for C18H26N2O6: C,
3
26
White solid (93%): mp 53–55 °C; ½aꢂD ꢀ62.1 (c 1,
59.00; H, 7.15; N, 7.64. Found: C, 58.96; H, 7.12; N,
7.63.
CHCl3); 1H NMR (CDCl3) dglucose 5.93 (d, H, J1,2

432
B. Lakhrissi et al. / Carbohydrate Research 343 (2008) 421–433
3.7.2. 1-N-(6-Deoxy-3-O-methyl-D-glucopyranos-6-yl)-3-
N-hexylbenzimidazol-2-one (15b). White solid (89%,
chromatographied on silica gel (4:1 hexane–EtOAc),
giving the corresponding products 18a–b.
26
a/b, 9:7): mp 64–66 °C; ½aꢂD ꢀ35.5 to 39.2 (c 1, MeOH);
13C NMR (CDCl3) dglucose 96.7 (C-1b), 92.1 (C-1a),
86.0, 82.8 (C-3), 74.2–69.5 (C-2, C-4, C-5), 59.9
(OCH3), 42.6 (C-6) dbenzimidazolone 153.5 (CO), 129.6,
128.8 (C-8, C-9), 120.6 (C-5, C-6), 108.5, 107.5 (C-4,
3.8.1. 1-N-Isopropenyl-3-N-(3,5,6-tri-O-benzyl-1-deoxy-
b-D-glucofuranos-1-yl)benzimidazol-2-one (18a). Col-
20
ourless syrup: 370 mg (61%); ½aꢂD ꢀ23 (c 0.35, CH2Cl2);
1H NMR (CDCl3) dglucose 7.34–7.25 (m, 15H, Ph), 5.98
(s, 1H, J1,2 0 Hz, H-1), 4.90–4.50 (m, 7H, H-4, 3CH2),
4.33–4.24 (m, 3H, H-2, H-3, H-5), 3.87 (dd, 1H, J5,6a
5.2 Hz, J6a,6b 10.4 Hz, H-6a), 3.67 (dd, 1H, J5,6b
8.8 Hz, J6a,6b 10.4 Hz, H-6b) dbenzimidazolone 7.11–7.03
(m, 4H, Harom), 5.38, 5.16 (2s, 2H, C@CH2), 2.18 (s,
3H, CH3); 13C NMR (CDCl3) dglucose 129.3–122.46
(Ph), 91.0 (C-1), 85.3 (C-2), 79.3 (C-3), 78.3 (C-4),
76.0 (C-5), 73.9, 73.4, 71.8 (CH2 (Bn)), 71.7 (C-6)
dbenzimidazolone 152.6 (C@O), 137.9 (C@CH2), 128.8,
127.8 (C-8, C-9), 122.4, 121.8 (C-5, C-6), 114.3
(C@CH2), 110.27, 109.3 (C-4, C-7), 20.5 (CH3); HRE-
SIMS: m/z 629.2637. Calcd for C37H38N2NaO6,
606.2730; Anal. Calcd for C37H38N2O6: C, 73.25; H,
6.31; N, 4.62. Found: C, 73.52; H, 6.22; N, 4.70.
C-7), 40.2 (CHa), 30.7–21.9 (CH2) 13.7 (CH3); Anal.
2
Calcd for C20H30N2O6: C, 60.90; H, 7.66; N, 7.10.
Found: C, 60.86; H, 7.64; N, 7.07.
3.7.3. 1-N-(6-Deoxy-3-O-methyl-D-glucopyranos-6-yl)-3-
N-octylbenzimidazol-2-one (15c). White solid (84%,
26
a/b, 4:3): mp 54–56 °C; ½aꢂD ꢀ33.3 to 38.8 (c 1, MeOH);
13C NMR (CDCl3) dglucose 96.8 (C-1b), 92.2 (C-1a),
85.9, 82.8 (C-3), 74.2–69.6 (C-2, C-4, C-5), 59.9
(OCH3), 42.6 (C-6) dbenzimidazolone 153.5 (CO), 129.7,
128.6 (C-8, C-9), 120.5 (C-5, C-6), 108.7, 107.4 (C-4,
C-7), 40.2 (N–CHa), 31.1–21.9 (CH2) 13.7 (CH3); Anal.
2
Calcd for C22H34N2O6: C, 62.53; H, 8.11; N, 6.63.
Found: C, 62.48; H, 8.04; N, 6.67.
3.7.4. 3-N-Decyl-1-N-(6-deoxy-3-O-methyl-D-glucopyr-
anos-6-yl)benzimidazol-2-one (15d). White solid (93%,
3.8.2. [1-N-(1-Deoxy-3,4-O-isopropylidene-a-D-arabino-
pyranos-1-yl)-3-N-isopropenylbenzimidazol-2-one (18b).
26
20
a/b, 5:3): mp 51–53 °C; ½aꢂD ꢀ29.3 to 35.5 (c 1, MeOH);
Colourless syrup: 376 mg (62%); ½aꢂD ꢀ17 (c 0.43,
13C NMR (CDCl3) dglucose 96.7 (C-1b), 92.2 (C-1a),
85.9, 82.8 (C-3), 74.2–69.5 (C-2, C-4, C-5), 59.8
(OCH3), 42.6 (C-6) dbenzimidazolone 153.5 (CO), 129.7,
128.8 (C-8, C-9), 120.6 (C-5, C-6), 108.5, 107.5 (C-4,
1
CH2Cl2); H NMR (CDCl3) darabinose 5.25 (d, 1H, J1,2
9.8 Hz, H-1), 4.45–4.40 (m, 2H, H-2, H-5a), 4.28–4.24
(m, 2H, H-3, H-4), 4.03 (dd, 1H, J4,5b 2.1 Hz, J5a,5b
13.7 Hz, H-5b), 3.88 (s, 1H, OH), 1.62, 1.41 (2s,
2 ꢁ 3H, CH3iso) dbenzimidazolone 7 28–7.07 (m, 4H,
C-7), 40.2 (N–CHa), 31.2–22.0 (CH2) 13.8 (CH3); Anal.
2
Calcd for C24H38N2O6: C, 63.98; H, 8.50; N, 6.22.
Found: C, 63.76; H, 8.41; N, 5.96.
H
arom), 5.35, 5.18 (2s, 2H, C@CH2), 2.15 (s, 3H, CH3);
13C NMR (CDCl3) darabinose 110.4 (Ciso), 83.3 (C-1),
79.9 (C-3), 74.1 (C-4), 70.3 (C-2), 66.3 (C-5), 28.7, 26.6
(CMe2) dbenzimidazolone 152.6 (C@O), 138.0 (C@CH2),
129.6, 128.0 (C-8, C-9), 122.4, 122.3 (C-5, C-6), 114.3
(C@CH2), 110.7, 109.6 (C-4, C-7), 20.4 (CH3); HRE-
SIMS: m/z 369.1414. Calcd for C18H22N2NaO5:
369.1426; Anal. Calcd for C18H22N2O5: C, 62.42; H,
6.40; N, 8.09. Found: C, 62.48; H, 6.37; N, 8.13.
3.7.5. 1-N-(6-Deoxy-3-O-methyl-D-glucopyranos-6-yl)-3-
N-dodecylbenzimidazol-2-one (15e). White solid (72%,
26
a/b, 1): mp 44–46 °C; ½aꢂD ꢀ25.5 to 32.1 (c 1, MeOH);
13C NMR (CDCl3) dglucose 96.7 (C-1b), 92.2 (C-1a),
86.0, 82.9 (C-3), 74.2–69.5 (C-2, C-4, C-5), 59.8
(OCH3), 42.6 (C-6) dbenzimidazolone 153.6 (CO), 129.7,
128.8 (C-8, C-9), 120.5 (C-5, C-6), 108.7 107.4 (C-4,
C-7), 40.2 (N–CHa), 31.2–22.0 (CH2) 13.8 (CH3); Anal.
2
Calcd for C26H42N2O6: C, 65.25; H, 8.84; N, 5.85.
Found: C, 65.19; H, 8.76; N, 5.86.
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