An expedient one-step synthesis of polysubstituted guanidinoglucosides using HgO-4 A molecular sieves as catalyst

Article abstract of DOI:10.1016/j.carres.2008.07.016

A novel one-step method of preparing polysubstituted guanidinoglucosides using peracetylated methyl 6-deoxy-6-thioureidoglucosides as starting materials and employing HgO in combination with molecular sieves as an efficient catalyst is reported. The structures of three methyl 2,3,4-tri-O-acetyl-6-[N²-(benzothiazol-2-yl)-N³-(oxydi-1,2-ethandiyl)]guanidino-6-deoxy-α-d-glucopyranosides were unambiguously confirmed by X-ray crystallography. The methodology affords new compounds in good yields and also provides a promising route for the synthesis of carbamate-protected guanidines.

Full text of DOI:10.1016/j.carres.2008.07.016

Carbohydrate Research 343 (2008) 2376–2383
Contents lists available at ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
An expedient one-step synthesis of polysubstituted guanidinoglucosides
using HgO–4 Å molecular sieves as catalyst
*
Yong-Hua Liu, Ling-Hua Cao
College of Chemistry and Chemical Engineering, Xinjiang University, Urumqi 830046, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 10 June 2008
Received in revised form 11 July 2008
Accepted 18 July 2008
Available online 29 July 2008
A novel one-step method of preparing polysubstituted guanidinoglucosides using peracetylated methyl
6-deoxy-6-thioureidoglucosides as starting materials and employing HgO in combination with molecular
sieves as an efficient catalyst is reported. The structures of three methyl 2,3,4-tri-O-acetyl-6-[N2-(ben-
zothiazol-2-yl)-N3-(oxydi-1,2-ethandiyl)]guanidino-6-deoxy-
a-D-glucopyranosides were unambiguously
confirmed by X-ray crystallography. The methodology affords new compounds in good yields and also
provides a promising route for the synthesis of carbamate-protected guanidines.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords:
Sugar–thiourea
Guanidinoglucoside
2-Aminobenzothiazole
HgO
4 Å MS
1. Introduction
tuted sugar guanidines. In the latter case, topically, a nucleophilic
amine is reacted with a electrophilic carbodiimide to afford poly-
Guanidino-containing sugars have a wide range of biologically
important uses such as inhibition of the replication of HIV,1 the
inhibition of enzymes including thrombin,2 glycosidases,3–7 neur-
aminidase,8 and nitric oxide synthases,9 antibacterial activity,10
antihypertensive activity,11 the treatment of non-insulin-depen-
dent diabetes,12 and efficient recognition of anionic substrates such
as carboxylate, phosphate, and nitronate functionalities.13,14
Therefore, the synthesis of this class of guanidines has attracted
continued research interests in recent years. In fact, the prepara-
tion protocols of guanidines have been intensively investigated in
recent years,15–22 and some new, efficient, synthetic methods and
new guanidinylation reagents have been used for different classes
of guanidine compounds. However, most of these synthetic meth-
ods are not favorable to guanidino-containing sugars which suffer
from some disadvantages such as inconvenient preparation of the
reagents, limited substrate scope, or incompatibility of sensitive
groups to the reaction conditions.
Synthetic approaches to guanidinoglycosides grossly include
two general strategies: a guanidinylation reaction or a guanylation
reaction. In the former, a pre-formed guanidine, such as 3,5-di-
methylpyrazoylformamidinium nitrate (DPFN),2 dicyandiamide
[H2NC(@NH)NHCN],12 1H-pyrazolecarboxamidine hydrochloride,23
or N,N0-diBoc-N00-triflylguanidine,24 is reacted with amino sugars to
give their guanidino derivatives, most of which are monosubsti-
substituded guanidines.7,14,25 The carbodiimide precursors are
obtained by either the desulfurization of thiourea or are employed
in an iminophosphorescence-based approach.
In order to search for new polysubstituted sugar guanidines, our
research group has continued work in the area of heavy-metal-pro-
moted guanidinylation reaction of amines with sugar thioureas.
Previously, we had described the one-step synthesis of guanidino-
glucoside by the HgCl2–Et3N method.26 Later, during the course of
synthesizing peracetated methyl 6-deoxy-6-guanidinoglucosides,
the reaction of peracetated methyl 6-deoxy-6-thioureidogluco-
sides with low-reactive aryl amines only led to low yields (32–
56%) by the HgCl2-promoted protocol. It was clear that there was
a need for an improved, facile synthetic route for the study of
diversity among guanidino-containing glycosides. Mercury(II)
oxide, which is widely used in industry, is considered as a good
inorganic thiophile.27 To the best of our knowledge, only two
examples of thiourea conversion into guanidine using HgO as the
desulfurizing reagent have been described. One was to convert
bis-Boc-thiourea to guanidine, where it was considered that HgO
was much inferior to HgCl2 and CuCl2.28 The other was to convert
resin-bound thiourea to guanidine, where it was considered that
HgO was superior to AgNO3, Hg(OAc)2, and the Mukaiyama
reagent.29 A heavy metal salt–4 Å molecular sieve complex has
widely been applied in the synthesis of oligosaccharides as an
effective catalytic system30,31 in which molecular sieves were
reported as an efficient dehydrating agent. In this paper, we em-
ployed HgO as the desulfurizing reagent and 4 Å molecular sieves
* Corresponding author.
E-mail address: clhxj@xju.edu.cn (L.-H. Cao).
0008-6215/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2008.07.016

Y.-H. Liu, L.-H. Cao / Carbohydrate Research 343 (2008) 2376–2383
2377
N3R2
S
S
C
N3R2
N2
H
N
S
N
S
N
HN1
C
O
N2
R1
HN1
C
R1
HN
R1
N
O
AcO
AcO
AcO
AcO
O
HO
HO
Amines, MeCN
HgO, 4Å MS
MeOH, NaOMe
AcO
AcO
OMe
OH
OMe
OMe
1a−1c
2a−2h, 3a−3h, 4a−4h
5c−5h, 6c−6h, 7c−7h
R1: 1a, 2, 5: H; 1b, 3, 6: 6-OCH3; 1c, 4, 7: 6-CH3;
R2: a, (CH3)2CH–;
b, C6H11–; c, C6H5CH2–;
d, p-CH3C6H4–;
e, p-CH3OC6H4–; f, p-ClC6H4–; g, O(CH2CH2)2=; h, C2H5O2C–
Scheme 1.
as the dehydrating agent and alkaline catalyst to synthesize a ser-
ies of new trisubstituted guanidino-containing sugars in one-step
(Scheme 1). HgO in combination with 4 Å molecular sieves showed
much higher reactivity than the HgCl2–EtN3 protocol, being appli-
cable to the guanidinylation reaction of low reactive sugar thio-
ureas with low reactive amines. The method is economical,
operationally simple, and allows the reaction to proceed under
mild conditions.
efficiently removed by simple filtration of the cleavage solution
over a thin pad of Celite. The filtrate was concentrated and purified
by column chromatography to afford the target products (2d) in
65% yield. It is well known that the title compounds could be syn-
thesized through a carbodiimide intermediate,14 and here 4 Å
molecular sieves act as a weak base and dehydrating agent to facil-
itate the formation of the carbodiimide.
2.2. The synthesis of guanidinoglucosides
2. Results and discussion
With the optimal conditions in hand, amines of varying reactiv-
ity were investigated in order to gauge the scope of the reaction.
The synthetic yields and reaction conditions for this series of reac-
tions of sugar thioureas with amines are shown in Table 2. Isopro-
pylamine and cyclohexylamine gave high yields of peracetylated
guanidinoglucosides (Table 2, entries 1 and 2) within 6 h or less
at 20–30 °C, while deacetylated guanidinoglucosides (5a and 5b)
were major products obtained in 38–45% yields, and compounds
2a and 2b were only obtained in 12–16% yields under warm con-
ditions. Although the electronic nature of p-chloroaniline reduces
the efficiency of the reaction of this amine to form a guanidine, aro-
matic amines also give the guanidinoglycosides in good to excel-
lent yields under warm conditions (Table 2, entries 4–6). The
results indicated that the strongly alkaline aliphatic amines [pKa
9–11 (H2O, 25 °C)] could lead the sugar to deacetylate easily under
the conditions of heating, while the relatively weakly alkaline aro-
matic amines [pKa 4–5 (H2O, 25 °C)] could not do so. The secondary
amine, morphiline, reacted with thioureidoglucosides 1a–c to give
the corresponding guanidinoglucosides 2g–4g in 67–72% yields,
the structures of which were unambiguously confirmed by X-ray
crystallography (Figs. 1–3). Most noticeably, an attempt to
increase the diversity of the products by incorporation of ethyl
carbamate in this method succeeded, which gives rise to another
route to synthesize carbamate-protected guanidines,36,37 albeit in
2.1. Optimization of guanidine formation
Methyl 2,3,4-tri-O-acetyl-6-deoxy-6-thioureido-
anosides 1a–c were synthesized starting from methyl 2,3,4-tri-O-
a-D-glucopyr-
acetyl-6-deoxy-6-isothiocyanato-a-D-glucopyranoside and 2-ami-
nobenzothiazole derivatives using a well-established method.26
Methyl 2,3,4-tri-O-acetyl-6-[N-(benzothiazol-2-yl)]thioureido-6-
deoxy-a-D-glucopyranoside (1a) and p-toluidine were chosen as
test substrates to investigate various reaction conditions (Table
1). According to the method in Cunha’s report,32,33 the sugar thio-
urea was not desulfurized by BiCl3 or Bi(NO3)3ꢀ5H2O, even after
warming for several hours, and the solution became green-yellow.
TLC showed that strongly polar compounds were formed. We spec-
ulated that Bi3+ as an efficient Lewis acid34 preferentially catalyzes
the deacetylation of the sugar. The desulfurization reaction of
PbO35 and CuCl2 occurred very slowly, and several products tended
to be formed as evidenced from TLC. However, the process of
desulfurization was smooth and faster in the presence of Hg2+
While HgCl2 displayed moderate reactivity, use of HgO led to high-
er conversion and shorter reaction time in general. Moreover, the
reaction rate could be significantly increased, and the reaction
.
was complete within 12 h when the reaction was carried out in
0
the presence of 4 AÅ molecular sieves (5 wt equiv to HgO). In the ab-
sence of molecular sieves, the reaction time was extended twofold,
with yields of less than 19% along with some deacetylated guanidi-
noglucosides. As noted in entry 6 (Table 1), traces of the insoluble
black mercuric sulfide that formed and molecular sieves could be
Table 2
The reaction conditions and yields of guanidines 2a–h, 3a–h, and 4a–h
Entry
Amine
Yield (%)a
R1: H
R1: 6-OCH3
R1: 6-CH3
Table 1
Optimization of guanidine formation
1
2
3
4
5
6
7
8
Isopropylamine
Cyclohexyl amine
Benzylamine
p-Methylphenylamine
p-Methoxyphenylamine
p-Chlorophenylamine
Morpholine
85
81
57
65
64
43
67
41
/
/
/
/
Entry
Reaction conditions
Convn (yield, %)
Reference
65
69
64
49
72
45
61
63
62
45
71
44
1
2
3
4
5
6
7
CuCl2, DMF, Et3N, 36 h
34
nr
nr
54
62
65
48
28
32
33
26
BiCl3, DMF, Et3N, 50 °C, 24 h
Bi(NO3)3ꢀ5H2O, DMF, Et3N, 24 h
HgCl2, DMF, Et3N, 36 h
HgO, MeCN, 50 °C, 24 h
HgO, MeCN, 50 °C, 12 h, 4 Å MS
PbO, EtOH, 60 °C, 24 h 4 Å MS
Ethyl carbamate
a
In HgO–4 Å MS–MeCN, reaction conditions: entries 1 and 2, 25 °C, 6 h; entries
3–8, 50 °C, 12 h.
35

2378
Y.-H. Liu, L.-H. Cao / Carbohydrate Research 343 (2008) 2376–2383
Figure. 1. X-ray crystallographic structure of compound 2g with 30% thermal
ellipsoids.
Figure. 3. X-ray crystallographic structure of compound 4g with 30% thermal
ellipsoids.
3. Experimental
3.1. Materials and general methods
Melting points were determined on a Yanaco MP-S3 micro
melting point apparatus and are uncorrected. The IR spectra were
recorded as KBr pellets on a Bruker FTIR Equinox 55 instrument.
The 1H and 13C NMR spectra were recorded on an Inova 400 (using
TMS as the internal standard, with chemical shifts expressed in
d-units (ppm) in CDCl3 or DMSO-d6 as solvent). The mass spectra
were recorded on a Hewlett–Packard I000 LC–MS spectrometer
(ESI). Elemental analyses were performed on a Thermo Flash EA-
1112 elemental analyzer. Analytical thin-layer chromatography
(TLC) was performed on silica gel GF254 (Qingdao, China) with
EtOAc and light petroleum (fraction boiling in the range of 60–
90 °C) and detection by UV light or iodine vapor. Column chroma-
tography was performed on silica gel (100–200 mesh). All reagents
were commercial products of analytical grade and were used
directly without processing unless otherwise specified. The 4 Å
molecular sieves were purchased in a powder form, crushed,
sieved at 100 mesh screen and then activated at 200 °C for 4 h. Pyr-
idine was dried over KOH and distilled prior to use. DMF and MeCN
were dried over 4 Å molecular sieves. MeOH and EtOH were dried
over magnesium and distilled prior to use.
Figure. 2. X-ray crystallographic structure of compound 3g with 30% thermal
ellipsoids.
lower yields than with aromatic amines. All new guanidinoglucos-
ides (2–4) were further deacetylated in methanol under standard
NaOMe-catalyzed conditions to provide methyl 6-deoxy-6-guani-
dinoglucosides 5–7 in good yields.
The structures of new compounds were established by elemen-
tal analyses and by IR, 1H, and 13C NMR spectroscopy. In the 1H
NMR spectra of the peracetylated guanidinoglucosides, a broad sig-
nal around 9–12 ppm was detectable related to one N–H proton,
suggesting the participation of one intramolecular hydrogen bond.
As noted in Figure 1 of 2g, Figure 2 of 3g and Figure 3 of 4g, strong
hydrogen- bonding occurs between the benzothiazolyl nitrogen
and the guanidino NH group (intermolecular hydrogen bonds:
N1–Hꢀ ꢀ ꢀN4 [2.670(3) Å], N1–Hꢀ ꢀ ꢀN4 [2.6317(16) Å], and N1–
Hꢀ ꢀ ꢀN3 [2.636(2) Å]) providing a pseudo six-membered ring, which
conjugates with the benzothiazol-ring to contribute to the planar-
ity of the conjugated moiety of 2g, 3g, and 4g.
In summary, we have demonstrated a simple and efficient
method for the one-step synthesis of trisubstituted guanidinoglu-
cosides employing HgO as the desulfurizing reagent and 4 Å mole-
cular sieves as an efficient dehydrating agent. This protocol could
also be used to synthesize a variety of carbomate-protected
guanidinoglycosides.
Methyl 2,3,4-tri-O-acetyl-6-deoxy-6-thioureido-
anosides 1a–c were synthesized starting from methyl 2,3,4-tri-O-
acetyl-6-deoxy-6-isothiocyanato- -glucopyranoside and 2-ami-
nobenzothiazole derivatives using a well-established method.26
Methyl 2,3,4-tri-O-acetyl-6-deoxy-6-isothiocyanato- -gluco-
pyranoside was obtained from the reaction of the corresponding
a-D-glucopyr-
a-D
a
-D
methyl 2,3,4-tri-O-acetyl-6-azido-6-deoxy-a-D-glucopyranoside
with PPh3 and CS2 as reported.38 2-Aminobenzothiazole deriva-
tives were prepared according to the reported method.39
3.2. General procedure for the reaction of sugar thioureas 1a–c
with aliphatic amines
Sugar thiourea (1.0 mmol), 4 Å molecular sieves (1.0 g), and
HgO (1.2 mmol) were added to 10 mL of MeCN and stirred under
reflux for 30 min. Formation of carbodiimide was invariably
completed. The solution was cooled to 25 °C, and a solution of

Y.-H. Liu, L.-H. Cao / Carbohydrate Research 343 (2008) 2376–2383
2379
isopropylamine or cyclohexylamine (1.2 mmol) in MeCN (5 mL)
was added to the reaction mixture, and the mixture was stirred
at 25 °C until the reaction was completed (TLC, 1:1 EtOAc–petro-
leum ether). The reaction mixture was diluted with EtOAc and fil-
tered through Celite, and the Celite cake was washed with
additional EtOAc. The filtrate, together with the combined wash-
ings, was concentrated under reduced pressure to afford the
desired guanidines (2a and 2b).
(100 MHz, CDCl3): d 172.5, 170.2, 170.1, 169.8, 155.5, 145.9,
132.5, 129.0, 127.9, 127.2, 119.6, 113.3, 104.7, 96.5, 70.7, 69.8,
69.1, 55.8, 55.4, 45.3, 41.2, 20.8, 20.7; ESIMS: m/z 615 (100%,
[M+H]+), 637 (24%, [M+Na]+). Anal. Calcd for C29H34N4O9S: C,
56.67; H, 5.58; N, 9.11. Found: C, 56.59; H, 5.55; N, 9.01.
3.3.3. Methyl 2,3,4-tri-O-acetyl-6-[N3-benzyl-N2-(6-methyl-
benzothiazol-2-yl)]guanidino-6-deoxy-a-D-glucopyranoside
(4c)
3.2.1. Preparation of methyl 2,3,4-tri-O-acetyl-6-[N2-(benzo-
White solid; yield 364 mg (61%); mp 97–98 °C; IR (KBr): 3369,
1754, 1602, 1590, 1468, 1227, 1028 cmꢁ1 1H NMR (400 MHz,
thiazol-2-yl)-N3-isopropyl]guanidino-6-deoxy-
a
-D
-
;
glucopyranoside (2a)
CDCl3): d 2.00, 2.06, and 2.09 (3s, each 3H, 3MeCO), 2.40 (s, 3H,
Me), 3.23 (s, 3H, OMe), 3.46–3.58 (br s, 2H, CH2), 3.83 (s, 3H,
OMe), 3.83–3.96 (br s, 1H, H-6a), 4.47–4.60 (m, 2H, H-6b, H-5),
4.60–4.70 (br s, 1H, H-4), 4.70–4.87 (m, 2H, H-2, H-1), 5.42 (t,
J2,3 = J3,4 9.6 Hz, 1H, H-3), 6.85–7.60 (m, 8H, ArH), 10.02–10.85
(br s, 1H, NH); 13C NMR (100 MHz, CDCl3): d 173.0, 170.7, 170.5,
170.2, 155.3, 145.2, 131.6, 128.4, 126.4, 126.3, 121.6, 113.5, 96.7,
70.8, 70.2, 69.9, 55.4, 45.2, 41.0, 23.5, 21.0, 20.9; ESIMS: m/z 598
(100%, [M+H]+), 620 (30%, [M+Na]+). Anal. Calcd for C29H34N4O8S:
C, 58.18; H, 5.72; N, 9.36. Found: C, 58.07; H, 5.68; N, 9.27.
White solid; yield 455 mg (85%); mp 85–86 °C. The product was
analyzed by IR and 1H NMR spectroscopy and used without further
purification. The 1H and 13C NMR data were in full agreement with
those reported in the literature.26
3.2.2. Preparation of methyl 2,3,4-tri-O-acetyl-6-[N2-(benzo-
thiazol-2-yl)-N3-cyclohexyl] guanidino-6-deoxy-
a-D-
glucopyranoside (2b)
White solid; yield 466 mg (81%); mp 88–89 °C. The 1H and 13C
NMR data were in full agreement with those reported in the
literature.26
3.3.4. Methyl 2,3,4-tri-O-acetyl-6-[N2-(benzothiazol-2-yl)-N3-
(p-methylphenyl)]guanidino-6-deoxy-
White solid; yield 379 mg (65%); mp 133–134 °C; IR (KBr):
3380, 1750, 1603, 1592, 1464, 1230, 1037 cmꢁ1 1H NMR
a-D-glucopyranoside (2d)
3.3. General procedure for the reaction of sugar thioureas 1a–c
with aromatic amines
;
(400 MHz, CDCl3): d 2.00, 2.07, and 2.10 (3s, each 3H, 3MeCO),
2.36 (s, 3H, Me), 3.29 (s, 3H, OMe), 3.50–3.63 (m, 1H, H-6a),
3.64–3.75 (m, 1H, H-6b), 3.85–4.00 (m, 1H, H-5), 4.79 (dd, J1,2
3.6 Hz, J2,3 9.6 Hz,1H, H-2), 4.81–4.86 (m, 1H, H-4), 4.89 (d, J1,2
3.6 Hz, 1H, H-1), 5.44 (t, J2,3 = J3,4 9.6 Hz, 1H, H-3), 6.96–7.55 (m,
8H, ArH), 11.43–11.76 (br s, 1H, NH); 13C NMR (100 MHz, CDCl3):
d 173.2, 170.4, 170.3, 170.0, 153.6, 150.1, 135.8, 130.9, 129.7,
129.4, 126.7, 125.9, 125.4, 121.4, 116.6, 96.5, 70.9, 69.9, 69.5,
69.4, 55.2, 41.3, 29.7, 21.0, 20.9, 20.7; ESIMS: m/z 585 (100%,
[M+H]+), 607 (26%, [M+Na]+). Anal. Calcd for C28H32N4O8S: C,
57.52; H, 5.52; N, 9.58. Found: C, 57.44; H, 5.46; N, 9.47.
Sugar thiourea (1.0 mmol), 4 Å molecular sieves (1.0 g), and
HgO (1.2 mmol) were added to 10 mL of MeCN and stirred under
reflux for 30 min. Formation of the carbodiimide was invariably
complete by this time. An aromatic amine (1.3 mmol) was added
to the reaction mixture, and the mixture was stirred at 50 °C until
the reaction was complete (TLC, 1:2–1:1 EtOAc–petroleum ether).
The reaction mixture was diluted with EtOAc and filtered through
Celite, and the Celite cake was washed with additional EtOAc. The
filtrate, together with the combined washings, was concentrated
under reduced pressure to afford the desired guanidine. The resi-
due that remained after removal of solvent under reduced pressure
was purified by silica column chromatography (eluent: 1:4–1:1
EtOAc–petroleum ether) to afford the guanidines 2–4.
3.3.5. Methyl 2,3,4-tri-O-acetyl-6-deoxy-6-[N2-(6-methoxy-
benzothiazol-2-yl)-N3-(p-methylphenyl)]guanidino-
a-D-
glucopyranoside (3d)
3.3.1. Methyl 2,3,4-tri-O-acetyl-6-[N2-(benzothiazol-2-yl)-N3-
White solid; yield 423 mg (69%); mp 147–148 °C; IR (KBr):
benzyl]guanidino-6-deoxy-
White solid; yield 333 mg (57%); mp 83–84 °C; IR (KBr): 3374,
1752, 1601, 1587, 1465, 1225, 1029 cmꢁ1 1H NMR (400 MHz,
a-
D-glucopyranoside (2c)
3365, 1751, 1601, 1595, 1463, 1227, 1037 cmꢁ1 1H NMR
;
(400 MHz, CDCl3): d 2.00, 2.07, and 2.09 (3s, each 3H, 3MeCO),
2.37 (s, 3H, Me), 3.29 (s, 3H, OMe), 3.51–3.62 (m, 1H, H-6a),
3.63–3.76 (m, 1H, H-6b), 3.83 (s, 3H, OMe), 3.86–3.97 (m, 1H,
H-5), 4.78 (dd, J1,2 3.6 Hz, J2,3 9.6 Hz, 1H, H-2), 4.80–4.85 (m, 1H,
H-4), 4.88 (d, J1,2 3.6 Hz, 1H, H-1), 5.45 (t, J2,3 = J3,4 9.6 Hz, 1H,
H-3), 7.00–7.56 (m, 7H, ArH), 11.46–11.78 (br s, 1H, NH); 13C
NMR (100 MHz, CDCl3): d 172.5, 170.2, 170.1, 169.8, 155.5, 150.0,
136.9, 133.8, 132.2, 131.5, 129.9, 126.5, 125.2, 120.8, 118.3,
116.5, 96.7, 70.8, 69.9, 69.8, 68.0, 55.7, 55.4, 41.3, 29.8, 21.1,
20.9, 20.8, 20.7; ESIMS: m/z 615 (100%, [M+H]+), 637 (35%,
[M+Na]+). Anal. Calcd for C29H34N4O9S: C, 56.67; H, 5.58; N, 9.11.
Found: C, 56.59; H, 5.53; N, 9.05.
;
CDCl3): d 2.00, 2.05, and 2.09 (3s, each 3H, 3MeCO), 3.23 (s, 3H,
OMe), 3.47–3.58 (br s, 2H, CH2), 3.81–3.95 (m, 1H, H-6a), 4.47–
4.61 (m, 2H, H-6b, H-5), 4.61–4.70 (br s, 1H, H-4), 4.71–4.84 (m,
2H, H-2, H-1), 5.42 (t, J2,3 = J3,4 9.6 Hz, 1H, H-3), 6.86–7.63 (m,
9H, ArH), 10.00–10.86 (br s, 1H, NH); 13C NMR (100 MHz, CDCl3):
d 173.5, 170.7, 170.5, 170.2, 153.8, 145.4, 130.6, 128.9, 127.9,
127.4, 122.4, 121.3, 103.9, 96.7, 70.7, 69.8, 69.0, 55.4, 45.3, 41.5,
20.9, 20.8, 20.7; ESIMS: m/z 585 (100%, [M+H]+), 607 (30%,
[M+Na]+). Anal. Calcd for C28H32N4O8S: C, 57.52; H, 5.52; N, 9.58.
Found: C, 57.38; H, 5.49; N, 9.50.
3.3.2. Methyl 2,3,4-tri-O-acetyl-6-[N3-benzyl-N2-(6-methoxy-
3.3.6. Methyl 2,3,4-tri-O-acetyl-6-deoxy-6-[N2-(6-methyl-
benzothiazol-2-yl)]guanidino-6-deoxy-
a-
D-glucopyranoside
benzothiazol-2-yl)-N3-(p-methylphenyl)]guanidino-
a-D-
(3c)
glucopyranoside (4d)
White solid; yield 398 mg (65%); mp 87–88 °C; IR (KBr): 3375,
1752, 1601, 1588, 1465, 1227, 1029 cmꢁ1 1H NMR (400 MHz,
White solid; yield 376 mg (63%); mp 153–154 °C; IR (KBr):
;
3373, 1753, 1601, 1597, 1470, 1227, 1028 cmꢁ1 1H NMR
;
CDCl3): d 1.99, 2.07, and 2.08 (3s, each 3H, 3MeCO), 3.23 (s, 3H,
OMe), 3.47–3.57 (br s, 2H, CH2), 3.83 (s, 3H, OMe), 3.83–3.97 (br
s, 1H, H-6a), 4.49–4.61 (m, 2H, H-6b, H-5), 4.61–4.70 (br s, 1H,
H-4), 4.71–4.85 (m, 2H, H-2, H-1), 5.41 (t, J2,3 = J3,4 9.6 Hz, 1H, H-
3), 6.85–7.67 (m, 8H, ArH), 10.00–10.88 (br s, 1H, NH); 13C NMR
(400 MHz, CDCl3): d 2.00, 2.10, and 2.12 (3s, each 3H, 3MeCO),
2.39 (s, 3H, Me), 2.41 (s, 3H, Me), 3.29 (s, 3H, OMe), 3.49–3.61
(m, 1H, H-6a), 3.65–3.78 (m, 1H, H-6b), 3.87–3.95 (m, 1H, H-5),
4.78 (dd, 1H, J1,2 4.0 Hz, J2,3 9.6 Hz, H-2), 4.81–4.87 (m, 1H, H-4),
4.89 (d, 1H, J1,2 4.0 Hz, H-1), 5.45 (t, 1H, J2,3 = J3,4 9.6 Hz, H-3),

2380
Y.-H. Liu, L.-H. Cao / Carbohydrate Research 343 (2008) 2376–2383
7.02–7.54 (m, 7H, ArH), 11.47–11.74 (br, 1H, NH); 13C NMR
(100 MHz, CDCl3): d 173.1, 170.3, 170.1, 169.9, 153.5, 149.5,
137.0, 133.6, 132.0, 131.4, 130.6, 126.6, 126.2, 120.8, 118.9, 96.5,
70.9, 69.9, 69.6, 68.0, 55.2, 41.1, 29.7, 21.4, 21.0, 20.8, 20.7; ESIMS:
m/z 599 (100%, [M+H]+), 621 (30%, [M+Na]+). Anal. Calcd for
5H, 2CH2, H-6a), 3.44–3.54 (m, 1H, H-6b), 3.60–3.82 (m, 4H,
2CH2), 3.82–3.91 (m, 1H, H-5), 4.78 (dd, J1,2 3.6 Hz, J2,3 9.6 Hz,
1H, H-2), 4.94 (t, J3,4 = J4,5 9.8 Hz, 1H, H-4), 4.98 (d, J1,2 3.6 Hz, 1H,
H-1), 5.46 (t, J2,3 = J3,4 9.8 Hz, 1H, H-3), 7.12–7.68 (m, 4H, ArH),
9.60–9.80 (br s, 1H, NH); 13C NMR (100 MHz, CDCl3): d 172.3,
170.1, 170.0, 169.7, 160.1, 149.3, 132.3, 126.8, 126.5, 120.9,
119.8, 96.6, 70.9, 70.0, 69.4, 68.5, 66.7, 55.3, 48.5, 45.6, 21.4,
20.7, 20.6; ESIMS: m/z 565 (100%, [M+H]+), 587 (35%, [M+Na]+).
Anal. Calcd for C25H32N4O9S: C, 53.18; H, 5.71; N, 9.92. Found: C,
53.10; H, 5.68; N, 9.86.
C29H34N4O8S: C, 58.18; H, 5.72; N, 9.36. Found: C, 58.09; H, 5.68;
N, 9.25.
3.3.7. Methyl 2,3,4-tri-O-acetyl-6-[N2-(benzothiazol-2-yl)-N3-
(p-chlorophenyl)]guanidino-6-deoxy-
White solid; yield 259 mg (43%); mp 163–164 °C; IR (KBr):
3379, 1752, 1602, 1595, 1463, 1225, 1035 cmꢁ1 1H NMR
a-D-glucopyranoside (2f)
;
3.3.11. Methyl 2,3,4-tri-O-acetyl-6-deoxy-6-[N2-(6-methoxy-
(400 MHz, CDCl3): d 2.00, 2.08, and 2.11 (3s, each 3H, 3MeCO),
3.33 (s, 3H, OMe), 3.54–3.63 (m, 1H, H-6a), 3.63–3.78 (m, 1H,
H-6b), 3.86–4.03 (m, 1H, H-5), 4.78 (dd, J1,2 3.6 Hz, J2,3 9.6 Hz, 1H,
H-2), 4.84–5.00 (m, 2H, H-4, H-1), 5.48 (t, J2,3 = J3,4 9.6 Hz, 1H,
H-3), 7.12–7.67 (m, 8H, ArH), 11.49–11.96 (br s, 1H, NH); 13C
NMR (100 MHz, CDCl3): d 173.6, 170.2, 170.1, 169.9, 153.1, 151.3,
135.4, 132.8, 131.4, 130.0, 127.2, 125.4, 122.5, 120.9, 119.4, 96.6,
71.1, 70.8, 69.8, 69.4, 68.0, 55.4, 41.2, 29.7, 22.7, 20.8, 20.7; ESIMS:
m/z 605 (100%, [M+H]+), 627 (32%, [M+Na]+). Anal. Calcd for
benzothiazol-2-yl)-N3-(oxydi-1,2-ethandiyl)]guanidino-
a-D-
glucopyranoside (3g)
Transparent colorless crystals were obtained by slow evapora-
tion over several days from ethanol solution. Yield 430 mg (72%);
mp 152–153 °C; IR (KBr): 3212, 1743, 1598, 1576, 1475, 1446,
1225, 1041, 747 cmꢁ1 1H NMR (400 MHz, CDCl3): d 2.00, 2.02,
;
and 2.06 (3s, each 3H, 3MeCO), 3.18 (s, 3H, OMe), 3.34–3.45 (m,
5H, 2CH2, H-6a), 3.45–3.55 (m, 1H, H-6b), 3.60–3.83 (m, 4H,
2CH2), 3.84 (s, 3H, OMe), 3.83–3.89 (m, 1H, H-5), 4.78 (dd, J1,2
3.6 Hz, J2,3 9.6 Hz, 1H, H-2), 4.95 (t, J3,4 = J4,5 9.8 Hz, 1H, H-4), 4.97
(d, J1,2 3.6 Hz, 1H, H-1), 5.46 (t, J2,3 = J3,4 9.8 Hz, 1H, H-3), 7.10–
7.64 (m, 3H, ArH), 9.62–9.84 (br s, 1H, NH);13C NMR (100 MHz,
CDCl3): d 172.3, 170.2, 170.0, 169.7, 160.1, 155.4, 149.3, 132.5,
120.9, 119.5, 108.1, 96.6, 70.9, 70.0, 69.4, 68.8, 66.6, 55.7, 55.4,
48.6, 45.5, 21.4, 20.8, 20.7; ESIMS: m/z 595 (100%, [M+H]+), 617
(30%, [M+Na]+). Anal. Calcd for C26H34N4O10S: C, 52.52; H, 5.76;
N, 9.42. Found: C, 52.44; H, 5.73; N, 9.34.
C27H29ClN4O8S: C, 53.60; H, 4.83; N, 9.26. Found: C, 53.48; H,
4.76; N, 9.19.
3.3.8. Methyl 2,3,4-tri-O-acetyl-6-[N3-(p-chlorophenyl)-N2-
(6-methoxybenzothiazol-2-yl)]guanidino-6-deoxy-
a-D-
glucopyranoside (3f)
White solid; yield 310 mg (49%); mp 147–148 °C; IR (KBr):
3370, 1753, 1601, 1589, 1475, 1225, 1034 cmꢁ1 1H NMR
;
(400 MHz, CDCl3): d 2.01, 2.06, and 2.11 (3s, each 3H, 3MeCO),
3.32 (s, 3H, OMe), 3.52–3.64 (br s, 1H, H-6a), 3.64–3.82 (br s, 1H,
H-6b), 3.86 (s, 3H, OMe), 3.84–4.03 (m, 1H, H-5), 4.79 (dd, J1,2
3.6 Hz, J2,3 9.6 Hz, 1H, H-2), 4.83–4.96 (m, 1H, H-4), 4.89 (d, J1,2
3.6 Hz, 1H, H-1), 5.46 (t, J2,3 = J3,4 9.6 Hz, 1H, H-3), 7.10–7.66 (m,
7H, ArH), 11.47–11.98 (br s, 1H, NH); 13C NMR (100 MHz, CDCl3):
d 173.2, 170.7, 170.3, 170.2, 155.4, 151.4, 149.6, 135.6, 132,5,
130.2, 127.4, 127.3, 122.4, 119.3, 117.6, 103.9, 96.5, 70.9, 70.2,
69.9, 68.0, 55.7, 55.4, 41.3, 29.3, 21.0, 20.9, 20.7; ESIMS: m/z 634
(100%, [M+H]+), 656 (23%, [M+Na]+). Anal. Calcd for C28H31ClN4O9S:
C, 52.95; H, 4.92; N, 8.82. Found: C, 52.87; H, 4.89; N, 8.76.
3.3.12. Methyl 2,3,4-tri-O-acetyl-6-deoxy-6-[N2-(6-methyl-
benzothiazol-2-yl)-N3-(oxydi-1,2-ethandiyl)]guanidino-
a-D-
glucopyranoside (4g)
Transparent colorless crystals were obtained by slow evapora-
tion over several days from ethanol solution. Yield 410 mg (71%);
mp 186–187 °C; IR (KBr): 3210, 1742, 1600, 1581, 1477, 1441,
1224, 1041, 749 cmꢁ1 1H NMR (400 MHz, CDCl3): d 2.00, 2.03,
;
and 2.08 (3s, each 3H, 3MeCO), 2.40 (s, 1H, Me), 3.18 (s, 3H,
OMe), 3.33–3.45 (m, 5H, 2CH2, H-6a), 3.45–3.56 (m, 1H, H-6b),
3.60–3.84 (m, 4H, 2CH2), 3.87 (m, 1H, H-5), 4.78 (dd, J1,2 3.6 Hz,
J2,3 9.6 Hz, 1H, H-2), 4.96 (t, J3,4 = J4,5 9.8 Hz, 1H, H-4), 4.97 (d, J1,2
3.6 Hz, 1H, H-1), 5.46 (t, J2,3 = J3,4 9.8 Hz, 1H, H-3), 7.08–7.65 (m,
3H, ArH), 9.60–9.82 (br s, 1H, NH); 13C NMR (100 MHz, CDCl3): d
172.2, 170.1, 170.0, 169.6, 160.1, 149.3, 132.5, 132.3, 126.8,
120.9, 119.5, 96.6, 70.9, 70.1, 69.5, 68.5, 66.6, 55.3, 48.5, 45.6,
21.4, 20.7, 20.6; ESIMS: m/z 579 (100%, [M+H]+), 610 (28%,
[M+Na]+). Anal. Calcd for C26H34N4O9S: C, 53.97; H, 5.92; N, 9.68.
Found: C, 53.84; H, 5.89; N, 9.59.
3.3.9. Methyl 2,3,4-tri-O-acetyl-6-[N3-(p-chlorophenyl)-N2-
(6-methylbenzothiazol-2-yl)]guanidino-6-deoxy-
a-D-
glucopyranoside (4f)
White solid; yield 278 mg (45%); mp 155–156 °C; IR (KBr):
3371, 1751, 1603, 1587, 1465, 1226, 1029 cmꢁ1 1H NMR
;
(400 MHz, CDCl3): d 2.01, 2.07, and 2.10 (3s, each 3H, 3MeCO),
2.42 (s, 3H, Me), 3.32 (s, 3H, OMe), 3.49–3.62 (br s, 1H, H-6a),
3.62-3.82 (br s, 1H, H-6b), 3.84–4.03 (m, 1H, H-5), 4.79 (dd, J1,2
3.6 Hz, J2,3 9.6 Hz, 1H, H-2), 4.81–4.96 (m, 1H, H-4), 4.89 (d, J1,2
3.6 Hz, 1H, H-1), 5.45 (t, J2,3 = J3,4 9.6 Hz, 1H, H-3), 7.09–7.68 (m,
7H, ArH), 11.50–11.97 (br s, 1H, NH); 13C NMR (100 MHz, CDCl3):
d 173.3, 170.6, 170.5, 170.0, 153.8, 152.4, 150.0, 145.3, 133.6,
130.5, 128.4, 128.3, 126.4, 119.3, 117.6, 103.9, 96.5, 70.9, 69.9,
69.5, 68.0, 55.4, 41.3, 29.7, 22.7, 20.9, 20.8; ESIMS: m/z 619
(100%, [M+H]+), 641 (26%, [M+Na]+). Anal. Calcd for C28H31ClN4O8S:
C, 54.32; H, 5.05; N, 9.05. Found: C, 54.20; H, 5.01; N, 8.95.
3.3.13. Methyl 2,3,4-tri-O-acetyl-6-[N2-(benzothiazol-2-yl-N3-
(ethoxycarbonyl))]guanidino-6-deoxy-
(2h)
a-D-glucopyranoside
White solid; yield 231 mg (41%); mp 145–146 °C; IR (KBr):
3469, 3240, 1754, 1611, 1496, 1440, 1218, 1066, 1040 cmꢁ1 1H
;
NMR (400 MHz, CDCl3): d 1.34 (t, J 7.2 Hz, 3H, Me), 2.02, 2.05,
and 2.09 (3s, each 3H, 3MeCO), 3.36–3.46 (m, 4H, H-6b, OMe),
3.58–3.64 (m, 1H, H-6a), 3.93–4.00 (m, 1H, H-5), 4.40 (q, J 7.2 Hz,
2H, CH2), 4.89 (dd, J1,2 3.6 Hz, J2,3 9.6 Hz, 1H, H-2), 4.97 (t,
J3,4 = J4,5 9.6 Hz, 1H, H-4), 5.02 (d, J1,2 3.6 Hz, 1H, H-1), 5.51 (t,
J2,3 = J3,4 9.6 Hz, 1H, H-3), 7.14–7.68 (m, 4H, ArH), 10.02–10.06
(br s, 1H, NH); 13C NMR (100 MHz, CDCl3): d 172.6, 170.2, 170.1,
169.9, 157.3, 151,4, 150.0, 132.0, 125.5, 122.8, 121.0, 119.8, 96.5,
70.9, 70.5, 69.9, 67.8, 63.7, 55.4, 41.8, 20.8, 20.7, 14.5; ESIMS: m/z
567 (100%, [M+H]+), 589 (16%, [M+Na]+). Anal. Calcd for
3.3.10. Methyl 2,3,4-tri-O-acetyl-6-[N2-(benzothiazol-2-yl)-N3-
(oxydi-1,2-ethandiyl)]guanidino-6-deoxy-a-D-glucopyranoside
(2g)
Transparent colorless crystals were obtained by slow evapora-
tion over several days from ethanol solution. Yield 377 mg (67%);
mp 178–179 °C; IR (KBr): 3209, 1745, 1598, 1579, 1476, 1443,
1222, 1043, 748 cmꢁ1
;
1H NMR (400 MHz, CDCl3): d 1.98, 2.03,
C24H30N4O10S: C, 50.88; H, 5.34; N, 8.95. Found: C, 50.76; H,
and 2.06 (3s, each 3H, 3MeCO), 3.18 (s, 3H, OMe), 3.35–3.44 (m,
5.29; N, 9.02.

Y.-H. Liu, L.-H. Cao / Carbohydrate Research 343 (2008) 2376–2383
2381
3.3.14. Methyl 2,3,4-tri-O-acetyl-6-deoxy-6-[N3-(ethoxy-
carbonyl)-N2-(6-methoxybenzothiazol-2-yl)]guanidino-
3.34 (br s, 2H, H-2, H-6a), 3.46 (br s, 4H, H-5, OMe), 3.53–3.65
(m, 2H, H-6b, H-3), 3.75 (s, 3H, OMe), 4.42–4.58 (m, 2H, CH2Ph),
4.65 (br s, 1H, H-1), 6.79–7.38 (m, 8H, ArH), 8.24 (br s, 1H, NH);
13C NMR (100 MHz, DMSO-d6): d 173.1, 154.8, 153.7, 145.9,
135.6, 129.0, 127.8, 127.2, 119.6, 113.4, 99.9, 73.6, 72.6, 71.0,
70.5, 55.7, 55.2, 45.5, 43.8; ESIMS: m/z 489 (100%, [M+H]+), 501
(30%, [M+Na]+). Anal. Calcd for C23H28N4O6S: C, 56.54; H, 5.78; N,
11.47. Found: C, 56.40; H, 5.74; N, 11.39.
a-
D
-glucopyranoside (3h)
White solid; yield 268 mg (45%); mp 146–147 °C; IR (KBr):
3468, 3245, 1753, 1611, 1499, 1441, 1217, 1067, 1042 cmꢁ1 1H
;
NMR (400 MHz, CDCl3): d 1.34 (t, J 7.2 Hz, 3H, Me), 2.01, 2.06,
and 2.09 (3s, each 3H, 3MeCO), 3.34–3.45 (m, 4H, H-6b, OMe),
3.59–3.65 (m, 1H, H-6a), 3.85 (s, 3H, OMe), 3.91–3.96 (m, 1H,
H-5), 4.41 (q, J 7.2 Hz, 2H, CH2), 4.89 (dd, J1,2 3.6 Hz, J2,3 9.6 Hz,
1H, H-2), 4.96 (t, J3,4 = J4,5 9.6 Hz, 1H, H-4), 5.02 (d, J1,2 3.6 Hz, 1H,
H-1), 5.52 (t, J2,3 = J3,4 9.6 Hz, 1H, H-3), 7.12–7.67 (m, 4H, ArH),
10.00–10.06 (br s, 1H, NH); 13C NMR (100 MHz, CDCl3): d 172.7,
170.3, 170.1, 170.0, 157.3, 154.6, 151,4, 150.0, 132.0, 125.5,
121.0, 115.8, 96.5, 70.9, 70.5, 69.8, 67.9, 63.7, 55.7, 55.3, 41.6,
20.7, 14.5; ESIMS: m/z 597 (100%, [M+H]+), 619 (18%, [M+Na]+).
Anal. Calcd for C25H32N4O11S: C, 50.33; H, 5.41; N, 9.39. Found: C,
50.25; H,5.38; N, 9.27.
3.4.3. Methyl 6-[N3-benzyl-N2-(6-methylbenzothiazol-2-
yl)]guanidino-6-deoxy-
White solid; mp 232–234 °C; IR (KBr): 3471, 1602, 1556, 1494,
1037 cmꢁ1 1H NMR (400 MHz, DMSO-d6): d 2.34 (s, 3H, Me), 2.96
a-D-glucopyranoside (7c)
;
(br s, 1H, H-4), 3.14 (br s, 1H, H-2), 3.43 (br s, 4H, H-6a, OMe), 3.54
(br s, 1H, H-5), 3.56–3.64 (m, 2H, H-3, H-6b), 4.41–4.58 (m, 2H,
CH2Ph), 4.64 (br s, 1H, H-1), 6.70–7.40 (m, 9H, ArH), 10.80 (br s,
1H, NH); 13C NMR (100 MHz, DMSO-d6): d 173.2, 154.6, 149.4,
135.6, 131.6, 128.4, 126.4, 126.0, 121.6, 113.9, 100.0, 73.5, 72.4,
70.6, 55.1, 45.3, 43.7, 21.2; ESIMS: m/z 473 (100%, [M+H]+), 595
(15%, [M+Na]+). Anal. Calcd for C23H28N4O5S: C, 58.46; H, 5.97; N,
11.86. Found: C, 58.35; H, 5.92; N, 11.76.
3.3.15. Methyl 2,3,4-tri-O-acetyl-6-deoxy-6-[N3-(ethoxy-
carbonyl)-N2-(6-methylbenzothiazol-2-yl)]guanidino-
a-D-
glucopyranoside (4h)
White solid; yield 255 mg (44%); mp 204–205 °C; IR (KBr):
3240, 3152, 1756, 1612, 1497, 1439, 1218, 1062, 1038 cmꢁ1 1H
;
3.4.4. Methyl 6-[N2-(benzothiazol-2-yl)-N2-(p-methylphenyl)-
NMR (400 MHz, CDCl3): d 1.35 (t, J 7.2 Hz, 3H, Me), 2.02, 2.06,
and 2.08 (3s, each 3H, 3MeCO), 2.43 (s, 3H, Me), 3.35–3.47 (m,
4H, H-6b, OMe), 3.60–3.64 (m, 1H, H-6a), 3.92–3.97 (m, 1H, H-5),
4.43 (q, J 7.2 Hz, 2H, CH2), 4.90 (dd, J1,2 3.6 Hz, J2,3 9.6 Hz, 1H,
H-2), 4.97 (t, J3,4 = J4,5 9.6 Hz, 1H, H-4), 5.01 (d, J1,2 3.6 Hz, 1H,
H-1), 5.53 (t, J2,3 = J3,4 9.6 Hz, 1H, H-3), 7.13–7.68 (m, 4H, ArH),
10.02–10.05 (br s, 1H, NH); 13C NMR (100 MHz, CDCl3): d 172.3,
170.2, 170.1, 170.0, 157.4, 151,3, 150.2, 132.5, 132.3, 125.7,
121.3, 117.3, 96.6, 70.9, 70.4, 69.8, 68.0, 63.8, 55.3, 41.6, 22.6,
20.7, 20.6, 14.4; ESIMS: m/z 581 (100%, [M+H]+), 603 (30%,
[M+Na]+). Anal. Calcd for C25H32N4O10S: C, 51.72; H, 5.56; N,
9.65. Found: C, 51.67; H, 5.52; N, 9.58.
]guanidino-6-deoxy-a-D-glucopyranoside (5d)
White solid; mp 163–164 °C; IR (KBr): 3383, 1614, 1566, 1463,
1347, 1043 cmꢁ1; 1H NMR (400 MHz, DMSO-d6): d 2.29 (s, 3H, Me),
3.11 (br s, 1H, H-4), 3.34 (br s, 1H, H-2), 3.36 (s, 3H, OMe), 3.40–
3.54 (m, 2H, H-5, H-6a), 3.59 (br s, 1H, H-3), 3.71–3.89 (m, 1H,
H-6b), 4.67 (br s, 1H, H-1), 4.88 (d, JOH,H 6.0 Hz, OH,), 4.94 (d, JOH,H
4.4 Hz, OH), 5.27 (d, JOH,H 5.2 Hz, 1H, OH), 7.04–7.60 (m, 8H, ArH),
8.58 (br s, 1H, NH), 10.01 (br s, 1H, NH); 13C NMR (100 MHz,
DMSO-d6): d 173.1, 154.5, 149.6, 131.8, 129.2, 126.8, 122.9,
119.0, 114.5, 100.7, 73.6, 72.6, 70.5, 55.2, 43.7, 21.1; ESIMS: m/z
459 (100%, [M+H]+), 581 (32%, [M+Na]+). Anal. Calcd for
C22H26N4O5S: C, 57.63; H, 5.72; N, 12.22. Found: C, 57.56; H,
5.69; N, 12.15.
3.4. General procedure for the preparation of methyl 6-deoxy-
6-guanidino-
a-
D-glucopyranosides 5–7
3.4.5. Methyl 6-deoxy-6-[N2-(6-methoxybenzothiazol-2-yl)-N3-
(p-methylphenyl)]guanidino-a-D-glucopyranoside (6d)
To a solution of the corresponding guanidines 2–4 (0.05 mmol)
in MeOH (5 mL) was added NaOMe (0.1 M, 0.2 mL), and the reac-
tion mixture was stirred at room temperature for 0.5–5 h when
TLC (9:1 CH3Cl–MeOH) revealed complete consumption of the
starting material. The reaction mixture either crystallized on
standing at 4 °C or some water was added to induce crystallization.
The solution was filtered and washed with water to give the crude
product, which was recrystallized from 90% alcohol to give the
deacetylated guanidines 5–7.
White solid; mp 149–150 °C; IR (KBr): 3365, 1611, 1576, 1484,
1364, 1047 cmꢁ1; 1H NMR (DMSO-d6, 400 MHz): d 2.28 (s, 3H, Me),
3.14 (br s, 1H, H-4), 3.33 (br s, 1H, H-2), 3.35 (s, 3H, OMe), 3.38–
3.55 (m, 2H, H-5, H-6a), 3.60 (br s, 1H, H-3), 3.70–3.89 (m, 4H,
H-6b, OMe), 4.67 (br s, 1H, H-1), 4.88 (d, JOH,H 6.0 Hz, OH), 4.93
(d, JOH,H 4.4 Hz, OH), 5.26 (d, JOH,H 4.4 Hz, 1H, OH), 7.05–7.62 (m,
7H, ArH), 8.39 (br s, 1H, NH), 10.04 (br s, 1H, NH); 13C NMR
(100 MHz, DMSO-d6): d 173.0, 155.8, 153.2, 145.8, 133.4, 131.6,
129.6, 127.4, 113.1, 105.6, 100.4, 73.6, 72.5, 70.6, 55.7, 55.3, 43.9,
21.1; ESIMS: m/z 489 (100%, [M+H]+), 581 (26%, [M+Na]+). Anal.
Calcd for C23H28N4O6S: C, 56.54; H, 5.78; N, 11.47. Found: C,
56.42; H, 5.72; N, 11.36.
3.4.1. Methyl 6-(N2-(benzothiazol-2-yl)-N3-benzyl)]guanidino-
6-deoxy-a-D-glucopyranoside (5c)
White solid; mp 189–190 °C; IR (KBr): 3489, 3390, 3348, 1603,
1578, 1490, 1033 cmꢁ1; 1H NMR (CDCl3, 400 MHz): d 3.12 (br s, 2H,
H-4, H-2), 3.34 (br s, 4H, H-6a, OMe), 3.54 (br s, 1H, H-5), 3.73 (br s,
1H, H-3), 4.32 (br s, 1H, H-6b), 4.55 (s, 2H, CH2Ph), 4.61 (br s, 1H,
H-1), 7.11–7.72 (m, 9H, ArH), 10.82 (br s, 1H, NH); 13C NMR
(100 MHz, CDCl3): d 173.5, 155.8, 145.6, 135.6, 127.4, 122.4,
117.6, 113.9, 99.7, 73.5, 72.6, 70.4, 55.4, 45.6, 43.8; ESIMS: m/z
459 (100%, [M+H]+), 481 (35%, [M+Na]+). Anal. Calcd for
C22H26N4O5S: C, 57.63; H, 5.72; N, 12.22. Found: C, 57.50; H,
5.65; N, 12.14.
3.4.6. Methyl 6-deoxy-6-[N2-(6-methylbenzothiazol-2-yl)-N3-
(p-methylphenyl)]guanidino-a-D-glucopyranoside (7d)
White solid; mp 147–148 °C; IR (KBr): 3383, 1614, 1566, 1459,
1347, 1043 cmꢁ1; 1H NMR (DMSO-d6, 400 MHz): d 2.29 (s, 3H, Me),
2.34 (s, 3H, Me), 3.12 (br s, 1H, H-4), 3.20–3.39 (m, 4H, H-2, OMe),
3.40–3.54 (m, 2H, H-5, H-6a), 3.58 (br s, 1H, H-3), 3.69–3.86 (m,
1H, H-6b), 4.67 (br s, 1H, H-1), 4.88 (d, JOH,H 6.0 Hz, OH,), 4.94 (d,
JOH,H 4.4 Hz, OH), 5.27 (d, JOH,H 5.2 Hz, 1H, OH), 7.02–7.57 (m, 7H,
ArH), 8.59 (br s, 1H, NH), 9.95 (br s, 1H, NH); 13C NMR (100 MHz,
DMSO-d6): d 172.9, 154.3, 149.9, 132.0, 131.3, 129.7, 127.3,
123.9, 121.5, 119.0, 100.7, 73.6, 72.5, 70.6, 55.2, 43.8, 21.5, 21.1;
ESIMS: m/z 473 (100%, [M+H]+), 595 (32%, [M+Na]+). Anal. Calcd
for C23H28N4O5S: C, 58.46; H, 5.97; N, 11.86. Found: C, 58.56; H,
5. 94; N, 11.80.
3.4.2. Methyl 6-[N3-benzyl-N2-(6-methoxybenzothiazol-2-yl)]-
guanidino-6-deoxy-
White solid; mp 214–215 °C; IR (KBr): 3433, 1590, 1559, 1470,
1028 cmꢁ1 1H NMR (400 MHz, DMSO-d6): d 3.13 (br s, 1H, H-4),
a-D-glucopyranoside (6c)
;

2382
Y.-H. Liu, L.-H. Cao / Carbohydrate Research 343 (2008) 2376–2383
3.4.7. Methyl 6-[N2-(benzothiazol-2-yl)-N3-(p-chloro-
phenyl)]guanidino-6-deoxy- -glucopyranoside (5f)
White solid; mp 232–233 °C; IR (KBr): 3314, 1603, 1569, 1487,
1365, 1050, 1031 cmꢁ1; 1H NMR (400 MHz, DMSO-d6): d 3.08–3.19
(m, 1H, H-4), 3.21–3.38 (br s, 4H, H-2, OMe), 3.38–3.50 (m, 1H,
H-2, H-6a), 3.57–3.72 (br s, 2H, H-3, H-6b), 3.72–3.85 (m, 8H, H-
5, CH2OCH2, OMe), 4.67 (br s, 1H, H-1), 7.04–7.65 (m, 3H, ArH),
8.40 (br s, 1H, NH); 13C NMR (100 MHz, CDCl3): d 160.3, 157.1,
155.7, 145.5, 133.0, 120.2, 113.7, 104.8, 99.6, 74.1, 72.0, 70.5,
66.5, 55.7, 55.2, 47.8, 41,8; ESIMS: m/z 469 (100%, [M+H]+), 491
(25%, [M+Na]+). Anal. Calcd for C20H28N4O7S: C, 51.27; H, 6.02; N,
11.96. Found: C, 51.22; H, 5. 99; N, 11.89.
a-D
H-5), 3.53 (dd, J5,6 2.0 Hz, J6a,6b 12.3 Hz, 1H, H-6a), 3.61 (t, J2,3
J3,4 9.6 Hz, 1H, H-3), 3.80 (d, J6a,6b 12.3 Hz, 1H, H-6b), 4.67 (d, J1,2
=
1H, H-1), 4.88 (d, JOH,H 6.0 Hz, OH,), 4.94 (d, JOH,H 4.4 Hz,
3.6 Hz,
OH), 5.27 (d, JOH,H 5.2 Hz, 1H, OH), 6.81–7.79 (m, 8H, ArH), 8.59
(br s, 1H, NH), 10.02 (br s, 1H, NH); 13C NMR (100 MHz, DMSO-
d6): d 171.7, 154.5, 149.6, 131.8, 129.2, 126.8, 122.9, 121.5, 119.0,
114.5, 100.7, 73.6, 72.6, 70.5, 55.2, 43.7; ESIMS: m/z 479 (100%,
[M+H]+), 601 (18%, [M+Na]+). Anal. Calcd for C21H23ClN4O5S: C,
52.66; H, 4.84; N, 11.70. Found: C, 52.48; H, 4.80; N, 11.65.
3.4.12. Methyl 6-deoxy-6-[N2-(6-methylbenzothiazol-2-yl)-
N3-(oxydi-1,2-ethandiyl)]guanidino-
a-D-glucopyranoside (7g)
White solid; mp 186–187 °C; IR (KBr): 3443, 3356, 1601, 1595,
1576, 1463, 1369, 1045 cmꢁ1; 1H NMR (400 MHz, CDCl3): d 2.35 (s,
3H, Me), 3.23 (br s, 4H, H-4, OMe), 3.39–3.58 (m, 6H, CH2NCH2, H-
2, H-6a), 3.58–3.69 (br s, 2H, H-3, H-6b), 3.69–3.85 (m, 5H, H-5,
CH2OCH2), 4.67 (br s, 1H, H-1), 7.03–7.65 (m, 3H, ArH), 8.36 (br
s, 1H, NH); 13C NMR (100 MHz, CDCl3): d 160.2, 154.9, 143.8,
133.8, 132.5, 122.5, 119.6, 109.7, 99.9, 74.2, 72.1, 70.7, 66.6, 55.4,
47.8, 41.7, 21.6; ESIMS: m/z 453 (, 100%, [M+H]+), 475 (32%,
[M+Na]+). Anal. Calcd for C20H28N4O6S: C, 53.08; H, 6.24; N,
12.38. Found: C, 52.98; H, 6.21; N, 12.29.
3.4.8. Methyl 6-[N3-(p-chlorophenyl)-N2-(6-methoxy-
benzothiazol-2-yl)]guanidino-6-deoxy-a-D-glucopyranoside
(6f)
White solid; mp 206–207 °C; IR (KBr): 3435, 3354, 1608, 1562,
1470, 1361, 1049, 1028 cmꢁ1 1H NMR (400 MHz, DMSO-d6): d
;
3.08–3.19 (m, 1H, H-4), 3.21–3.38 (br s, 4H, H-2, OMe), 3.39–3.49
(m, 1H, H-5), 3.53 (dd, J5,6 2.0 Hz, J6a,6b 12.3 Hz, 1H, H-6a), 3.61
(t, J2,3 = J3,4 9.6 Hz, 1H, H-3), 3.65–3.86 (m, 4H, H-6b, OMe), 4.70
(d, J1,2 3.6 Hz, 1H, H-1), 4.91 (d, JOH,H 6.0 Hz, 1H, OH,), 4.96 (d, JOH,H
4.4 Hz, 1H, OH), 5.31 (d, JOH,H 5.2 Hz, 1H, OH), 6.79–7.70 (m, 7H,
ArH), 8.77 (br s, 1H, NH), 9.90 (br s, 1H, NH); 13C NMR (100 MHz,
DMSO-d6): d 171.7, 156.0, 153.7, 146.0, 132.4, 129.0, 124.6 122.9,
120.0, 114.3, 105.7, 100.7, 73.6, 72.5, 70.6, 56.2, 55.3, 43.9; ESIMS:
m/z 509 (100%, [M+H]+), 531 (32%, [M+Na]+). Anal. Calcd for
3.4.13. Methyl 6-[N2-(benzothiazol-2-yl)-N3-(ethoxy-
carbonyl)]guanidino-6-deoxy-
White solid; mp 145–146 °C; IR (KBr): 3463, 3354, 1751, 1613,
1469, 1218, 1066 cmꢁ1 1H NMR (400 MHz, CDCl3): d 1.33 (t, J
a-D-glucopyranoside (5h)
;
7.0 Hz, 3H, Me), 3.05 (br s, 1H, H-4), 3.31–3.52 (m, 4H, H-2,
OMe), 3.57 (d, J5,6a 5.6 Hz, 1H, H-6a), 3.65–3.83 (m, 2H, H-5,
H-6b), 4.37 (q, J 7.0 Hz, 2H, CH2), 4.81 (d, J1,2 3.2 Hz, 1H, H-1),
6.88–7.45 (m, 4H, ArH), 9.79 (br s, 1H, NH); 13C NMR (100 MHz,
CDCl3): d 170.9, 157.3, 143.5, 125.9, 122.6, 121.0, 109.6, 99.3,
74.6, 72.4, 71.5, 70.1, 63.4, 55.3, 42.2, 14.3; ESIMS: m/z 441
(100%, [M+H]+), 463 (16%, [M+Na]+). Anal. Calcd for C18H24N4O7S:
C, 49.08; H, 5.49; N, 12.72. Found: C, 49.01; H, 5.47; N, 12.68.
C22H25ClN4O6S: C, 51.92; H, 4.95; N, 11.01. Found: C, 51.84; H,
4.93; N, 10.96.
3.4.9. Methyl 6-[N3-(p-chlorophenyl)-N2-(6-methyl-
benzothiazol-2-yl)]guanidino-6-deoxy-
(7f)
a-D-glucopyranoside
3.4.14. Methyl 6-deoxy-6-[N3-(ethoxycarbonyl)-N2-
White solid; mp 209–210 °C; IR (KBr): 3442, 3338, 1617, 1573,
1488, 1460, 1354, 1048, 1026 cmꢁ1; 1H NMR (400 MHz, DMSO-d6):
d 2.35 (s, 3H, Me), 3.15 (t, J3,4 = J4,5 9.6 Hz, 1H, H-4), 3.30 (dd, J1,2
3.6, J2,3 9.6 Hz, 1H, H-2), 3.35 (s, 3H, OMe), 3.45 (t, J2,3 = J3,4
9.60 Hz, 1H, H-3), 3.51 (br s, 4H, H-6a, OMe), 3.54–3.68 (m, 1H,
H-5), 3.78 (dd, J5,6 2.0 Hz, J6a,6b 12.8 Hz, 1H, H-6a), 4.71 (d, J1,2
3.6 Hz, 1H, H-1), 4.98 (d, JOH,H 6.0 Hz, OH), 5.02 (d, JOH,H 4.4 Hz,
OH), 5.37 (d, JOH,H 5.2 Hz, 1H, OH), 7.10–7.60 (m, 7H, ArH), 8.30
(s, 1H, NH); 13C NMR (100 MHz, DMSO-d6): d 171.6, 154.3, 149.8,
133.8, 131.1, 129.2, 126.8, 121.5, 119.0, 100.7, 73.5, 72.5, 70.7,
55.2, 43.9, 21.6; ESIMS: m/z 493 (100%, [M+H]+), 515 (24%,
[M+Na]+). Anal. Calcd for C22H25ClN4O5S: C, 53.60; H, 5.11; N,
11.37. Found: C, 53.51; H, 5.09; N, 11.28.
(6-methoxybenzothiazol-2-yl)]guanidino-
(6h)
a-D-glucopyranoside
White solid; mp 146–147 °C; IR (KBr): 3458, 3383, 1754, 1613,
1463, 1210, 1057 cmꢁ1 1H NMR (400 MHz, CDCl3): d 1.34 (t, J
;
7.0 Hz, 3H, Me), 3.03 (br s, 1H, H-4), 3.34–3.50 (m, 4H, H-2, OMe),
3.56 (d, J5,6a 5.6 Hz, 1H, H-6a), 3.64–3.85 (m, 5H, H-5, H-6b, OMe),
4.37 (q, J 7.0 Hz, 2H, CH2), 4.81 (d, J1,2 3.2 Hz, 1H, H-1), 6.85–7.44
(m, 3H, ArH), 9.78 (br s, 1H, NH); 13C NMR (100 MHz, CDCl3): d
170.8, 157.2, 155.9, 145.5, 133.0, 120.1, 113.7, 104.6, 99.1, 74.6,
72.3, 71.6, 70.0, 63.5, 55.7, 55.4, 42.1, 14.5; ESIMS: m/z 471 (100%,
[M+H]+), 493 (15%, [M+Na]+). Anal. Calcd for C19H26N4O8S: C,
48.50; H, 5.57; N, 11.91. Found: C, 48.38; H, 5.54; N, 11.84.
3.4.15. Methyl 6-deoxy-6-[N3-(ethoxycarbonyl)-N2-(6-
3.4.10. Methyl 6-[N2-(benzothiazol-2-yl)-N3-(oxydi-1,2-
ethandiyl)]guanidino-6-deoxy-a-D-glucopyranoside (5g)
methylbenzothiazol-2-yl)]guanidino-
White solid; mp 204–205 °C; IR (KBr) 3452, 3368, 1753, 1612,
1469, 1223, 1066 cmꢁ1 1H NMR (CDCl3, 400 MHz): d 1.34 (t, J
a-D-glucopyranoside (7h)
White solid; mp 178–179 °C; IR (KBr): 3465, 3346, 2898, 1588,
1576, 1476, 1370, 1043 cmꢁ1; 1H NMR (400 MHz, CDCl3): d 3.21 (br
s, 4H, H-4, OMe), 3.38–3.52 (m, 6H, CH2NCH2, H-2, H-6a), 3.58–
3.70 (br s, 2H, H-3, H-6b), 3.70–3.84 (m, 5H, H-5, CH2OCH2), 4.66
(br s, 1H, H-1), 7.05–7.64 (m, 4H, ArH), 8.38 (br s, 1H, NH); 13C
NMR (100 MHz, CDCl3): d 160.1, 143.9, 125.8, 122.8, 121.1, 109.3,
99.5, 74.0, 72.1, 70.5, 66.2, 55.2, 47.9, 41.7; ESIMS: m/z 439
(100%, [M+H]+), 461 (30%, [M+Na]+). Anal. Calcd for C19H26N4O6S:
C, 52.04; H, 5.98; N, 12.78. Found: C, 51.95; H, 5.96; N, 12.74.
;
7.0 Hz, 3H, Me), 2.34 (s, 3H, Me), 3.03 (br s, 1H, H-4), 3.32–3.54
(m, 4H, H-2, OMe), 3.57 (d, J5,6a 5.6 Hz, 1H, H-6a), 3.64–3.76 (m,
1H, H-5), 3.89 (br s, 1H, H-6b), 4.37 (q, J 7.0 Hz, 2H, CH2), 4.82 (d,
J1,2 3.2 Hz, 1H, H-1), 6.84–7.45 (m, 3H, ArH), 9.76 (br s, 1H, NH);
13C NMR (100 MHz, CDCl3): d 170.7, 157.3, 145.7, 133.2, 132.5,
122.1, 119.7, 109.6, 99.2, 74.5, 72.3, 71.5, 70.0, 63.5, 55.4, 42.1,
21.5, 14.5; ESIMS: m/z 455 (100%, [M+H]+), 477 (22%, [M+Na]+).
Anal. Calcd for C19H26N4O7S: C, 50.21; H, 5.77; N, 12.33. Found:
C, 50.14; H, 5.74; N, 12.26.
3.4.11. Methyl 6-deoxy-6-[N2-(6-methoxybenzothiazol-2-yl)-
N3-(oxydi-1,2-ethandiyl)]guanidino-
a
-
D
-glucopyranoside (6g)
White solid; mp 152–153 °C; IR (KBr): 3468, 3374, 2899, 1596,
1552, 1471, 1346, 1038 cmꢁ1 1H NMR (400 MHz, CDCl3): d 3.23
(br s, 1H, H-4), 3.29 (s, 3H, OMe), 3.36–3.53 (m, 6H, CH2NCH2,
Acknowledgment
;
This work was supported by the National Natural Science Foun-
dation of China (Grant No. 20462006).

Y.-H. Liu, L.-H. Cao / Carbohydrate Research 343 (2008) 2376–2383
2383
13. Schneider, S. E.; O’Neil, S. N.; Anslyn, E. V. J. Am. Chem. Soc. 2000, 122, 542–
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Supplementary data
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Complete crystallographic data for the structural analysis of
compounds 2g, 3g, and 4g have been deposited with the Cam-
bridge Crystallographic Data Centre, CCDC Nos. 673146, 675337,
and 675338, respectively. Copies of this information may be ob-
tained free of charge from the Director, Cambridge Crystallographic
Data Centre, 12 Union Road, Cambridge, CB2 1EZ, UK. (tel.: +44-
01223-762910, fax: +44-01223-336033, e-mail: deposit@ccdc.
cam.ac.uk or via: http://www.ccdc.cam.ac.uk). Tables containing
selected bond lengths and bond angles for the compounds 2g, 3g,
and 4g are available at http://www.ccdc.cam.ac.uk/deposit. Sup-
plementary data associated with this article can be found, in the
online version, at doi:10.1016/j.carres.2008.07.016.
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