Synthesis and antifungal activity of d-glucopyranosyl ureas and d-glucofurano-imidazolidine-2-ones

Article abstract of DOI:10.1007/s11164-012-0596-8

A series of N-β-d-glucopyranosyl-N'-substituted phenyl ureas were synthesized by reaction of glucosyl isocyanate with arylamines and glycosamine with aryl isocyanates, and a series of d-glucofurano-imidazolidine-2-ones were obtained via deacetylation of glycosylureas. Although some of the compounds have already been described, most were prepared for the first time in this work. The structures of all the compounds synthesized were confirmed by IR, ¹H NMR, and, in part, by ¹³C NMR. Antifungal activity of the title compounds was determined against four kinds of plant pathogenic fungi, Sclerotinia sclerotiorum, Fusarium graminearum, Fusarium oxysporum, and Bipolaris maydis. Preliminary bioassay indicates that most of glycosylureas had some activity against S. sclerotiorum; for some, the antifungal activity was strong. However, most of the imidazolidine-2-ones had weak antifungal activity.

Full text of DOI:10.1007/s11164-012-0596-8

Res Chem Intermed (2013) 39:805–820
DOI 10.1007/s11164-012-0596-8
Synthesis and antifungal activity of D-glucopyranosyl
ureas and D-glucofurano-imidazolidine-2-ones
•
Xuan Tang Feng Xue Hongju Ma Xiufang Cao
•
•
•
•
Changshui Chen Xuegang Li
Received: 26 March 2012 / Accepted: 6 May 2012 / Published online: 30 June 2012
Ó Springer Science+Business Media B.V. 2012
Abstract A series of N-b-D-glucopyranosyl-N’-substituted phenyl ureas were
synthesized by reaction of glucosyl isocyanate with arylamines and glycosamine
with aryl isocyanates, and a series of D-glucofurano-imidazolidine-2-ones were
obtained via deacetylation of glycosylureas. Although some of the compounds have
already been described, most were prepared for the first time in this work. The
structures of all the compounds synthesized were confirmed by IR, 1H NMR, and, in
part, by 13C NMR. Antifungal activity of the title compounds was determined
against four kinds of plant pathogenic fungi, Sclerotinia sclerotiorum, Fusarium
graminearum, Fusarium oxysporum, and Bipolaris maydis. Preliminary bioassay
indicates that most of glycosylureas had some activity against S. sclerotiorum; for
some, the antifungal activity was strong. However, most of the imidazolidine-2-ones
had weak antifungal activity.
Keywords Glycosylureas ꢀ Imidazolinone ꢀ Synthesis ꢀ Antifungal activity
Introduction
Glucose, an energy source of living cells and an intermediate of metabolism, exists
widely in nature and is important in biology. Because modification of medicines by
glycosyl can not only prolong and enhance their effect but also efficiently reduce
X. Tang ꢀ F. Xue ꢀ X. Cao ꢀ C. Chen (&) ꢀ X. Li (&)
College of Science, Huazhong Agricultural University, Wuhan 430070,
People’s Republic of China
e-mail: chenchang@mail.hzau.edu.cn
X. Li
e-mail: lixuegang@mail.hzau.edu.cn
H. Ma
Department of Plant Protection, Huazhong Agricultural University, Wuhan, China
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X. Tang et al.
toxicity and side effects, they are widely used as bactericides [1, 2], fungicides [3,
4], insecticides [5], and antidiabetic agents [6].
Urea functionality is a well known attractive structural feature with a wide range
of biological activity, for example, herbicidal [7], antifungal [8], antibacterial [9],
and anti-HIV [10, 11]. Also, imidazolinone, a type of heterocyclic compound, has
been reported to have a wide variety of biological properties, viz., antibacterial,
antifungal [12, 13], anticancer [14], and antiviral [15].
Fungal diseases, which cause extensive crop losses in yield and quality, are one
of the most serious problems for cultivation [16]. Discovery of novel fungicides
with high efficiency and low toxicity is, therefore, a trend in research and
development. Encouraged by the above observations, herein we report the synthesis
of some urea and imidazolinone derivatives containing, respectively, glucopyran-
osyl and glucofuranosyl. Although some have already been described, most have
been prepared for the first time. The antifungal activity of the compounds has been
evaluated and compared.
Results and discussion
Synthesis of N-(1,3,4,6-tetra-O-acetyl)-2-deoxy-b-D-glucopyranosyl-N’-substituted
phenylureas 4s–4u
The synthetic route adopted for preparation of N-(1,3,4,6-four-O-acetyl)-2-deoxy-b-
D-glucopyranosyl-N’-substitutedphenyl urea derivatives is depicted in Scheme 1.
Traditionally, glycosylureas have been obtained by reaction of glycosylamine
with aryl isocyanates in anhydrous solvents [17], but the yields were invariably low
because of hydrolysis of the aryl isocyanates. Maya proposed a one-pot, two-phase
procedure for preparation of glycosylureas starting from glycosyl isocyanate and
OAc
O
AcO
OAc
O
OAc
O
AcO
OAc
NH
AcO
AcO
i
AcO
AcO
ii
OAc
OAc
a:
NH2 HCl
NH
NCO
O
1
b
2
:
R
i
i
i
v
i
4
OAc
O
AcO
OAc
AcO
NH2
3
Scheme 1 General synthetic route for N-(1,3,4,6-four-O-acetyl)-2-deoxy-b-D-glucopyranosyl-N’-
substituted phenylureas 4. Reagents and conditions: a i BTC, dichloromethane, sat NaHCO3, 0 °C,
1 h. ii Substituted aniline, dichloromethane/chloroform, 25/55 °C, 8/120 h. b iii CH3COONa, water,
25 °C, 1 h. iv RNCO, 25 °C, dichloromethane, 4 h
123

Synthesis and antifungal activity of D-glucopyranosyl ureas
807
aryl amines and using triphosgene in the isocyanation step; this was more
convenient and the products were readily obtained [18]. In the work discussed in
this paper, using different substituents on benzene, we used two different routes for
synthesis of the target compounds. The first route to, 4a–q, involves treatment of
isocyanate 2 with aryl amines (Scheme 1a); the second, to 4r–u, is reaction of
glycosylamine 3 with aryl isocyanates (Scheme 1b, the reaction conditions and
physical data of compounds 4 were listed in Table 1). Generally, most glycosylureas
4 can be synthesized by the first route, because of the relative stability to hydrolysis
of isocyanate 2 and the aryl isocyanates. To obtain products in high yield, we
separated the isocyanate 2 and, after purification, added the substituted aniline. But
when an inactive aromatic amine participates in the reaction, it is necessary to pay
attention to three key factors:
1
the isocyanate 2 must remove the water and the redundant hydrochloride as
much as possible;
2
3
the temperature must be raised to 55 °C;
the reaction time must be prolonged to five days.
Only in this way can the reaction occur, producing, for example, 4i, 4m, 4n, 4o.
The temperature cannot exceed 65 °C, however, otherwise, the isocyanates will
polymerize to gels, and the time cannot exceed seven days, or the isocyanates will
decompose, furnishing N, N’-glycosyl urea. If a strong electron-withdrawing
OH
OH
OAc
O
O
HO
HO
O
HO
HO
AcO
AcO
i
OH
NH
OAc
NH
NH
OH
NH
NH
O
NH
R
O
O
R
R
4
6
5
R
CH2OH
ii
O
HO
+
O
OH
N
R
N
N
HO
H
H
O
N
HO
OH
OH
H
CH2OH
7
8
Scheme 2 General synthetic route for 1-aryl-(1,2-dideoxy-a-D-glucofurano)[2,1-d]imidazolidine-2-ones
8. Reagents and conditions: i MeOH/MeONa, dichloromethane, methanol, 25 °C. ii Amberlite 732 (H?
form), acetic acid (30 mL, 30 %), 100 °C, 30 min
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X. Tang et al.
substituent is on the aniline, however, the aniline will be too inactive to undergo
nucleophilic substitution with isocyanate 2, and the reaction will not proceed by the
first route, so 4r, 4s, 4t, 4u cannot be obtained in this way. In these circumstances,
glycosylureas were obtained by reaction of glycosylamine with aryl isocyanates in
anhydrous solvents, in accordance with Scheme 1b. Alkyl isocyanates are freshly
prepared and dropped into glycosylamine at 40 °C, to reduce condensation with
themselves and avoid hydrolysis side reactions.
Deacetylation of compounds 4 gave anomeric mixtures of the a and b urea
derivatives (5, 6), together with monocyclic imidazolidin-2-ones 7. In neutral
medium, compounds 6 were slowly converted into monocyclic imidazolidin-2-ones
7 and this transformation proceeds rapidly in basic media. Then, under acidic
conditions, both ureas and monocyclic compounds were transformed into furanoid
bicyclic imidazolidin-2-ones 8 [19].
´
The deacetylation of compounds 4 has been reported by Avalos, who used
ammonia in ethanol as the deacetylating reagent [20]. Herein, we used sodium
methoxide (Scheme 2) as the deacetylating reagent, which was more easy to
perform in the laboratory. During the procedure, the pH of the reaction solution
cannot exceed 10 and sodium methoxide must be added slowly; in more basic
media, the reaction will cause epimerisation at C-2 of compound 7.
Table 1 Respective different reaction conditions and physical data for compounds 4a–u
Compound
R
Temperature (°C)
Time (h)
Yield (%)
M.P. (°C)
4a
4b
4c
4d
4e
4f
H
25
25
25
25
25
25
25
25
55
25
25
25
55
55
55
25
25
25
25
25
25
8
8
74.5
74.2
58.3
64.1
74.6
76.1
62.9
75.7
56.4
65.7
72.5
68.3
55.7
58.4
52.5
82.4
70.3
79.8
35.7
38.2
40.3
203–205
202–203
202–203
187–189
198–200
201–202
205–207
202–203
212–214
245–247
210–212
217–219
203–205
229–231
224–226
202–204
229–231
197–199
220–222
195–197
188–190
2-OCH3Ph
2-OC2H5Ph
2-ClPh
8
8
4-CH3Ph
4-OC2H5Ph
4-ClPh
8
8
4g
4h
4i
8
4-BrPh
8
2,6-di-F
120
8
4j
2,6-di-CH3Ph
3-OCH3
4k
4l
8
3,4-di-CH3
2-CH3-4-NO2
4-CH3-2-NO2
2-OCH3-4-NO2
5-Cl-2-CH3
2,5-di-CH3
4-OF3CPh
2-NO2
8
4m
4n
4o
4p
4q
4r
4s
120
120
120
8
8
4
4
4t
3-NO2
4
4u
3-CF3
4
123

Synthesis and antifungal activity of D-glucopyranosyl ureas
809
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X. Tang et al.
We synthesized the target compounds selectivity, because compounds 8 can
generate rotational isomers because of substituents on benzene with different spatial
positions. To afford the product exclusively, we chose the symmetric substituted
aniline which had no isomer and the ortho-substitute aniline which had a large steric
effect and resulted in a stable conformation.
Biological activity evaluation
The antifungal activity of the title compounds 4a–4u, 8a–8j, 8r, and 8s against four
kinds of plant pathogenic fungi (Sclerotinia sclerotiorum, Fusarium graminearum,
Fusarium oxysporm, and Bipolaris maydis) were investigated at dosages of 100 mg/
L according to the method described in the ‘‘Antifungal activity testing’’ section; the
results are shown in Table 2. To enable discussion of structure–activity relation-
ships, for compounds with the same substituted phenyl we list the percentage
inhibition values in the same row.
As shown in Table 2, Most of compounds 4 had some activity against
S. sclerotiorum, some of the compounds, for example 4h, 4m, 4q, 4r, 4s, 4u, had
somewhat stronger antifungal activity. However, most of compounds 4 had weak
antifungal activity against the other three fungi; only compound 4u had strong
antifungal activity compared with the other compounds. Most imidazolidine-2-ones
8 had weak antifungal activity against the four fungi, weaker than compounds 4
with the same substituent on the benzene. The antifungal activity of deacetylated
compounds 8 was not increased. It is possible compounds 8 cannot combine with
the active site very well because of their rigid structure.
Conclusions
The title compounds 4 were designed, and synthesized by reaction of glucosyl
isothiocyanates with a substituted aniline or by reaction of glycosylamine with aryl
isocyanates. Compounds 8 were obtained by deacetylation of glycosylureas. Most of
the compounds 4 had some activity against S. sclerotiorum, and most compounds 8
had weak antifungal activity against the four strains. Introduction of an acetylated
glucopyranosyl group to the urea was useful for improvement of the antifungal
activity against S. sclerotiorm. However, although introduction of a glucofuranosyl
to imidazolinone can enhance water solubility and reduce toxicity, it cannot
improve antifungal activity.
Experimental
Instrumentation and chemicals
All reagents were commercially available and all solvents and liquid reagents were
dried by standard methods and distilled before use. Melting points were determined
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Synthesis and antifungal activity of D-glucopyranosyl ureas
811
with a digital melting-point apparatus and are uncorrected. FT-IR spectra were
1
recorded in KBr. H NMR and 13C NMR spectra were recorded on a Bruker AM
spectrometer at room temperature with tetramethylsilane (TMS) as internal standard
and CDCl3 or dimethyl sulfoxide (DMSO)-d6 as solvent. The progress of reactions
was monitored by TLC on silica gel plates visualized with UV light. Chemical shifts
are reported in ppm units with the use of the d scale.
General procedure for preparation of N-(1,3,4,6-tetra-O-acetyl)-2-deoxy-b-D-
glucopyranosyl-N’-substituted phenylurea derivatives 4a–q
To a vigorously stirred solution of BTC (bis(trichloromethyl) (2.5 mmol) in an 1:1
mixture of CH2Cl2 and saturated aqueous NaHCO3 (60 mL) at 0 °C in an ice bath
was added hydrohalides 1 (5 mmol), while maintaining stirring for 60 min. The
organic layer was separated and then extracted three times with dichloromethane
(20 mL). The combined organic fractions were washed with saturated aqueous
NaHCO3 and water successively, and dried over anhydrous magnesium sulfate.
After drying, the substituted aniline in 30 mL dry dichloromethane was added
dropwise to the separated liquid compound 2 while the reaction was monitored by
TLC. After evaporation to dryness, the crude products were purified by recrystal-
lization (water–acetone).
N-(1,3,4,6-tetra-O-acetyl)-2-deoxy-b-D-glucosyl-N’-phenyl-urea (4a)
White crystals. IR (KBr) cm-1: m 3318 (N–H), 1756/1743 (C=O), 1637 (C=O), 1218
1
(O–C–O); H NMR (600 MHz, CDCl3), d 7.31 (m, 4H, ArH), 7.11 (t, J = 7.2 Hz,
1H, ArH), 6.57 (br s, 1H, ArNH), 5.75 (d, J = 8.4 Hz, 1H, H-1), 5.17 (m, 2H, H-3,
0
H-4), 4.91 (d, J = 9.6 Hz, 1H, gly–NH), 4.29 (dd, J5,6 = 4.2 Hz, J6,6 = 12.6 Hz,
1H, H-6), 4.15 (m, 2H, H-2, H-60), 3.82 (m, 1H, H-5), 2.14 (s, 3H, OAc), 2.11 (s,
3H, OAc), 2.07 (s, 3H, OAc), 2.04 (s, 3H, OAc).
N-(1,3,4,6-tetra-O-acetyl)-2-deoxy-b-D-glucosyl-N’-(2-methoxyphenyl)urea (4b)
White crystals. IR (KBr) cm-1: m 3395 (N–H), 3329 (N’–H), 1758 (C=O), 1676
1
(C=O), 1225 (O–C–O); H NMR (600 MHz, CDCl3), d 8.01 (d, J = 7.8 Hz, 1H,
ArH), 7.00 (t, J = 6.6 Hz, J = 7.8 Hz, 1H, ArH), 6.93 (t, J = 7.8 Hz, J = 7.2 Hz,
1H, ArH), 6.88 (br s, 1H, ArNH), 6.84 (d, J = 7.8 Hz, 1H, ArH), 5.69 (d,
J = 9.0 Hz, 1H, H-1), 5.16 (m, 2H, H-3, H-4), 4.90 (d, J = 9.0 Hz, 1H, gly–NH),
0
4.29 (dd, J5,6 = 4.8 Hz, J6,6 = 12.6 Hz, 1H, H-6), 4.22 (m, 1H, H-2), 4.14 (m, 1H,
H-60), 3.83 (s, 4H, H-5, OCH3), 2.12 (s, 3H, OAc), 2.10 (s, 3H, OAc), 2.05 (s, 6H,
OAc).
N-(1,3,4,6-tetra-O-acetyl)-2-deoxy-b-D-glucosyl-N’-(2-ethoxylphenyl)urea (4c)
White crystals. IR (KBr) cm-1: m 3387 (N–H), 3314 (N’–H), 1752 (C=O), 1643
1
(C=O), 1218 (O–C–O); H NMR (600 MHz, CDCl3), d 8.00 (d, J = 7.2 Hz, 1H,
ArH), 6.98 (m, 1H, ArH), 6.93 (t, J = 7.8 Hz, J = 7.2 Hz, 1H, ArH), 6.85 (d,
123

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X. Tang et al.
J = 8.4 Hz, 2H, ArH, ArNH), 5.70 (d, J = 9.0 Hz, 1H, H-1), 5.16 (m, 2H, H-3,
0
H-4), 4.82 (d, J = 9.6 Hz, 1H, gly–NH), 4.28 (dd, J5,6 = 4.2 Hz, J6,6 = 12.0 Hz,
1H, H-6), 4.22 (m, 1H, H-2), 4.16 (m, 1H, H-60), 4.08 (m, 2H, OCH2CH3), 3.82 (m,
1H, H-5), 2.13 (s, 3H, OAc), 2.11 (s, 3H, OAc), 2.05 (s, 6H, OAc), 1.45 (t,
J = 7.2 Hz, J = 6.6 Hz, 3H, OCH2CH3).
N-(1,3,4,6-tetra-O-acetyl)-2-deoxy-b-D-glucosyl-N’-(2-chlorophenyl)urea (4d)
White crystals. IR (KBr) cm-1: m 3344 (N–H), 3310 (N’–H), 1762/1733(C=O),
1
1689 (C=O), 1222 (O–C=O); H NMR (600 MHz, CDCl3), d 8.04 (d, J = 7.8 Hz,
1H, ArH), 7.34 (d, J = 7.8 Hz, 1H, ArH), 7.25 (d, J = 8.4 Hz, 1H, ArH), 7.01 (t,
J = 7.2 Hz, 1H, ArH), 6.83 (br s, 1H, ArNH), 5.72 (d, J = 8.4 Hz,1H, H-1), 5.17
(m, 2H, H-3, H-4), 5.14 (d, J = 9.0 Hz, 1H, gly–NH), 4.30 (dd, J5,6 = 4.8 Hz,
0
0
J6,6 = 12.6 Hz, 1H, H-6), 4.20 (m, 1H, H-2), 4.14 (dd, J5,6 = 1.8 Hz,
0
J6,6 = 12.6 Hz, 1H, H-60), 3.83 (m, 1H, H-5), 2.15 (s, 3H, OAc), 2.11 (s, 3H,
OAc), 2.07 (s, 3H, OAc), 2.06 (s, 3H, OAc).
N-(1,3,4,6-tetra-O-acetyl)-2-deoxy-b-D-glucosyl-N’-(4-methyphenyl)urea (4e)
White crystals. IR (KBr) cm-1: m 3389 (N–H), 3353 (N’–H), 1756/1734 (C=O),
1
1683 (C=O), 1231 (O–C–O); H NMR (600 MHz, CDCl3), d 7.13 (br s, 4H, ArH),
6.44 (br s, 1H, ArNH), 5.73 (d, J = 8.4 Hz, 1H, H-1), 5.15 (m, 2H, H-3, H-4), 4.83
0
(d, J = 9.6 Hz, 1H, gly–NH), 4.28 (dd, J5,6 = 4.8 Hz, J6,6 = 12.6 Hz, 1H, H-6),
4.15 (m, 2H, H-2, H-60), 3.80 (m, 1H, H-5), 2.32 (s, 3H, CH3), 2.14 (s, 3H, OAc),
2.10 (s, 3H, OAc), 2.06 (s, 3H, OAc), 2.03 (s, 3H, OAc).
N-(1,3,4,6-tetra-O-acetyl)-2-deoxy-b-D-glucosyl-N’-(4-ethoxylphenyl)urea (4f)
White crystals. IR (KBr) cm-1: m 3310 (N–H), 1757 (C=O), 1637 (C=O), 1228 (O–
1
C–O); H NMR (600 MHz, CDCl3), d 7.16 (d, J = 7.8 Hz, 2H, ArH), 6.89 (br s,
1H, ArNH), 6.84 (d, J = 7.8 Hz, 2H, ArH), 5.80 (d, J = 8.4 Hz, 1H, H-1), 5.24 (m,
2H, H-3, H-4), 5.14 (d, J = 6.6 Hz, 1H, gly–NH), 4.28 (dd, J5,6 = 4.8 Hz,
0
J6,6 = 12.0 Hz, 1H, H-6), 4.13 (m, 2H, H-2, H-60), 4.01 (m, 2H, OCH2CH3), 3.86
(m, 1H, H-5), 2.11 (s, 3H, OAc), 2.09 (s, 3H, OAc), 2.05 (s, 3H, OAc), 2.03 (s, 3H,
OAc), 1.41 (t, J = 7.2 Hz, 3H, OCH2CH3).
N-(1,3,4,6-tetra-O-acetyl)-2-deoxy-b-D-glucosyl-N’-(4-chlorophenyl)urea (4g)
White crystals. IR (KBr) cm-1: m 3346 (N–H), 1755 (C=O), 1655 (C=O), 1234 (O–
1
C–O); H NMR (600 MHz, CDCl3), d 7.28 (d, J = 7.8 Hz, 2H, ArH), 7.25 (d,
J = 7.8 Hz, 2H, ArH), 7.23 (br s, 1H, ArNH), 5.77 (d, J = 8.4 Hz, 1H, H-1), 5.70
(d, J = 9.0 Hz, 1H, gly–NH), 5.24 (t, J = 9.6 Hz, 1H, H-3), 5.15 (t, J = 9.6 Hz,
1H, H-4), 4.27 (m, 1H, H-6), 4.13 (m, 2H, H-2, H-60), 3.86 (m, 1H, H-5), 2.10 (s,
3H, OAc), 2.07 (s, 3H, OAc), 2.05 (s, 3H, OAc), 2.04 (s, 3H, OAc).
123

Synthesis and antifungal activity of D-glucopyranosyl ureas
813
N-(1,3,4,6-tetra-O-acetyl)-2-deoxy-b-D-glucosyl-N’-(4-bromomethyphenyl)urea (4h)
White crystals. IR (KBr) cm-1: m 3394 (N–H), 1750 (C=O), 1682 (C=O), 1237 (O–
1
C–O); H NMR (600 MHz, CDCl3), d 7.42 (d, J = 7.8 Hz, 2H, ArH), 7.24 (d,
J = 7.8 Hz, 2H, ArH), 6.90 (br s, 1H, ArNH), 5.75 (d, J = 8.4 Hz, 1H, H-1), 5.18
(m, 2H, H-3, H-4), 5.15 (d, J = 9.6 Hz, 1H, gly–NH), 4.30 (m, 1H, H-6), 4.18 (m,
2H, H-2, H-60), 3.84 (m 1H, H-5), 2.15 (s, 3H, OAc), 2.12 (s, 3H, OAc), 2.08 (s, 3H,
OAc), 2.07 (s, 3H, OAc).
N-(1,3,4,6-tetra-O-acetyl)-2-deoxy-b-D-glucosyl-N’-(2,6-difluorophenyl)urea (4i)
White crystals. IR (KBr) cm-1: m 3330 (N–H), 1746 (C=O), 1663 (C=O), 1221 (C–
1
O–C); H NMR (600 MHz, CDCl3), d 7.15 (t, J = 7.2 Hz, 1H, ArH), 6.90 (t,
J = 7.2 Hz, J = 8.4 Hz, 2H, ArH), 6.62 (br s, 1H, ArNH), 5.75 (d, J = 9.0 Hz, 1H,
H-1), 5.41 (d, J = 9.6 Hz, 1H, gly–NH), 5.24 (t, J = 9.6 Hz, J = 10.2 Hz, 1H,
H-3), 5.12 (t, J = 9.6 Hz, J = 9.0 Hz, 1H, H-4), 4.26 (dd, J5,6 = 4.2 Hz,
J6,6 = 12.0 Hz, 1H, H-6), 4.15 (m, 2H, H-2, H-60), 3.86 (m, 1H, H-5), 2.13 (s,
0
3H, OAc), 2.08 (s, 3H, OAc), 2.07 (s, 3H, OAc), 2.04 (s, 3H, OAc).
N-(1,3,4,6-tetra-O-acetyl)-2-deoxy-b-D-glucosyl-N’-(2,6-dimethyphenyl)urea (4j)
White crystals. IR (KBr) cm-1: m 3382 (N–H), 1743 (C=O), 1672 (C=O), 1225 (O–
1
C=O); H NMR (600 MHz, CDCl3), d 7.11 (m, 3H, ArH), 6.11 (br s, 1H, ArNH),
5.70 (d, J = 6.6 Hz, 1H, H-1), 5.16 (t, J = 9.0 Hz, J = 9.6 Hz, 1H, H-3), 5.07 (t,
0
J = 9.0 Hz, J = 9.6 Hz, 1H, H-4), 4.24 (dd, J5,6 = 4.2 Hz, J6,6 = 12.0 Hz, 1H,
H-6), 4.08 (d, J = 12.0 Hz, 2H, H-2, H-60), 3.78 (m, 1H, H-5), 2.19 (s, 6H, CH3),
2.12 (s, 3H, OAc), 2.07 (s, 3H, OAc), 2.03 (s, 3H, OAc), 1.99 (s, 3H, OAc).
N-(1,3,4,6-tetra-O-acetyl)-2-deoxy-b-D-glucosyl-N’-(3-methoxyphenyl)urea (4k)
White crystals. IR (KBr) cm-1: m 3380 (N–H), 3328 (N’–H), 1750 (C=O), 1679
1
(C=O), 1224 (C–O–C); H NMR (600 MHz, CDCl3), d 7.30 (s, 1H, ArH), 7.17 (t,
J = 8.4 Hz, 1H, ArH), 6.99 (br s, 1H, ArNH), 6.81 (d, J = 8.4 Hz, 1H, ArH), 6.60
(d, J = 8.4 Hz, 1H, ArH), 5.84 (d, J = 8.4 Hz, 1H, H-1), 5.53 (d, J = 9.6 Hz, 1H,
gly–NH), 5.31 (t, J = 9.6 Hz, J = 10.2 Hz, 1H, H-3), 5.14 (t, J = 9.6 Hz, 1H,
H-4), 4.28 (dd, J5,6 = 4.8 Hz, J6,6 = 12.6 Hz, 1H, H-6), 4.12 (m, 2H, H-2, H-60),
0
3.88 (m, 1H, H-5), 3.76 (s, 3H, OCH3), 2.12 (s, 3H, OAc), 2.09 (s, 3H, OAc), 2.05
(s, 3H, OAc), 2.03 (s, 3H, OAc).
N-(1,3,4,6-tetra-O-acetyl)-2-deoxy-b-D-glucosyl-N’-(3,4-dimethyphenyl)urea (4l)
White crystals. IR (KBr) cm-1: m 3386 (N–H), 3353 (N’–H), 1755 (C=O), 1685
(C=O), 1227 (C–O–C); 1H NMR (600 MHz, CDCl3), d 7.09 (br s, 1H, ArNH), 7.04
(d, J = 9.6 Hz, 2H, ArH), 7.00 (d, J = 7.8 Hz, 1H, ArH), 5.82 (d, J = 9.0 Hz, 1H,
H-1), 5.42 (d, J = 9.6 Hz, 1H, gly–NH), 5.29 (t, J = 9.6 Hz, J = 10.2 Hz, 1H,
0
H-3), 5.12 (t, J = 9.6 Hz, 1H, H-4), 4.28 (dd, J5,6 = 4.8 Hz, J6,6 = 12.6 Hz, 1H,
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H-6), 4.12 (d, J = 12.6 Hz, 1H, H-60), 4.07 (m, 1H, H-2), 3.84 (m, 1H, H-5), 2.19
(s, 3H, CH3), 2.18 (s, 3H, CH3), 2.10 (s, 3H, OAc), 2.08 (s, 3H, OAc), 2.05 (s, 3H,
OAc), 2.02 (s, 3H, OAc).
N-(1,3,4,6-tetra-O-acetyl)-2-deoxy-b-D-glucosyl-N’-(2-methyl-4-nitrophenyl)urea (4m)
Yellow crystals. IR (KBr) cm-1: m 3327 (N–H), 1756 (C=O), 1649 (C=O), 1217 (C–
O–C); 1H NMR (600 MHz, CDCl3), d 8.11 (d, J = 9.0 Hz, 1H, ArH), 8.07 (m, 1H,
ArH), 8.04 (s, 1H, ArH), 6.73 (br s, 1H, ArNH), 5.77 (d, J = 8.4 Hz, 1H, H-1), 5.42
(d, J = 8.4 Hz, 1H, gly–NH), 5.19 (m, 2H, H-3, H-4), 4.29 (dd, J5,6 = 4.8 Hz,
J6,6 = 12.6 Hz, 1H, H-6), 4.20 (m, 1H, H-2), 4.15 (d, J = 12.6 Hz, 1H, H-60), 3.87
0
(m, 1H, H-5), 2.28 (s, 3H, CH3), 2.14 (s, 3H, OAc), 2.11 (s, 3H, OAc), 2.07 (s, 3H,
OAc), 2.06 (s, 3H, OAc).
N-(1,3,4,6-tetra-O-acetyl)-2-deoxy-b-D-glucosyl-N’-(2-nitro-4-methylphenyl)urea (4n)
Yellow crystals. IR (KBr) cm-1: m 3338 (N–H), 3276 (N’–H), 1760 (C=O), 1649
(C=O), 1222 (C–O–C); 1H NMR (600 MHz, CDCl3), d 9.59 (br s, 1H, ArNH), 8.46
(d, J = 9.0 Hz, 1H, ArH), 7.94 (s, 1H, ArH), 7.41 (d, J = 9.0 Hz, 1H, ArH), 5.92
(d, J = 9.0 Hz, 1H, H-1), 5.81 (d, J = 9.0 Hz, 1H, gly–NH), 5.34 (t, J = 10.2 Hz,
0
1H, H-3), 5.16 (t, J = 9.6 Hz, 1H, H-4), 4.31 (dd, J5,6 = 4.2 Hz, J6,6 = 12.6 Hz,
1H, H-6), 4.23 (m, 1H, H-2), 4.17 (d, J = 12.6 Hz, 1H, H-60), 3.93 (m, 1H, H-5),
2.35 (s, 3H, CH3), 2.12 (s, 3H, OAc), 2.11 (s, 3H, OAc), 2.08 (s, 3H, OAc), 2.07 (s,
3H, OAc).
N-(1,3,4,6-tetra-O-acetyl)-2-deoxy-b-D-glucosyl-N’-(2-methoxy-4-nitrophenyl)urea (4o)
Yellowish crystals. IR (KBr) cm-1: m 3319 (N–H), 1758 (C=O), 1652 (C=O), 1228
(C–O–C); 1H NMR (600 MHz, CDCl3), d 8.37 (d, J = 9.0 Hz, 1H, ArH), 7.90 (m,
1H, ArH), 7.70 (d, J = 2.4 Hz, 1H, ArH), 7.29 (br s, 1H, ArNH), 5.72 (d,
J = 8.4 Hz, 1H, H-1), 5.18 (m, 3H, H-3, H-4, gly–NH), 4.30 (dd, J5,6 = 4.8 Hz,
0
0
J6,6 = 12.6 Hz, 1H, H-6), 4.22 (m, 1H, H-2), 4.16 (dd, J5,6 = 2.4 Hz,
0
J6,6 = 12.6 Hz, 1H, H-60), 3.85 (m, 1H, H-5), 3.95 (s, 3H, OCH3), 2.12 (s, 3H,
OAc), 2.11 (s, 3H, OAc), 2.07 (s, 3H, OAc), 2.06 (s, 3H, OAc).
N-(1,3,4,6-tetra-O-acetyl)-2-deoxy-b-D-glucosyl-N’-(2-methyl-5-chlorophenyl)urea (4p)
White crystals. IR (KBr) cm-1: m 3324 (N–H), 1756 (C=O), 1648 (C=O), 1231 (C–
1
O–C); H NMR (600 MHz, CDCl3), d 7.47 (s, 1H, ArH), 7.13 (d, J = 8.4 Hz, 1H,
ArH), 7.10 (m, 1H, ArH), 6.23 (br s, 1H, ArNH), 5.78 (d, J = 9.0 Hz, 1H, H-1),
5.20 (t, J = 9.6 Hz, J = 10.2 Hz, 1H, H-3), 5.15 (t, J = 9.6 Hz, 1H, H-4), 4.83 (d,
0
J = 8.4 Hz, 1H, gly–NH), 4.28 (dd, J5,6 = 4.8 Hz, J6,6 = 12.6 Hz, 1H, H-6), 4.12
(m, 2H, H-2, H-60), 3.82 (m, 1H, H-5), 2.18 (s, 3H, CH3), 2.15 (s, 3H, OAc), 2.10 (s,
3H, OAc), 2.08 (s, 3H, OAc), 2.04 (s, 3H, OAc); 13C NMR (125 MHz, CDCl3), dC
171.1, 170.7, 169.5, 169.3, 155.3, 136.9, 132.0, 131.6, 129.3, 125.1, 124.1, 92.7,
72.7, 68.2, 63.1, 54.3, 21.0, 20.8, 20.6, 20.4, 17.2.
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Synthesis and antifungal activity of D-glucopyranosyl ureas
815
N-(1,3,4,6-tetra-O-acetyl)-2-deoxy-b-D-glucosyl-N’-(2,5-dimethylphenyl)
urea (4q)
White crystals. IR (KBr) cm-1: m 3399 (N–H), 3310 (N’–H), 1749 (C=O), 1665
(C=O), 1230 (C–O–C); 1H NMR (600 MHz, CDCl3), d 7.77 (s, 1H, ArH), 7.37 (br
s, 1H, ArNH), 7.01 (d, J = 7.8 Hz, 1H, ArH), 6.77 (d, J = 7.8 Hz, 1H, ArH), 6.45
(d, J = 9.0 Hz, 1H, gly–NH), 5.86 (d, J = 9.0 Hz, 1H, H-1), 5.32 (t, J = 9.6 Hz,
J = 10.2 Hz, 1H, H-3), 4.91 (t, J = 9.6 Hz, 1H, H-4), 4.20 (dd, J5,6 = 4.8 Hz,
J6,6 = 12.6 Hz, 1H, H-6), 4.08 (m, 1H, H-2), 4.01 (d, J = 12.6 Hz, 1H, H-60), 3.89
0
(m, 1H, H-5), 2.22 (s, 3H, CH3), 2.08 (s, 3H, CH3), 2.06 (s, 3H, OAc), 2.02 (s, 3H,
OAc), 1.99 (s, 3H, OAc), 1.95 (s, 3H, OAc).
General procedure for preparation of N-(1,3,4,6-tetra-O-acetyl)-2-deoxy-b-D-
glucopyranosyl-N’-substituted phenylurea derivatives 4r–u
To a solution of 1,3,4,6-tetra-O-acetyl-2-amino-2-deoxy-b-D-glucopyranose hydro-
halide 1 (1.92 g, 5 mmol) in water (20 mL), sodium acetate (0.82 g, 10 mmol) was
added, and the reaction was stirred for 60 min. Much white solid appeared. This was
extracted three times with 20 mL CH2Cl2, and the extract was dried with anhydrous
magnesium sulfate, filtered, and the liquid was added dropwise to a solution of aryl
isocyanate (5 mmol) in dichloromethane (20 mL). The progress of the reaction was
monitored by TLC. After evaporation to dryness, the crude product was purified by
recrystallization (water–acetone).
N-(1,3,4,6-tetra-O-acetyl)-2-deoxy-b-D-glucosyl-N’-(4-trifluoromethoxyphenyl)
urea (4r)
White crystals. IR (KBr) cm-1: m 3339 (N–H), 1753 (C=O), 1681 (C=O), 1233 (O–
1
C–O); H NMR (600 MHz, CDCl3), d 7.32 (d, J = 9.0 Hz, 2H, ArH), 7.12 (d,
J = 9.0 Hz, 2H, ArH), 7.02 (br s, 1H, ArNH), 5.77 (d, J = 9.0 Hz, 1H, H-1), 5.22
(m, 2H, gly–NH, H-3), 5.14 (t, J = 9.6 Hz, 1H, H-4), 4.28 (dd, J5,6 = 4.8 Hz,
0
J6,6 = 12.6 Hz, 1H, H-6), 4.13 (m, 2H, H-2, H-60), 3.84 (m, 1H, H-5), 2.11 (s, 3H,
OAc), 2.08 (s, 3H, OAc), 2.05 (s, 3H, OAc), 2.03 (s, 3H, OAc).
N-(1,3,4,6-tetra-O-acetyl)-2-deoxy-b-D-glucosyl-N’-(2-nitrophenyl)urea (4s)
Yellowish crystals. IR (KBr) cm-1: m 3353 (N–H), 3275 (N’–H), 1760 (C=O), 1651
(C=O), 1213 (C–O–C); 1H NMR (600 MHz, CDCl3), d 9.72 (br s, 1H, ArNH), 8.61
(d, J = 8.4 Hz, 1H, ArH), 8.14 (d, J = 8.4 Hz, 1H, ArH), 7.59 (t, J = 7.8 Hz, 1H,
ArH), 7.06 (t, J = 7.8 Hz, 1H, ArH), 6.24 (s, 1H, gly–NH), 5.82 (d, J = 9.0 Hz,
1H, H-1), 5.37 (t, J = 9.6 Hz, J = 10.2 Hz, 1H, H-3), 5.17 (t, J = 9.6 Hz, 1H,
0
H-4), 4.32 (dd, J5,6 = 4.2 Hz, J6,6 = 12.6 Hz, 1H, H-6), 4.26 (m, 1H, H-2), 4.18 (d,
J = 12.6 Hz, 1H, H-60), 3.95 (m, 1H, H-5), 2.13 (s, 3H, OAc), 2.11 (s, 3H, OAc),
2.09 (s, 3H, OAc), 2.08 (s, 3H, OAc).
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N-(1,3,4,6-tetra-O-acetyl)-2-deoxy-b-D-glucosyl-N’-(3-nitrophenyl)urea (4t)
Yellowish crystals. IR (KBr) cm-1: m 3359 (N–H), 3275 (N’–H), 1752 (C=O), 1655
1
(C=O), 1231 (C–O–C); H NMR (600 MHz, CDCl3), d 8.09 (s, 1H, ArH), 7.83 (d,
J = 7.8 Hz, 1H, ArH), 7.79 (d, J = 7.8 Hz, 1H, ArH), 7.58 (br s, 1H, ArNH), 7.41 (t,
J = 8.4 Hz, J = 7.8 Hz, 1H, ArH), 5.89(d, J = 8.4 Hz, 1H, H-1), 5.54(d, J = 8.4 Hz,
1H, gly–NH), 5.34 (t, J = 10.2 Hz, J = 9.0 Hz, 1H, H-3), 5.18 (t, J = 9.6 Hz, 1H,
H-4), 4.31 (dd, J5,6 = 4.2 Hz, J6,6 = 12.0 Hz, 1H, H-6), 4.19 (m, 2H, H-2, H-60),
0
3.95(m, 1H, H-5), 2.15 (s, 3H, OAc), 2.10 (s, 3H, OAc), 2.09 (s, 3H, OAc), 2.06 (s, 3H,
OAc); 13C NMR (125 MHz, CDCl3), dC 171.4, 170.8, 169.7, 169.5, 154.5, 148.4, 140.0,
131.3, 129.7, 125.0, 92.9, 72.7, 70.1, 62.4, 54.7, 21.0, 20.9, 20.6, 20.5.
N-(1,3,4,6-tetra-O-acetyl)-2-deoxy-b-D-glucosyl-N’-(3-trifluoromethylphenyl)urea (4u)
White crystals. IR (KBr) cm-1: m 3371 (N–H), 1754 (C=O), 1677 (C=O), 1228 (C–
1
O–C); H NMR (600 MHz, CDCl3), d 7.59 (s, 1H, ArH), 7.55 (d, J = 6.6 Hz, 1H,
ArH), 7.39 (t, J = 7.2 Hz, 1H, ArH), 7.29 (d, J = 7.8 Hz, 1H, ArH), 7.17 (br s, 1H,
ArNH), 5.81 (d, J = 8.4 Hz, 1H, H-1), 5.24 (t, J = 10.8 Hz, J = 9.6 Hz, 2H, H-3,
gly–NH), 5.17 (t, J = 9.0 Hz, J = 9.6 Hz, 1H, H-4), 4.29 (dd, J5,6 = 4.2 Hz,
J6,6 = 12.6 Hz, 1H, H-6), 4.16 (m, 2H, H-2, H-60), 3.87 (m, 1H, H-5), 2.14 (s, 3H,
0
OAc), 2.11 (s, 3H, OAc), 2.07 (s, 3H, OAc), 2.05 (s, 3H, OAc).
General procedure for preparation of 1-aryl-(1,2-dideoxy-a-D-glucofurano)-
[2,1-d] imidazolidine-2-one derivatives 8a–j, 8r, and 8s
To a solution N-(1,3,4,6-four-O-acetyl)-2-deoxy-b-D-glucopyranosyl-N’-substituted
phenylureas 4 (2.5 mmol) in an 2:1 mixture of dichloromethane (40 mL) and
methanol (20 mL) at 25 °C, a solution of sodium methoxide (135 mg, 2.5 mmol) in
methanol (50 mL) was slowly added with stirring. The reaction was controlled by
TLC (acetic ether–petroleum ether = 3:1). After the reaction was complete, the
solution was neutralized by addition of Amberlite 732 (H? form). The resulting
solution was filtered, washed with MeOH, and the filtrate was evaporated, then
treated with aqueous acetic acid (30 mL, 30 %) and heated at 100 °C (external
bath), for 30 min. After evaporation to dryness, the solid was crystallized from
96 % ethanol, affording 8.
1-(Phenyl)-(1,2-dideoxy-a-D-glucofurano)[2,1-d]imidazolidine-2-one (8a)
White crystals, yield 51 %, m.p. 212–215 °C. IR (KBr) cm-1: m 3,400–3,100 (OH,
1
NH), 1662 (C=O), 1074, 1023 (C–O); H NMR (600 MHz, DMSO-d6), d 7.60 (d,
J = 8.0 Hz, 2H, ArH), 7.53 (s, 1H, NH), 7.31 (t, J = 7.8 Hz, 2H, ArH), 7.05
(t, J = 7.2 Hz, 1H, ArH), 5.95 (d, J = 6.0 Hz, 1H, H-1), 4.08 (m, 1H, H-2), 3.98 (br
d, J = 6.0 Hz, 1H, H-3), 3.75 (m, 1H, H-5), 3.68 (dd, J3,4 = 1.6 Hz, J4,5 = 8.4 Hz,
1H, H-4), 3.57 (dd, J5,6 = 2.0 Hz, J6,6 = 11.2 Hz, 1H, H-6), 3.35 (m, 1H, H-60).
0
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Synthesis and antifungal activity of D-glucopyranosyl ureas
817
1-(2-Methoxyphenyl)-(1,2-dideoxy-a-D-glucofurano)[2,1-d]imidazolidine-2-one (8b)
White crystals, yield 43 %, m.p. 226–229 °C. IR (KBr) cm-1: m 3,500–3,000 (OH,
1
NH), 1686 (C=O), 1068, 1024 (C–O); H NMR (600 MHz, DMSO-d6), d 7.27 (t,
J = 7.5 Hz,1H, ArH), 7.19 (s, 1H, NH), 7.14 (d, J = 7.8 Hz, 1H, ArH), 7.05 (d,
J = 8.4 Hz, 1H, ArH), 6.92 (t, J = 7.5 Hz, 1H, ArH), 5.73 (d, J = 6.0 Hz, 1H,
H-1), 4.01 (br s,1H, H-2), 3.96 (br d, J = 6.0 Hz, 1H, H-3), 3.76 (s, 3H, OCH3),
3.69 (m, 2H, H-4, H-5), 3.47 (d, J = 10.8 Hz,1H, H-6), 3.30 (m, 1H, H-60); 13C
NMR (125 MHz, DMSO-d6), dC 158.2, 155.5, 130.3, 128.2, 125.7, 120.2, 112.0,
89.8, 79.1, 74.5, 68.4, 64.0, 61.4, 55.5.
1-(2-Ethoxylphenyl)-(1,2-dideoxy-a-D-glucofurano)[2,1-d]imidazolidine-2-one (8c)
White crystals, yield 54 %, m.p. 234–236 °C. IR (KBr) cm-1: m 3,400–3,100 (OH,
1
NH), 1662 (C=O), 1086, 1025 (C–O); H NMR (600 MHz, DMSO-d6), d 7.24 (t,
J = 7.8 Hz, 1H, ArH), 7.20 (s, 1H, NH), 7.13 (d, J = 7.8 Hz, 1H, ArH), 7.04 (d,
J = 8.4 Hz, 1H, ArH), 6.91 (t, J = 7.8 Hz, 1H, ArH), 5.81 (d, J = 6.0 Hz, 1H,
H-1), 5.45 (br s, 1H, C3-OH), 5.05 (br s, 1H, C5-OH), 4.47 (br s, 1H, C6-OH),
4.05–4.00 (m, 3H, H-2, OCH2CH3), 3.96 (br d, J = 6.0 Hz, 1H, H-3), 3.72 (br d,
J = 8.4 Hz, 1H, H-4), 3.68 (m, 1H, H-5), 3.45 (br d, J = 10.2 Hz, 1H, H-6), 3.28
(m, 1H, H-60), 1.31 (t, J = 6.6 Hz, 3H, OCH2CH3).
1-(2-Chlorophenyl)-(1,2-dideoxy-a-D-glucofurano)[2,1-d]imidazolidine-2-one (8d)
White crystals, yield 34 %, m.p. 257–260 °C. IR (KBr) cm-1: m 3,600–3,100 (OH,
1
NH), 1669 (C=O), 1085, 1036 (C–O); H NMR (600 MHz, DMSO-d6), d 7.53 (m,
1H, ArH), 7.37 (m, 4H, ArH, NH), 5.76 (d, J = 6.4 Hz, 1H, H-1), 4.03 (m, 2H, H-2,
H-3), 3.81 (dd, J3,4 = 1.2 Hz, J4,5 = 8.8 Hz, 1H, H-4), 3.71 (m, 1H, H-5), 3.51 (dd,
J5,6 = 2.0 Hz, J6,6 = 10.8 Hz, 1H, H-6), 3.35 (m, 1H, H-60).
0
1-(4-Methyphenyl)-(1,2-dideoxy-a-D-glucofurano)[2,1-d]imidazolidine-2-one (8e)
White crystals, yield 38 %, m.p. 226–228 °C. IR (KBr) cm-1: m 3,450–3,100 (OH,
1
NH), 1666 (C=O), 1084, 1037 (C–O); H NMR (600 MHz, DMSO-d6), d 7.47
(s, 1H, NH), 7.44 (d, J = 6.4 Hz, 2H, ArH) 7.11 (d, J = 8.0 Hz, 2H, ArH), 5.91
(d, J = 6.0 Hz, 1H, H-1), 4.05 (m, 1H, H-2), 3.97 (br d, J = 6.0 Hz, 1H, H-3), 3.74
(m, 1H, H-5), 3.68 (dd, J3,4 = 1.2 Hz, J4,5 = 8.0 Hz, 1H, H-4), 3.56 (dd,
J5,6 = 2.0 Hz, J6,6 = 11.2 Hz, 1H, H-6), 3.40 (m, 1H, H-60), 2.25 (s, 3H, CH3).
0
1-(4-Ethoxyphenyl)-(1,2-dideoxy-a-D-glucofurano)[2,1-d]imidazolidine-2-one (8f)
White crystals, yield 58 %, m.p. 227–229 °C. IR (KBr) cm-1: m 3391, 3261 (OH,
1
NH), 1661 (C=O), 1084, 1025 (C–O); H NMR (600 MHz, DMSO-d6), d 7.42
(d, J = 8.4 Hz, 2H, ArH), 7.36 (s, 1H, NH), 6.88 (d, J = 9.0 Hz, 2H, ArH), 5.84 (d,
J = 6.0 Hz, 1H, H-1), 5.39 (br s, 1H, C3-OH), 4.89 (br s, 1H, C5-OH), 4.51 (br s,
1H, C6-OH), 4.03(m, 2H, H-2, H-3), 3.98 (t, J = 6.9 Hz, 2H, OCH2CH3), 3.95
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(m, 1H, H-4), 3.73 (m, 1H, H-5), 3.68 (br d, J = 8.4 Hz, 1H, H-6), 3.57 (m, 1H, H-60),
1.30 (t, J = 6.9 Hz, 3H, OCH2CH3); 13C NMR (125 MHz, DMSO-d6), dC 157.5, 154.8,
132.0, 128.2, 122.0, 114.3, 90.1, 79.2, 74.2, 68.5, 63.8, 63.1, 60.6, 14.7.
1-(4-Chlorophenyl)-(1,2-dideoxy-a-D-glucofurano)[2,1-d]imidazolidine-2-one (8g)
White crystals, yield 37%, m.p. 216–220 °C. IR (KBr) cm-1: m 3,450–3,100(OH,
1
NH), 1689 (C=O), 1081, 1028 (C–O); H NMR (600 MHz, DMSO-d6), d 7.62 (d,
J = 7.8 Hz, 2H, ArH), 7.60 (s, 1H, NH), 7.37 (d, J = 9.0 Hz, 2H, ArH), 5.97 (d,
J = 6.0 Hz, 1H, H-1), 5.32 (br s, 1H, C3–OH), 4.74 (br s, 1H, C5-OH), 4.54 (br s,
1H, C6-OH), 4.05(m, 1H, H-2), 3.93 (m, 1H, H-3), 3.74 (m, 1H, H-4), 3.69 (m, 1H,
H-5), 3.56 (m, 1H, H-6), 3.36 (m, 1H, H-60).
1-(4-Bromophenyl)-(1,2-dideoxy-a-D-glucofurano)[2,1-d]imidazolidine-2-one (8h)
White crystals, yield 36 %, m.p. 236–238 °C. IR (KBr) cm-1: m 3412, 3279 (OH,
1
NH), 1670 (C=O), 1085, 1020 (C–O); H NMR (600 MHz, DMSO-d6), d 7.66 (s,
1H, NH), 7.57 (d, J = 8.4 Hz, 2H, ArH), 7.49 (d, J = 8.4 Hz, 2H, ArH), 5.95 (d,
J = 6.6 Hz, 1H, H-1), 4.06 (br s, 1H, H-2), 3.96 (br d, J = 5.4 Hz, 1H, H-3), 3.73
(m, 1H, H-5), 3.64 (br d, J = 8.4 Hz, 1H, H-4), 3.53 (br d, J = 11.4 Hz, H-6), 3.32
(m, 1H, H-60).
1-(2,6-Difluorophenyl)-(1,2-dideoxy-a-D-glucofurano)[2,1-d]imidazolidine-
2-one (8i)
White crystals, yield 38 %, m.p. 236–238 °C. IR (KBr) cm-1: m 3,500–3,100 (OH,
1
NH), 1693 (C=O), 1086, 1025 (C–O); H NMR (600 MHz, DMSO-d6), d 7.59 (s,
1H, NH), 7.44 (m, 1H, ArH), 7.20 (d, J = 7.2 Hz, 2H, ArH), 5.71 (d, J = 6.0 Hz,
1H, H-1), 5.31 (d, J = 4.2 Hz, 1H, C3-OH), 4.83 (br s, 1H, C5-OH), 4.44 (br s, 1H,
C6-OH), 4.09 (br d, J = 6.0 Hz, 1H, H-2), 4.03 (m, 1H, H-3), 3.71 (m, 2H, H-4,
H-5), 3.47 (br d, J = 10.8 Hz, 1H, H-6), 3.25 (m, 1H, H-60).
1-(2,6-Dimethyl)-(1,2-dideoxy-a-D-glucofurano)[2,1-d]imidazolidine-2-one (8j)
White crystals, yield 37 %, m.p. 246–248 °C. IR (KBr) cm-1: m 3483, 3387, 3252
(OH, NH), 1665 (C=O), 1084, 1037 (C–O); 1H NMR (600 MHz, DMSO-d6), d 7.25
(s, 1H, NH), 7.13 (t, J = 7.8 Hz, J = 7.2 Hz, 1H, ArH), 7.09 (t, J = 7.8 Hz, 2H,
ArH), 5.64 (d, J = 6.0 Hz, 1H, H-1), 4.10 (m, 2H, H-2, H-3), 3.83 (br d,
J = 9.0 Hz, 1H, H-4), 3.72 (m, 1H, H-5), 3.55 (m, 1H, H-6), 3.32 (m, 1H, H-60),
2.17 (s, 3H, CH3), 2.12 (s, 3H, CH3).
1-(4-Trifluoromethoxy)-(1,2-dideoxy-a-D-glucofurano)[2,1-d]imidazolidine-
2-one (8r)
White crystals, yield 42 %, m.p. 214–216 °C. IR (KBr) cm-1: m 3419, 3278 (OH,
1
NH), 1640 (C=O), 1084, 1023 (C–O); H NMR (600 MHz, DMSO-d6), d 7.71 (d,
123

Synthesis and antifungal activity of D-glucopyranosyl ureas
819
J = 9.0 Hz, 2H, ArH), 7.68 (s, 1H, NH), 7.33 (d, J = 8.4 Hz, 2H, ArH), 5.98 (d,
J = 6.6 Hz, 1H, H-1), 4.08 (br s, 1H, H-2), 3.97 (br d, J = 6.0 Hz, 1H, H-3), 3.75
(m, 1H, H-4), 3.65 (m, 1H, H-5), 3.55 (m, 1H, H-6), 3.34 (m, 1H, H-60).
1-(2-Nitrophenyl)-(1,2-dideoxy-a-D-glucofurano)[2,1-d]imidazolidine-2-one (8s)
White crystals, yield 43 %, m.p. 236–238 °C. IR (KBr) cm-1: m 3,430–3,300 (OH,
NH), 1696 (C=O), 1526, 1359 (NO2), 1083, 1024 (C–O); H NMR (600 MHz,
1
DMSO-d6), d 7.92 (d, J = 7.8 Hz, 1H, ArH), 7.74 (t, J = 8.1 Hz, 1H, ArH), 7.66(d,
J = 7.2 Hz, 2H, ArH, NH), 7.46 (t, J = 7.5 Hz, 1H, ArH), 6.02 (d, J = 6.0 Hz, 1H,
H-1), 5.28 (d, J = 4.8 Hz, 1H, C3-OH), 4.73 (d, J = 5.4 Hz, 1H, C5-OH), 4.46 (t,
J = 5.4 Hz, 1H, C6-OH), 4.06–4.03 (m, 2H, H-2, H-3), 3.85 (dd, J3,4 = 1.8 Hz,
J4,5 = 9.6 Hz, 1H, H-4), 3.76 (m, 1H, H-5), 3.58 (m, 1H, H-6), 3.41 (m, 1H, H-60);
13C NMR (125 MHz, DMSO-d6), dC 156.6, 145.3, 133.8, 131.0, 127.3, 126.7,
125.0, 90.1, 79.6, 74.1, 68.4, 64.0, 61.8.
Antifungal activity testing
The antifungal activity of compounds 4 and 8 against four kinds of plant pathogenic
fungi (S. sclerotiorum, F. graminearum, F. oxysporm and B. maydis) was tested in a
greenhouse, at 27 °C, for 1–3 days. Solutions of the title compounds in a small
amount of DMSO were diluted to a concentration of 1,000 mg/L with distilled water
containing 0.1 % Tween 80. The agar medium (9.9 mL) which had been autoclaved
at 121 °C for 20 min and kept at 55 °C was then poured into culture dishes
containing 0.1 mL (1000 mg/L) of the synthesized compounds, allowed to solidify,
then inoculated. A mixture of the same amount of water, DMSO, and Tween 80 was
used as the control. Strains treated with water were the blank test. Each treatment
was repeated three times and the diameters of inhibition zone in each dish were
measured by the crossing method. The inhibition observed is summarized in
Table 2.
Acknowledgments The authors gratefully acknowledge financial support by ‘‘the Fundamental
Research Funds for the Central Universities’’ (program no. 2010JC002), and thank Professor Jianhong
Li for providing bioactivity research facilities.
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