Synthesis of furan derivatives condensed with carbohydrates

Article abstract of DOI:10.3390/60900728

Eight new furan derivatives have been prepared and characterized. These compounds were obtained by condensation of aminosugar and aminocyclitol intermediates with furan derivatives.

Full text of DOI:10.3390/60900728

Molecules 2001, 6, 728-735
molecules
ISSN 1420-3049
http://www.mdpi.org
Synthesis of Furan Derivatives Condensed with Carbohydrates
Mauro V. de Almeida*, Mireille Le Hyaric, Leonardo J. A. Siqueira, Luciana D. Pinto, Marcelo
S. Valle and Wendel A. Alves
Departamento de Química, ICE ,Universidade Federal de Juiz de Fora, 36036-330 Juiz de Fora- MG,
Brazil. Phone: (+55)32-3229-3310 ; Fax (+55)32-3229-3314
* Author to whom correspondence should be addressed; e-mail: mvieira@quimica.ufjf.br
Received: 29 June 200; in revised form 21 August 2001 / Accepted: 22 August 2001 / Published: 31
August 2001
Abstract: Eight new furan derivatives have been prepared and characterized. These
compounds were obtained by condensation of aminosugar and aminocyclitol
intermediates with furan derivatives.
Keywords: nitrofurans, aminosugar, aminocyclitol
Introduction
Synthetic antibacterial compounds which do not derive from sulfonamide are numerous and
chemically varied. An important group is formed by the 5-nitrofurfural derivatives (eg.- nitrofurazone,
furazolidone, nitrofurantoin, Figure 1), generically known as nitrofurans [1].
Figure 1: Antibacterial nitrofurans
O
O
O
CH=N N
furazolidone
CH=N-NHCONH2
nitrofurazone
CH=N N
nitrofurantoin
O2N
O2N
O2N
O
O
O
NH
O

Molecules 2001, 6
729
The antimicrobial activity of nitroaromatic compounds is related to an enzymatic reduction of the
nitro group in vivo, yielding toxic species: nitro compounds can be reductively metabolized to form
highly potent cytotoxins and can act as radiosensitizers of hypoxic cells [2-5]. Despite its rare
occurrence in natural products, the nitro group is present in various synthetic substances used as
antibacterials, trypanocides, fungicides, vasodilatators, tranquilizers, antivirals and others. The nitro
group is also present in compounds with antiparasitic activity [6].
The therapeutic use of nitrofurans is severely limited by their toxic effects: nausea, vomiting,
pulmonary and allergic reactions, mutagenicity and carcinogenicity [7-9]. The use of nitrofuran drugs
as a prophylactic feed additive in animal husbandry is no longer allowed by the FDA since 1992, these
drugs being unsafe for oral or parenteral use: residues of both the parent compound and its toxic
metabolites in edible tissues of treated animals represent a health hazard for the consumer [10].
These side effects are mainly due to the weak hydrosolubility of these compounds. Thus, the
introduction of hydrophilic groups in the furan ring could compensate the negative effect of the nitro
group on water solubility. With this aim, we synthesized intermediates from carbohydrates and cyclitol
which were afterwards condensed with furan derivatives. D-Glucosamine, D-galactose, D-fructose and
D-quinic acid were chosen as starting materials.
Results and Discussion
During this work, we synthesized eight final compounds by condensing furfural, furoic acid and 5-
nitro furoic acid with three different aminosugars obtained by described methods [11-12], and with an
aminocyclitol derived from D-quinic acid [13]. The amide 6 was obtained in quantitative yield by
treating 2-D-glucosamine 1 with furoyl chloride 4 in dichloromethane, in the presence of pyridine.
Compound 7 was synthesized in 92 % yield using the same reaction conditions as for 6, but with 5-
nitrofuroyl chloride 5 (Scheme 1). The imine 8 was prepared in 32% yield by condensing 1 with
furfural in anhydrous methanol in the presence of sodium bicarbonate (Scheme 1).
Scheme 1
AcO
AcO
AcO
OAc
OAc
O
OAc
O
OAc
+
AcO
X
O
COCl
H N C
X
NH2.HCl
O
O
4; X= H
5; X=NO2
6; X= H
7; X=NO2
1
AcO
AcO
OAc
OAc
O
OAc
O
N
OAc
Furfural
MeOH
AcO
AcO
NH2.HCl
C
H
1
8
O

Molecules 2001, 6
730
Using a similar method, amines 2 and 3 were treated with furoyl chloride 4 or 5-nitrofuroyl
chloride 5, in dichloromethane in the presence of pyridine, leading to compounds 9 (yield 87%), 10
(yield 93%), 11 and 12, respectively (both in quantitative yields) (Scheme 2).
Scheme 2
O
H2N
O
X
HN
1- Acetone, TsOH
2- TsCl, Py
O
O
O
4 or 5
O
O
O
D-galactose
3- NaN3, DMF
O
O
O
4- H2, Pd/C, EtOH
O
O
2
9 X=H
10 X=NO2
O
O
O
1- Acetone, TsOH
2- TsCl, Py
O
O
O
O
4 or 5
O
X
D-fructose
O
3- NaN3, DMF
4- H2, Pd/C, EtOH
C
NH
O
NH2
O
3
11 X=H
12 X=NO2
To prepare D-quinic acid derivatives, compound 13 [13, 14] was converted to the corresponding
monotosylate 14 in 60% yield by treatment with p-toluenesulfonyl chloride in pyridine (Scheme 3).
Scheme 3
OH
OH
OTs
HOH2C
HO
TsOH2C
HO
TsOH2C
HO
TsOH
Py
+
O
O
O
O
O
O
14
13
18
NaN3
DMF
NO2
O2N
O
O
O
O
O
OH
OH
HNH2C
N3H2C
HO
H2NH2C
HO
H2, Pd/C
EtOH
5
CH2Cl2, Py
O
O
O
O
O
HO
O
15
16
17

Molecules 2001, 6
731
Following this procedure the ditosylated compound 18 was also isolated in 15% yield. Treatment
of 14 with sodium azide in DMF gave compound 15 in 95% yield. The latter was hydrogenated in
ethanol in the presence of Pd/C 10% to furnish the amine 16 in 88% yield. Condensation of 16 with 5-
nitrofuroyl chloride, as described above, afforded the target compound 17 in 60% yield. Deprotection
reactions and biological evaluation of the final compounds are under investigation
Acknowledgments
We wish to thank Drs. M.V.N. De Souza, R. Dodd, J. Cleophax and R. Grazul for many helpful
discussions; CNPq and FAPEMIG (Brazil) for a fellowship and financial support.
Experimental
General
Melting points were determined on a MQAPF-301 apparatus and are uncorrected. Infrared spectra
1
were obtained on a Bomem FT IR MB-102 spectrometer in KBr pellets. H-NMR (400 MHz) and
13C-NMR (100 MHz) spectra were recorded on Bruker Avance DRX 400 spectrometer at the Federal
University of Minas Gerais. The [α]D were recorded on Perkin-Elmer 241-MC sodium absorption at
20 °C. Column chromatography was performed using silica gel 60 G (0.063-0.200 mm. E. Merck).
Elemental analyses were done at the Laboratory of Elemental Analyses of ICSN-CNRS, Gif sur
Yvette, France. All chemicals were reagent grade and were used without further purification.
General method for preparation of acid chlorides.
Furoyl chloride 4 and 5-nitrofuroyl chloride 5 were prepared by reacting the corresponding acids with
thionyl chloride in dichloromethane. The mixture was heated at reflux for 12 h and the solvent was
removed under reduced pressure. The residue was used without further purification.
General method for condensation reactions: preparation of compounds 6, 7 and 9-12.
To a stirred solution of the amine (1 mmol) in anhydrous dichloromethane (10 mL) at 0 °C, were
slowly added the acid chloride (1.5 mmol) and pyridine (3 mmol). The resulting mixture was stirred at
0 °C for 4 h and partitioned between water and dichloromethane. The organic phase was evaporated
under vacuum to dryness and the residue was purified by column chromatography on silica gel, eluting
with AcOEt/hexane.
2-Deoxy-2-(2-furamido)-1,3,4,6-tetra-O-acetyl-β-D-glucopyranoside (6): m p 208-210 °C; [α]D +55(c
1, CH2Cl2); IR (KBr) 1650 (NHC=O); 1750 (OC=O) cm-1; 1H-NMR (CDCl3) δ 1.99; 2.05; 2.08; 2.11;
(4s, 12H, CH3); 3.87 (ddd, 1H, H5, J5-4=9.6 Hz; J5-6=4.6 Hz; J5-6'=2.2 Hz); 4.15 (dd, 1H, H6', J6'-6=12.5

Molecules 2001, 6
732
Hz); 4.30 (dd, 1H, H6); 4.47 (q, 1H, H2); 5.19 (t, 1H, H4, J4-3=9.6 Hz); 5.30 (dd, 1H, H3, J3-2=10.4
Hz); 5.81 (d, 1H, H1, J1-2=8.7 Hz); 6.47 (d, 1H, NH, JNH-2=9.4 Hz); 6.49 (dd, 1H, H4a, J4a-3a=3.5 Hz,
J4a-5a=1.2 Hz); 7.11 (dd, 1H, H3a); 7.43 (d, 1H, H5a); 13C-NMR (CDCl3) δ 20.56, 20.57, 20.72, 20.85
(CH3); 52.51 (C2); 61.68 (C6); 67.88; 72.43; 72.97 (C3, C4, C5); 92.63 (C1); 112.21; 115.16 (C3a,
C4a); 144.56 (C5a); 146.93 (C2a); 158.10 (NHC=O); 169.29; 169.49; 170.67; 171.03 (OC=O); Anal.
Calcd. for C19H23NO11: C, 51.70; H, 5.25; N, 3,17. found: C, 52.06; H, 4.92; N, 3.12.
2-Deoxy-2-(5-nitro-2-furamido)-1,3,4,6-tetra-O-acetyl-β-D-glucopyranoside (7): m p 109-111 °C;
1
[α]D +48 (c 0.7, DMSO); IR (KBr) 1660 (NHC=O); 1740 (OC=O) cm-1; H- NMR (CDCl3) δ 2.03;
2.09; 2.10 (3s, 12H, CH3); 3.98 (ddd, 1H, H5, J5-4=9.6 Hz; J5-6=4.9 Hz; J5-6'=2.3 Hz); 4.17 (dd, 1H,
H6', J6'-6=12.5 Hz); 4.32 (dd, 1H, H6); 4.51 (q, 1H, H2); 5.20 (t, 1H, H4, J4-3 = J4-5=9.6 Hz); 5.50 (dd,
1H, H3, J3-2=10.4 Hz); 5.89 (d, 1H, H1, J1-2=8.7 Hz); 7.27 (d, 1H, H3a, J3a-4a=3.9 Hz); 7.30 (d, 1H,
13
H4a); 7.41 (d, 1H, NH, JNH-2=9.6 Hz); C-NMR (CDCl3) δ 20.49, 20.59, 20.67, 20.86 (CH3); 52.58
(C2); 61.79 (C6); 68.11; 72.47; 72.81 (C3, C4, C5); 91.97 (C1); 112.31; 116.70 (C3a, C4a); 147.15;
151.19 (C2a, C5a); 156.30 (NHC=O); 169.28; 169.36; 170.64; 171.46 (OC=O); Anal. Calcd. for
C19H22N2O13: C, 46.92; H, 4.56; N, 5,76. found: C, 46.98; H, 4.79; N, 5.49.
6-Deoxy-6-(2-furamido)-1,2;3,4-di-O-isopropylidene-α-D-galacto-pyranoside (9): oil; [α]D -35 (c 1,
1
CH2Cl2); IR (KBr) 1650 (C=O) cm-1; H-NMR (CDCl3) δ 1.27; 1.32; 1.48 (3s, 12H, CH3); 3.42 (ddd,
1H, H6, J6-6'=14 Hz; J6-5=4 Hz); 3.89 (ddd, 1H, H6', J6'-5=4 Hz); 4.00 (ddd, 1H, H5, J5-4=1.8 Hz); 4.27
(dd, 1H, H4, J4-3=8.0 Hz); 4.32 (dd, 1H, H2, J2-1=5.0 Hz, J 2-3=2.4 Hz); 4.62 (dd, 1H, H3); 5.54 (d,1H,
H1); 6.48 (dd, 1H, H4a, J4a-3a=3.5 Hz, J4a-5a=1.8 Hz); 6.80 (sl, 1H, NH); 7.10 (d, 1H, H3a); 7.43 (d, 1H,
13
H5a); C-NMR (CDCl3) δ 24.33; 24.94; 25.93; 26.01 (CH3); 39.65 (C6); 66.27; 70.53; 70.82; 71.79
(C2, C3, C4, C5); 96.29 (C1); 108.81, 109.48 [C(CH3)2]; 111.95; 114.01 (C3a, C4a); 143.86 (C5a);
147.97 (C2a); 158.58 (C=O); Anal. Calcd. for C17H23NO7: C, 57.78; H, 6.56; N, 3,96. found: C, 57.67;
H, 6.86; N, 3.78.
6-Deoxy-6-(5-nitro-2-furamido)-1,2;3,4-di-O-isopropylidene-α-D-galactopyranoside (10): oil; IR
(KBr) 1650 (C=O) cm-1; 1H-NMR (CDCl3) δ 1.32; 1.38; 1.49; 1.54 (4s, 12H, CH3); 3.46 (ddd, 1H, H6,
J6-6'=13.8 Hz; J6-5=4.2 Hz); 3.97 (ddd, 1H, H6', J6'-5=4.2 Hz); 4.02 (ddd, 1H, H5, J5-4=1.7 Hz); 4.30 (dd,
1H, H4, J4-3=7.9 Hz); 4.33 (dd, 1H, H2, J2-1=5.0 Hz, J2-3=2.4 Hz); 4.64 (dd, 1H, H3); 5.55 (d,1H, H1);
13
7.30 (sl, 1H, NH); 7.24; 7.34 (2d, 2H, H3a, H4a, J3a-4a=3.7 Hz); C-NMR (CDCl3) δ 24.30; 24.93;
25.96; 26.05 (CH3); 40.60 (C6); 65.23; 70.47; 70.94; 72.35 (C2, C3, C4, C5); 96.42 (C1); 108.87;
109.79 [C(CH3)2]; 112.36; 115.76 (C3a, C4a); 148.18; 151.20 (C2a, C5a); 156.56 (C=O); Anal. Calcd.
for C17H22N2O9: C, 51.26; H, 5.57; N, 7.03. found: C, 51.53; H, 5.87; N, 6.67.
1-Deoxy-1-(2-furamido)-2,3;4,5-di-O-isopropylidene-β-D-fructopyranoside (11): oil; [α]D -16 (c 1.3,
1
CH2Cl2); IR (KBr) 1640 (C=O) cm-1; H-NMR (CDCl3) δ 1.33; 1.41; 1.43; 1.54 (4s, 12H, CH3); 3.72
(dd, 1H, H1, J1-NH=6.0 Hz; J1-1'=14 Hz); 3.76 (d, 1H, H6, J6-6'=13.2 Hz); 3.85 (dd, 1H, H1', J1'-NH=6.0

Molecules 2001, 6
733
Hz); 3.90 (dd, 1H, H6'); 4.22 (dd, 1H, H5, J5-4=7.7 Hz; J5-6'=2.1 Hz); 4.33 (d, 1H, H3, J3-4=2.6 Hz);
4.57 (d, 1H, H4); 6.49 (dd, 1H, H4a, J4a-3a=3.5 Hz, J4a-5a=1.8 Hz); 6.84 (sl, 1H, NH); 7.12 (dd, 1H,
H3a); 7.42 (d, 1H, H5a); 13C-NMR (CDCl3) δ 23.85, 24.95, 25.69, 26.20 (CH3); 46.06 (C1); 61.48
(C6); 70.24; 70.45; 71.91 (C3, C4, C5); 102.69 (C2); 108.39; 109.01 [C(CH3)2]; 112.13; 114.44 (C3a,
C4a); 143.66 (C5a); 147.89 (C2a); 158.52 (C=O); Anal. Calcd. for C17H23NO7: C, 57.78; H, 6.56; N,
3.96. found: C, 57.91; H, 6.41; N, 3.75.
1-Deoxy-1-(5-nitro-2-furamido)-2,3;4,5-di-O-isopropylidene-β-D-fructopyranoside (12): m p 159-162
1
°C; [α]D -27 (c 0.5, DMSO); IR (KBr) 1650 (C=O) cm-1; H-NMR (CDCl3) δ 1.37; 1.42; 1.48; 1.55
(4s, 12H, CH3); 3.72 (dd, 1H, H1, J1-NH=5.4 Hz; J1-1'=14 Hz); 3.77 (d, 1H, H6, J6-6'=13.1Hz); 3.86 (dd,
1H, H1', J1'-NH=5.8 Hz); 3.90 (dd, 1H, H6'); 4.24 (dd, 1H, H5, J5-4=7.7 Hz; J5-6= 2.0 Hz); 4.31 (d, 1H,
H3, J3-4= 2.7 Hz); 4.60 (dd, 1H, H4); 7.16 (sl, 1H, NH); 7,28, 7.37 (2d, 2H, H3a, H4a, J3a-4a=3.7 Hz;
13C-NMR (CDCl3) δ 24.05, 24.86, 25.75, 26.13 (CH3); 46.79 (C1); 61.74 (C6); 70.22; 70.54; 71.91
(C3, C4, C5); 102.30 (C2); 108.77; 109.42 [C(CH3)2]; 112.38; 116.20 (C3a, C4a); 148.00; 151.20
(C2a, C5a); 156.50 (C=O); Anal. Calcd. for C17H22N2O9: C, 51.26; H, 5.57; N, 7.03. found: C, 51.46;
H, 5.45; N, 6.85.
2-Deoxy-2-(furfural)-imino-1,3,4,6-tetra-O-acetyl-β-D-glucopyranoside (8). To a stirred solution of
hydrochloride 1 (1 mmol) in anhydrous methanol (10 mL) at room temperature was added sodium
bicarbonate (1.2 mmol) and distilled furfural (2 mmol). The mixture was heated at reflux for 12 h and
the solvent was removed. The residue was redissolved in dichloromethane and filtered on celite. The
solvent was removed in vacuo and the residue was crystallized from AcOEt/hexane, yielding 32% of
8. Attempts to purify compound 8 by chromatography led to decomposition of the product. m p 114-
116 °C; IR (KBr) 1640 (C=N); 1740 (C=O) cm-1; 1H-NMR (CDCl3) δ 1.92; 2.03; 2.04; 2.09 (4s, 12H,
CH3); 3.43 (dd, 1H, H2, J2-1=8.4 Hz; J2-3=9.6 Hz); 3.96 (ddd, 1H, H5, J5-4=9.6 Hz; J5-6=4.5 Hz; J5-6'=2.2
Hz); 4.12 (dd, 1H, H6', J6'-6=12.5 Hz); 4.37 (dd, 1H, H6); 5.13 (t, 1H, H4, J4-3=9.6 Hz); 5.43 (t, 1H,
H3); 5.94 (d, 1H, H1); 6.50 (dd, 1H, H4a, J4a-3a=3.5 Hz; J4a-5a=1.8 Hz); 6.84 (d, 1H, H3a); 7.54 (d, 1H,
H5a); 8.04 (s, 1H, HC=N); 13C-NMR (CDCl3) δ 20.48; 20.58; 20.63; 20.77 (CH3); 61.73 (C6); 68.07;
72.64; 73.08; 73.19 (C2, C3, C4, C5); 93.08 (C1); 111.86, 115.89 (C3a, C4a); 145.67 (C5a); 150.70
(C2a); 153.2 (C=N); 168.50; 169.40; 169.90; 170.61 (C=O);
Preparation of compounds 14 and 18.
To a solution of compound 13 (2.58 g, 10 mmol) in pyridine (20 mL) at 0 °C was added, in small
portions, p-toluenesulfonyl chloride (2.28 g, 12 mmol). The mixture was stirred for 24 h at room
temperature and extracted with AcOEt. The organic phase was concentrated in vacuo and the residue
was chromatographed on silica gel to give the desired compound 14 and the ditosylate 18 in 60% and
15% yield, respectively.

Molecules 2001, 6
734
(1R,2S,3R,5R)-1,2-O-cyclohexylidene-5-C-[(O-tosyl)-hydroxymethyl]-cyclohexane-1,2,3,5-tetrol (14):
1
m p 134-136 °C; [α]D -16 (c 0.5, DMSO); IR (KBr) 1350 (ROSO2R) cm-1; H-NMR (CDCl3) δ 1.60
(m, 11H, cyclohex., H6); 1.86 (ddd, 1H, H6', J6'-6=13.5 Hz); 1.90 (dd, 1H, H4, J4-4'=15.4 Hz); 2.18 (d,
1H, OH); 2.20 (dt, 1H, H4'); 2.45 (s, 3H, CH3); 3.24 (s, 1H, OH); 3.82 (d, 1H, H7); 3.86 (d, 1H, H7',
J7-7'=9.7 Hz); 3.90 (t, 1H, H2, J2-1=J2-3=6.0 Hz); 4.09 (m, 1H, H1); 4.42 (m, 1H, H3); 7.35; 7.80 (2d,
4H, Ph); 13C-NMR (CDCl3) δ 25.65 (CH3); 23.61; 23.97; 24.87; 33.15; 34.81; 38.05; 38.16 (cyclohex.,
C4, C6); 69.21; 73.71; 79.79; (C1, C2, C3); 71.13 (C5); 75.36 (C7); 110.05 (OCO); 127.98; 129.92;
132.63; 145.02 (Ph). Anal. Calcd. for C20H28O7S: C, 58.24; H, 6.84. found: C, 58.17; H, 6.82.
(1R,2S,3R,5R)-1,2-O-cyclohexylidene-3-O-tosyl-5-C-[(O-tosyl)-hydroxy-methyl]-cyclohexane-1,2,3,5-
1
tetrol (18): m p 124-126 °C (lit [13] m p 123-125 °C); IR (KBr) 1350 (ROSO2R) cm-1; H-NMR
(CDCl3) δ 1.50 (m, 10H, cyclohex.); 1.89 (dd, 1H, H4, J4-4'=15.7 Hz); 1.99 (dt, 1H, H6, J6-6'=13.6 Hz;
J6-1=J6-5=3.2 Hz); 2.07(ddd, 1H, H6'); 2.20 (dt, 1H, H4'); 2.46; 2.48 (2s, 6H, CH3); 3.20 (sl, 1H, OH);
3.77 (d, 1H, H7); 3.83 (d, 1H, H7', J7'-7=9.7 Hz); 4.06 (t, 1H, H2, J2-1=J2-3=6.0 Hz); 4.44 (m, 1H, H1);
13
4.75 (ddd, 1H, H3); 7.34; 7.37; 7.80; 7.82 (4d, 8H, Ph); ); C-NMR (CDCl3) δ 21.64; 21.73 (CH3);
23.48; 23.83; 24.83; 32.82; 34.53; 36.62; 37.43 (cyclohex., C4, C6); 73.62; 76.00; 79.77 (C1, C2, C3);
70.86; 75.00 (C5, C7); 110.35 (OCO); 128.00; 128.15; 129.77; 130.01; 132.49; 133.60; 144.78; 145.20
(Ph).
(1R,2S,3R,5R)-1,2-O-cyclohexylidene-5-C-azidomethyl-cyclohexane-1,2,3,5-tetrol (15). Sodium azide
(0.65 g, 10 mmol) was added to a solution of the tosylate 14 (2.06 g, 5 mmol) in DMF (20 mL). The
mixture was stirred overnight at 140 °C and extracted with AcOEt. The organic phase was
concentrated in vacuo and the residue was chromatographed on silica gel to afford the azide derivative
1
15 in 95% yield; m p 100-102 °C; IR (KBr) 2100 (N3) cm-1; H-NMR (CDCl3) δ 1.60 (m, 11H,
cyclohex., H6); 1.80 (dd, 1H, H4, J4-4'=15.5 Hz); 2.02 (ddd, 1H, H6', J6'-6=13.4 Hz); 2.30 (dt, 1H, H4');
2.59 (d, 1H, OH); 3.13 (d,1H, H7, J7-7'=12.3 Hz); 3.28 (d, 1H, H7'); 3.37 (s, 1H, OH); 3.93 (t, 1H, H2,
J2-1=J2.3=6.0 Hz); 4.11 (m, 1H, H1); 4.45 (ddd, 1H, H3); 13C-NMR (CDCl3) δ 23.64; 24.01; 24.90;
34.84; 35.82; 38.22; 39.20 (cyclohex.; C4, C6); 60.55 (C7); 69.50; 74.47; 80.80 (C1, C2, C3); 73.92
(C5); 110.04 (OCO).
(1R,2S,3R,5R)-1,2-O-cyclohexylidene-5-C-aminomethyl-cyclohexane-1,2,3,5-tetrol (16). The azide 15
(0.85 g, 3 mmol), dissolved in 10 mL of ethanol, was hydrogenated for 4 h in the presence of Pd/C
10% (0.1 g). The catalyst was removed by filtration and the solvent was evaporated in vacuo. The
residue was purified by flash chromatography on silica gel and the amine 16 was isolated in 88%
yield; oil; IR (KBr) 3100-3500 (NH, OH) cm-1; 1H-NMR (C5D5N) δ 1.60 (m, 11H, cyclohex., H6; 1.88
(dd, 1H, H4, J4-4'=13.6 Hz); 2.13 (dd, 1H, H6', J6'-6= 14.6 Hz); 2.40 (m, 1H, H4'); 2.88 (2d, 2H, H7,
H7', J7-7'=12.8 Hz); 4.34 (t, 1H, H2, J2-1=J2-3=6.0 Hz); 4.60 (m, 2H, H1, H3); 4.83 (sl, 4H, NH2, OH);
13C-NMR (C5D5N) δ 24.31; 24.58; 25.59; 35.40; 36.29; 38.64; 41.20 (cyclohex., C4, C6); 53.61 (C7);
68.95; 72.50; 74.40; 81.51 (C1, C2, C3, C5); 109.15 (OCO).

Molecules 2001, 6
735
(1R,2S,3R,5R)-1,2-O-cyclohexylidene-3-O-(5-nitro-2-furoyl)-5-C-[(5-nitro-2-furamide)methyl]cyclo-
hexane-1,2,3,5-tetrol (17). To a stirred solution of 16 (0.257 g, 1 mmol) in anhydrous CH2Cl2 at 0 °C,
were slowly added 5-nitrofuroyl chloride 5 (0.53 g, 3 mmol) and pyridine (0.5 mL). The resulting
mixture was stirred at room temperature for 4 h and extracted with dichloromethane. The solvent was
removed by evaporation and the residue was purified by column chromatography on silica gel, to give
the desired compound 17 in 60% yield; m p 129-131°C; IR (KBr) 1650 (NHC=O), 1740 (OC=O) cm-1;
1H-NMR (CDCl3) δ 1.60 (m, 12H, cyclohex., H6, H6'); 1.94 (dd, 1H, H4, J4-4'=15.4 Hz); 2.35 (dt, 1H,
H4'); 3.50 (dd, 1H, H7, J7-7'=13.6 Hz; J7-NH=7.1 Hz); 3.65 (dd, 1H, H7', J7'-NH=5.7 Hz); 4.24 (t, 1H, H2,
J2-1=J2-3=5.5 Hz); 4.54 (m, 1H, H1); 5.56 (m, 1H, H3); 7.15-7.40 (m, 5H, NH, Hfuranic); 13C-NMR
(CDCl3) δ 23.58; 23.92; 24.83; 33.85; 34.77; 36.85; 37.83 (cyclohex., C4, C6); 48.89 (C7): 72.12;
73.82; 73.91; 76.23 (C1, C2, C3, C5); 110.79 (OCO); 111.56; 112.36; 116.26; 119.30 (C3a, C3b, C4a,
C4b); 144.61; 147.71 (C2a, C2b); 151.40; 153.00 (C5a, C5b); 156.15; 156.80 (NHC=O, OC=O).
References
1. Sanders, H. J.; Edmunds, R. T. and Stillman, W. B. Ind. Eng. Chem., 1995, 47, 358.
2. Adams, G. E.; Breccia, A.; Fielden, E. M. and Wardman, P.; in Selective Activation of Drugs by
Redox Processes, Plenum Press: New York, 1990.
3. Miura, K. and Reckendorf, H. K. Prog. Med. Chem., 1967, 5, 320.
4. Pires, J. R.; Saito, C. S.; Gomes, S. L.; Giesbrecht, A. and Amaral, A. T. 12th European
Symposium on Quantitative Structure-Activity Relationships-Molecular Modelling and
Prediction of Bioactivity, Copenhagen, 1998.
5. Novison, T.; Bhooshan, B.; Okade, T.; Revankar, G. R.; Robins, R. K.; Senga, K. and Wilson, R.
J. Med. Chem., 1976, 19, 512.
6. Naylor, M. A.; Stephens, M. A.; Cole, S.; Threadgill, M. D.; Stratford, I. J.; O’Neill, P.; Fielden,
E. M. and Adams, G. E. J. Med. Chem., 1990, 33, 2508.
7. Wang, C. Y.; Croft, W. A. and Bryan, G. T. Cancer Lett., 1984, 21, 303.
8. Rossi, L.; De Angelis, I.; Pedersen, J. Z.; Marchese, E.; Stammati, A.; Rotilio, G. and Zucco, F.
Mol. Pharmacol., 1996, 49, 547.
9. Holla, B. S.; Kalluraya, B. and Ambekar, S. Y. J. Indian Chem. Soc. 1987, 64, 494.
10. McCalla, D. R. Environ. Mutagen., 1983, 5, 745
11. Humberto, J. L. Ph.D. Thesis, Federal University of Minas Gerais, 1995.
12. Goodwin, C. Carbohydr. Res., 1985, 195, 150.
13. Mercier, M. Ph.D. Thesis, University Paris XI, 1972.
14. Gero, S. D.; Mercier, D.; Leboul, J. and Cleophax, J. Carbohydr. Res., 1972, 20, 299.
Sample Availability: Samples of compounds 1, 2, 3, 6, 7, 8, 9 and 10 are available from MDPI.
© 2001 by MDPI (http://www.mdpi.org). Reproduction is permitted for noncommercial purposes.