Synthesis of new optically active D-glucosamine-pyrrole derivatives

Article abstract of DOI:10.1055/s-0028-1087968

From D-glucosamine hydrochloride was synthesized, for the first time, three new optically active derivatives of D-glucosamine-pyrrole with the pyrrole group unsubstituted in the 2- and 5-positions. New N-benzylpyrrole-D-glucosamine derivatives were also prepared from the same substrate. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0028-1087968

980
PAPER
Synthesis of New Optically Active D-Glucosamine–Pyrrole Derivatives
D
-Glucosamine-P
e
yrrole
D
er
r
Gustavo A. García de la Mora,b Manuel Salmón*a
a
Instituto de Química, Universidad Nacional Autónoma de México, Circuito Exterior, Ciudad Universitaria,
Coyoacán, 04510, D. F. México City, México
E-mail: bafrontu@servidor.unam.mx; E-mail: salmon@servidor.unam.mx
Facultad de Química, Universidad Nacional Autónoma de México, Circuito Exterior, Ciudad Universitaria,
b
Coyoacán, 04510, D. F. México City, México
Fax +52(55)56162203
Received 13 October 2008; revised 5 November 2008
In the present study, D-glucosamine (1) was selected be-
cause it is an economical and abundant source of chirality.
Due to its availability in pure form and at low cost, it has
been used as a chiral template for the synthesis of glyco-
peptides and other interesting bioactive compounds.13,14
Furthermore, there is only one previous example in the lit-
erature, published by Boons,15 concerning the synthesis of
a D-glucosamine–pyrrole derivative. Nevertheless, the
pyrrole they synthesized was substituted at positions 2 and
5, thereby inhibiting polymerization.4 Considering the im-
portance of these chiral molecules as potential monomers
in conducting polymer synthesis, we report a new ap-
proach to the synthesis of chiral pyrrole derivatives that
are free of substitution, using D-glucosamine as a starting
material.
Abstract: From D-glucosamine hydrochloride was synthesized, for
the first time, three new optically active derivatives of D-glu-
cosamine–pyrrole with the pyrrole group unsubstituted in the 2- and
5-positions. New N-benzylpyrrole–D-glucosamine derivatives were
also prepared from the same substrate.
Key words: glycosides, heterocycles, pyrroles, chirality, D-glu-
cosamine
Chiral pyrrole derivatives are significant compounds in
flavors, aromas,1 pharmaceuticals2, as well as in material
science, where they serve as chiral conducting polymers
precursor monomers.3,4 Thus, in the last twenty five years
a great deal of attention has focused on electrodes covered
with chiral conducting polymers5,6 due to their possibility
to induce chirality in prochiral molecules, as demonstrat-
ed in organic electrosynthesis.7–9 In addition, analytical
applications for these electrodes, including chiral recogni-
tion, have been developed.10–12 Despite interest in using
chiral pyrroles in these important applications, their use is
limited by the synthesis of suitable and inexpensive chiral
pyrrole units.
All the initial efforts to obtain the 2-deoxy-2-(1H-pyrrol-
1-yl)-b-D-glucopyranose (6), using 1 and 2,5-dimethoxy-
tetrahydrofuran through the typical Paal–Knorr synthesis
conditions (AcOH, reflux) and Boons methodology15
failed, yielding an intractable mixture of compounds.
Nevertheless, the synthesis of the pyrrole derivatives 5, 6,
O
OH
N
O
OAc
N
O
OH
HO
AcO
AcO
HO
HO
salicylaldehyde
NaHCO3 (aq)
Ac2O, Pyr
(88%);
NH3Cl
HO
(92%)
OH
OAc
OH
3
1
2
HO
HO
acetone
HCl (concd) (85%)
O
OH
N
HO
HO
biphasic system
OH
O
OAc
5
6
O
OAc
(DCE/H2O)
6
i) NaOMe
AcO
1
2
AcO
ii) Dowex H+
2,5-dimethoxytetrahydrofuran
4
2'
4'
3
+
AcO
N
3'
(65%)
AcO
NH3Cl
6 (12%)
7 (70%)
OAc
5'
5
O
OH
N
OAc
HO
HO
4
7
Scheme 1 Synthesis of D-glucosamine–pyrrole derivatives 5, 6, and 7
SYNTHESIS 2009, No. 6, pp 0980–0984
x
x
.
x
x
.2
0
0
9
Advanced online publication: 24.02.2009
DOI: 10.1055/s-0028-1087968; Art ID: M06008SS
© Georg Thieme Verlag Stuttgart · New York

PAPER
D-Glucosamine-Pyrrole Derivatives
981
and 7 was performed via the tetraacetylated D-glu- unit cell packing (Figure 2) is ordered having two pyrrole
cosamine hydrochloride 4 (Scheme 1).
units parallel and perpendicular to the glucosamine group
probably by a p–p interaction that stabilized the unit cell,
whereas all the acetate groups are equatorial relative to the
pyran ring plane in order to avoid steric hindrance.
Thus, the preparation of 4 from 1 required the protection
of the amino group with salicylaldehyde in aqueous sodi-
um hydrogen carbonate solution,16 which afforded iso-
meric imines 2 in 92% yield. The acetylation of the
hydroxy groups in 2 using acetic anhydride/pyridine pro-
duced 3 in high yield. The further hydrolysis of the imine
using concentrated hydrochloric acid in acetone afforded
the protected glucosamine 4 containing a free amino
group in 85% yield.17
The reaction between 4 and 2,5-dimethoxytetrahydrofu-
ran under biphasic conditions18 (H2O/DCE), afforded the
acetylated glucosamine pyrrole 5 in 65% yield. This pro-
cedure has almost equivalent yields (45% for the four re-
actions) compared to the 2,5-dimethylated pyrrole–
glucosamine derivative reported by the Boons method
(51%).15 The hydrolysis of the acetyl groups in 5 in basic
medium after further treatment with an acid exchange
resin19 provided pyrrole 6 in 12% yield. Additionally, the
pyrrole derivative 7 was isolated in 70% yield as an ano-
meric mixture (1:1). Probably the use of a milder ester hy-
drolysis method, such as the use of trimethyltin
Figure 1 X-ray crystal structure of compound 1,3,4,6-tetra-O-ace-
tyl-2-amino-2-deoxy-2-(1H-pyrrol-1-yl)-b-D-glucopyranose (5)
hydroxide,20 could produce 6 in higher yield. This proce- Compound 5 has an optical rotation value of [a]D +62
dure furnished the first synthesis of three new optically (c 0.15, MeOH), in agreement with the rotation sign ob-
active derivatives of D-glucosamine–pyrrole 5, 6, and 7. served in the D-glucosamine hydrochloride (1). Circular
This synthetic method has the advantage of using simple dichroism spectra of 5 showed a positive maxima at
chemical reactions and inexpensive reagents, features that l = 221 nm. Pyrrole 6, similar to 5, has an optical rotation
facilitate scale-up. In order to confirm that 7 was generat- value of same sign observed for D-glucosamine hydro-
ed during the basic or acid medium treatment, 6 was react- chloride {[a]D +73.6 (c 0.19, MeOH)}. Its circular dichro-
ed under the same condition used for the ester hydrolysis ism also showed maxima at 215 and 221 nm. These results
of 5. TLC showed clean transformation of 6 into 7 in 30 confirmed that the optical activity of b-D-glucosamine
minutes. The proposed mechanism for this transformation used as the starting material is conserved in the pyrrole de-
is shown in Scheme 2. Similar mechanisms have been rivatives. Compound 7 showed low optical activity, prob-
proposed for the dehydration of other glucosides.21,22
ably due to epimerization at C2 and the loss of two chiral
carbons when the double bond was generated.
This first family of heterocyclic chiral compounds is char-
acterized by the direct linkage between the pyrrole and the Considering the importance of the chiral pyrroles, it was
sugar moiety, without modification of the D-glucosamine decided to synthesize a second family of D-glucosamine
1
stereochemistry. The H NMR coupling constants estab- heterocyclic derivatives. Thus, our interest was focused
lish that all the substituents of 5 and 6 are equatorial. Ad- on developing a simple method to produce chiral pyrroles
ditional support for this conclusion was obtained from X- 8 and 9 using 4 as the starting material (Scheme 3). There-
ray diffraction, which established the structure of 5 de- fore, 4-(1H-pyrrol-1-yl)benzaldehyde was prepared via
picted in Figure 1. It is also interesting to observe that the Paal–Knorr reaction with 2,5-dimethoxytetrahydrofuran
MeO
O
OH
N
O
OH
O
O
HO
HO
HO
HO
HO
HO
– MeOH
H
N
N
OH
OH
OH
6
– OH
O
OH
OH
O
N
HO
HO
HO
HO
N
7
Scheme 2 Proposed mechanism for the formation of compound 7
Synthesis 2009, No. 6, 980–984 © Thieme Stuttgart · New York

982
B. A. Frontana-Uribe et al.
PAPER
O
OAc
N
AcO
AcO
O
OAc
AcO
AcO
OAc
NH3Cl
OAc
biphasic system
(CH2Cl2/H2O)
TBAB
4
8
(60%)
4-(pyrrol-1-yl)benzaldehyde
N
NaBH3CN,
MeCN–AcOH
O
OAc
NH
AcO
AcO
OAc
9
(95%)
N
Scheme 3 Synthesis of derivatives containing the 4-(1H-pyrrol-1-
yl)benzyl unit coupled to the D-glucosamine moiety
sis of chiral pyrroles with reasonable yields on a
multigram scale.
Figure 2 Unit cell of the crystal 1,3,4,6-tetra-O-acetyl-2-amino-2-
deoxy-2-(1H-pyrrol-1-yl)-b-D-glucopyranose (5)
and 4-aminobenzaldehyde, this last obtained from the re-
duction of the 4-nitrobenzaldehyde with tin(II) chloride.23
The imine 8 was synthesized in a biphasic media under
strong stirring using tetrabutylammonium bromide as a
phase-transfer agent in 60% yield. The imine of 8 showed
an optical rotation value of [a]D +26 (c 0.4, MeOH), in
agreement with the D-glucosamine hydrochloride (1). It
also showed a positive maxima at l = 206 nm. The selec-
tive imino reduction to amino derivative 9 was achieved
with sodium cyanoborohydride/acetonitrile and a catalyt-
ic amount of acetic acid in 57% yield. This derivative
showed an [a]D +21 (c 0.4, MeOH), with a positive maxi-
ma in CD at l = 210 nm. As far as we know, both products
8 and 9 have no precedents in the chemical literature and
this procedure corresponds to their first synthesis. Thus,
with this method we were able to prepare new D-glucopy-
ranose–pyrrole derivatives with a benzylic spacer be-
tween both chemical units.
D-Glucosamine hydrochloride, salicylaldehyde, and 2,5-dimethoxy-
tetrahydrofuran were of the highest purity available and were used
as received from commercial suppliers. Melting points are uncor-
rected and were determined using a Fisher-Johns apparatus. EI-MS
were obtained at 70 eV by direct inlet and HRMS were obtained by
FAB+ technique. 1H NMR (500 MHz or 300 MHz) and 13C NMR
(125 MHz or 75 MHz) spectra were recorded using TMS as the in-
ternal standard in the solvent noted. TLC was performed on alumi-
num sheets pre-coated with silica gel; Flash column
chromatography was carried out on silica gel (0.030–0.075 mm) us-
ing hexanes–EtOAc mixtures. X-ray crystal structure determination
was carried out at 298 K using wavelength equal to 0.71073 Å.
1,3,4,6-Tetra-O-acetyl-2-amino-2-deoxy-b-D-glucopyranose
Hydrochloride (4)
White crystals (EtOAc–MeOH); mp 225–230 °C (dec) [Lit.17 230
°C (dec)].
IR (KBr): 3300–2500 (br), 2002, 1761, 1594, 1513, 1433, 1365,
1201, 1038, 898, 666, 639, 600 cm–1.
1H NMR (300 MHz, CD3OD): d = 5.88 (d, J = 8.7 Hz, 1 H, H1),
In this paper the synthesis of two new families of optically 5.37 (dd, J = 10.5, 9.3 Hz, 1 H, H3), 5.08 (dd, J = 10.2, 9.3 Hz, 1 H,
+
H4), 4.82 (s, 3 H, NH3 ), 4.3 (dd, J = 12.6, 4.5 Hz, 1 H, H6), 4.11
active pyrroles containing a glucopyranose group, starting
(dd, J = 12.6, 2.7 Hz, 1 H, H6), 4.03 (m, 1 H, H5), 3.62 (dd,
from b-D-glucosamine derivative is reported. The first
J = 10.5, 9 Hz, 1 H, H2), 2.19 (s, 3 H, CH3CO), 2.09 (s, 3 H,
family has the pyrrole ring directly attached to the sugar
CH3CO), 2.029 (s, 3 H, CH3CO), 2.022 (s, 3 H, CH3CO).
13C NMR (75 MHz, CD3OD): d = 172.1, 171.9, 171.1, 170.0, 91.6,
74.0, 72.1, 69.3, 62.6, 54.4, 20.7, 20.6, 20.45 (2 C).
MS (EI): m/z (%) = 347 ([M – HCl]+, 9), 305 (3), 287 (24), 245 (21),
227 (13), 199 (10), 185 (31), 168 (14), 156 (16), 138 (12), 125 (18),
114 (83), 101 (38), 96 (32), 72 (63), 59 (53), 43 (100).
moiety whereas the second family has a benzylic spacer
between them. The synthesized pyrroles have positions 2
and 5 free and could be used for oxidative polymerization
reactions in material science. Notwithstanding the use of
classical reactions during the synthesis, which is an addi-
tional advantage, this is a suitable method for the synthe-
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D-Glucosamine-Pyrrole Derivatives
983
HRMS (FAB+): m/z [M – HCl]+ calcd for C14H21NO9: 348.1295;
found: 348.1293.
H2O (5 mL). H2O was evaporated under high vacuum at 50–60 °C
and the residue dissolved in acetone and adsorbed on Celite. The
mixture of products was separated by flash column chromatography
(silica gel, EtOAc–hexanes, 50:50). Compound 6 (51 mg, 12%) was
eluted first and the second, 7 (300 mg, 70%), was obtained after
concentration of the fractions.
1,3,4,6-Tetra-O-acetyl-2-amino-2-deoxy-2-(1H-pyrrol-1-yl)-b-
D-glucopyranose (5)
In a round-bottomed flask fitted with a condenser, 4 (2.8 g, 7.3
mmol), H2O (35 mL), DCE (30 mL), and 1,5-dimethoxytetrahydro-
furan were added. The mixture was refluxed and magnetically
stirred, vigorously, for 45 min. The reaction was neutralized with
sat. NaHCO3 soln and the organic compounds were separated by ex-
traction with DCE (3 × 25 mL). The combined organic extracts
were dried (MgSO4) and concentrated using a rotary evaporator un-
der vacuum. The product was purified by column chromatography
to give 5 (1.9 g, 65%) as a white amorphous solid. Recrystallization
(Et2O–hexanes) gave a white foamy product; mp 107–108 °C. From
slow evaporation of a soln of 5 (acetone–hexane), monocrystals
were obtained and the X-ray crystal structure was obtained (vide in-
fra).
2-Deoxy-2-(1H-pyrrol-1-yl)-b-D-glucopyranose (6)
White powder; mp 135–136 °C.
[a]D +73.6 (c 0.19, MeOH); CD lmax = 215, 221 nm.
IR (KBr): 3439, 3404, 3112, 2950, 1489, 1287, 1122, 1074, 1038,
1005, 956, 840, 733 cm–1.
1H NMR (300 MHz, CDCl3 + 1 drop DMSO-d6): d = 7.37 (s, 1 H,
exch D2O, OH), 6.68 (t, J = 2.1 Hz, 2 H, H2¢), 6.16 (t, J = 2.1 Hz, 2
H, H3¢), 5.61 (s, 1 H, H1), 4.97 (dd, J = 5.9, 5.9 Hz, 1 H, H4), 4.56
(s, 1 H, H2), 4.71 (d, J = 5.9 Hz, 1 H, H3), 4.4 (br s, 3 H, exch D2O,
3 OH), 4.26 (ddd, J = 5.9, 5.4, 4.8 Hz, 1 H, H5), 4.02 (dd, J = 9.6,
4.8 Hz, 1 H, H6), 3.80 (dd, J = 9.6, 5.4 Hz, 1 H, H6).
[a]D +62 (c 0.15, MeOH); CD lmax = 221 nm.
13C NMR (75 MHz, CDCl3 + 1 drop DMSO-d6): d = 118.9, 108.8,
103.4, 88.03, 84.4, 74.01 (t), 70.81, 70.70.
IR (CHCl3): 3050, 2950, 1754, 1485, 1425, 1367, 1283, 1077, 1044,
903 cm–1.
MS (EI): m/z (%) = 211 ([M+ – H2O], 100), 182 (8), 166 (12), 150
(22), 136 (13), 122 (14), 118 (17), 104 (17), 93 (30), 80 (43), 68
(62), 67 (27), 55 (18).
HRMS (FAB+): m/z [M+ – H2O] calcd for C10H13NO4: 212.0923;
found: 212.0921.
1H NMR (300 MHz, CDCl3): d = 6.64 (t, J = 2.1 Hz, 2 H, H2¢), 6.12
(t, J = 2.1 Hz, 2 H, H3¢), 5.95 (d, J = 9 Hz, 1 H, H1), 5.56 (dd,
J = 11.1, 9.3 Hz, 1 H, H3), 5.16 (dd, J = 10.2, 9.3 Hz, 1 H, H4), 4.37
(dd, J = 12.0, 4.2 Hz, 1 H, H6), 4.11 (dd, J = 12.0, 2.1 Hz, 1 H, H6),
3.62 (dd, J = 11.1, 9 Hz, 1 H, H2), 3.98 (m, 1 H, H5), 2.1 (s, 3 H,
CH3CO), 2.04 (s, 3 H, CH3CO), 1.98 (s, 3 H, CH3CO), 1.86 (s, 3 H,
CH3CO).
2,3-Dideoxy-2-(1H-pyrrol-1-yl)-D-erythro-hex-2-enopyranose
(7)
Transparent oil; mixture of C2 anomers.
13C NMR (75 MHz, CDCl3): d = 170.4, 169.5, 169.3, 168.4, 119.5,
109.2, 92.1, 72.8, 72.1, 68.3, 61.9, 61.5, 20.6, 20.5 (2 C), 20.1.
MS (EI): m/z (%) = 397 ([M]+, 82), 338 (11), 260 (25), 235 (7), 218
(18), 190 (24), 188 (21), 176 (26), 164 (25), 146 (18), 134 (29), 130
(43), 122 (58), 109 (24), 97 (9), 80 (12), 68 (17), 43 (100).
HRMS (FAB+): m/z [M]+ calcd for C18H23NO9: 397.1373; found:
397.1365.
IR (CHCl3): 3379 (br), 2931, 2891, 1671, 1489, 1370, 1315, 1074
(br), 731 cm–1.
1H NMR (300 MHz, acetone-d6): d = 7.1 (q, J = 2.1 Hz, 2 H, H2¢
epimer A), 7.05 (t, J = 2.1 Hz, 2 H, H2¢ epimer B), 6.24 (m, 1 H, H3
epimer A), 6.17 (s, 1 H, H1 epimer B), 6.14 (q, J = 2.1 Hz, 2 H, H3¢
epimer A), 6.11 (t, J = 2.1 Hz, 2 H, H3¢ epimer B), 6.03 (d, J = 1.2
Hz, 1 H, H1 epimer A), 6.01 (dd, J = 4.5, 5.1 Hz, 1 H, H3 epimer
B), 5.75 (m, 1 H, 5-OH), 4.92 (ddd, J = 5.7, 4.2, 1.5 Hz, 1 H, H4
epimer A), 4.84 (ddd, J = 4.5, 1.8, 0.6 Hz, 1 H, H4 epimer B), 3.9–
3.5 (m, 3 H, H5 and H6 both epimers).
13C NMR (75 MHz, CDCl3): d = 139.9, 139.3, 120.1, 110.6, 110.5,
109.6, 108.5, 100.4, 99.7, 85.5, 84.6, 75.5, 74.5, 64.2, 64.0.
MS (EI): m/z (%) = 211 ([M+ – H2O] 100), 182 (8), 166 (12), 150
(22), 136 (13), 122 (14), 118 (17), 104 (17), 93 (30), 80 (43), 68
(62), 67 (27), 55 (18).
Monocrystal data for X-ray diffraction:24 T = 298(2) K; l = 0.71073
Å; crystal system: monoclinic; space group P21; unit cell dimen-
sions: a = 9.180(1) Å, a = 90°, b = 6.701(1) Å, b = 104.501(3)°,
c = 16.909(2) Å, g = 90°; volume: 1007.0(2) Å3; Z = 2; density (cal-
cd): 1.311 mg/m3; absorption coefficient: 0.106 mm–1;
F(000) = 420; crystal size/color/shape: 0.276 × 0.176 × 0.034 mm/
colorless/plates; q range for data collection = 1.24 to 25.33°; index
ranges: –11 £ h £ 10, –8 £ k £ 8, –20 £ l £ 20; reflections collected:
8501; independent reflections: 2008 [Rint = 0.0638]; completeness
to q = 25.33° 99.9%; absorption correction: semi-empirical from
equivalents; max. and min. transmission: 0.99592 and 0.97444; re-
finement method: full-matrix least-squares on F2; data/restraints/
parameters: 2008/245/343; goodness-of-fit on F2: 1.022; final R in-
dices [I >2s(I)]: R1 = 0.0529, wR2 = 0.0971; R indices (all data):
R1 = 0.0941, wR2 = 0.1114; largest diff. peak and hole: 0.133 and –
0.133 e Å–3; remarks: main residue disorder: 24%.
HRMS (FAB+): m/z [M]+ calcd for C10H13NO4: 212.0923; found:
212.0921.
1,3,4,6-Tetra-O-acetyl-2-deoxy-2-{[4-(1H-pyrrol-1-yl)ben-
zylidene]amino}-b-D-glucopyranose (8)
To a round-bottomed flask were added 4 (1 g, 2.62 mmol), NaHCO3
(137 mg), TBAB (100 mg), 4-(1H-pyrrol-1-yl)benzaldehyde (448
mg, 2.6 mmol), CH2Cl2 (5 mL), and H2O (5 mL). The mixture was
magnetically stirred, vigorously, for 48 h. The organic compounds
were separated by extraction with CH2Cl2 (3 × 15 mL). The com-
bined organic extracts were dried (Na2SO4), filtered over Celite, and
concentrated on a rotary evaporator under vacuum. The product was
purified by column chromatography to give 8 (786 mg, 60%) as an
amorphous solid. Recrystallization (acetone–hexane) gave a white
product; mp 191–192 °C.
2-Deoxy-2-(1H-pyrrol-1-yl)-b-D-glucopyranose (6) and 2,3-
Dideoxy-2-(pyrrol-1-yl)-D-erythro-hex-2-enopyranose (7)
Na metal (50 mg, 2.1 mmol) was cut in small pieces and added to a
one-necked round-bottomed flask (dried overnight) containing an-
hyd MeOH (15 mL). The flask was closed with a septa and was
maintained under N2 with a balloon under magnetic stirring. When
the Na had reacted completely, 5 (795 mg, 2 mmol) was added to
the soln and the mixture was stirred at r.t. for 1 h; TLC showed com-
plete disappearance of 5 and the presence of 2 new compounds of
higher polarity [TLC (silica gel, EtOAc): Rf = 0.70 (6), 0.50 (7)].
MeOH was evaporated under high vacuum and the residue was re-
dissolved in H2O (10 mL) and treated with resin Dowex 50W H+ (2
g) for 1 min. After this period the resin was filtered and rinsed with
[a]D +26 (c 0.4, CH2Cl2); CD lmax = 206 nm.
IR (KBr): 2922, 2876, 1746, 1215, 1075, 1038 cm–1.
Synthesis 2009, No. 6, 980–984 © Thieme Stuttgart · New York

984
B. A. Frontana-Uribe et al.
PAPER
1H NMR (300 MHz, CDCl3): d = 8.4 (s, 1 H, H2¢), 7.78 (d, J = 4.3
Hz, 2 H, H4¢), 7.42 (d, J = 4.3 Hz, 2 H, H5¢) 7.13 (t, J = 2.1 Hz, 2
H, H8¢), 6.37 (t, J = 2.1 Hz, 2 H, H9¢), 5.95 (d, J = 9 Hz, 1 H, H1),
5.46 (dd, J = 11.1, 9.3 Hz, 1 H, H3), 5.16 (dd, J = 10.2, 9.3 Hz, 1 H,
H4), 4.37 (dd, J = 12.0, 4.2 Hz, 1 H, H6), 4.17 (dd, J = 12.0, 2.1 Hz,
1 H, H6), 4.15 (m, 1 H, H5), 3.51 (dd, J = 11.1, 9 Hz, 1 H, H2), 2.1
(s, 3 H, CH3CO), 2.04 (s, 3 H, CH3CO), 2.03 (s, 3 H, CH3CO), 1.89
(s, 3 H, CH3CO).
Acknowledgment
The authors acknowledge Mrs. Isabel Chávez, Rocío Patiño, Javier
Pérez, Luis Velazco, Elizabeth Huerta, Ma de los Angeles Peña, and
M. Nieves Zavala for their technical assistance. Financial support
from the CONACYT-Mexico projects No. 57856 and No. 059935
is also acknowledged.
13C NMR (75 MHz, CDCl3): d = 170.4, 169.7, 169.3, 168.5, 163.8,
143.2, 132.6, 131.4, 129, 123.9, 120.0, 119.7, 119, 111.2, 93.2,
73.3, 73.1, 73, 68.4, 62.0, 20.6, 20.5, 20.3.
MS (EI): m/z (%) = 500 ([M]+, 20), 440 (62), 398 (20), 355 (18), 339
(21), 295 (16), 267 (48), 250 (28), 225 (52), 212 (23), 156 (70), 43
(100), 18 (41).
References
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(4) Heinze, J. In Encyclopedia of Electrochemistry, Vol. 8;
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2004, Chap. 16.
HRMS (FAB+): m/z [M]+ calcd for C25H28N2O9: 501.1873; found:
501.1867.
UV (MeOH): l = 300, 219.5, 205 nm.
(5) Salmon, M.; Aguilar, M. M. Curr. Top. Electrochem. 1994,
3, 53.
(6) Nonaka, T. In Organic Electrochemistry; Lund, H.; Baizer,
M. M., Eds.; Marcel Dekker: New York, 1991, 3rd ed., 1131.
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1983, 56, 2778.
(8) Komori, T.; Nonaka, T. J. Am. Chem. Soc. 1984, 106, 2656.
(9) Schwientek, M.; Pleus, S.; Hamann, C. H. J. Electroanal.
Chem. 1999, 461, 94.
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Utille, J.-P. Adv. Mater. (Weinheim, Ger.) 1992, 4, 511.
(11) Pleus, S.; Schwientek, M. Synth. Met. 1998, 95, 233.
(12) Stefan, R.-I.; Aboul-Enein, H. Y.; van Staden, J. F. Sensors
Update 2002, 10, 123.
1,3,4,6-Tetra-O-acetyl-2-deoxy-2-{[4-(1H-pyrrol-1-yl)ben-
zyl]amino}-b-D-glucopyranose (9)
A 2-mL syringe was charged with 8 (1 g, 2 mmol) dissolved in an-
hyd MeCN (1 mL) and this soln was slowly added to a 25-mL mag-
netically stirred round-bottomed flask containing NaBH3CN (320
mg, 5.09 mmol) in MeCN (5 mL). The flask was under N2 atmo-
sphere (balloon) during the reaction. The pH of the soln was adjust-
ed to approx. 5–7 with glacial AcOH (4 drops). The reaction was
stirred at r.t. for 45 min; TLC showed complete disappearance of 8
[TLC (hexane–EtOAc, 1:1): Rf = 0.50 (8), 0.40 (9)]. The soln was
diluted with CH2Cl2 and washed with sat. NaHCO3 soln and brine.
Organic phase collected was dried (Na2SO4), filtered over Celite,
concentrated on a rotary evaporator under vacuum and dried over-
night (house vacuum). Compound 9 (953 mg, 95%) was obtained as
a viscous yellow oil.
(13) Ichikawa, Y.; Ohara, F.; Kotsuki, H.; Nakano, K. Org. Lett.
2006, 8, 5009.
(14) Kunz, H.; Rück, K. Angew. Chem., Int. Ed. Engl. 1993, 32,
[a]D +21 (c 0.4 MeOH); CD lmax = 210 nm.
336.
IR (KBr): 3358, 3141, 2925, 1705, 1522, 1369, 1328, 1224, 1114,
1070, 1044 cm–1.
(15) Bowers, S. G.; Coe, D. M.; Boons, G.-J. J. Org. Chem. 1998,
63, 4570.
1H NMR (300 MHz, CDCl3): d = 7.32 (d, J = 4.3 Hz, 2 H, H4¢), 7.26
(d, J = 4.3 Hz, 2 H, H5¢) 7.13 (t, J = 2.1 Hz, 2 H, H8¢), 6.34 (t,
J = 2.1 Hz, 2 H, H9¢), 6.60 (d, J = 9 Hz, 1 H, H1), 5.10 (dd, J = 11.1,
9.3 Hz, 1 H, H3), 5.00 (dd, J = 10.2, 9.3 Hz, 1 H, H4), 4.30 (dd,
J = 12.0, 4.2 Hz, 1 H, H6), 4.09 (dd, J = 12.0, 2.1 Hz, 1 H, H6), 3.89
(m, 1 H, H5), 3.83 (d, 2 H, H2¢), 2.95 (dd, J = 11.1, 9 Hz, 1 H, H2),
2.1 (s, 3 H, CH3CO), 2.07 (s, 3 H, CH3CO), 2.03 (s, 3 H, CH3CO),
2.02 (s, 3 H, CH3CO), 2.0 (s, 1 H, H1¢).
(16) Irving, J. C.; Earl, J. C. J. Chem. Soc. 1922, 2376.
(17) (a) Bergmann, M.; Zervas, L. Ber. Dtsch. Chem. Ges. B
1931, 64, 975. (b) White, T. J. Chem. Soc. 1938, 1498.
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Acta 1995, 78, 1511.
(19) Kawana, M.; Emoto, S. Bull. Chem. Soc. Jpn. 1969, 42,
3539.
(20) (a) Nicolaou, K. C.; Estrada, A. A.; Zak, M.; Lee, S. H.;
Safina, B. S. Angew. Chem. Int. Ed. 2005, 44, 1378.
(b) Nicolaou, K. C.; Bulger, P. G.; Brenzovich, W. E. Org.
Biomol. Chem. 2006, 4, 2158.
13C NMR (75 MHz, CDCl3): d = 170.8, 170.6, 169.6, 169.0, 139.9,
137.3, 129.2, 120.5, 119.2, 110.4, 94.9, 73.9, 72.6, 68.3, 61.8, 60.3,
51.5, 21, 20.6.
(21) Dawe, R. D.; Fraser-Reid, B. J. Org. Chem. 1984, 49, 522.
(22) Allevi, P.; Anastasia, M.; Ciuffreda, P.; Fiecchi, A.; Scala,
A. J. Chem. Soc., Perkin Trans. 1 1989, 1275.
(23) Bellamy, F.; Ou, K. Tetrahedron Lett. 1984, 25, 839.
(24) Crystallographic data for compound 5 were deposited at the
Cambridge Crystallographic Data Centre with deposit
number CCDC-644070.
MS (EI): m/z (%) = 502 ([M]+ 1), 442 (4), 425 (1), 411 (1), 383 (1),
323 (1), 295 (1), 256 (3), 231 (2), 214 (14), 171 (11), 156 (100), 128
(5), 43 (20), 18 (5).
HRMS (FAB+): m/z [M]+ calcd for C25H30N2O9: 503.2030; found:
503.2034.
UV (MeOH): l = 257, 206 nm.
Synthesis 2009, No. 6, 980–984 © Thieme Stuttgart · New York