A very simple synthesis of 1-(ethyl 6-O-acetyl-2,3,4-trideoxy-α-D- erythro-hex-2-enopyranos-4-yl)-1,2,3-triazole derivatives

Article abstract of DOI:10.1055/s-2006-926280

The copper-catalyzed reaction of ethyl 4-azido-6-O-acetoxy-2,3,4-trideoxy- α-D-erythro-hex-2-enopyranoside with various functionalized alkynes gave the corresponding 1-(ethyl 6-O-acetyl-2,3,4-trideoxy-α-D-erythro-hex-2- enopyranos-4-yl)-1,2,3-triazole der

Full text of DOI:10.1055/s-2006-926280

PAPER
467
A Very Simple Synthesis of 1-(Ethyl 6-O-Acetyl-2,3,4-trideoxy-
a-D-erythro-hex-2-enopyranos-4-yl)-1,2,3-triazole Derivatives
1
-(1-
O
-Ethyl 6-
O
o
-Acetyl-2,3,
n
4-trideoxy-
a
-
d-erythro-h
l
ex-2-e
d
nopyranos-4
o
-yl)-1,2,3-triazole
D
N
erivative
s
. de Oliveira,a,b Denis Sinou,*a Rajendra M. Srivastava*b
a
Laboratoire de Synthèse Asymétrique, UMR 5181, ESCPE Lyon, Université Claude Bernard Lyon1, 43 boulevard du 11 Novembre
1918, 69662, Villeurbanne Cedex, France
Fax +33(4)78898914; E-mail: sinou@univ-lyon1.fr
Departamento de Quimica Fundamental, Universidade Federal de Pernambuco, Cidade Universitaria, 50740-540, Recife, PE, Brazil
b
Received 25 July 2005; revised 16 August 2005
Ethyl
6-O-acetyl-4-azido-2,3,4-trideoxy-a-D-erythro-
Abstract: The copper-catalyzed reaction of ethyl 4-azido-6-O-ace-
toxy-2,3,4-trideoxy-a-D-erythro-hex-2-enopyranoside with various
functionalized alkynes gave the corresponding 1-(ethyl 6-O-acetyl-
2,3,4-trideoxy-a-D-erythro-hex-2-enopyranos-4-yl)-1,2,3-triazole
hex-2-enopyranoside (2) reacted with ethynylbenzene in a
1:1 mixture of water and tert-butyl alcohol in the presence
of copper(II) acetate and sodium ascorbate at room
derivatives in quite good yields, which could be transformed into temperature to give ethyl 6-O-acetyl-2,3,4-trideoxy-4-(4-
(ethyl 2,3,6-tri-O-acetyl-4-deoxy-a-D-mannopyranosyl)-1H-1,2,3-
triazole by a simple bis-hydroxylation.
phenyl-1H-1,2,3-triazol-1-yl)-a-D-erythro-hex-2-enopy-
ranoside (3a) as the sole product in 82% yield after col-
umn chromatographical purification (Scheme 1). The
regioselectivity of the 1,3-dipolar cycloaddition reaction
was explained according to the previous results using this
methodology and to the mechanism proposed by Sharp-
Key words: 1,2,3-triazole based-carbohydrate, hexenopyranoside,
cycloaddition, Cu catalyst
Glycoconjugates play important roles in many biological less.28
processes,1–3 including particularly cellular recognition in
The scope of this copper-catalyzed introduction of the tri-
the case of inflammation,4–6 tumor metastasis,7 immune
response,8,9 and bacterial and viral infections.1 In the
course of a project involving the synthesis and biological
evaluation of a series of new aminosugars,10–13 we were
attracted by N-triazole derivatives of unsaturated carbo-
hydrates where this heterocyclic nucleus is located at C-4
of the pyranosyl structure. Substituted triazoles have been
shown to display important biological activity.14–17 Sur-
prisingly, in view of the ready availability of these poten-
tial glycomimetics, the literature reports only a handful
examples of N-substituted triazole carbohydrates, most of
them bearing the triazole structure at the anomeric posi-
tion.18–26 Herein, we describe some preliminary results
dealing with the synthesis of some 1-(ethyl 6-O-acetyl-
2,3,4-trideoxy-a-D-erythro-hex-2-enopyranos-4-yl)-
1,2,3-triazole derivatives.
azole moiety at C-4 of the unsaturated carbohydrate is re-
markably efficient and can be used to link a variety of
functionalities to this position of monosaccharides. Con-
densation of azido carbohydrate 2 with propargylic alco-
hol, methyl propiolate, and but-3-yn-2-one, gave the
corresponding triazoles 3b, 3c, and 3d, in 70%, 75%, and
83% yields, respectively, after purification by column
chromatography. Reaction of tert-butyl prop-2-ynylcar-
bamate with azido carbohydrate 2 gave the unsaturated
triazolylglycoside 3e in 82% yield, showing the compati-
bility of the Boc group with the reaction conditions. More-
over, reaction of
a racemic mixture of N-Boc-
propargylglycine methyl ester gave triazole 3f in 88%
yield as a 1:1 mixture of the two epimers.
Condensation of unsaturated azido carbohydrate 2 (2
equiv) with 1,4-diethynylbenzene (1 equiv) afforded also
cleanly 4,4¢-[(1,4-phenylene)-bis(ethyl 6-O-acetyl-2,3,4-
trideoxy-a-D-erythro-hex-2-enopyranosyl)]-di-1H-1,2,3-
triazole (4) in 89% yield after column chromatography
(Scheme 2). Compound 4 was then subjected to the bis-
hydroxylation reaction in the presence of a catalytic
amount of OsO4 and N-methylmorpholine-N-oxide
(NMO). As expected, 4,4¢-[(1,4-phenylene)-bis(ethyl
2,3,6-O-acetyl-4-deoxy-a-D-mannopyranosyl)]-1H-1,2,3-
triazole (5) was obtained in 86% yield after acetylation of
the crude mixture as the unique product. This compound
resulted from the bis-hydroxylation on the less hindered
side of the double bond, as expected from preceding re-
sults in this field.30,31 The assigned configurations are
mainly based on the coupling constants J4,5 = 10.6 Hz and
J3,4 = 10.9 Hz, which are characteristic for axial–axial
coupling of H-4/H-5 and H-3/H-4.
We have recently described an easy access to ethyl 4-azi-
do-6-O-acetoxy-2,3,4-trideoxy-a-D-erythro-hex-2-eno-
pyranoside (2) from unsaturated carbohydrate 1 by
reaction of the latter with NaN3 in the presence of
Pd(PPh3)4 and 1,4-bis(diphenylphosphino)butane
(dppb).27 We expected that this unsaturated azido carbohy-
drate could be the precursor of the corresponding unsatur-
ated 1,2,3-triazole derivative, which could be synthesized
via a copper-catalyzed 1,3-dipolar cycloaddition reaction
with the appropriate alkyne.28,29 It is noteworthy that this
copper-catalyzed reaction generally proceeds quantita-
tively under very mild conditions with very high regiose-
lectivity and high tolerance of functionalities.
SYNTHESIS 2006, No. 3, pp 0467–0470
x
x
.
x
x
.2
0
0
5
Advanced online publication: 11.01.2006
DOI: 10.1055/s-2006-926280; Art ID: Z14905SS
© Georg Thieme Verlag Stuttgart · New York

468
R. N. de Oliveira et al.
PAPER
Copper-catalyzed [3+2] cycloaddition of ethyl 4-azido- 13C (75 MHz), internal standard CDCl3 at d = 77.23 ppm.
2,3,4-trideoxy-a-D-erythro-hex-2-enopyranoside (2) with Ethyl 4-azido-6-O-acetoxy-2,3,4-trideoxy-a-D-erythro-
various functionalized alkynes afforded the correspond- hex-2-enopyranoside (2)27 and racemic N-Boc-propar-
ing 1-(ethyl 2,3,4-trideoxy-a-D-erythro-hex-2-enopyran- gylglycine methyl ester32 were prepared according to the
os-4-yl)-1,2,3-triazole derivatives 3a–f in quite good literature. Hexanes used have bp 40–65 °C.
yields. Bis-hydroxylation of these intermediates gave the
corresponding
1,2,3-triazole.
(4-deoxy-a-D-mannopyranosyl)]-1H-
Preparation of 1,4-Disubstituted 1,2,3-Triazoles (3); General
Procedure
AcO
4-Azido sugar 2 (241 mg, 1.05 mmol) and alkyne derivative (3
mmol) were suspended in tert-BuOH–H2O (1:1, 4 mL). To this so-
lution was added a mixture of Cu(OAc)2 (36 mg, 0.20 mmol) and
sodium ascorbate (79.5 mg, 0.401 mmol) in tert-BuOH–H2O (1:1,
1 mL). The contents were stirred overnight under N2 at r.t. When
TLC analysis indicated complete consumption of the product, H2O
(3 mL) was added and the product was extracted with CH2Cl2 (3 × 5
mL). The combined organic layers were dried over Na2SO4. Evap-
oration of the solvent under reduced pressure gave a residue that
was purified by column chromatography (hexanes–EtOAc, ratios as
specified below) to give compounds 3.
AcO
O
AcO
O
O
i
ii
N
N
OC2H5
AcO
OC2H5
N3
OC2H5
N
R
1
3 a–f
2
a: R = C6H5 (82% yield)
b: R = C6H4Br (67% yield)
c: R = CO2Me (75% yield)
d: R = COCH3 (83% yield)
e: R = CH2NHBoc (82% yield)
f: R = (R,S)-CH2CH(CO2Et)NHBoc (88% yield)
Ethyl 6-O-Acetyl-2,3,4-trideoxy-4-(4-phenyl-1H-1,2,3-triazol-1-
yl]-a-D-erythro-hex-2-enopyranoside (3a)
Scheme 1 Reagents and conditions: i) NaN3, cat. Pd(PPh3)4 + dppb,
THF, 25 °C; ii) R–C≡C–H, H2O–tert-BuOH (1:1), Cu(OAc)2 (20
mol%), and sodium ascorbate (40 mol%)
Colorless oil; yield: 295 mg (82%); Rf = 0.3 (hexanes–EtOAc, 7:3);
[a]D20 +169 (c 2.0, CH2Cl2).
1H NMR (300 MHz, CDCl3): d = 1.31 (t, J = 7.1 Hz, 3 H, CH3,),
2.08 (s, 3 H, CH3CO), 3.67 (dq, J = 9.7, 7.1 Hz, 1 H, OCH2CH3),
3.90 (dq, J = 9.7, 7.1 Hz, 1 H, OCH2CH3), 4.12 (dd, J = 12.2, 5.1
Hz, 1 H, H-6), 4.23 (dd, J = 12.2, 2.8 Hz, 1 H, H-6), 4.35 (ddd,
J = 9.9, 5.1, 2.8 Hz, 1 H, H-5), 5.20 (br s, 1 H, H-1), 5.47 (dd,
J = 9.9, 1.7 Hz, 1 H, H-4), 6.05 (br d, J = 10.0 Hz, 1 H, H-3), 6.40
(ddd, J = 10.0, 2.8, 2.8 Hz, 1 H, H-2), 7.36 (dd, J = 7.5, 7.5 Hz, 1 H,
All commercially available reagents were used as re-
ceived. All reactions were monitored by TLC analysis
(TLC plates GF254, Merck). Air- and moisture-sensitive
reactions were performed with inert-atmosphere tech-
niques. Melting points were determined on a Büchi appa-
ratus and are uncorrected. Column chromatography was
performed on silica gel 60 (230–240 mesh, Merck). Opti-
cal rotations were recorded using a Perkin-Elmer 241 po-
larimeter. NMR spectra were recorded with a Bruker
AMX 300 spectrometer and were referenced as follows:
1H (300 MHz), internal standard SiMe4 at d = 0.00 ppm,
Harom), 7.43 (dd, J = 7.5 Hz, 2 H, Harom), 7.83–7.87 (m, 3 H, Harom,
Htriaz).
13C NMR (75 MHz, CDCl3): d = 15.7, 21.1, 55.8, 63.3, 65.0, 68.7,
94.4, 118.4, 126.1, 129.3, 127.8, 128.8, 130.0, 130.6, 148.8, 170.8.
Anal. Calcd for C18H21O4N3: C, 62.96; H, 6.16. Found: C, 62.66; H,
5.98.
AcO
O
AcO
N
OC2H5
O
N
i
N
N
+
C2H5O
N
N
O
N3
OC2H5
OAc
2
4
ii, iii
AcO
AcO OAc
O
N
OC2H5
N
N
N
C2H5O
N
N
O
OAc
AcO OAc
5
Scheme 2 Reagents and conditions: i) H2O–tert-BuOH (1:1), Cu(OAc)2 (20 mol%), and sodium ascorbate (40 mol%); ii) cat. OsO4, NMO,
acetone–water, r.t.; iii) Ac2O, pyridine
Synthesis 2006, No. 3, 467–470 © Thieme Stuttgart · New York

PAPER
1-(Ethyl 6-O-Acetyl-2,3,4-trideoxy-a-D-erythro-hex-2-enopyranos-4-yl)-1,2,3-triazole Derivatives
469
Ethyl 6-O-Acetyl-[4-(4-bromophenyl)-1H-1,2,3-triazol -1-yl]-
2,3,4-trideoxy-a-D-erythro-hex-2-enopyranoside (3b)
Colorless oil; yield: 297 mg (67%); Rf = 0.4 (hexanes–EtOAc, 6:4);
[a]D20 +154.6 (c 1.0, CH2Cl2).
H-4), 5.94 (br d, J = 10.1 Hz, 1 H, H-3), 6.07 (ddd, J = 10.1, 2.6, 2.6
Hz, 1 H, H-2), 7.57 (s, 1 H, Htriaz).
13C NMR (75 MHz, CDCl3): d = 15.6, 21.1, 28.8, 36.5, 55.6, 63.1,
65.0, 68.6, 80.2, 94.4, 120.8, 127.6, 129.9, 146.5, 156.2, 170.8.
1H NMR (300 MHz, CDCl3): d = 1.29 (t, J = 7.1 Hz, 3 H, CH3),
2.06 (s, 3 H, CH3CO), 3.64 (dq, J = 9.7, 7.1 Hz, 1 H, OCH2CH3),
3.87 (dq, J = 9.7, 7.1 Hz, 1 H, OCH2CH3), 4.09 (dd, J = 12.2, 5.1
Hz, 1 H, H-6), 4.22 (dd, J = 12.2, 2.9 Hz, 1 H, H-6), 4.32 (ddd,
J = 10.0, 5.1, 2.9 Hz, 1 H, H-5), 5.18 (br s, 1 H, H-1), 5.44 (br dd,
J = 10.0, 1.7 Hz, 1 H, H-4), 6.01 (br d, J = 10.2 Hz, 1 H, H-3), 6.13
(ddd, J = 10.2, 2.8, 2.8, Hz, 1 H, H-2), 7.55 (d, J = 8.5 Hz, 2 H,
Anal. Calcd for C18H28O6N4: C, 54.53; H, 7.12. Found: C, 54.36; H,
7.16.
Ethyl 6-O-Acetyl-2,3,4-trideoxy-4-[4-(R,S)-tert-butyloxycarbo-
nyl)-2-amino-2-ethoxycarbonylethyl)-1H-1,2,3-triazol-1-yl]-a-
D-erythro-hex-2-enopyranoside (3f)
Colorless oil; yield: 446 mg (88%); Rf = 0.6 (hexanes–EtOAc, 4:6).
Harom), 7.70 (d, J = 8.5 Hz, 2 H, Harom), 7.84 (s, 1 H, Htriaz).
1H NMR (300 MHz, CDCl3): d = 1.25 (t, J = 7.1 Hz, 3 H, CH3),
1.26 (t, J = 7.1 Hz, 3 H, CH3), 1.43 (s, 9 H, Me3C), 2.07 (s, 3 H,
CH3CO), 3.23 (d, J = 5.3 Hz, 2 H, CH2CH), 3.62 (dq, J = 9.7, 7.1
Hz, 1 H, OCH2CH3), 3.84 (dq, J = 9.7, 7.1 Hz, 1 H, OCH2CH3),
3.98 and 4.00 [dd, J = 12.2, 5.1 Hz, 1 H, H-6 (R) and H-6 (S) 1:1],
4.13–4.27 (m, 4 H, OCH2CH3, H-5, H-6), 4.58 (br s, 1 H, CH), 5.14
(br s, 1 H, H-1), 5.35 (br d, J = 9.8 Hz, 1 H, H-4), 5.48 [d, J = 7.7
Hz, 0.5 H, NH (R) or (S)], 5.53 [d, J = 8.1 Hz, 0.5 H, NH (S) or (R)],
5.92 (br d, J = 10.0 Hz, 0.5 H, H-3), 5.94 (br d, J = 10.0 Hz, 0.5 H,
H-3), 6.06 (ddd, J = 10.0, 2.6, 2.6 Hz, 1 H, H-2), 7.43 (s, 1 H, Htriaz).
13C NMR (75 MHz, CDCl3): d = 15.7, 21.1, 55.8, 63.2, 65.1, 68.7,
94.4, 118.5, 122.7, 127.6, 130.1, 127.6, 132.4, 129.6, 129.6, 147.8,
170.8.
Anal. Calcd for C18H20O4N3Br: C, 51.20; H, 4.77. Found: C, 51.26;
H, 4.95.
Ethyl 6-O-Acetyl-2,3,4-trideoxy-4-(4-methoxycarbonyl-1H-
1,2,3-triazol-1-yl)-a-D-erythro-hex-2-enopyranoside (3c)
Colorless oil; yield: 256 mg (75%); Rf = 0.2 (hexanes–EtOAc, 6:4);
[a]D20 +101.5 (c 1.3, CH2Cl2).
1H NMR (300 MHz, CDCl3): d = 1.27 (t, J = 7.1 Hz, 3 H, CH3),
2.06 (s, 3 H, CH3CO), 3.63 (dq, J = 9.7, 7.1 Hz, 1 H, OCH2CH3),
3.85 (dq, J = 9.7, 7.1 Hz, 1 H, OCH2CH3), 3.96 (s, 3 H, OCH3), 4.04
(dd, J = 12.2, 5.0 Hz, 1 H, H-6), 4.20 (dd, J = 12.2, 3.0 Hz, 1 H, H-
6), 4.30 (ddd, J = 9.8, 5.0, 3.0 Hz, 1 H, H-5), 5.17 (br s, 1 H, H-1),
5.45 (dd, J = 9.8, 1.5 Hz, 1 H, H-4), 5.95 (br d, J = 10.2 Hz, 1 H, H-
3), 6.1 (ddd, J = 10.2, 2.8, 2.8 Hz, 1 H, H-2), 8.18 (s, 1 H, Htriaz).
13C NMR (75 MHz, CDCl3): d = 14.5, 15.6, 21.1, 28.7, 29.0, 55.5,
61.9, 63.1, 65.0, 68.7, 80.2, 94.4, 120.9, 127.6, 129.9, 144.1, 155.8,
170.8, 171.7 and 171.8 (R and S).
Anal. Calcd for C22H34O8N4: C, 54.76; H, 7.10. Found: C, 54.90; H,
7.26.
4,4¢-[(1,4-Phenylene)-bis(ethyl 6-O-acetyl-2,3,4-trideoxy-a-D-
erythro-hex-2-enopyranosyl)]-di-1H-1,2,3-triazole (4)
13C NMR (75 MHz, CDCl3): d = 15.6, 21.0, 52.7, 56.1, 63.0, 65.1,
68.7, 94.3, 126.7, 126.8, 130.6, 140.9, 161.2, 170.7.
4-Azido carbohydrate 2 (53 mg, 0.22 mmol) and 1,4-diethynylben-
zene (13 mg, 0.10 mmol) were suspended in tert-BuOH–H2O (1:1,
2 mL). To this solution was added a mixture of Cu(OAc)2 (8 mg,
0.045 mmol) and sodium ascorbate (18 mg, 0.091 mmol) in tert-
BuOH–H2O (1:1) (1 mL). H2O (3 mL) was added and the product
was extracted with CH2Cl2 (3 × 5 mL). The combined organic lay-
ers were dried over Na2SO4. Evaporation of the organic solvent un-
der reduced pressure gave a mixture that was purified by column
chromatography (hexanes–EtOAc, 2:8) to give compound 4.
Anal. Calcd for C14H19O6N3: C, 51.69; H, 5.89. Found: C, 52.26; H,
6.28.
Ethyl 6-O-Acetyl-4-(4-acetyl-1H-1,2,3-triazol-1-yl)-2,3,4-
trideoxy-a-D-erythro-hex-2-enopyranoside (3d)
White solid; yield: 269 mg (83%); mp 65–66 °C; Rf = 0.4 (hexanes–
EtOAc, 1:1); [a]D20 +118.0 (c 1.7, CH2Cl2).
White solid; yield: 56 mg (89%); mp 120–123 °C; Rf = 0.6 (hex-
anes–EtOAc, 2:8); [a]D20 +245 (c 1.0, CH2Cl2).
1H NMR (300 MHz, CDCl3): d = 1.27 (t, J = 7.2 Hz, 3 H, CH3),
2.07 (s, 3 H, CH3CO), 2.69 (s, 3 H, CH3CO), 3.60 (dq, J = 9.7, 7.2
Hz, 1 H, OCH2CH3), 3.80 (dq, J = 9.7, 7.2 Hz, 1 H, OCH2CH3),
4.04 (dd, J = 12.3, 5.0 Hz, 1 H, H-6), 4.19 (dd, J = 12.3, 2.8 Hz, 1
H, H-6), 4.29 (ddd, J = 9.9, 5.0, 2.8 Hz, 1 H, H-5), 5.17 (br s, 1 H,
H-1), 5.43 (ddd, J = 9.9, 3.6, 1.9 Hz, 1 H, H-4), 5.94 (br d, J = 10.0
Hz, 1 H, H-3), 6.13 (ddd, J = 10.0, 2.6, 2.6 Hz, 1 H, H-2), 8.15 (s, 1
H, Htriaz).
1H NMR (300 MHz, CDCl3): d = 1.29 (t, J = 7.0 Hz, 6 H, CH3),
2.07 (s, 6 H, CH3CO), 3.65 (dq, J = 9.7, 7.0 Hz, 2 H, OCH2CH3),
3.88 (dq, J = 9.7, 7.0 Hz, 2 H, OCH2CH3), 4.11 (dd, J = 12.2, 5.1
Hz, 2 H, H-6), 4.23 (dd, J = 12.2, 2.8 Hz, 2 H, H-6), 4.35 (ddd,
J = 9.9, 5.1, 2.8 Hz, 2 H, H-5), 5.19 (br s, 2 H, H-1), 5.47 (dd,
J = 9.9, 1.7 Hz, 2 H, H-4), 6.03 (br d, J = 10.0 Hz, 2 H, H-3), 6.14
(ddd, J = 10.0, 2.8, 2.8 Hz, 2 H, H-2), 7.88 (s, 2 H, Htriaz), 7.91 (s, 4
H, Harom).
13C NMR (75 MHz, CDCl3): d = 15.6, 21.0, 27.6, 55.9, 63.0, 65.1,
68.8, 94.4, 124.5, 126.7, 130.6, 148.9, 170.7, 193.0.
13C NMR (75.5 MHz, CDCl3): d = 15.7, 21.1, 55.8, 63.2, 65.1, 68.8,
94.4, 118.5, 126.6, 127.7, 130.1, 130.6, 148.4, 170.8.
Anal. Calcd for C14H19O5N3: C, 54.36; H, 6.19. Found: C, 54.57; H,
6.09.
Anal. Calcd for C30H36O8N6: C, 59.20; H, 5.96. Found: C, 59.11; H,
5.72.
HRMS-FAB: m/z [M + H]+ calcd for C30H37O8N6: 609.2673; found:
Ethyl 6-O-Acetyl-2,3,4-trideoxy-4-[4-N-(tert-butoxycarbon-
yl)methyl-1H-1,2,3-triazol-1-yl]-a-D-erythro-hex-2-enopyrano-
side (3e)
609.2671.
Colorless oil; yield: 341 mg (82%); Rf = 0.4 (hexanes–EtOAc, 3:7);
[a]D20 +86.8 (c 2.2, CH2Cl2).
4,4¢-[(1,4-Phenylene)-bis(ethyl 2,3,6-tri-O-acetyl-4-deoxy-a-D-
mannopyranosyl)]-di-1H-1,2,3-triazole (5)
1H NMR (300 MHz, CDCl3): d = 1.25 (t, J = 7.1 Hz, 3 H, CH3),
1.45 (s, 9 H, Me3Si), 2.07 (s, 3 H, CH3CO), 3.62 (dq, J = 9.8, 7.1 Hz,
1 H, OCH2CH3), 3.85 (dq, J = 9.8, 7.1 Hz, 1 H, OCH2CH3), 4.01
(dd, J = 12.2, 5.1 Hz, 1 H, H-6), 4.16 (dd, J = 12.2, 2.6 Hz, 1 H, H-
6), 4.28 (ddd, J = 9.9, 5.1, 2.6 Hz, 1 H, H-5), 4.40 (d, J = 5.8 Hz, 2
H, CH2N), 5.15 (br s, 2 H, H-1, NH), 5.37 (dd, J = 9.9, 1.7 Hz, 1 H,
To a solution of 2,3-unsaturated triazole carbohydrate 4 (30 mg,
0.049 mmol) in acetone–H2O (4:1, 2 mL) was added OsO4 (0.25
mg, 1.0 mmol, 2 mol%) and NMO (465 mg, 3.97 mmol) at 0 °C. Af-
ter stirring at r.t. for 20 h, NaHSO3 (25 mg, 0.24 mmol) was added,
and the mixture was stirred at r.t. for 30 min. H2O (2.5 mL) was add-
ed, the mixture was extracted with EtOAc (2 × 5 mL), and the or-
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R. N. de Oliveira et al.
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ganic layers were dried over Na2SO4. Evaporation of the solvent
under reduced pressure gave a residue that was directly acetylated
using Ac2O (102 mg, 1.00 mmol) in pyridine (2 mL) for 1 d. After
removing the solvent under reduced pressure, the residue was puri-
fied by column chromatography on silica gel (EtOAc) to afford
compound 5.
(12) de Brito, T. M. B.; da Silva, L. P.; Siqueira, V. L.;
Srivastava, R. M. J. Carbohydr. Chem. 1999, 18, 609.
(13) de Freitas Filho, J. R.; Srivastava, R. M.; Soro, Y.; Cottier,
L.; Descotes, G. J. Carbohydr. Chem 2001, 20, 561.
(14) Lalezari, I.; Gomez, L. A.; Khorshidi, M. J. Heterocycl.
Chem. 1990, 27, 687.
(15) Alvarez, R.; Velazquez, S.; San, F.; Aquaro, S.; De, C.;
Perno, C. F.; Karlsson, A.; Balzarini, J.; Camarasa, M. J. J.
Med. Chem. 1994, 37, 4185.
(16) Genin, M. J.; Hutchinson, D. K.; Allwine, D. A.; Hester, J.
B.; Emmert, D. E.; Garmon, S. A.; Ford, C. W.; Zurenko, G.
E.; Hamel, J. C.; Schaadt, R. D.; Stapert, D.; Yagi, B. H.;
Friis, J. M.; Shobe, E. M.; Adams, W. J. J. Med. Chem. 1998,
41, 5144.
(17) Genin, M. J.; Allwine, D. A.; Anderson, D. J.; Barbachyn,
M. R.; Emmert, D. E.; Garmon, S. A.; Graber, D. R.; Grega,
K. C.; Hester, J. B.; Hutchinson, D. K.; Morris, J.; Reischer,
R. J.; Ford, C. W.; Zurenko, G. E.; Hamel, J. C.; Schaadt, R.
D.; Stapert, D.; Yagi, B. H. J. Med. Chem. 2000, 43, 963.
(18) Bröder, W.; Kunz, H. Carbohydr. Res. 1993, 249, 221.
(19) Marco-Contelles, J.; Jiménez, C. A. Tetrahedron 1999, 55,
10511.
White solid; yield: 36 mg (86%); mp 116–118 °C; Rf = 0.5
(EtOAc); [a]D20 +57.6 (c 1.5, CH2Cl2).
1H NMR (300 MHz, CDCl3): d = 1.32 (t, J = 7.0 Hz, 6 H, CH3),
1.86 (s, 6 H, CH3CO), 2.04 (s, 6 H, CH3CO), 2.22 (s, 6 H, CH3CO),
3.63 (dq, J = 9.8, 7.0 Hz, 2 H, OCH2CH3), 3.84 (dq, J = 9.8, 7.0 Hz,
2 H, OCH2CH3), 3.98 (dd, J = 12.4, 4.7 Hz, 2 H, H-6), 4.15 (dd,
J = 12.4, 3.2 Hz, 2 H, H-6), 4.35 (ddd, J = 10.6, 4.7, 3.2 Hz, 2 H, H-
5), 4.96 (br s, 2 H, H-1), 5.00 (dd, J = 10.9, 10.6 Hz, 2 H, H-4), 5.37
(dd, J = 3.2, 1.9 Hz, 2 H, H-2), 5.88 (br d, J = 10.9 Hz, 2 H, H-3),
7.88 (s, 2 H, Htriaz), 7.91 (s, 4 H, Harom).
13C NMR (75 MHz, CDCl3): d = 15.7, 20.8, 21.0, 21.3, 57.9, 63.0,
64.8, 68.7, 69.0, 69.2, 97.9, 118.5, 126.6, 130.4, 147.8, 169.6,
170.6, 170.7.
Anal. Calcd for C38H48O16N6: C, 54.02; H, 5.73. Found: C, 53.66;
H, 5.84.
(20) Al-Masoudi, N. A.; Al-Soud, Y. A. Tetrahedron Lett. 2002,
43, 4021.
+
HRMS-FAB: m/z [M + H] calcd for C38H48O16N6: 845.3205;
found: 845.3209.
(21) Calvo-Flores, F. G.; Isac-Garcia, J.; Hernàndez-Mateo, F.;
Pérez-Balderas, F.; Calvo-Asin, J. A.; Sanchéz-Vaquero, E.;
Santoyo-Gonzàlez, F. Org. Lett. 2000, 2, 2499.
(22) Pérez-Balderas, F.; Ortega-Munoz, M.; Morales-Sanfrutos,
J.; Hernàndez-Mateo, F.; Calvo-Flores, F. G.; Calvo-Asin, J.
A.; Isac-Garcia, J.; Santoyo-Gonzàlez, F. Org. Lett. 2003, 5,
1951.
(23) Casas-Solvas, J.; Vargas-Berenguel, A.; Capitàn-Vallvey, L.
F.; Santoyo-Gonzàlez, F. Org. Lett. 2004, 6, 3687.
(24) Dondoni, A.; Giovannini, P. P.; Massi, A. Org. Lett. 2004, 6,
2929.
(25) Kuijpers, B. H. M.; Groothuys, S.; Keereweer, A. B. R.;
Quaedflieg, P. J. L. M.; Blaauw, R. H.; van Delft, F. L.;
Rutjes, F. P. J. T. Org. Lett. 2004, 6, 3123.
(26) Chittaboina, S.; Xie, F.; Wang, Q. Tetrahedron Lett. 2005,
46, 2331.
(27) de Oliveira, R. N.; Cottier, L.; Sinou, D.: Srivastava, R. M.
Tetrahedron 2005, 61, 8271.
(28) Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.; Sharpless, K.
B. Angew. Chem. Int. Ed. 2002, 41, 2596.
(29) Tornoe, C. W.; Christensen, C.; Meldal, M. J. Org. Chem.
2002, 67, 3057.
(30) Stevens, C. L.; Filippi, J. B.; Taylor, K. G. J. Org. Chem.
Acknowledgment
We are indebted to the CAPES/COFECUB program no. 334/01 for
financial support and CNPq-Brazil for providing a fellowship to one
of us (R.N.O.).
References
(1) Varski, A. Glycobiology 1993, 3, 97.
(2) Sears, P.; Wong, C.-H. Cell. Mol. Life Sci. 1998, 54, 223.
(3) Bertozzi, C. R.; Kiessling, L. L. Science 2001, 291, 2355.
(4) Phillips, M. L.; Nudelman, E.; Gaeta, F. C. A.; Perez, M.;
Singhal, A. K.; Hakomori, S.; Paulson, J. C. Science 1990,
250, 1130.
(5) Giannis, A. Angew. Chem., Int. Ed. Engl. 1994, 33, 178.
(6) Yuen, C.-T.; Bezouska, K.; O’Brien, J.; Stoll, M.; Lemoine,
R.; Lubineau, A.; Kiso, M.; Hasegawa, A.; Bockovich, N. J.;
Nicolaou, K. C.; Feizi, T. J. Biol. Chem. 1994, 269, 1595.
(7) Feizi, T. Curr. Opin. Struct. Biol. 1993, 3, 701.
(8) Ryan, C. A. Proc. Natl. Acad. Sci. U.S.A. 1994, 91, 1.
(9) Rudd, P. M.; Elliott, T.; Cresswell, P.; Wilson, I. A.; Dwek,
R. A. Science 2001, 291, 2370.
1966, 31, 1292.
(31) Donohoe, T. J.; Garg, R.; Moore, P. R. Tetrahedron Lett.
1996, 37, 3407.
(32) Kotha, S.; Halder, S.; Brahmachary, E. Tetrahedron 2002,
(10) de Freitas Filho, J. R.; Srivastava, R. M.; da Silva, W. J. P.;
Cottier, L.; Sinou, D. Carbohydr. Res. 2003, 338, 673.
(11) de Freitas Filho, J. R.; Cottier, L.; Srivastava, R. M.; Sinou,
D. Synlett 2003, 1358.
58, 9203.
Synthesis 2006, No. 3, 467–470 © Thieme Stuttgart · New York