Microwave-assisted stereoselective α-2-deoxyglycosylation of hex-1-en-3-uloses

Article abstract of DOI:10.1016/j.tetlet.2009.10.049

α-2-Deoxyglycosides were successfully synthesized by means of microwave-assisted glycosylation. Hex-1-en-3-uloses were treated with a catalytic amount of AlCl₃ and various O-nucleophiles including alcohols and sugars under microwave conditions.

Full text of DOI:10.1016/j.tetlet.2009.10.049

Tetrahedron Letters 50 (2009) 7327–7329
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Microwave-assisted stereoselective
hex-1-en-3-uloses
a-2-deoxyglycosylation of
a
a
a
b
c,d
Hui-Chang Lin a, , Hsu-Hsuan Wu , Zi-Ping Lin , Chih-Yuan Lin , Chun-Hung Lin , Kun-Lung Chen
,
*
Fung Fuh Wong a
a Graduate Institute of Pharmaceutical Chemistry, China Medical University, No. 91, Hsueh-Shih Rd., Taichung 40402, Taiwan, ROC
b Institute of Biological Chemistry, Academia Sinica, No. 128, Academia Road Section 2, Nan-Kang, Taipei 11529, Taiwan, ROC
c Sustainable Environment Research Center, National Cheng Kung University, No. 500, Sec. 3, An-Ming Rd., Tainan City 709, Taiwan, ROC
d Department of Resources Engineering, National Cheng Kung University, No 1, Ta Hsueh Rd., Tainan 70101, Taiwan, ROC
a r t i c l e i n f o
a b s t r a c t
Article history:
a
-2-Deoxyglycosides were successfully synthesized by means of microwave-assisted glycosylation. Hex-
1-en-3-uloses were treated with a catalytic amount of AlCl3 and various O-nucleophiles including alco-
hols and sugars under microwave conditions. The desired -2-deoxy-ulosides products were obtained
in good to excellent yields with high stereoselectivity ( /b P 88/12).
Received 4 August 2009
Revised 6 October 2009
Accepted 9 October 2009
Available online 30 October 2009
a
a
Crown Copyright Ó 2009 Published by Elsevier Ltd. All rights reserved.
Keywords:
2-Deoxyglycosides
Microwave-assisted glycosylation
a-2-Deoxy-ulosides
Michael-type additions
1. Introduction
2. Result and discussion
Many antibiotic and antitumor natural products contain one or
more 2-deoxyglycosides in their scaffolds, such as the angucycline
family of antibiotics (landomycin A), the aureolic acid antibiotics
(olivomycin A, chromomycin A3), the enediynes (calicheamycin
Hex-l-en-3-uloses are attractive starting materials for glycosy-
lations via Michael-type additions.2–8 Hex-l-en-3-uloses 1 and 2
were synthesized from 3,4,6,-tri-O-acetyl-D-glucal through depro-
tection with methanolic sodium methoxide,9 oxidation by pyridi-
nium dichromate10 and acetylation11 or benzoylation. Many
c
1I, esperamicins A1 and C), the avermectins (avermectin B1a, iver-
mectin), cholestane glycosides (OSW-1) and cardiac glycosides.1
The carbohydrate moieties were necessary in these compounds
for their bioactivity.
methods were reported to synthesize a
-2-deoxy-ulosides.2–8 How-
ever, their syntheses are not straightforward and smooth for the
reaction time and the quantitative yield. In this Letter, we first used
the microwave-assisted reaction and AlCl3-catalyzed conjugation
addition of acetyling hex-1-en-3-ulose (1) and benzoyling hex-1-
In the literature, several reports were made previously on the
synthesis of
a-2-deoxy-ulosides by means of the acid-mediated
conjugate addition2, the base-catalyzed Michael-type reaction,3
the enolate alkylation,4 the rhodium(I)-catalyzed 1,4-addition,5
the organocopper addition6,7 and the palladium-catalyzed addi-
tion.8 However, long reaction time and low stereoselective result
were required in these cases. In this work, we reported a new
microwave-assisted methodology for the synthesis of O-2-deoxy-
glycoside by reacting hex-1-en-3-uloses with O-nucleophiles in
the presence of AlCl3 as the catalyst. In this new microwave-as-
en-3-ulose (2) to synthesize a-2-deoxyglycosylation; representa-
tive examples are shown in Scheme 1. In the microwave-assisted
method, the reliable molding procedure involved the treatment
of acetyling hex-1-en-3-ulose (1) with a catalytic amount of AlCl3
and various alcohol reactants, such as benzyl alcohol, cyclohexa-
nol, isopropanol and n-hexyl alcohol, at 60 °C with 100 W of
sisted method, the reaction provided the corresponding
deoxyglycosylation as the high kinetic stereoselective products.
a-2-
OR
O
OR
O
AlCl3 (cat)
MW
RO
R1OH
+
RO
O
O
O
R1
* Corresponding author. Tel.: +886 4 2205 3366x5612; fax: +886 4 2207 8083.
E-mail addresses: lhc550005@yahoo.com.tw, huichang@mail.cmu.edu.tw (H.-C.
1. R = Ac, 2. R = Bz
Lin).
Scheme 1.
0040-4039/$ - see front matter Crown Copyright Ó 2009 Published by Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.10.049

7328
H.-C. Lin et al. / Tetrahedron Letters 50 (2009) 7327–7329
Table 1
Glycosylation of Hex-1-en-3-uloses (1 and 2) with simple alcohols
Entry
Substrate
Nucleophile
Product
a
/b ratioa
Yield (%)
92
OAc
O
HO
AcO
O
a
1
94/6
91/9
3
O
OAc
O
HO
HO
AcO
O
b
c
1
1
4
76
72
O
OAc
O
AcO
O
5
6
89/11
O
HO
HO
OAc
O
AcO
O
d
e
1
2
93/7
92/8
89
92
OBn
OBz
O
BzO
O
7
O
OBz
O
HO
BzO
O
f
2
2
88/12
74
8
O
OBz
O
HO
HO
BzO
O
g
94/6
96/4
68
90
9
O
OBz
O
BzO
O
h
2
10
OBn
a
The
a
/b ratios were determined by 1H NMR.
microwave energy within 6–10 min. After the reaction was com-
pleted, the reaction mixture was worked-up and purified by column
chromatography on silica gel to give the desired O-2-deoxyglyco-
side products in good yields (3–6, 72–92%, see Table 1). All the
products were fully characterized by spectroscopic methods. For
example, the 1H NMR spectrum of compound 4 showed a doublet
of doublets at 5.30 ppm for the characteristic peak at the
anomeric centre and a multiplet at 3.83 ppm for –CH(Me)2 peak.
A few reported literatures2,3 provided the direct and smooth
method by using hex-l-en-3-uloses as substrates to generate
disaccharides with high
a-stereoselectivity and in moderate
yields. Herein, we explored the newly developed method towards
sugar alcohols 11–13. When we treated a CH2Cl2 solution of acet-
yling hex-1-en-3-ulose (1) with a catalytic amount of AlCl3 at
50 °C with 100 W of microwave energy within 25–30 min, the
corresponding products 14–16 were produced in 59–72% yields
The 13C NMR spectrum possessed
a
characteristic peak at
and the ratios of
a/b 2-deoxy-uloside stereoselectivity were more
197.96 ppm for the –C@O group, at 96.53 ppm for the C-1 and at
46.56 ppm for the C-2 of hex-3-ulose. The IR absorptions of 4 pro-
vided main peaks at 1741 cmÀ1 for stretching of the –C@O group.
The synthetic strategy is applicable to the benzoylated hex-1-en-
3-ulose (2) as the substrate under the same condition to afford
the corresponding O-2-deoxyglycoside products 7–10 in 68–92%
yields (see Table 1).
than 93/7 ( /b, see Table 2). Furthermore, we tried to prolong the
a
reaction time under the same microwave process, the reaction re-
sults were not optimized clearly. When applying sugar alcohols
11–13 under the same conditions to benzoylated hex-1-en-3-
ulose (2), we obtained the
63–71% yields (see Table 2). During the study of the synthesis
of -disaccharides, we found that the high stereoselectivity could
a-2-deoxy-uloside products 17–18 in
a
We have also compared the stereoselective behaviour of various
be accomplished in our new method. All of the product structures
were determined by DEPT, NOESY and other spectroscopic
spectra.
In conclusion, we have found a practical methodology for the
synthesis of a-2-deoxyglycosides by using a catalytic quantity of
alcohols in the Michael glycosylation,
predominantly generated as the main isomeric products. The
2-deoxy-uloside stereoselectivity was determined by 1H NMR
and the ratios were greater than 88/12 ( /b, see Table 1).
a-2-deoxy-ulosides were
a/b
a

H.-C. Lin et al. / Tetrahedron Letters 50 (2009) 7327–7329
7329
Table 2
Glycosylation of Hex-1-en-3-uloses (1 and 2) with sugar alcohols
Entry
Substrate
Nucleophile
Product
a
/b ratioa
Yield (%)
OH
O
OAc
O
AcO
O
11
MeO
MeO
MeO
OMe
O
O
a
1
14
93/7
68
MeO
MeO
MeO
OMe
OH
O
OAc
O
AcO
O
BnO
BnO
12
BnO
OMe
O
O
b
1
1
2
15
95/5
59
BnO
BnO
BnO
OMe
OH
O
OAc
O
O
O
AcO
O
13
O
O
O
O
O
c
96/4
96/4
93/7
72
63
71
16
O
O
O
OH
O
OBz
O
BzO
MeO
MeO
11
O
MeO
OMe
O
O
17
d
MeO
MeO
MeO
OMe
OH
O
OBz
O
O
BzO
O
O
13
O
O
O
O
O
e
2
18
O
O
O
a
The
a
/b ratios were determined by 1H NMR.
AlCl3 under microwave irradiation condition. The newly devel-
oped method could be applied to O-nucleophile alcohols, including
aliphatic, benzyl and sugar alcohols. The 2-deoxyglycoside prod-
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The authors thank the National Science Council of Taiwan
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Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2009.10.049.
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