Tetrahedron Letters
A convenient and efficient method for the synthesis of 2-hydroxy glycals
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Bin Qian, Qi-Dong You
State Key Laboratory of Natural Medicines, Department of Medicinal Chemistry, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
A convenient and efficient method for preparing 2-hydroxy glycals was developed from thioglycosides by
using 1,4-dioxane–bromine complex/DMAP as an efficient promoter with good yield (61–85%). In this
synthetic method, a wide range of sugar thioglycosides could be used as substrates.
Ó 2012 Elsevier Ltd. All rights reserved.
Received 22 February 2012
Revised 26 April 2012
Accepted 4 May 2012
Available online 11 May 2012
Keywords:
Preparation
2-Hydroxy glycals
1,4-Dioxane–bromine complex/DMAP
Thioglycosides
Introduction
inconvenient post-reaction handling. In view of the importance
of glycals and their derivatives in the synthesis of oligosaccharides
2-Hydroxy glycal is an important and versatile chiral building
block in organic synthesis. They could be used extensively in the
synthesis of O-glycosides,1 C-glycosides,2 S-glycosides,3 N-glyco-
sides,4 and chiral natural products5 (Fig. 1). In carbohydrate chem-
istry, 2-hydroxy glycal could also be used to synthesize many
and natural products, a strong impetus has been given to develop a
mild and more convenient method for the synthesis of 2-hydroxy
glycals.
In the literature,10 the preparation of 2-hydroxy glycals is
through glycosyl bromides in the presence of strong bases, such
as DBU and 1,5-diazabicyclo[4.3.0]-5-nonene DBN. These strong
bases are more chemically reactive and not suitable for the com-
pounds with basic sensitive group. It was reported that the O-gly-
cosides could be obtained gently from thioglycosides in one-step
by treatment with bromine in the presence of a promoter such
as silver triflate or mercuric cyanide.16 In this method, the thiogly-
coside was firstly converted into a glycosyl bromide and then the
produced glycosyl bromide was converted into O-glycosides. In-
spired by this method, we developed a one-pot 1,4-dioxane–bro-
mine complex/DMAP catalyzed thioglycosides that convert into
2-hydroxy glycals at room temperature with good yield.
At first, we designed the reaction system in which the 2,3,4-tri-
b-
L
-rhamnosidic,6 and b-
D
-mannopyranosidic7 linkages, which are
-rhamnosyl and b- -mannosyl donors
normally prepared from b-
L
D
by multistage synthesis with poor appreciable b-selectivity in gly-
cosylations. In addition, 2-hydroxy glycals have been used in the
synthesis of seven-membered cyclic sugar derivatives, which are
less commonly known sugar homologues.8 Recently, 2-hydroxy
glycals were used in the synthesis of sulfonamidoglycoside with
inhibiting activities to human hepatocellular liver carcinoma
(HepG2) and human lung adenocarcinoma (A549) cell lines.9
The traditional method for the synthesis of 2-hydroxy glycals
was reported by treating a peracetylated glycopyranosyl bromide
with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in dichloroethane
at low temperature (À20 °C).10 Over the years, some synthetic
methods for 2-hydroxy glycals have been developed. In these
methods, peracetylated glycopyranosyl bromide was treated
respectively by Bu4NBr/Et2NH,5e CsF/CH3CN,11 AgF/pyridine,12
and NaH/HMPA.13 In addition, the thermal elimination of glycosyl
sulfoxides14 or the oxidation/elimination of selenoglycoside15 was
also applied to prepare 2-hydroxy glycals. However, there are sev-
eral drawbacks in the above mentioned methods, for example, the
use of very expensive and toxic reagents, low temperatures, and
O-acetyl-1-thio-b-D-glucuronide methyl ester 1 was treated with
Br2, after 30 min bases were added at 0 °C, and the reactions were
maintained for 24 h. We tested many bases such as DBU, Et2NH,
N,N-diisopropylethylamine, 2,6-dimethylpyridine, and KF, but the
product 1a was not obtained (Table 1, entries 1–5). Only when
the base was changed into DMAP, 15% 1a was obtained (Table 1,
entry 6). However, when Br2 was changed into 1,4-dioxane–bro-
mine complex17 in the above reaction, the yield of compound 1a
increased to 46% (Table 1, entry 7). Then we changed the reaction
solvent to dry dichloroethane and treated 1 with 1,4-dioxane–bro-
mine complex at room temperature. DMAP was added 30 min la-
ter, and then the reaction time shortened to 12 h with good yield
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0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.