5
78 Letters in Organic Chemistry, 2012, Vol. 9, No. 8
Huang and Cheng
ethanesulfonate (TMSOTf) as promoter for the activation of
trichloroacetimidate donor. At low temperature, TMSOTf-
promoted glycosylation of the N-benzyloxycarbonyl (Cbz)
protected ꢀ-trichloroacetimidate donor 11 [6] with 6-O-
benzylallosamizoline alcohol acceptor 10 giving the corre-
sponding O-perprotected ꢁ-pseudodisaccharide in 78% yield.
The yield was analyzed by high pressure liquid chromatog-
raphy (HPLC) after cleavage of polystyrene and linker by
irradiation from the O-perprotected ꢁ-pseudodisaccharide.
Cleavage of the levulinoyl ester was performed using hydra-
zine acetate dissolved in MeOH to obtain the acceptor 12.
After the acceptor 12 was glycosylated with N-Cbz protected
OBn
O
OBn
HO
HO
HO
O
a. Bu SnO
O
2
S
S
b.
Cl
N
N
10
9
a. 11, TMSOTf
.
b. N H4 HOAc
2
OBn
OBn
O
HO
O
O
O
AcO
NHCbz
ꢀ-trichloroacetimidate donor 13 [6], the saccharide bound
S
N
resin was catalytically hydrogenated for cleavage of Cbz and
Bn to obtain the building block 14 in 95% yield. Then, the
12
a. 13, TMSOTf
resulting mixture was acetylated with Ac
2
O/pyridine and
OAc
b. H , Pd/C
deacetylated with NH /MeOH, respectively. After every
2
3
AcO
AcO
O
above-mentioned reaction was finished, the resin was filtered
and washed in turn. Efficient cleavage of the di-N-acetyl-ꢁ-
chitobiosyl NAG-thiazoline fragment from resin was demon-
strated by irradiation of building block 15 to afford target di-
N-acetyl-ꢁ-chitobiosyl NAG-thiazoline 2 in 95% yield,
which was not needful to further purify by flash column
chromatography. The allosamidin 1 was also synthesized
with the similar process.
OH
O
OH
O
AcO
O
O
O
NH2
NH2
S
N
1
4
a. Ac O, pyridine
2
OH
b. NH , MeOH
3
HO
HO
O
OH
In summary, the solid-phase synthesis of allosamidin 1
and its analogue di-N-acetyl-ꢁ-chitobiosyl NAG-thiazoline 2
was studied. With polystyrene resin as support and o-
nitrobenzyl ether tether as linker, good yield was obtained by
iterative glycosylation reactions, catalytic hydrogenation,
acetylation, deacetylation, and photolysis, respectively.
OH
O
HO
O
O
O
O
NHAc
NHAc
S
N
1
5
hv
.
OH
OH
OH
HO
HO
O
HO
O
CONFLICT OF INTEREST
O
O
O
HO
The authors confirm that this article content has no
conflicts of interest.
NHAc
NHAc
S
N
2
ACKNOWLEDGEMENTS
Scheme 2. The solid-phase synthesis of di-N-acetyl-ꢁ-chitobiosyl
NAG-thiazoline 2.
The work was supported by Open Foundation from Ter-
tiary College of Chongqing Engineering Research Center of
Bioactive Substance and Ministry of Education Engineering
Research Center of Active Substance & Biotechnology (No.
GCZX2012-2), Chongqing Education Commission Founda-
tion (No. KJ080810), and Natural Science Foundation Pro-
ject of CQ CSTC (No. cstc2012jjA10101), China.
RESULTS AND DISCUSSION
Polystyrene 3 (Scheme 1) was functionalized to phenolic
polystyrene 4 by reaction with n-BuLi, oxygen, and PPh ,
3
respectively. The linker, o-nitrobenzyl ether tether, was util-
ized because it was easy to attach and cleave. So, the avail-
able 5-hydroxy-2-nitrobenzaldehyde 5 was reacted with 1,3-
diiodopropane in DMF under the alkaline condition, and
SUPPLEMENTARY MATERIAL
4
then directly was reduced with NaBH to afford iodobenzyl
alcohol 6 in 93% yield for the above two steps. The com-
pound 6 was attached to phenolic polystyrene 4 via its linker
Supplementary material is available on the publishers
Web site along with the published article.
in the presence of Cs
based on mass gain of the polymer. The chlorination of
2 3
CO to afford conjugate 7 in 91% yield
REFERENCES
3 4
compound 7 with Ph P/CCl obtained chloride 8 in 86%
yield.
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1]
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[2]
The C-3 hydroxyl group of diol 9 [6] (Scheme 2) was se-
lectively benzylated by the way of stannylene methodology
[3]
[
7] to provide the dibenzylated building block 10 in 65%
yield. Glycosylation reactions were performed using 3.0
equiv. of donor and 0.1 equiv. of trimethylsilyl triflurom-
Huang, Gangliang
