Synthesis of the repeating trisaccharide unit of the cell wall lipopolysaccharide of Escherichia coli type 8

Article abstract of DOI:10.1016/j.tetlet.2008.07.089

NIS/TfOH mediated glycosidation of methyl 3,4,6-tri-O-benzyl-α-d-mannopyranoside with phenyl 2-O-acetyl-3,4,6-tri-O-benzyl-1-thio-α-d-mannopyranoside furnished the corresponding disaccharide derivative in excellent yield and α-selectivity. Ze?mplen deacet

Full text of DOI:10.1016/j.tetlet.2008.07.089

Tetrahedron Letters 49 (2008) 5847–5849
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Synthesis of the repeating trisaccharide unit of the cell wall
lipopolysaccharide of Escherichia coli type 8
Sajal K. Maity a, Swarupananda Maity a, Amarendra Patra b, Rina Ghosh a,
*
a Department of Chemistry, Jadavpur University, Kolkata 700 032, India
b Department of Chemistry, University College of Science, Kolkata 700 009, India
a r t i c l e i n f o
a b s t r a c t
Article history:
NIS/TfOH mediated glycosidation of methyl 3,4,6-tri-O-benzyl-a-D-mannopyranoside with phenyl 2-O-
Received 30 May 2008
Revised 24 June 2008
Accepted 5 July 2008
Available online 19 July 2008
acetyl-3,4,6-tri-O-benzyl-1-thio-
derivative in excellent yield and
a
a
-
D
-mannopyranoside furnished the corresponding disaccharide
-selectivity. Zémplen deacetylation of the same followed by reaction
-mannopyranoside
-mannopyranosyl-(1?2)-3,4,6-tri-O-benzyl-
-mannopyranoside in very good yield and excellent
with BSP/Tf2O-preactivated phenyl 4,6-O-benzylidene-2,3-di-O-benzyl-1-thio-
generated methyl 4,6-O-benzylidene-2,3-di-O-benzyl-b-
-mannopyranosyl-(1?2)-3,4,6-tri-O-benzyl-
a-D
D
a-
D
a-D
Keywords:
Escherichia coli 8
O-Antigen
Trisaccharide
Cell wall polysaccharide
b-Mannoside
b-selectivity. Pd/C catalyzed hydrogenation of the latter finally afforded the repeating trisaccharide of
Escherichia coli 8 O-antigen as its methyl glycoside.
Ó 2008 Elsevier Ltd. All rights reserved.
Escherichia coli type 8 strain F492 is a gram-negative entero-
toxic and enteropathogenic bacterium. The structure of the repeat-
ing unit 1 of the O-antigen is a mannose trisaccharide (Fig. 1)
containing (1?2)-b-linked mannoside at the non-reducing end.1
In continuation of our research based on carbohydrates2 and also
as part of our ongoing research programme on the synthesis of
oligosaccharides related to bacterial antigens, we have synthesized
the trisaccharide repeating unit of the O-antigen of E. coli 8 strain
492 and report herein the synthesis of 1 as its methyl glycoside
(Scheme 2). Surprisingly, the synthesis of 1 has not yet been
reported and to the best of our knowledge this is the first report
of this repeating unit.
β-D-Manp-(1→2)-α-D-Manp-(1→2)-D-Manp.
1
Figure 1. The trisaccharide repeating unit of the O-antigen of E. coli type 8.
methodology to the synthesis of b-(1?2)-mannosides is virtually
absent from the literature except those by Crich et al.7e,f or that
of Mallet and co-workers.9 Unlike these reports, we have used a
thioglycoside donor in place of the corresponding sulfoxide.
Thus, the glycosyl donor 710 was synthesized from phenyl
1-thio-b-D-mannoside (6). Benzylidination of 6 with dimethoxytol-
The O-specific polysaccharide of the lipopolysaccharide is a
mannan.
uene in the presence of NaHSO4–SiO2 catalyst11 followed by benzy-
lation with NaH and benzyl bromide produced 7. This glycosyl
donor was then preactivated with 1-benzenesulfinyl piperidene
(BSP)12 and Tf2O at –60 °C and the resulting mixture was reacted
with the glycosyl acceptor 9 at –78 °C to afford the corresponding
trisacchharide 10 in very good yield.13 We could not detect the for-
Retrosynthetic analysis of 1 gives probable protected building
blocks 3, 4 and 7 (Scheme 1). The glycosyl acceptor 33 and the gly-
cosyl donor 44 were prepared from the common building block 23
following literature procedures (Scheme 2). NIS/TfOH mediated
glycosidation5 of 3 with 4 produced the corresponding
a-glycoside
mation of any
a-anomer in the product; 2,3-di-O-benzyl-4,6-O-
8 in a better yield than that reported earlier.6 The next glycosyl
acceptor 9 was generated from 8 by Zémplen deacetylation. We
then adopted Crich’s b-mannosidation technique7 for the next
glycosidation step. Although Crich’s general approach of direct
b-mannosidation7 has been applied widely to synthesize various
complex oligosaccharides,8 remarkably, the application of this
benzylidene- -glucose, however, was also formed as a side prod-
D
uct. The reaction proceeds with in situ generation of the corres-
ponding glycosyl triflate7c,d,g,14 from 7, which as an intimate ion
pair gives preferred displacement via the acceptor from the b-face,
giving finally b-mannoside. The appearance of a single proton mul-
tiplet at d 2.97 confirmed the generation of b-mannoside.7c–f The
structure of 10 was also confirmed by 13C NMR, COSYGP, TOCSY,
HMBC, HSQC and NOESY techniques. The three consecutive
anomeric protons of 10 from the non-reducing end appeared at d
* Corresponding author. Fax: +91 033 2414 6266.
E-mail addresses: ghoshrina@yahoo.com, ghosh_rina@hotmail.com (R. Ghosh).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.07.089

5848
S. K. Maity et al. / Tetrahedron Letters 49 (2008) 5847–5849
BnO
BnO
BnO
OH
O
OH
HO
HO
OBn
O
O
O
Ph
HO
O
O
+
BnO
HO
HO
O
BnO
BnO
BnO
O
SPh
HO
O
7
HO
HO
O
OMe
O
9
HO
OH
BnO
BnO
BnO
OH
BnO
OAc
O
O
BnO
BnO
1
+
OMe
4
3
SR
Scheme 1. Retrosynthetic analysis of 1.
BnO
BnO
OAc
O
BnO
OH
OMe
O
BnO
BnO
BnO
O
O
BnO
O
d
BnO
b or c
BnO
4
5
2
SR
SR
HO
HO
OH
a
BnO
BnO
OR
O
O
HO
BnO
BnO
BnO
BnO
OH
O
4a or 4b, e
6
SPh
O
BnO
BnO
f
O
3
OMe
BnO
OBn
O
O
O
BnO
Ph
OMe
8, R =Ac
9, R =H
SPh
7
OBn
O
OH
O
O
Ph
HO
HO
O
BnO
HO
O
O
O
BnO
BnO
HO
HO
O
h
HO
g
BnO
7 + 9
O
O
BnO
BnO
HO
O
O
HO
BnO
HO
OMe
OMe
11
10
Scheme 2. Reagents and conditions: (a) MeOH/CH3COCl (5 equiv)/reflux/10 h, 88%; (b) HgBr2 (0.1 equiv)/PhSH/CH3CN/4 Å MS/Ar/60 °C/4 h, 92%; (c) BF3ꢀEt2O (2 equiv)/EtSH/
0 °C/30 min, 88%; (d) NaOMe (0.02 M)/MeOH/5 h, quantitative; (e) TfOH (15 mol %)/NIS (1 equiv)/DCM/4 Å MS/0 °C/Ar/30 min, 84–88%; (f) (i) dimethoxytoluene/
NaHSO4ꢀSiO2/MeCN/rt/2 h, 65%; (ii) NaH/BnBr (1.2 equiv)/DMF/2 h, 98%; (g) BSP/Tf2O/TTBP/4 Å MS/Ar/ꢁ78 °C/2 h, 78%; (h) 10% Pd/C/H2/AcOH/MeOH/24 h, 86%. Synthesis
of the repeating unit of the O-antigen of E. coli type 8.
4.35, 5.09 and 4.76, respectively. The chemical shifts of the two
successive non-reducing end anomeric carbons merged at
Catalytic hydrogenation of 10 with Pd/C finally afforded the tar-
get trisaccharide as its methyl glycoside 11. Compound 11 showed
three equally strong anomeric proton signals appearing succes-
sively from the non-reducing end at d 4.62, 5.02 and 4.88 with cor-
responding anomeric 13C-chemical shifts at d 99.8 (JC,H 158.8 Hz),
100.7 (JC,H 171.6 Hz) and 101.5 (JC,H 170.7 Hz), respectively; the J
d
99.98 and the reducing end anomeric carbon appeared at d 99.9.
Interestingly, COSYGP and TOCSY did not show any correlation of
H-100 with any other proton, probably due to very small coupling
between H-100 and H-200 and consequent magnetization transfer.
However, H-100 could be identified from the NOESY and HSQC of
10. As expected, the NOESY experiment showed a distinct correl-
ation between protons H-100 and H-500 (which again established
the b-glycoside linkage of the non-reducing mannose) and also
with H-200, 300 and 10 of compound 10; H-100 and H-10 are thus also
within the NOE spin cross-relaxation distance.
values indicated15 the presence of one b-linkage and two
a-link-
ages in the final trisaccharide glycoside.
In summary, the methyl glycoside of the repeating trisaccharide
unit of the O-antigen of E. coli type 8 was synthesized starting from
the reducing end. The crucial step was the b-(1?2)-mannosidation
on the (1?2)-linked disaccharide derived acceptor using BSP-pre-

S. K. Maity et al. / Tetrahedron Letters 49 (2008) 5847–5849
5849
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activated thioglycoside donor, which proceeded in very good yield
and with excellent b-selectivity.
Acknowledgements
9. Dromer, F.; Chevalier, R.; Sendid, B.; Improvisi, L.; Jouault, T.; Robert, R.; Mallet,
J. M.; Poulain, D. Antimicrob. Agents Chemother. 2002, 46, 3869–3876.
10. (a) Oshitari, T.; Shibasaki, M.; Yoshizawa, T.; Tomita, M.; Takao, Ken-ichi.;
Kobayashi, S. Tetrahedron 1997, 53, 10993–11006; (b) Crich, D.; Sun, S.
Tetrahedron 1998, 54, 8321–8348.
11. Niu, Y.; Wang, N.; Cao, X.; Ye, X.-S. Synlett 2007, 2116–2120.
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Financial assistance from the CSIR, New Delhi to R.G. (Scheme
No. 01/1951/04/EMR-II) and S.K.M. (SRF) is gratefully acknow-
ledged. Dr. Bikash C. Pal, Department of Chemistry, IICB, Kolkata
700 032 is warmly thanked for providing us with HPLC facilities.
13. Methyl
2,3-Di-O-benzyl-4,6-O-benzylidene-b-D-mannopyranosyl-(1?2)-3,4,6-
a-D-mannopyranosyl-(1?2)-3,4,6-tri-O-benzyl-a-D-mannopyranoside
Supplementary data
tri-O-benzyl-
(10). A stirred solution of thioglycoside 7 (236 mg, 0.437 mmol), BSP14 (101 mg,
The 1H and 13C NMR spectra of compounds 10 and 11 and the
COSYGP, NOESY, HSQCGP, TOCSY and HMBC spectra of compound
10 are available. Supplementary data associated with this article
can be found, in the online version, at doi:10.1016/j.tetlet.2008.
07.089.
0
0.483 mmol), TTBP (217.2 mg, 0.874 mmol) and activated 4ÅA powdered
molecular sieves in dichloromethane (10 mL) under an argon atmosphere was
kept at ꢁ60 °C for 30 min. Then, Tf2O (88.4
lL, 0.525 mmol) was added, and
after 5 min acceptor 9 (353 mg, 0.394 mmol) in dry dichloromethane (2 mL)
was added via syringe and the reaction mixture was cooled down to ꢁ78 °C and
stirred for an additional 2 h before the molecular sieves were filtered off. The
organic layer was washed sequentially with saturated aqueous NaHCO3
solution, brine and dried (Na2SO4). The organic layer was concentrated under
reduced pressure. Purification by silica gel column chromatography (10% ethyl
acetate in hexane) afforded compound 10 as foamy material (406 mg, 78%),
References and notes
½
a 2D5
ꢂ
ꢁ38.90 (c 1.5, CHCl3); 1H NMR (600 MHz, CDCl3): d 7.47–7.46 (m, 4H, Ph-
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2.97 (m, 1H, H-500); 13C NMR (75 MHz, CDCl3): d 138.79, 138.59, 138.44, 138.29,
138.18, 138.07, 137.80, 128.77, 128.58, 128.53, 128.34, 128.30, 128.27, 128.23,
128.12, 128.04, 127.99, 127.78, 127.71, 127.61, 127.55, 127.44, 127.38, 127.32,
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Methyl
b-D-mannopyranosyl-(1?2)-a-D-mannopyranosyl-(1?2)-a-D-manno-
pyranoside (11). A mixture of trisaccharide derivative (10, 80 mg, 0.154 mmol)
and 10% Pd/C (100 mg) in MeOH–AcOH (10:1, 3 mL) was stirred under an
atmosphere of H2 for 24 h. The reaction mixture was then filtered through Celite
and the filtrate was concentrated. The product was purified by reverse phase
HPLC to give 11 (27 mg, 86%), ½a D25
ꢂ
ꢁ61.02 (c 0.48, H2O); 1H NMR (300 MHz,
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(q, J = 3.0 Hz, 1H), 3.84–3.37 (m, 17H), 3.31 (s, 3H, OMe), 3.19 (m, 1H); 13C NMR
(75 MHz, CD3OD–D2O: 4:1): d 101.48, 100.76, 99.81, 80.13, 78.32, 77.97, 74.58,
74.13, 72.26, 71.79, 71.37, 68.73, 68.54, 68.14, 62.47, 62.41 (2C), 55.54; ESI-
HRMS (TOF), calcd for C19H34O16Na ([M+Na]+): 541.1745; found: 541.1743.
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