3218
G. J. Miller, J. M. Gardiner / Tetrahedron Letters 52 (2011) 3216–3218
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OBn
OBn
BnO
3. Pieters, R. J. Org. Biomol. Chem. 2009, 7, 2013–2025.
BnO
BnO
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O
O
BnO
OBn
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O
BnO
BnO
i
CO2H
7
BnO
NH
O
BnO
O
H2N
NH2
BnO
N
H
CO2R
8 R = Me
9 R = H
10. Dondoni, A.; Marra, A. Synlett 2009, 2679–2681.
ii
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O
OMe
Scheme 4. Reagents and conditions: (i) TBTU, HOBt, DIPEA, DMF, rt, 16 h, 57%; (ii)
NaOH, THF/H2O, rt, 3 h, 72%.
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ate terminated multivalent saccharide modules to provide hetero-
geneous higher-valent structures. The aryl ester would also remain
available for attaching a handle for immobilization once the amino
group were employed for conjugation, providing potential for dou-
ble reporter group attachment. Thus, compound 6 offers potential
access to novel diversity for applications to arrays of higher valent,
fluorescently labelled C-glycosidic ligands.
2.3. Addressing individual saccharide valency
Having demonstrated that DABME could be singly conjugated
with a larger trivalent mannoside and in order to investigate the
assembly of more complex/higher valency multivalent architec-
tures, we undertook the synthesis of bivalent C-glycosidic deriva-
tive 9 through amidation of DABME with a smaller, monovalent
C-glycoside unit (Scheme 4). In this case we employed the known
C-galactoside monomer 7,30,31 which was efficiently di-coupled
with DABME to furnish 8 and following saponification, yielded
the desired acid 9.
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T.; Chen, C. T.; Chen, C. C.; Lin, C. C. Chem. Biol. Chem. 2008, 9, 1100–1109.
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28. Selected data for 5: 1H NMR (CDCl3, 300 MHz) d 7.33–7.18 (m, 65H, Ar CH), 7.04
(s, 1H, NH), 6.60 (s, 1H, NH), 6.35 (t, J = 5.4, 3H, NH), 4.71 (d, J = 11.4, 3H,
OCH2Ph), 4.63–4.47 (m, 21H, OCH2Ph), 3.98 (td, J = 9.6, 4.7, 3H, H1 sugar),
3.79–3.60 (m, 26H, sugar ring + CH2O + PhCH2S), 3.39–3.20 [m, 16H, OCH2
core, CH2NHC(O), 2 Â CH2O tether], 2.97–3.04 [m, 2H, CH2NHC(O) tether],
2.57–2.38 [m, 6H, 2 Â CH2C(O)NH + BnSCH2], 2.32–2.20 [m, 6H, CH2C(O)NH],
1.82–1.87 (m, 6H, CH2 alkyl), 1.76–1.46 (m, 14H, CH2 alkyl); 13C NMR (CDCl3,
100 MHz) d 173.1 (C@O amide), 172.8 (2 Â C@O amide), 138.6–138.5 (4° Ar C),
130.4–127.3 (Ar CH), 77.6 (CH sugar), 76.4 (CH sugar), 75.3 (CH sugar), 74.3
(CH2), 73.6 (CH sugar), 73.5 (CH2), 72.5 (CH2), 72.4 (CH sugar), 72.1 (CH2), 71.2
(CH2 tether), 70.0 (CH2), 69.5 (CH2 core), 69.3 (CH2, tether), 69.1 (CH2 core),
60.1 (4° C core), 40.5 [CH2NHC(O)], 37.0 [CH2NHC(O)], 36.7 (PhCH2S), 32.9
[CH2C(O)], 32.6 (CH2 alkyl), 31.6 (BnSCH2), 30.1 [CH2C(O)], 30.1 [CH2C(O)], 29.7
[CH2CH2C(O)NH], 29.7 (CH2 alkyl), 29.4 (CH2 alkyl), 25.9 (CH2 alkyl), 25.9 (CH2
3. Conclusion
We report the synthesis of two novel multivalent C-glycosidic
mannosyl ligands, 5 and 6, whose differing functional tethers facil-
itate future utilization as probes to investigate multivalent carbo-
hydrate interactions. Inclusion of an embedded fluorescent label
combined with bidirectional further functionalization options pro-
vides a valuable and versatile tool to explore the potential of novel
C-glycosidic ligands.
Acknowledgements
The BBSRC are thanked for a Committee Studentship (to G.J.M.)
and EPSRC for instrumentation grants GR/L52246 (NMR), GR/
M30135 (IR). The EPSRC Mass Spectrometry Service at Swansea
is thanked for mass spectral analyses.
alkyl); MS m/z 2400 (MNa+, 100%); IR (neat)
cm-1; specific rotation [ 26 = + 28.3 (c 0.5, CHCl3).
mmax 3433, 1654, 1456, 1269, 1102
a]
29. Selected data for 6: 1H NMR (CDCl3, 300 MHz) d 7.53–7.18 (m, 63H, Ar CH), 6.97
(s, 1H, NH), 6.52 (s, 1H, NH), 6.31 (t, J = 5.7, 3H, NH), 4.73–4.45 (m, 24H,
OCH2Ph), 3.95–4.01 (m, 3H, H1 sugar), 3.79–3.61 (m, 24H, sugar ring, CH2O,
OCH3), 3.37–3.34 (t, J = 5.6, 6H, OCH2), 3.23-3.21 [m, 6H, CH2NHC(O)], 2.65–
2.48 [m, 4H, 2 Â CH2C(O)NH], 2.32–2.24 [m, 6H, CH2C(O)NH], 1.91–1.85 (m,
6H, CH2 alkyl), 1.61–1.57 (m, 6H, CH2 alkyl); 13C NMR (CDCl3, 75 MHz) d 173.2
(C@O amide), 172.9 (2 Â C@O amide), 171.4 (C@O ester), 140.2 (Ar CH), 138.6-
138.5 (4° Ar C), 128.7–128.1 (Ar CH), 77.6 (CH sugar), 76.6 (CH sugar), 75.4 (CH
sugar), 74.2 (CH2), 73.6 (CH sugar), 73.6 (CH2), 72.6 (CH2), 72.5 (CH sugar), 72.2
(CH2), 70.2 (CH2), 69.5 (CH2 core), 69.2 (CH2 core), 60.0 (4° C core), 52.3 (OCH3),
37.2 [CH2NHC(O)], 33.0 [CH2C(O)], 30.1 [CH2C(O)], 30.1 [CH2C(O)], 29.8
[CH2CH2C(O)NH], 25.9 (CH2 alkyl core); MS m/z 2299 (MNa+, 100%), 2178
(40%); IR (neat) mmax 3338, 3089, 3062, 3027, 2929, 2863, 1723, 1645, 1548,
Supplementary data
Supplementary data (experimental details for the synthesis of
compounds 3–6, 8 and 9, details of UV and fluorescence experi-
ments for compound 6 and copies of 1H and 13C NMR spectra for
compounds 3–6, 8 and 9 and MS spectra for compounds 5, 6, 8
and 9, and COSY, NOESY, TOCSY spectra of the C-allyl precursor
of 7) associated with this article can be found, in the online version,
1450, 1365, 1217, 1096 cmÀ1; specific rotation [ 26 = +37.7 (c 0.3, CHCl3).
a]
30. Fletcher, S.; Jorgensen, M. R.; Miller, A. D. Org. Lett. 2004, 6, 4245–4248. The a-
stereoselectivity for the C-allyl precursor of 7 was first reported by Kishi et al.31
Confirmation in our case of the selectivity was provided by COSY, NOESY and
TOCSY data.
References and notes
31. Lewis, M. D.; Cha, J. K.; Kishi, Y. J. Am. Chem. Soc. 1982, 104, 4976–4978.
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