5366
S. Mignani et al. / Tetrahedron Letters 51 (2010) 5364–5367
O
( )3
References and notes
O
+
OH
BocHN
NH2
1. For recent reviews, see: (a) Sutherland, A. J. Curr. Opin. Solid State Mater. Sci.
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S
S
7
4
6
a)
87%
H
N
H
N
NHBoc
( )3
O
S
S
O
7
12
b)
100%
H
N
H
N
NH2
( )3
O
S
S
O
7
13
c)
76%
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14; (b) Pathak, S.; Choi, S.-K.; Thompson, M. E. J. Am. Chem. Soc. 2001, 123,
4103–4104.
H
H
N
H
3. (a) Rongchao, Z. L.; Mirkin, C. A.; letsinger, R. L. Nucleic Acids Res. 2002, 30,
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N
N
CO2H
( )3
O
O
S
S
O
7
14
d)
43%
H
N
H
N
H
N
CO2H
( )3
O
O
SH SH
O
7
3
Scheme 5. Synthetic approach to the surface ligand 3. Reagents and conditions: (a)
(1) DMF, Et3N, DPPA, 80 °C until the end of nitrogen production (ꢀ15 min); (2) DMF,
4, 12 h, 80 °C; (3) NaHCO3, 12 h, rt; (4) column chromatography (silica gel, eluent:
90:10 CH2Cl2–MeOH mixture). (b) MeOH, HClÁdiethyl ether, 4 h, rt. (c) (1) pyridine,
succinic anhydride, 48 h, rt; (2) column chromatography (silica gel, eluent: 90:10
CH2Cl2–MeOH mixture). (c) (1) 1:1 EtOH–water mixture, TCEPÁHCl, pH ꢀ4 (0.1 M
NaOH), 2 h, rt; (2) preparative HPLC.19
7. (a) Pathak, S.; hoi, S. K.; Arnheim, N.; Thompson, M. E. J. Am. Chem. Soc. 2001,
123, 4103–4104; (b) Dhar, S.; Daniel, W. L.; Gijohann, D. A.; Mirkin, C. A.;
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J. L. L.; Peng, X. Chem. Mater. 2003, 15, 3125–3133.
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O
( )3
H
N
a)
O
OH
( )3
OH
O
S
S
47%
S
S
O
12
6
15
b)
55%
H
N
12. Two other ligands 17 and 18 have been prepared. They showed good water-
solubility but they have obtained in poor yields due to purification difficulties.
O
OH
( )3
O
SH SH
O
12
16
O
( )3
O
O
OH
Scheme 6. Synthetic route to the ligand 16. Reagents and conditions: (a) (1)
dodecaethyleneglycol, DPPA, Et3N, 12 h, 80 °C; (2) column chromatography (silica
gel, eluent: 80:20 CH2Cl2–MeOH mixture). (b) (1) 4:1 MeOH–water mixture, NaBH4,
2.5 h, rt; (2) column chromatography (silica gel, eluent: 90:10 CH2Cl2–MeOH
mixture).
SH SH
SH SH
12
19
17
O
O
( )3
N
H
NH2
18
carbamates from 6.13b Reduction of the 1,2-dithiolane ring of 15 by
NaBH4 afforded the desired compound 16.
In conclusion, we have prepared the macromolecular, function-
alized carboxylic-acid–PEG–DHLA ligands 1, 2, and 3 as capping
molecules. These compounds were easily synthesized from the
commercially available (+/À)-lipoic acid 6 through an amidifica-
tion reaction or a Curtius rearrangement. Further studies on the
use of compounds 1–3 as capping ligands are in progress.
13. (a) Takao, T.; Zenzaburo, T. U.S. Patent 4,349, 552, 1980.; (b) Takeshi, F.;
Tomihisa, Y. Eur. Pat. 98-302532, 1998 and 2000169371, 2000.; (c) Bourgouin,
A. WO 01/68643, 2001.
14. For an analogous reductive de-tritylation using triethylsilane, see: Vedejs, E.;
Little, J. J. Am. Chem. Soc. 2002, 124, 748–749.
15. For uses of the disulfide reductant TCEP, see: Kizek, R.; Vacek, J.; Trnková, L.;
Jelen, F. Bioelectrochemistry 2004, 63, 19–24.