V. Haridas et al. / Tetrahedron 67 (2011) 1873e1884
1883
filtered, and evaporated to yield 0.90 g of the compound Boc-Asp-
finally with water. The organic layer was dried over anhydrous
Na2SO4, filtered, and evaporated to yield the dendrimer.
dialkyne.
Yield: 85%; 1H NMR (CDCl3, 300 MHz)
d 1.45 (m, 9H), 2.23 (m,
2H), 2.57 (m, 1H), 2.89 (m, 1H), 4.04 (m, 4H), 4.48 (m, 1H), 6.14 (br s,
1H), 6.39 (br s, 1H), 7.19 (br s, 1H); IR (KBr) 3312, 2932, 2127, 1694,
4.28.1.1. Dendrimer 25a. Yield: 87%; [
a
]
27.1 ꢀ16.3 (c 0.08, CHCl3);
D
d
mp 148e150 ꢂC; 1H NMR (CDCl3, 300 MHz)
1.79 (s, 9H), 2.02 (br s,
1643, 1532, 1443, 1332, 1276, 1167 cmꢀ1
;
HRMS calcd for
18H), 2.22 (s, 9H), 4.17 (d, J¼5.4 Hz, 6H), 4.33 (t, J¼6.3 Hz, 3H), 4.74 (br
m, 6H), 5.30 (d, J¼10.2 Hz, 3H), 5.56 (br s, 3H), 5.64 (t, J¼9.75 Hz, 3H),
5.96(d, J¼9.3Hz,3H), 8.02(s, 3H), 8.12(brs, 3H), 8.21(s, 3H); 13CNMR
C15H21N3O4Na m/z 330.1430, found m/z 330.1429.
To an ice-cooled solution of Boc-Asp-dialkyne (0.700 g,
2.28 mmol) in 6 ml of dry CH2Cl2 was added 3 ml of TFA. The so-
lution was left stirred for 2 h and completion of the reaction was
monitored by TLC. The reaction mixture was subjected to high
vacuum to yield 0.472 g of the NH2-Asp-dialkyne 20. It was used as
such without further purification.
(CDCl3, 75 MHz) d 20.2, 20.5, 20.67, 20.70, 35.5, 61.1, 66.8, 68.0, 70.8,
73.9, 86.2,121.6, 128.7, 134.8,145.4, 166.1, 169.3,169.9,170.1, 170.3; IR
(KBr) 3390, 2929, 1750, 1660, 1534, 1430, 1373, 1224, 1056 cmꢀ1
;
HRMS calcd for C60H72N12O30Na m/z 1463.4375, found 1463.4369.
24.3
4.28.1.2. Dendrimer 25b. Yield: 90%; [
a]
ꢀ31.53 (c 0.33,
D
4.26.2. Preparation of 21. BocLys(Boc)-OH (0.788 g, 2.28 mmol) was
dissolved in 90 ml of dry dichloromethane, cooled to 0 ꢂC. To this
ice cold solution was added N-hydroxysuccinimide (0.262 g,
2.27 mmol), DCC (0.469 g, 2.27 mmol), and stirred for 10 min.
Afterwards NH2-Asp-dialkyne 20 (0.472 g, 2.28 mmol) and trie-
thylamine (1.268 ml, 9.11 mmol) were added. The reaction mixture
was stirred overnight and filtered. Washed the filtrate with 0.2 N
H2SO4, water, and finally with saturated aqueous NaHCO3 solution.
The organic layer was dried over anhydrous Na2SO4, filtered, and
CHCl3); mp 132e134 ꢂC; 1H NMR (CD3OD, 300 MHz)
d 1.82 (s, 9H),
1.97 (s, 9H), 2.01 (s, 9H), 2.07 (s, 9H), 4.18 (br d, J¼11.1 Hz, 3H),
4.24e4.34 (br m, 6H), 4.74 (br m, 6H), 5.32 (t, J¼9.1 Hz, 3H), 5.56 (t,
J¼9.3 Hz, 3H), 5.73 (t, J¼9.1 Hz, 3H), 6.19 (d, J¼9.0 Hz, 3H), 8.33 (s,
3H), 8.35 (s, 3H); IR (KBr) 3418, 2925, 2858, 1748, 1652, 1533, 1463,
1423, 1379, 1324, 1226 cmꢀ1; HRMS calcd for C60H72N12O30Na m/z
1463.4375, found 1463.4375.
4.28.2. Synthesis of dendrimers 27a,b. To an ice-cooled solution of
hexaalkyne 26 (0.05 g, 0.064 mmol) in 20 ml of dry acetonitrile
under nitrogen atmosphere was added diisopropylethylamine
(0.076 ml, 0.446 mmol), azido sugar (24a or 24b) (0.167 g,
0.446 mmol), and CuI (0.01 g, 0.045 mmol). The reaction mixture
was stirred under N2 atmosphere for 17 h and solvent was evapo-
rated. The solid thus obtained was dissolved in ethyl acetate,
washed with 0.2 N H2SO4, water, NH4Cl/NH4OH (9:1) solution, and
finally with water. The organic layer was dried over anhydrous
Na2SO4, filtered, and evaporated to yield the dendrimer.
evaporated to yield compound 21.
23.9
Yield: 80%; [
300 MHz)
a]
þ1.8 (c 0.50, CHCl3); 1H NMR (CDCl3,
D
d
1.35e2.00 (sþm, 24H), 2.20 (m, 2H), 2.55 (m, 1H), 2.95
(m, 1H), 3.12 (m, 2H), 4.01 (m, 4H), 4.73 (br s, 2H), 5.61 (br s, 1H),
6.68 (br s, 1H), 7.27 (br s, 1H), 7.73 (br s, 1H), 8.04 (br s, 1H); IR (KBr)
3289, 2977, 2933, 2110, 1689, 1647, 1529, 1447, 1367, 1250,
1172 cmꢀ1; HRMS calcd for C26H41N5O7Na m/z 558.2904, found m/z
558.2904.
4.28.2.1. Dendrimer 27a. Yield: 80%; [
a
]
26.1 ꢀ3.3 (c 0.18, CHCl3);
D
d
4.27. Preparation of Asp dendrimer 22 with LyseAsp as the
central core
mp 138e140 ꢂC; 1H NMR (CDCl3, 300 MHz)
1.84 (s, 18H), 2.01 (m,
18H), 2.03 (m, 18H), 2.23 (s, 18H), 3.10 (m, 6H), 4.17 (m, 12H), 4.30
(m, 6H), 5.12 (m, 3H), 5.15e5.45 (br m, 18H), 5.55 (m, 12H), 5.92 (d,
J¼8.1 Hz, 6H), 7.97 (m, 9H), 8.41 (d, J¼6.3 Hz, 3H); 13C NMR (CDCl3,
To an ice-cooled solution of 21 (0.050 g, 0.093 mmol) in 20 ml of
dry acetonitrile under nitrogen was added diisopropylethylamine
(0.016 ml, 0.093 mmol), N3-Asp-(Asp$diOMe)Asp$diOMe 1a
(0.094 g, 0.187 mmol), and CuI (0.004 g, 0.021 mmol). The reaction
mixture was stirred under N2 atmosphere for 18 h. The reaction
mixture was evaporated, dissolved in chloroform, and filtered.
Washed the filtrate with 0.2 N H2SO4, water, NH4CI/NH4OH (9:1)
solution, and finally with water. The organic layer was dried over
anhydrous Na2SO4, filtered, and evaporated to yield 0.10 g of the
dendrimer 22.
75 MHz) d 20.2, 20.5, 20.7, 36.1, 49.6, 57.8, 58.5, 61.1, 61.2, 66.8, 67.9,
68.0, 70.7, 73.8, 73.9, 86.0, 86.1, 122.7, 123.1, 129.5, 134.4, 142.8,
165.7, 165.8, 169.2, 169.9, 170.1, 170.13, 170.2, 170.3, 170.4; IR (KBr)
3475, 2932,1752, 1668,1531, 1375, 1227, 1058 cmꢀ1; HRMS calcd for
C123H147N21O69Na m/z 3044.8537, found 3044.8397.
4.28.2.2. Dendrimer 27b. Yield: 80%; [
a
]
26.6 ꢀ29.2 (c 0.11, CHCl3);
D
mp 140e142 ꢂC; 1H NMR (CDCl3, 300 MHz)
d 1.75e1.92 (m, 18H),
1.97e2.12 (m, 54H), 3.08 (m, 6H), 4.00e4.22 (m,12H), 4.24e4.38 (br
m, 6H), 5.05e5.38 (br m, 21H), 5.45 (t, J¼9.3 Hz, 6H), 5.51e5.62 (m,
6H), 5.96 (m, 6H), 7.90 (m, 3H), 7.90e8.15 (m, 6H), 8.37 (d, J¼8.7 Hz,
Yield: 70%; 1H NMR (DMSO-d6, 300 MHz)
d
1.10e1.60 (sþm,
24H), 2.60e2.93 (m, 16H), 3.61 (s, 24H), 3.82 (m, 2H), 4.29 (m, 4H),
4.48e4.72 (m, 6H), 5.07 (m, 4H), 6.71 (br s, 1H), 6.94 (br s, 1H),
7.75e7.90 (m, 2H), 7.97e8.20 (m, 2H), 8.31e8.60 (m, 7H); IR (KBr)
3H); 13C NMR (CDCl3, 75 MHz)
d 20.1, 20.5, 21.0, 36.0, 49.5, 57.8, 58.6,
60.4, 61.6, 67.7, 70.2, 72.6, 75.0, 85.6, 122.8, 123.4, 129.4, 134.4, 142.7,
142.9, 165.6, 168.9, 169.4, 170.0, 170.3, 170.5; IR (KBr) 3403, 2942,
1752, 1667, 1531, 1447, 1376, 1227, 1042 cmꢀ1; HRMS calcd for
C123H147N21O69Na m/z 3044.8537, found 3044.8423.
3290, 3081, 2951, 1739, 1648, 1541, 1442, 1368, 1236, 1173 cmꢀ1
;
HRMS calcd for C62H93N17O29Na m/z 1562.6223, found m/z
1562.6230.
Acknowledgements
4.28. Preparation of carbohydrate dendrimers
Financial assistance from CSIR and DST, New Delhi, is acknowl-
edged. We thank Mr. Kashmiri Lal and Mr. K.Y. Kiran Kumar for their
help in the synthesis of dendrimers.
4.28.1. Synthesis of dendrimers 25aeb. To an ice-cooled and well-
stirred solution of trialkyne 23 (0.032 g, 0.10 mmol) in 20 ml of dry
acetonitrile under nitrogen atmosphere was added diisopropyle-
thylamine (0.06 ml, 0.35 mmol), azido sugar (24a or 24b) (0.131 g,
0.35 mmol), and CuI (0.007 g, 0.035 mmol). The reaction mixture
was stirred under N2 atmosphere for 17 h and solvent was evapo-
rated. The solid thus obtained was dissolved in ethyl acetate,
washed with 0.2 N H2SO4, water, NH4Cl/NH4OH (9:1) solution, and
Supplementary data
1H NMR, 13C NMR, and HRMS of all new compounds. Supple-
mentary data related to this article can be found online at