A. Patel, T. K. Lindhorst / Carbohydrate Research 341 (2006) 1657–1668
1667
observed for C121H213N O (2936.36); ESIMS (m/z):
22 (10 mg, 3.2 lmol, 29%) as a white lyophilisate (hygro-
13
68
+
i
2
937.3649 [M+H] (calcd 2937.3687).
scopic); R = 0.1 (7:3:1 PrOH/H O/NH , a-naphthol);
f
2
3
1
[
a]D +35 (c 1.0 in H O); H NMR (500 MHz, D O): d
2
2
4
.68 (br s, 9H, 9H-1), 3.89 (s, 6H, 3NHCH CO), 3.87
2
4
.4.2. Tris-[3-{(2-[tetrakis-(2-ethoxy)]-carbonylamido)-
(s, 6H, 3NHCH CO), 3.83 (dd, J = 1.7, J2,3 =
0
00
00
00
2 1,2
tris-[2 -[(6 -deoxy-1 -O-methyl-a-D-mannopyranos-6 -yl)-
carbamoyl]ethyl]-methyl}-propyloxy]-nitromethane (21).
The triester derivative 11 (60 mg, 64.0 lmol) was dis-
solved in MeOH/H O (1:2; 2 mL) and treated with LiO-
HÆH O (14 mg, 330 lmol) at 0 ꢁC for 12 h. Then the
basic reaction mixture was neutralized (pH 6) at 0 ꢁC
with HCl (2 N) solution and was freeze-dried to afford
the crude triacid 12 (60 mg, 64.0 lmol, quant.) as a
white lyophilisate. The crude derivative 12 (19 mg,
3
.5 Hz, 9H, 9H-2), 3.76 (s, 6H, 3NHCH CO), 3.64
2
(dd, J2,3 = 3.5, J3,4 = 9.4 Hz, 9H, 9H-3), 3.55–3.49 (m,
18H, 9H-6a, 3H-6b), 3.46 (dd, J3,4 = 9.5 Hz, 9H, 9H-
4), 3.37–3.31 (m, 9H, 9H-5), 3.28 (s, 27H, 9OCH3),
2.3–2.19 (m, 12H, 6CH ), 2.18–2.14 (m, 18H, 9CH ),
1
2
2
2
2
1
3
.92–1.86 (m, 18H, 9CH2); C NMR (125.75 MHz,
D O): d 176.5, 175.5 (9CONH), 172.6, 172.4, 170.4
2
(12gly-CONH), 101.2 (9C-1), 93.6 (NO –C ), 71.0 (9C-
2 q
4), 70.8 (9C-3), 70.3 (9C-2), 68.4 (9C-5), 58.7 (3NH–
2
0.0 lmol) was dissolved in dry DMF (3 mL) and the
amino-terminated mannoside cluster 16 (62 mg,
0.0 lmol), HATU (27 mg, 72.0 lmol), and DIPEA
0.03 mL, 180 lmol) were added at rt under argon atmo-
sphere. The reaction mixture was heated at 45–50 ꢁC for
2 h and then DMF was removed in vacuo. The result-
C ), 55.1 (9OCH ), 43.3, 43.0, 42.9 (9NHCH CO),
4
TOFMS: m/z = 3076.1 [M+Na]
C121 N O (3053.3); ESIMS (m/z): 3054.3288
q
3
2
0.5 (9C-6), 30.7, 30.4, 30.2, 30.1 (24CH ); MALDI-
2
8
(
+
observed for
H
204
+
22 68
[
M+H] (calcd 3054.3259).
1
ing pale syrup was subjected to two successive gel per-
meation chromatography steps on Bio-gel P-2, and P-6
to get the title glycodendron 21 (24 mg, 7.5 lmol, 38%)
0
00
4.4.4.
1,3,5-{Tris-[(triglycylamido)-tris-(2 -[(6 -deoxy-
0
0
00
1 -O-methyl-a-D-mannopyranos-6 -yl)carbamoyl]ethyl)-
methyl]} benzene-triamide (24). Trimesic acid (23) (2.2
mg, 10.0 lmol), the mannoside cluster 19 (41 mg, 40.0
lmol), HATU (15 mg, 40.0 lmol), and DIPEA (0.02
mL, 110 lmol) were dissolved in dry DMF (3 mL) under
argon atmosphere. The reaction mixture was stirred at
45–50 ꢁC for 12 h and then concentrated in vacuo. The
resulting syrup was subjected to two successive gel per-
meation chromatography steps, first on Bio-gel P-2,
then on Bio-gel P-6 to get the title triglycine spaced
glycodendrimer 24 (10 mg, 3.3 lmol, 33%) as a white
lyophilisate (hygroscopic); R = 0.1 (7:3:1 PrOH/H O/
NH , a-naphthol); [a]D +33 (c 0.6 in H O); H NMR
3 2
(500 MHz, D O): d 8.50 (s, 3H, 3aryl-H), 4.70 (br s,
9H, 9H-1), 4.22 (s, 6H, 3NHCH CO), 4.01 (s, 6H,
3NHCH CO), 3.90 (dd, J = 1.7, J2,3 = 3.5 Hz, 9H,
9H-2), 3.86 (s, 6H, 3NHCH CO), 3.71 (dd, J = 3.5,
2 2,3
J3,4 = 9.3 Hz, 9H, 9H-3), 3.61–3.49 (m, 27H, 9H-4,
9H-6a, 3H-6b), 3.40–3.36 (m, 9H, 9H-5), 3.35 (s, 27H,
9OCH ), 2.22–2.15 (m, 18H, 9CH ), 1.98–1.90 (m,
as a white lyophilisate (hygroscopic); R = 0.3 (7:3:1
f
i
PrOH/H O/NH , a-naphthol); [a] +40 (c 0.8 in
2
3
D
1
H O);
H
NMR (500 MHz, D O):
d
4.58 (d,
2
2
J1,2 = 1.8 Hz, 9H, 9H-1), 3.86 (s, 6H, 3OCH CO), 3.76
2
(
dd, J1,2 = 1.7, J2,3 = 3.5 Hz, 9H, 9H-2), 3.56 (dd,
J2,3 = 3.5, J3,4 = 9.3 Hz, 9H, 9H-3), 3.60–3.35 (m, 54H,
7OCH ), 3.56–3.43 (m, 18H, 9H-5, 9H-6a), 3.39 (dd,
2
2
J3,4 = 9.3 Hz, 9H, 9H-4), 3.27 (dd, 9H, 9H-6b), 3.22 (s,
7H, 9OCH ), 2.17–2.08 (m, 18H, 9CH ), 1.92–1.83
2
3
2
1
3
(
(
(
(
(
3
m, 24H, 12CH ), 1.28–1.26 (m, 6H, 3CH ); C NMR
125.75 MHz, D O): d 175.3, 170.7 (12CONH), 100.3
9C-1), 94.6 (NO –Cq), 70.0 (9C-5), 69.8 (9C-3), 69.8
3OCH , 9C-2), 69.7, 69.3, 69.2, 69.1, 69.0, 68.9, 68.6
2 2
i
2
f
2
1
2
2
2
27OCH ), 67.5 (9C-4), 60.6 (3NH–Cq), 54.0 (9OCH ),
2
3
2
9.5 (9C-6), 31.0, 29.4, 29.3 (21CH ), 22.5 (3CH );
2
2
2
1,2
+
MALDI-TOFMS: m/z = 3184.7 [Mꢀ16] , 3200.6
+
+
+
[
M] , 3223.7 [M+Na] , 3239.6 [M+K] observed for
C133 N O (3200.51); ESMS (m/z): 3201.5289
H
237
+
13 74
[
M+H] (calcd 3201.5260).
3
2
1
3
1
8H, 9CH2); C NMR (125.75 MHz, D O): d 176.4
2
(
1
9CONH), 172.5, 172.4, 170.5, 169.0 (12gly-CONH),
0
.4.3. Tris-{2-[carbonylamido-(triglycylamido)-tris-{2 -
4
[
34.6 (3aryl-C ), 130.2 (3aryl-CH), 101.2 (9C-1), 71.0
0
0
00
00
q
(6 -deoxy-1 -O-methyl-a-D-mannopyranos-6 -yl)carba-
(
(
(
(
9C-4), 70.7 (9C-3), 70.3 (9C-2), 68.5 (9C-5), 58.7
3NH–Cq), 55.0 (9OCH3), 43.7, 43.4, 43.1
9NHCH CO), 40.4 (9C-6), 30.4, 30.2 (18CH ); ESIMS
moyl]ethyl}-methyl]-ethyl}-nitromethane (22). Peptide
coupling between 4-(2-carbethoxy)-4-nitro-heptan-1,7-
dicarboxylicacid 13 (3.2 mg, 11.0 lmol) and the spaced
cluster 19 (44 mg, 46.0 lmol) was performed using
HATU (17 mg, 40.0 lmol) and DIPEA (0.02 mL,
2
2
+
m/z): 2496.0524 [M+Na]
(calcd 2473.0616 for
C102H168N O ).
12
57
1
20 lmol) in dry DMF (3 mL). The reaction mixture
was stirred under argon atmosphere at 45–50 ꢁC for
2 h and then concentrated in vacuo. The resulting pale
1
Acknowledgement
syrup was subjected to two successive gel permeation
chromatography steps, first on Bio-gel P-2, then on
Bio-gel P-6 to get the triglycine-spaced glycodendron
Support of our work by the DFG (SFB 470) is gratefully
acknowledged.