T. K. Lindhorst and C. D. Heidecke
heating and the crude product was purified by column chromatography
on silica (cyclohexane/EtOAc 4:1). Yield: 9.27 g (53%, over 2 steps) as a
colourless syrup; [a]D20 =ꢀ26 (c=0.52, CH2Cl2); 1H NMR (500 MHz,
CDCl3, TMS): d=8.79 (s, 1H; NH), 8.13 (m, 2H; 2H o-Ar), 8.07 (m, 2H;
2Ho-Ar), 7.62–7.58 (m, 2H; Hp-Ar), 7.50–7.45 (m, 4H; 4Hm-Ar), 6.48 (d,
3J=2.1Hz, 1H; H-1), 5.82 (dddd, 3J=17.2 Hz, 3J=10.4 Hz, 3J=5.6 Hz,
3J=5.6 Hz, 1H; CH=CH2), 5.75 (ddꢁt, 3J=10.0 Hz, 1H; H-4), 5.74 (dd,
3J=3.3 Hz, 3J=2.2 Hz, 1H; H-2), 5.70 (dddd, 3J=17.2 Hz, 3J=10.3 Hz,
3J=6.3 Hz, 3J=5.4 Hz, 1H; CH=CH2), 5.21(dddd, 3J=17.3 Hz, 2J=
1.7 Hz, 4J=1.7 Hz, 4J=1.7 Hz, 1H; CH=CHtransH), 5.16 (dddd, 3J=
17.2 Hz, J=1.6 Hz, J=1.6 Hz, J=1.6 Hz, 1H; CH=CHtransH), 5.10–5.05
(m, 2H; 2CH=CHcisH), 4.29 (ddd, 3J=10.1 Hz, 3J=4.0 Hz, 3J=4.0 Hz,
1H; H-5), 4.20 (dd, 3J=9.8 Hz, 3J=3.3 Hz, 1H; H-3), 4.14–4.09 (m, 1H;
CHHCH=CH2), 4.03–3.98 (m, 3H; 3CHHCH=CH2), 3.67 ppm (m, 2H;
H-6, H-6’); 13C NMR (125.76 MHz, CDCl3): d=165.52, 165.39 (2C=O),
159.79 (C=NH), 134.39, 134.00 (2CH=CH2), 133.46, 133.25 (2Cp-Ar),
130.10, 129.77 (4Co-Ar), 129.66, 129.27 (2CAr-quart), 128.50, 128.43 (4
2H; 2OH), 2.10 (br, 2H; 2OH), 1.91 (m, 2H; OCH2CH2CH2O),
1.85–1.70 (m, 6H; OCH2CH2CH2O, 2OCH2CH2CH2OH), 1.61–
1.50 ppm (m, 4H; 2OCH2CH2CH2OH); 13C NMR (76.47 MHz, CDCl3):
d=166.15, 166.02, 165.83, 165.69, 165.49 (6C=O), 133.50, 133.44,
133.41, 133.33, 133.27 (6Cp-Ar), 129.94, 129.92, 129.72, 129.71 (10Co-Ar),
129.70 (CAr-quart), 129.66 (2Co-Ar), 129.52, 129.46, 129.42, 129.40, 129.32
(5CAr-quart), 128.56–128.43 (12Cm-Ar), 98.82, 97.77, 97.73 (3C-1),
76.21, 76.13, 75.80 (3C-3), 70.20 (OCH2), 69.98, 69.96, 69.84 (3C-5),
69.46 (2OCH2), 69.31(2OCH ), 68.97, 68.85, 68.80, 68.77, 68.62, 68.56
2
(3C-2, 3C-4), 68.36, 67.46, 67.36, 66.57, 65.08, 64.95 (6OCH2), 60.35,
60.26, 59.70, 59.66 (4OCH2CH2CH2OH), 55.32 (OCH3), 32.27, 32.25,
2
4
4
32.10,
32.09
(4OCH2CH2CH2OH),
29.72,
29.66 ppm
(2
CH2CH2CH2O); IR (KBr): n˜max =3434, 2926, 2881, 1724, 1601, 1451,
1358, 1322, 1267, 1113, 1070, 1027, 712 cmꢀ1; HRMS (ESI): m/z: calcd for
C79H94NaO28: 1513.5824; found: 1513.5883 [M+Na]+.
Methyl
2,4-di-O-benzoyl-3,6-di-O-(3-{2,4-di-O-benzoyl-3,6-di-O-[3-
(2,3,4,6-tetra-O-benzoyl-a-d-mannopyranosyloxy)-propyl]-a-d-mannopyr-
anosyloxy}-propyl)-a-d-mannopyranoside (13): The acceptor tetraol 12
(76 mg, 51 mmol) was glycosylated with donor 4 (758 mg, 1.02 mmol) by
GP 4. For purification, the crude product was first chromatographed on
silica (toluene/EtOAc 8:1) and then on Sephadex LH-20 (CH2Cl2/MeOH
1:1). Yield: 105 mg (54%) as a white foam; [a]2D0 =ꢀ70 (c=1.6, CHCl3);
1H NMR (500 MHz, CDCl3, TMS): d=8.10–8.01 (m, 28H; 28Ho-Ar),
7.94–7.90 (m, 8H; 8Ho-Ar), 7.83–7.78 (m, 8H; 8Ho-Ar), 7.61–7.22 (m,
66H; 66HAr), 6.09 (ddꢁt, 3J=10.1 Hz, 2H; 2H-4), 6.01 (ddꢁt, 3J=
10.1 Hz, 1H; H-4), 6.00 (ddꢁt, 3J=10.1 Hz, 1H; H-4), 5.87 (dd, 3J=
10.1 Hz, 3J=3.3 Hz, 2H; 2H-3), 5.76 (2ddꢁmc, 2H; 2H-3), 5.68
C
m-Ar), 118.05, 117.00 (2CH=CH2), 95.18 (C-1), 90.83 (CCl3), 73.99 (C-
3), 73.16 (C-5), 72.50, 70.95 (2CH2CH=CH2), 69.14 (C-6), 68.22,
67.67 ppm (C-2, C-4); IR (KBr): n˜max =3447, 2921, 1729, 1676, 1452, 1320,
1264, 1107, 1069, 1028, 975, 934, 840, 796, 710, 644 cmꢀ1; HRMS (ESI):
m/z: calcd for C28H28Cl3NNaO8: 634.0773; found: 634.0757 [M+Na]+.
Methyl 3,6-di-O-(3-{3,6-di-O-allyl-2,4-di-O-benzoyl-a-d-mannopyranosyl-
oxy}-propyl)-2,4-di-O-benzoyl-a-d-mannopyranoside (11): The acceptor
alcohol 3 (478 mg, 0.921mmol) was glycosylated with donor 10 (3.75 g,
6.12 mmol) by GP 4. For purification, the crude product was chromato-
graphed on silica (toluene/EtOAc 8:1). Yield: 1.03 g (79%) as a colour-
less foam; [a]2D0 =ꢀ68 (c=0.51, CH2Cl2); 1H NMR (500 MHz, CDCl3,
TMS): d=8.12–8.04 (m, 12H; 12Ho-Ar), 7.59–7.47 (m, 6H; 6Hp-Ar),
7.47–7.39 (m, 12H; 12Hm-Ar), 5.81(m, 2H; 2C H=CH2), 5.66 (m, 2H;
2CH=CH2), 5.61(dd ꢁt, 3J=9.9 Hz, 1H; H-4), 5.61 (m, 1H; H-2), 5.58
(ddꢁt, 3J=10.1 Hz, 1H; H-4), 5.53 (ddꢁt, 3J=9.9 Hz, 1H; H-4), 5.51
(m, 1H; H-2), 5.44 (dd, 3J=3.3 Hz, 3J=1.9 Hz, 1H; H-2), 5.20 (dddd,
3J=17.3 Hz, 2J=1.7 Hz, 4J=1.7 Hz, 4J=1.7 Hz, 1H; CH=CHtransH), 5.19
(dddd, 3J=17.3 Hz, 2J=1.7 Hz, 4J=1.7 Hz, 4J=1.7 Hz, 1H; CH=
CHtransH), 5.11 (m, 2H; 2CH=CHtransH), 5.07 (m, 2H; 2CH=CHcisH),
3
3
3
(dd, J=3.3 Hz, J=1.8 Hz, 2H; 2H-2), 5.67 (ddꢁt, J=9.9 Hz, 1H; H-
4), 5.63–5.56 (m, 6H; 4H-2, 2H-4), 5.50 (dd, 3J=3.1Hz, 3J=1.9 Hz,
1H; H-2), 5.06 (d, 3J=1.6 Hz, 2H; 2H-1), 4.99 (d, 3J=1.7 Hz, 1H; H-
1), 4.89 (d, 3J=1.7 Hz, 1H; H-1), 4.71 (d, 3J=1.7 Hz, 1H; H-1), 4.70 (d,
3J=1.7 Hz, 2H; 2H-1), 4.65 (m, 2H; 2H-6), 4.49–4.42 (m, 4H; 4H-
6), 4.40–4.31(m, 4H; 2H-5, 2H-6), 4.15 (m, 2H; 2H-5), 4.08–3.98,
3.92–3.85 (2m, 8H; 3H-3, 3H-5, 2OCHHCH2CH2O), 3.84–3.76
(m, 4H; 4OCHHCH2CH2O), 3.71–3.33 (m, 24H; 6H-6, 18
OCHHCH2CH2O), 3.44 (s, 3H; OCH3), 1.97–1.87 (m, 6H; 3
OCH2CH2CH2O), 1.80–1.66 ppm (m, 6H; 3OCH2CH2CH2O);
13C NMR (125.47 MHz, CDCl3): d=166.09, 166.04, 165.65, 165.58, 165.51,
165.42, 165.39, 165.36, 165.26, 165.13 (22C=O), 133.33, 133.30, 133.23,
133.12, 133.06, 133.03, 133.02, 132.95 (22Cp-Ar), 129.91, 129.81, 129.75,
129.69, 129.66 (44Co-Ar), 129.49, 129.40, 129.18, 129.15, 129.05, 129.00
(22CAr-quart), 128.60–128.30, 128.23, 128.21 (44Cm-Ar), 98.80, 97.82,
97.80 (3C-1), 97.58 (2C-1), 97.44 (2C-1), 76.21, 76.13, 75.83 (3C-
3), 70.44, 70.38, 70.25, 70.11, 70.04, 69.99, 69.85, 69.11, 68.88, 68.83, 68.78,
68.70, 68.49 (7C-2, 4C-3, 3C-4, 7C-5), 70.02, 69.91(3C-6), 68.47,
68.15, 68.11 (3CH2), 66.90 (4C-4), 66.72, 66.56, 66.53, 65.48, 65.34,
65.13, 65.00 (9CH2), 62.85 (2C-6), 62.71(2C-6), 55.24 (OCH 3),
29.77, 29.71, 29.61 ppm (6OCH2CH2CH2O); IR (KBr): n˜max =2958,
3
4.98 (m, 2H; 2CH=CHcisH), 4.97 (d, J=2.0 Hz, 1H; H-1), 4.92 (d, 3J=
1.9 Hz, 1H; H-1), 4.67 (d, 3J=1.9 Hz, 1H; H-1), 4.10–3.88 (m, 14H; 3
H-3, 3H-5, 8OCHHCH=CH2), 3.80 (m, 2H; 2OCHHCH2), 3.69
2
3
2
3
(dd, J=10.7 Hz, J=3.0 Hz, 1H; H-6’), 3.65 (dd, J=10.7 Hz, J=5.5 Hz,
1H; H-6), 3.63–3.51 (m, 8H; 4H-6, 4OC HHCH2), 3.50–3.43 (m, 1H;
OCHHCH2), 3.47 (s, 3H; OCH3), 3.36 (m, 1H; OCHHCH2), 1.90 (m,
2H; OCH2CH2CH2O), 1.72 ppm (m, 2H; OCH2CH2CH2O); 13C NMR
(125.76 MHz, CDCl3): d=165.82, 165.73, 165.63, 165.57, 165.55 (6C=
O), 134.56, 134.54, 134.39, 134.36 (4CH=CH2), 133.33, 133.26, 133.24,
133.17, 133.16, 133.11 (6Cp-Ar), 130.03, 130.01 (Co-Ar), 129.93, 129.85
(CAr-quart), 129.78 (Co-Ar), 129.75 (CAr-quart), 129.73 (Co-Ar), 129.67 (CAr-quart),
128.54, 128.51, 128.44, 128.43, 128.40 (12Cm-Ar), 117.23, 117.18, 116.89,
116.85 (4CH=CH2), 98.88, 97.72, 97.70 (3C-1), 75.88, 74.69, 74.65 (3
C-3), 72.54, 72.50, 70.67, 70.60 (4CH2CH=CH2), 70.38 (C-6), 70.27,
70.17, 70.09 (3C-5), 69.58, 69.48 (2C-6), 69.36, 69.22 (2C-2), 69.11,
1727, 1602, 1584, 1451, 1316, 1266, 1177, 1109, 1068, 1026, 709 cmꢀ1
;
MALDI-TOF-MS: m/z: calcd for C215H198NaO64: 3826.21; found: 3826.41
[M+Na]+, 3842.38 [M+K]+.
69.07, 68.91(C-2, 3C-4), 68.54, 66.76, 65.06, 64.96 (4OCH CH2), 55.35
2
Methyl 3,6-di-O-(3-{3,6-di-O-[3-(a-d-mannopyranosyloxy)-propyl]-a-d-
mannopyranosyloxy}-propyl)-a-d-mannopyranoside (14): Deprotection of
compound 13 (89 mg, 23 mmol) was accomplished by GP 5. For purifica-
tion, the crude product was chromatographed on Sephadex LH-20
(MeOH), dissolved in H2O and lyophilised. Yield: 31mg (88%) as a col-
ourless amorphous solid; [a]2D0 =+70 (c=0.98, MeOH); 1H NMR
(500 MHz, [D4]MeOH): d=4.78–4.75 (m, 6H; 6H-1), 4.66 (d, 3J=
1.6 Hz, 1H; H-1), 3.98–3.94 (m, 3H; 3H-2), 3.91–3.49 (m, 60H; 4H-2,
4H-3, 7H-4, 7H-5, 14H-6, 24OCHH), 3.47–3.41(m, 3H; 3H-
3), 3.39 (s, 3H; OCH3), 1.96–1.83 ppm (m, 12H; 6OCH2CH2CH2O);
13C NMR (125.76 MHz, [D4]MeOH): d=102.70, 101.66 (2C-1), 101.62
(2C-1), 101.54 (3C-1), 81.10, 81.09, 81.02 (3C-3), 74.58 (2C-5),
74.51(2C-5), 73.62, 73.55, 73.52 (3C-5), 72.71(4C-3), 72.25 (4C-
2), 71.72, 71.64, 71.57, 69.56, 69.49 (CH2), 69.10, 68.92 (CH), 68.80 (2C-
4), 68.71(2C-4), 67.90, 67.80 (CH 2), 67.76, 67.71(CH), 65.77, 65.72,
65.42 (CH2), 63.06 (2C-6), 63.00 (2C-6), 55.43 (OCH3), 31.15 (2
OCH2CH2CH2O), 31.08 (OCH2CH2CH2O), 30.88 (2OCH2CH2CH2O),
30.84 ppm (OCH2CH2CH2O); IR (KBr): n˜max =3435, 2925, 1637, 1136,
(CH3), 29.80, 29.75 ppm (2OCH2CH2CH2O); IR (KBr): n˜max =2918,
1725, 1451, 1265, 1110, 1069, 1027, 711 cmꢀ1; HRMS (ESI): m/z: calcd for
C79H86NaO24: 1441.5401; found: 1441.5416 [M+Na]+.
Methyl
2,4-di-O-benzoyl-3,6-di-O-(3-{2,4-di-O-benzoyl-3,6-di-O-[3-hy-
droxypropyl]-a-d-mannopyranosyloxy}-propyl)-a-d-mannopyranoside
(12): Compound 12 was synthesised from mannoside 11 (216 mg,
0.152 mmol) by GP 2. The crude product was purified by column chroma-
tography on silica (EtOAc) and then on Sephadex LH-20 (CH2Cl2/
MeOH 1:1). Yield: 91 mg (40%) as a sticky white foam; [a]2D0 =ꢀ74 (c=
4.2, CHCl3); 1H NMR (300 MHz, CDCl3, TMS): d=8.14–8.00 (m, 12H;
12Ho-Ar), 7.64–7.50 (m, 6H; 6Hp-Ar), 7.50–7.37 (m, 12H; 12Hm-Ar),
5.68–5.53 (m, 5H; 2H-2, 3H-4), 5.51(dd, 3J=3.1Hz, 3J=1.9 Hz, 1H;
H-2), 5.00 (d, 3J=1.7 Hz, 1H; H-1), 4.91 (d, 3J=1.7 Hz, 1H; H-1), 4.69
(d, 3J=1.7 Hz, 1H; H-1), 4.10–4.02 (m, 1H; H-5), 4.05 (dd, 3J=9.7 Hz,
3J=3.3 Hz, 1H; H-3), 4.02–3.94 (m, 1H; H-5), 3.99 (dd, 3J=9.7 Hz, 3J=
3.3 Hz, 1H; H-3), 3.94–3.30 (m, 32H; H-3, H-5, 3H-6, 3H-6’, 2
OCH2CH2CH2O, 4 OCH2CH2CH2OH), 3.47 (s, 3H; OCH3), 2.85 (br,
9064
ꢁ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2007, 13, 9056 – 9067