P. Heller et al.
www.mbs-journal.de
was removed by rotary evaporation to obtain an orange oil, which
was used in the next reaction step without further purification.
was extracted with ice-cold water (3 ꢂ 200 mL). The organic layer
was neutralized by a saturated sodium bicarbonate solution,
washed with brine, dried over sodium sulfate and concentrated
under reduced pressure to give a yellow oil which was used in the
Yield: 7.8 g (40 mmol, 71%).
1
H NMR (300 MHz, CDCl
3
): d(ppm) ¼ 3.71–3.50 (14H, m, –CH
2
–
CH
2
–O), 2.87–2.84 (2H, t, J ¼ 4.2 Hz, –CH
2
2
–NH ).
next reaction without further purification. Yield 9.8 g (24 mmol,
[50]
þ
ESI-MS: (m/z) ¼ 194.14 ([M þ H] , ber.: 194.14).
93%). Lit.: 81%.
R ¼ 0.3 (n-hexane/EtOAc (6:4)).
f
ꢁ1
1
C
8
H19NO
4
(193.24 g ꢀ mol
)
HNMR(300 MHz, CDCl
3
):d(ppm) ¼ 6.26(1H,d, J ¼ 1.1 Hz,1), 5.67
(
1H, dd, J ¼ 3.4 Hz, 10.2 Hz, 3), 5.40 (1H, dd, J ¼ 1.6 Hz, 3.4 Hz, 2), 5.31
1H,t, J ¼ 10.1 Hz, 4),4.29(1H,dd,J ¼ 4.8 Hz,12.4 Hz,5),4.18(1H,ddd,
(
2
.3.4. 1-(Benzoyloxycarbonylamino-11-hydroxy-3,6,9-
[
49]
J ¼ 1.9 Hz, 4.9 Hz, 10.1 Hz, 6a), 4.09 (1H, dd, J ¼ 2.1 Hz, 12.4 Hz, 6b),
trioxa) undecan
2
.23–2.03 (12H, 4s, –CH
3
).
þ
To a solution of 7.8 g (40 mmol) 1-amino-11-hydroxy-3,6,9-triox-
aundecan in 270 mL water 6.7 g (80 mmol) NaHCO was dissolved
ESI-MS: (m/z) ¼ 412.16 ([M þ H] , ber.: 412.20).
ꢁ1
3
C
1
4 19 5
H O Br (411.20 g ꢀ mol
)
and the mixture was stirred at 0 8C. 8.6 mL (60 mmol) of benzyl
chloroformate were dissolved in 50 mL dioxan at 5 8C and added
dropwise to the reaction mixture. The solution was stirred for 2 h at
2
2
.3.7. 1-Benzyloxycarbonylamino-3,6,9-trioxaundecan-
,3,4,6-tetra-O-acetyl-b-d-mannopyranoside
0
8C and overnight at room temperature 50 mL water was added
and the water phase was extracted with ethyl acetate (2 ꢂ 150 mL).
2.4 g (5.9 mmol) 1,2,3,4,6-Penta-O-acetyl-D-mannopyranosyl bro-
mide and 2.9 g (8.9 mmol) 1-(benzoyloxycarbonylamino-11-
hydroxy-3,6,9-trioxa) undecan were dissolved in 100 mL dichloro-
The organic layers were collected and extracted with saturated
NaHCO
.0 m HCl to pH ¼ 1 and extracted with ethyl acetate (3 ꢂ 100 mL).
The organic layers were collected, dried over MgSO , filtrated, and
3
solution(2 ꢂ 150 mL).Theaqueouslayerswereacidifiedby
˚
1
methane. 3 g molecular sieve (3 A) was added and the reaction
4
mixture was stirred for 30 min at –20 8C and under argon
atmosphere in the absence of light. 1.9 g (7.5 mmol) silver
trifluoromethane sulfonate was added and the reaction was
stirred at room temperature overnight. After neutralizing with
triethylamine (pH ¼ 8) the mixture was filtered through Celite,
the solvent was removed by rotary evaporation. The yellow oil was
purified by column chromatography (eluent: EtOAc). Yield: 8.5 g
(
26 mmol, 65%). R
f
¼ 0.29 (EtOAc).
H NMR (300 MHz, CDCl
): d(ppm) ¼ 7.35–7.29 (5H, m, Ar–H),
.10 (2H, s, –O–CH –Ar), 3.66–3.53 (14H, m, –CH –CH –O–), 3.35
–CH –O).
ESI-MS: (m/z) ¼ 350.17 ([M þ Na] , ber.: 350.22).
1
3
5
2
2
2
4
washed with dichloromethane, and dried over MgSO . The solvent
(
2H, t, J ¼ 9.5 Hz, –NH–CH
2
2
was removed by rotary evaporation and the crude product was
purified by column chromatography to obtain a pale yellow oil.
þ
ꢁ1
C
16
H25NO
6
(327.24 g ꢀ mol
)
Yield 2.7 g (4.1 mmol, 70%). R
f
¼ 0.6 (EtOAc).
): d(ppm) ¼ 7.34 (5H, m, Ar–H), 5.34 (1H,
dd, J ¼ 3.2 Hz,10 Hz,4),5.28(1H,d, J ¼ 9.6 Hz,3),5.25(1H,t,J ¼ 1.6 Hz,
), 5.08 (2H, s, –O–CH
–Ar), 4.85 (1H, d, J ¼ 1.6, 1), 4.28 (1H, dd,
1
H NMR (400 MHz, CDCl
3
2
.3.5. 1,2,3,4,6-Penta-O-acetyl-D-mannopyranoside
2
2
To a solution of 5 g (27.7 mmol) D-mannose in 200 mL pyridine
9 mL (415 mmol) acetic anhydride was added and stirring was
J ¼ 5.2 Hz, 12 Hz, 5), 4.18 (1H, t, J ¼ 4.4 Hz, 6a), 4.06 (1H, m, 6b), 3.63–
3
3
2
–
.53 (14H, m, –CH
.13 (3H, s, –CH ), 2.08 (3H, s, –CH
CH ).
2
–CH
2
–O–), 3.38 (2H, q, J ¼ 5.2 Hz, –CH
2
–O–man),
continued overnight at room temperature. After co-evaporation
with toluene (3 ꢂ 40 mL), the residue was taken up in 200 mL ethyl
acetate, washed with 2 n HCl (3 ꢂ 50 mL), water (1 ꢂ 40 mL),
saturated sodium bicarbonate (3 ꢂ 50 mL), and brine (1 ꢂ 40 mL).
3
3
), 2.02 (3H, s, –CH ), 1.97 (3H, s,
3
3
þ
ESI-MS: (m/z) ¼ 680.28 ([M þ Na] , ber.: 680.64).
30
ꢁ1
C
H43NO15 (657.66 g ꢀ mol
)
2 4
The organic layers were dried with Na SO and rotary evaporation
gave an a,b mixture as a pale yellow oil, which was used in the next
2
.3.8. 11-Amino-3,6,9-trioxa-undecyl-2,3,4,6-tetra-O-
reaction without further purification. Yield 10 g (25.6 mmol, 92%).
acetyl-O-a-D-mannopyranoside
[
50]
Lit.: 100%.
R
f
¼ 0.57 (n-hexane/EtOAc 1:1).
1
H NMR (300 MHz, CDCl
3
): d(ppm) ¼ 6.06 (1H, d, J ¼ 1.8 Hz, 1a),
0.5 g (0.76 mmol) 1-Benzyloxycarbonylamino-3,6,9-trioxaundecan-
2,3,4,6-tetra-O-acetyl-b-D-mannopyranoside was dissolvedin 10mL
methanol. Acetic acid was added until a pH of 4–5 was reached and
the reaction mixture was degassed by a slight vacuum. The reaction
5
.84 (1H, d, J ¼ 1.2 Hz, 1b), 5.46 (1H, dd, J ¼ 1.1 Hz, 3.3 Hz, 2b), 5.24–
.34 (3H, m, 2a, 3a, 4a), 5.12 (1H, dd, J ¼ 3.3 Hz, 9.9 Hz, 3b), 4.23–4.32
5
(
2H, m, 4b, 5a), 4.12–4.02 (4H, m, 6aa, 6ba, 6ab, 6bb), 3.78 (1H, ddd,
J ¼ 2.4 Hz, 5.3 Hz, 9.8 Hz, 5b), 2.19–1.94 (5s, 15H, –CH
3
).
vessel was flushedwithargon and approximately0.5 g of Pd(OH) /C
2
þ
ESI-MS: (m/z) ¼ 413.52 ([M þ Na] , ber.: 413.11), 803.24 ([M –
(20%) as catalyst were added in counterflow. After degassing with a
þ
M þ Na] , ber.: 803.23).
slight vacuum the reaction vessel was flooded with H2 and the
mixture was stirred at room temperature overnight. The H2
atmosphere was changed into an argon atmosphere and the
catalyst was removed by filtration. The mixture was neutralized by
ꢁ1
C
16
H
22
O
11 (390.12 g ꢀ mol
)
2
.3.6. 2,3,4,6-Tetra-O-acteyl-D-mannopyranosyl bromide
3
saturated NaHCO solution until a pH value of 8. The solution was
1
0 g (25.6 mmol) 1,2,3,4,6-Penta-O-acetyl-D-mannopyranoside was
concentrated by rotary evaporation. Water was added and
lyophilization yielded a pale yellow oil. Yield: 0.4 g (0.76 mmol,
dissolved in 25 mL dichloromethane and stirred at room temper-
ature under argon. 20 mL of 33% HBr/acetic acid was added via
syringe and the reaction was stirred at room temperature for 2 h.
100%). R
f
¼ 0.2 (cyclohexane/EtOH/TEA (2:3:0.15)).
H NMR (400 MHz, CDCl
): d(ppm) ¼ 6.61 (br, –NH
J ¼ 3.2 Hz, 10 Hz, 4), 5.28 (1H, d, J ¼ 9.6 Hz, 3), 5.25 (1H, t, J ¼ 1.6 Hz, 2),
1
3
2
), 5.34 (1H, dd,
1
00 mL of dichloromethane was added and the reaction mixture
Macromol. Biosci. 2015, 15, 63–73
ß 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
66
www.MaterialsViews.com