Original Synthesis of Linear, Branched and Cyclic Oligoglycerol Standards
FULL PAPER
was refluxed with Dowex 50WX-8 200 ion exchange resin (Hϩ)
(150 mg/g) for 16 h. The resin was filtered off and the solvent was
evaporated under reduced pressure. The crude product was purified
by silica gel column chromatography, using petroleum ether/AcOEt
(3:7 to 1:9) as eluent, to yield 3.75 g (84%) of pure 16 as a colourless
vacuum and coevaporation with toluene, the crude product was
purified by silica gel column chromatography with AcOEt as elu-
ent. The solid 22b was recrystallised from an AcOEt/cyclohexane
(1:1) mixture to give 89% of a colourless solid. Ϫ [α]D ϭ ϩ 65 (c ϭ
1.0; CHCl3) (ref.[21]) ϩ73.0). Ϫ M.p. 99Ϫ100 °C (ref.[21]) 92Ϫ93
syrup. Ϫ [α]D ϭ 0 (c ϭ 1.0; CHCl3). Ϫ 1H NMR (CDCl3): δ ϭ °C). Ϫ 1H NMR (CDCl3): δ ϭ 1.37 and 1.53 (2 s, 6 H, 2 CH3 iPr),
3.52Ϫ3.83 (m, 10 H, H-1a, H-1b,H-2, H-3a, H-3b, H-5, H-6a, H- 3.18 (dd, J1b,2 ϭ 10.0 Hz, 1 H, H-1b), 3.97 (m, 5 H, H-2, H-3, H-
6b, H-6Јa and H-6Јb), 4.55 (s, 4 H, 2 CH2ϪPh), 7.29Ϫ7.36 (m, 10 5, H-6a and H-6b), 4.01 (dd, J1a,2 ϭ 5.3 Hz, J1a,1b ϭ 11.3 Hz, 1 H,
H, HAr Bn). Ϫ 13C NMR (CDCl3): δ ϭ 64.1, 70.6 and 73.0 (4 C, H-1a), 4.21 (dd, J3,4 ϭ 5.7 Hz, J4,5 ϭ 2.2 Hz, 1 H, H-4). Ϫ 13C
CH2, C-1, C-3, C-6 and C-6Ј), 73.9 (2 C, 2 CH2 Bn), 71.2 and 79.5 NMR (CDCl3): δ ϭ 26.6 and 28.5 (2 C, 2 CH3 iPr), 63.3 (1 C, C-
(2 C, CH, C-1 and C-5), 128.2 and 128.9 (10 C, CAr Bn), 138.1 (2 6), 68.4 (1 C, C-1), 74.5 (1 C, C-4), 69.8, 76.7 and 79.9 (3 C, C-2,
C, quaternary CAr Bn). Ϫ MS (Ionspray , MeOH ϩ 5Ϫ10% H2O):
C-3 and C-5), 110.5 (1 C, quaternary C iPr). Ϫ MS (IS, MeOH ϩ
m/z ϭ 347.0 [M ϩ H]ϩ, 364.0 [M ϩ NH4]ϩ, 369.0 [M ϩ Na]ϩ. Ϫ 5Ϫ10% H2O): m/z ϭ 205.0 [M ϩ H]ϩ, 227.0 [M ϩ Na]ϩ.
C20H27O5: calcd. 347.1858; found 347.1894 (HR-ESI-TOF-MS).
2,6-Di-O-acetyl-1,5-anhydro-3,4-O-isopropylidene-D-galactitol
5-Hydroxymethyl-1,2-O-isopropylidene-4-oxahexane-1,2,6-triol
(17): A solution of compound 15 (10.0 g, 25.87 mmol) in dry ethyl
acetate (100 mL) was treated with palladium on charcoal (10%)
(1.0 g, 10 wt-%) under H2 (1 bar) for 20 h. The catalyst was filtered
off through a pad of Celite and the filtrate was concentrated un-
der reduced pressure. The crude product was purified by silica gel
column chromatography, using ethyl acetate as eluent, to yield
3.91 g (73%) of 17 (pale yellowish syrup). Ϫ 1H NMR (MeOD):
[143916؊22؊7] (23b): 1,5-Anhydro-3,4-di-O-isopropylidene--gal-
actitol (22b) was acetylated in a pyridine/acetic anhydride mixture
at room temperature for 20 h. After methanolysis, the solvents were
removed under reduced pressure, then coevaporated with toluene,
and the crude product was purified by silica gel column chromato-
graphy, with a petroleum ether/AcOEt (1:1) mixture as eluent, to
yield 23b quantitatively, as a colourless solid. Ϫ [α]D ϭ ϩ 63 (c ϭ
1.0; CHCl3) (ref.[21]) ϩ70.8). Ϫ M.p. 100Ϫ102 °C (ref.[21]) 87Ϫ92
°C). Ϫ 1H NMR (CDCl3): δ ϭ 1.34 and 1.53 (2 s, 6 H, 2 CH3 iPr),
δ ϭ 1.32 and 1.37 (2 s, 6 H, 2 CH3 iPr), 3.42 (dd, J5,6a ϭ J5,6Јa
ϭ
5.0 Hz, J5,6b ϭ J5,6Јb ϭ 10.1 Hz, 1 H, H-5), 3.57 (d, 2 H, H-3a and 2.09 and 2.11 (2 s, 6 H, 2 CH3 acetates), 3.21 (dd, 1 H, H-1b), 3.89
H-3b), 3.63 (ddd, J6,OH ϭ 1.6 Hz, J6a,6b ϭ 10.1 Hz, 4 H, H-6a, H-
6b, H-6Јa and H-6Јb), 3.74 (dd, 1 H, H-1b), 4.04 (dd, J1a,1b
(ddd, J4,5 ϭ 2.0 Hz, 1 H, H-5), 4.08 (dd, J1a,1b ϭ 11.5 Hz, 1 H, H-
1a), 4.18 (dd or ft, 1 H, H-3), 4.22 (dd, J3,4 ϭ 5.4 Hz, 1 H, H-4),
ϭ
8.3 Hz, 1 H, H-1a), 4.26 (dddd, J1a,2 ϭ 6.4 Hz, J1b,2 ϭ 6.3 Hz, 4.24 (dd, J5,6b ϭ 7.9 Hz, 1 H, H-6b), 4.37 (dd, J5,6a ϭ 3.9 Hz,
2,3 ϭ 5.6 Hz, 1 H, H-2). Ϫ 13C NMR (MeOD): δ ϭ 26.8 and 28.2
J6a,6b ϭ 11.9 Hz, 1 H, H-6a), 4.97 (ddd, J1a,2 ϭ 5.2 Hz, J1b,2
(2 C, 2 CH3 iPr), 63.7 (2 C, C-6 and C-6Ј), 68.8 (1 C, C-1), 73.5 (1
9.1 Hz, J2,3 ϭ 6.2 Hz, 1 H, H-2). Ϫ 13C NMR (CDCl3): δ ϭ 21.3
C, C-3), 77.6 (1 C, C-2), 84.4 (1 C, C-5); 111.7 (1 C, quaternary C and 21.4 (2 C, 2 CH3 acetates), 26.4 and 27.9 (2 C, 2 CH3 iPr),
J
ϭ
iPr). Ϫ MS (Ionspray , MeOH ϩ 5Ϫ10% H2O): m/z ϭ 207.0 [M
64.6 (1 C, C-6), 65.5 (1 C, C-1), 70.5 (1 C, C-2), 73.8 (1 C, C-4),
74.0 (1 C, C-5), 75.6 (1 C, C-3), 110.8 (1 C, quaternary C iPr),
170.4 and 171.3 (2 C, 2 quaternary C acetates). Ϫ MS (IS, MeOH
ϩ 5Ϫ10% H2O): m/z ϭ 289.0 [M ϩ H]ϩ.
ϩ H]ϩ, 224.5 [M ϩ NH4]ϩ, 229.0 [M ϩ Na]ϩ, 245.0 [M ϩ K]ϩ.
1,5-Anhydro-D-galactitol [3971؊48؊0] (21b): 2,3,4,6-Tetra-O-
acetyl-1,5-anhydro--galactitol (20b) was deacetylated overnight at
room temperature according to Zemplen’s methodology, with a so-
lution of sodium methoxide in methanol. The solution was made
neutral using Amberlite IR-120 (Hϩ form), and the resin was re-
moved by filtration and the solvents evaporated under reduced
pressure. The crude product was purified by silica gel column chro-
matography, using a CH2Cl2/MeOH (20Ϫ30%) mixture as eluent.
The residue was recrystallised from ethanol to give 21b as a colour-
2,6-Di-O-acetyl-1,5-anhydro-
O-acetyl-3,4-di-O-isopropylidene--galactitol
D
-galactitol (24b): 1,5-Anhydro-2,6-di-
(23b) (4 g,
13.9 mmol) was dissolved in dry THF. Removal of the isopropylid-
ene moiety was effected in the presence of an acidic resin (Dowex
50WX8Ϫ200, Hϩ form) at 50Ϫ60 °C for 2 h. The resin was then
filtered off and the solvents were removed under reduced pressure.
The crude product was purified by silica gel column chromato-
less solid (90%). Ϫ [α]D ϭ ϩ 76 (c ϭ 1.0; H2O) (ref.[20]) ϩ 76.6; graphy, with a petroleum ether/AcOEt (2:8) mixture as eluent, to
c ϭ 1.08; H2O; ϩ 77; ϩ76 to ϩ77; ϩ 80; c ϭ 0.8; H2O). Ϫ M.p.
yield 24b as a colourless solid (82%) . Ϫ [α]D ϭ ϩ 30 (c ϭ 1.0;
CHCl3). Ϫ M.p. 108Ϫ110 °C. Ϫ H NMR (CDCl3): δ ϭ 2.08 and
2.09 (2 s, 6 H, 2 CH3 acetates), 3.18 (dd, J1b,2 ϭ J1a,1b ϭ 11.0 Hz,
1
121Ϫ122 °C (ref.[20]) 114Ϫ115 °C; 113Ϫ115 °C; 115Ϫ117 °C;
1
126Ϫ128 °C). Ϫ H NMR (D2O): δ ϭ 3.10 (dd, J1a,1b ϭ J1b,2
ϭ
10.8 Hz, 1 H, H-1b), 3.45Ϫ3.63 (m, 2 H, H-3 and H-5), 3.60 (s, 2
H, H-6a and H-6b), 3.73 (ddd, 1 H, H-2), 3.85 (d, J3,4 ϭ 3.3 Hz,
1 H, H-1b), 3.56Ϫ3.67 (m, 2 H, H-3 and H-5), 3.96 (br. d, J3,4
2.4 Hz, 1 H, H-4), 4.06 (dd, J1a,2 ϭ 6.0 Hz, J1a,1b ϭ 11.0 Hz, 1 H,
ϭ
J
4,5 Ͻ 1.0 Hz, 1 H, H-4), 3.91 (dd, J1a,2 ϭ 5.5 Hz, J1a,1b ϭ 10.8 Hz, H-1a), 4.22 (dd, J5,6b ϭ 7.2 Hz, 1 H, H-6b), 4.33 (dd, J5,6a
ϭ
1 H, H-1a). Ϫ 13C NMR (D2O): δ ϭ 61.7 (C-6), 67.0 (C-2), 69.4 5.0 Hz, J6a,6b ϭ 11.8 Hz, 1 H, H-6a), 5.05 (ddd, 1 H, H-2). Ϫ 13C
(C-4), 69.5 (C-1), 74.4 and 79.7 (C-3 and C-5). Ϫ MS (IS, MeOH
ϩ 5Ϫ10% H2O): m/z ϭ 165.0 [M ϩ H]ϩ, 187.0 [M ϩ Na]ϩ.
NMR (CDCl3): δ ϭ 21.3 and 21.4 (2 C, 2 CH3 acetates), 64.1 (1
C, C-6), 67.2 (1 C, C-1), 69.8 (1 C, C-4), 70.6 (1 C, C-2), 73.2 (1
C, C-3), 77.0 (1 C, C-5), 171.6 and 172.0 (2 C, quaternary C acet-
ates). Ϫ MS (IS, MeOH ϩ 5Ϫ10% H2O): m/z ϭ 249.0 [M ϩ H]ϩ,
266.0 [M ϩ NH4]ϩ, 271.0 [M ϩ Na]ϩ. Ϫ C10H17O7: calcd.
249.0974; found 249.0952 (HR-ESI-TOF-MS).
1,5-Anhydro-3,4-O-isopropylidene-D-galactitol
[143697؊37؊4]
(22b): 1,5-Anhydro--galactitol (21b) (5 g, 30.5 mmol) was sus-
pended in 2,2-dimethoxypropane (10 mL/mmol) containing a cata-
lytic amount of camphorsulfonic acid. The mixture was vigorously
stirred under inert atmosphere for 48 h at room temperature to
reach equilibrium. The reaction was stopped by addition of a few
drops of triethylamine, and the mixture was concentrated under
reduced pressure and the crude residue dissolved in a MeOH/H2O
(10:1) mixture (50 mL/g of crude product) containing a catalytic
amount of acetic acid. The solution was stirred at 50 °C for 30 min.
After addition of a few drops of triethylamine, concentration under
1,5,6-Triacetoxy-2-acetoxymethyl-3-oxahexane (25): The protected
1,5-anhydrohexitol 24b (2.2 g, 8.9 mmol) was treated with a 0.1
aqueous solution of sodium periodate (5 equiv., 450 mL) over
30 min at room temperature. The mixture was then concentrated
to dryness and the crude residue was dissolved in 400 mL of water
and treated with 6 equiv. of sodium borohydride. After 30 min of
stirring at room temperature, the excess of NaBH4 was decomposed
Eur. J. Org. Chem. 2001, 875Ϫ896
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