combined organic layers were washed with brine (100 cm3),
dried (MgSO4), and evaporated under reduced pressure.
Acetonitrile (≈250 cm3) was added and the crystalline pre-
cipitate (3.14 g), believed to be the 1-O-{2,7-dibromo-9-[3-
(trifluoromethyl)phenyl]xanthen-9-yl} derivative, was collected
by filtration. The filtrate was evaporated and the residue was
chromatographed on silica gel. The column was eluted with
hexane–diethyl ether (100:0 to 0:100 v/v). More of the putative
bined, evaporated under reduced pressure, and the residue was
fractionated by chromatography on silica gel. The column
was eluted with hexane–ethyl acetate (100:0 to 66:34 v/v).
Appropriate fractions, eluted with hexane–ethyl acetate
(80:20 to 74:26 v/v), were combined, and evaporated under
reduced pressure to give 6-O-{2,7-dibromo-9-[3-(trifluoro-
methyl)phenyl]xanthen-9-yl}-3-O-(Ϫ)-menthoxyacetyl-2-O-(4-
methoxytetrahydropyran-4-yl)-4,5-O-(1,1,3,3-tetraisopropyl-
disiloxane-1,3-diyl)--myo-inositol 19 as a colourless foam
(4.47 g, 25.6%); Rf 0.45 [hexane–diethyl ether (1:1 v/v)];
[α]D25 Ϫ16.2 (c 2.00, ethyl acetate); δH (CDCl3) 0.74–1.39 (42 H,
m), 1.48 (2 H, m), 1.63 (3 H, m), 1.74 (1 H, m), 2.01 (1 H, m),
2.23 (1 H, m), 2.70 (1 H, d, J 8.5), 2.80 (3 H, s), 3.10 (1 H, dt,
J 4.2 and 10.6), 3.22 (1 H, dt, J 2.6 and 8.8), 3.50 (2 H, m), 3.63
(2 H, m), 3.81 (1 H, m), 4.05 (5 H, m), 4.84 (1 H, m), 7.00 (1 H,
d, J 8.7), 7.08 (1 H, d, J 8.7), 7.30–7.45 (7 H, m), 7.80 (1 H,
d, J 7.6); δC (CDCl3) included the following signals: 12.52,
12.63, 12.69, 13.43, 14.13, 16.13, 17.21, 17.26, 17.28, 17.43,
17.70, 17.81, 18.03, 20.97, 22.23, 23.16, 25.32, 26.92, 31.55,
33.41, 34.29, 34.34, 39.83, 48.04, 48.68, 64.50, 64.80, 65.65,
70.68, 71.70, 72.36, 73.58, 75.78, 78.23, 78.67, 80.25, 99.31.
Later fractions, which were eluted from the column with
hexane–ethyl acetate (73:27 to 66:34 v/v), were concentrated
under reduced pressure. The residue was crystallized from
acetonitrile to give more -myo-inositol-derived diastereo-
isomer 20 [1.33 g; total yield of this diastereoisomer: 7.29 g
(41.7%)]. The mother liquor was concentrated and rechromato-
graphed to give more -myo-inositol-derived diastereoisomer
19 [2.62 g; total yield of this diastereoisomer, 7.09 g (40.5%)].
isomeric
1-O-{2,7-dibromo-9-[3-(trifluoromethyl)phenyl]-
xanthen-9-yl} derivative, which had Rf 0.55 [dichloromethane–
methanol (98:2 v/v)], was eluted first. The title compound
(14.88 g, 73%) [Found: (M Ϫ H)Ϫ (FAB), 1017.1849.
12
16
C
1H5679Br81Br19F3 28Si2 requires m/z, 1017.1710] had
O
44
10
Rf 0.25 [dichloromethane–methanol (98:2 v/v)]; δH (CDCl3)
1.12 (28 H, m), 1.48 (1 H, m), 1.76 (3 H, m), 2.58 (1 H, br), 2.81
(1 H, d, J 8.0), 2.91 (3 H, s), 3.18 (1 H, dt, J 2.6 and 8.3), 3.44
(1 H, d, J 8.6), 3.60 (3 H, m), 3.78 (2 H, m), 3.89 (1 H, t, J 8.6),
3.97 (1 H, t, J 8.4), 4.08 (1 H, t, J 2.3), 7.02 (1 H, d, J 8.7), 7.09
(1 H, d, J 8.8), 7.37 (7 H, m), 7.80 (1 H, d, J 8.4); δC (CDCl3)
included the following signals: 12.46, 12.60, 12.68, 13.45, 17.28,
17.34, 17.36, 17.41, 17.54, 17.67, 17.78, 18.02, 32.98, 34.36,
48.97, 64.58, 64.79, 71.33, 71.51, 72.18, 75.94, 76.56, 77.83,
79.00, 99.53.
6-O-{2,7-Dibromo-9-[3-(trifluoromethyl)phenyl]xanthen-9-yl}-
3-O-(؊)-menthoxyacetyl-2-O-(4-methoxytetrahydropyran-4-yl)-
4,5-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)-D- and -L-myo
inositol 19 and 20
Dry pyridine (80 cm3) was added slowly to a stirred mixture
of (Ϫ)-MacCl (6.30 g, 27.1 mmol) and freshly sublimed
1H-tetrazole (1.98 g, 28.3 mmol) in dry acetonitrile (15 cm3)
at room temperature. The resulting solution was added rapidly
6-O-{2,7-Dibromo-9-[3-(trifluoromethyl)phenyl]xanthen-9-yl}-
2-O-(4-methoxytetrahydropyran-4-yl)-D-myo-inositol 21
A solution of 6-O-{2,7-dibromo-9-[3-(trifluoromethyl)phenyl]-
xanthen-9-yl}-3-O-(Ϫ)-menthoxyacetyl-2-O-(4-methoxytetra-
hydropyran-4-yl)-4,5-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-
diyl)--myo-inositol 19 (7.09 g, 5.8 mmol) in 8 mol dmϪ3
ethanolic methylamine (40 cm3) was stirred at room tem-
perature for 90 min and was then evaporated under reduced
pressure. The residue was dissolved in a 1.0 mol dmϪ3 solution
of TEAF in acetonitrile (25 cm3) at room temperature. After
30 min, the products were concentrated under reduced pressure
and the residue was fractionated between ethyl acetate (300
cm3) and half-saturated aq. sodium hydrogen carbonate (200
cm3). The organic layer was separated, washed successively
with water (2 × 100 cm3) and brine (50 cm3), dried (MgSO4),
and evaporated under reduced pressure. The residue was
fractionated by chromatography on silica gel (200 g). The
column was eluted first with dichloromethane–acetonitrile
(100:0 to 50:50 v/v). Subsequent elution with dichloro-
methane–methanol (96:4 to 89:11 v/v) and evaporation of the
appropriate fractions gave the title compound (4.33 g, ≈95%) as
a colourless foam; Rf 0.42 [dichloromethane–ethanol (9:1 v/v)];
δH [(CD3)2SO] 1.55–1.75 (4 H, m), 3.05 (3 H, s), 3.10 (1 H, m),
3.30 (5 H, m), 3.50 (1 H, t, J 7.5), 3.56 (2 H, m), 3.99 (1 H, m),
4.19 (1 H, d, J 4.7), 4.27 (1 H, d, J 5.7), 4.52 (1 H, d, J 4.1), 4.70
(1 H, m), 7.08 (1 H, d, J 2.3), 7.16 (1 H, d, J 2.4), 7.20 (2 H, t,
J 9.0), 7.41 (1 H, d, J 8.0), 7.48 (3 H, m), 7.60 (1 H, d, J 7.6),
8.07 (1 H, br s); δC [(CD3)2SO] included the following signals:
34.32, 34.44, 48.37, 64.27, 71.14, 73.45, 73.67, 75.12, 76.76,
98.33.
to
a mixture of 6-O-{2,7-dibromo-9-[3-(trifluoromethyl)-
phenyl]xanthen-9-yl}-2-O-(4-methoxytetrahydropyran-4-yl)-
4,5-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)-myo-inositol
18 (14.62 g, 14.3 mmol) and DMAP (4.94 g, 40.4 mmol). After
45 min, when TLC [hexane–diethyl ether (1:1 v/v)] revealed
that the proportions of starting material (Rf 0.12) and the
putative bis[(Ϫ)-menthoxyacetate] (Rf 0.64) were approximately
equal, water (1 cm3) was added. The products were evaporated
under reduced pressure and the residue was re-evaporated with
toluene (3 × 50 cm3). Ethyl acetate (250 cm3) was added, and
after filtration the solution was washed with saturated aq.
sodium hydrogen carbonate (2 × 150 cm3). The combined
aqueous layers were back-extracted with ethyl acetate (100
cm3). Finally, the combined organic layers were washed succes-
sively with water (2 × 100 cm3) and brine (100 cm3), and were
then dried (MgSO4), and evaporated under reduced pressure.
When the residual glass was dissolved in acetonitrile, colour-
less crystals of 6-O-{2,7-dibromo-9-[3-(trifluoromethyl)phenyl]-
xanthen-9-yl}-3-O-(Ϫ)-menthoxyacetyl-2-O-(4-methoxytetra-
hydropyran-4-yl)-4,5-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-
diyl)--myo-inositol 20 were obtained (5.96 g, 34.2%) (Found,
in material recrystallized from acetonitrile–diethyl ether: C,
55.2; H, 6.25. C56H77Br2F3O12Si2 requires C, 55.35; H, 6.39%);
mp 217 ЊC; [α]D25 Ϫ25.3 (c 2.00, ethyl acetate); Rf 0.38 [hexane–
diethyl ether (1:1 v/v)]: δH (CDCl3) 0.73–1.35 (42 H, m), 1.47
(2 H, m), 1.62 (3 H, m), 1.77 (1 H, m), 1.99 (1 H, m), 2.25 (1 H,
m), 2.76 (1 H, d, J 8.5), 2.80 (3 H, s), 3.12 (1 H, dt, J 4.1 and
10.5), 3.23 (1 H, dt, J 2.6 and 8.8), 3.51 (2 H, m), 3.64 (2 H, m),
3.82 (1 H, m), 4.05 (5 H, m), 4.89 (1 H, m), 7.00 (1 H, d, J 8.7),
7.08 (1 H, d, J 8.7), 7.26–7.45 (7 H, m), 7.81 (1 H, d, J 7.5);
δC (CDCl3) included the following signals: 12.51, 12.59, 12.67,
13.40, 16.10, 17.23, 17.27, 17.43, 17.69, 17.79, 18.02, 20.98,
22.25, 23.14, 25.31, 31.47, 33.30, 34.27, 34.33, 39.65, 48.05,
48.75, 64.49, 64.80, 65.27, 70.68, 71.76, 72.08, 73.65, 75.78,
78.15, 78.64, 79.74, 99.30.
6-O-{2,7-Dibromo-9-[3-(trifluoromethyl)phenyl]xanthen-9-yl}-
2-O-(4-methoxytetrahydropyran-4-yl)-L-myo-inositol 22
A suspension of crystalline 6-O-{2,7-dibromo-9-[3-(trifluoro-
methyl)phenyl]xanthen-9-yl}-3-O-(Ϫ)-menthoxyacetyl-2-O-(4-
methoxytetrahydropyran-4-yl)-4,5-O-(1,1,3,3-tetraisopropyl-
disiloxane-1,3-diyl)--myo-inositol 20 (1.215 g, 1.0 mmol) in a
1.0 mol dmϪ3 solution of TEAF in acetonitrile (4 cm3) was
heated, under gentle reflux, for ca. 2 min until a homogeneous
The mother liquors from the above crystallizations (from
both acetonitrile and acetonitrile–diethyl ether) were com-
200
J. Chem. Soc., Perkin Trans. 1, 2001, 192–205