S. Ogawa et al. / Bioorg. Med. Chem. 10 (2002) 1967–1972
1971
mL) was stirred for 30 min at 80 ꢀC. The residue was
concentrated and co-evaporated with ethanol three
times and then with toluene. The residual product was
dissolved in DMF (40 mL), to which were added a,a-
dimethoxytoluene (2.0 mL, 13 mmol) and p-toluene-
sulfonic acid monohydrate (130 mg, 0.67 mmol). The
mixture was stirred for 2 h at 45 ꢀC under diminished
pressure (water aspirator). The mixture was diluted with
ethyl acetate (330 mL) and the solution was washed
with water, saturated aqueous sodium hydrogen car-
bonate, dried, and evaporated. The products (Rf 0.15
and 0.83, EtOAc:toluene, 1:5) were chromatographed
on a silica gel column (150 g) with EtOAc:toluene (gra-
dient elution 1:7!1:6) to give 11 (1.96 g, 63%) as a
syrup, together with a mixture (1.58 g, 37%) of isomeric
di-O-benzylidene derivatives. A 1.5 g portion of the lat-
ter was dissolved in methanol (50 mL) and treated with
p-toluenesulfonic acid monohydrate (47 mg) at 0 ꢀC.
After 10 min, the mixture was neutralized with triethyl-
amine and evaporated. The residue was purified on a
silica gel column (30 g, EtOAc:toluene, 1:6) to give 11
water, dried, and evaporated. The product was purified
by column chromatography (150 g, EtOAc:toluene,
1:15) to give 13 (2.61 g, 97%) as a syrup; Rf 0.56
(EtOAc:toluene, 1:5);[ a]2D3 À29ꢀ (c 0.95, CHCl3);IR
[300 MHz, (CD3)2SO, 150 ꢀC] d 8.03–7.30 (m, 15H,
3ÂPh), 5.87 (br s, 1H, 2-H), 5.76 (br s, 1H, 5a-H), 5.57
(dd, 1H, J2,3=9.8, J3,4=8.1 Hz, 3-H), 5.07–4.98 (m, 1H,
1-H), 5.03 and 4.92 (2 d, each 1H, Jgem=12.9 Hz, 6,6-
H), 4.74 (br d, 1H, 4-H), 3.37–3.27 (m, 2H, NCH2),
1.62–1.12 (m, 12H, 6ÂCH2), 0.83 (t, 3H, J=6.3 Hz,
CH2CH3). Anal. calcd for C38H40F3NO8: C, 65.60;H,
5.80;N, 2.01. Found: C, 65.68H; , 5.78;N, 2.05.
(neat) n 1730 (ester), 1695 (amide) cmÀ1 1H NMR
;
N-Octyl-N-trifluoroacetyl-4-O-(2,3,4,6-tetra-O-acetyl-ꢀ-
D-galactopyranosyl)-2,3,6-tri-O-benzoyl-5a-carba-ꢀ-D-
xylo-hex-5(5a)-enopyranosylamine (14). To a stirred
mixture of 13 (94 mg, 0.135 mmol), 2,3,4,6-tetra-O-ace-
tyl-b-d-galactopyranosyl trichloroacetimidate5 (200 mg,
0.406 mmol) and powdered 4 A molecular sieves (100
mg) in dichloromethane (2 mL) was added 47% tri-
fluoroborane etherate (110 mL, 0.41 mmol) at 0 ꢀC
under argon. The mixture was stirred for 30 min at
room temperature, then neutralized with sodium
hydrogen carbonate, and filtered through a Celite bed.
The filtrate was diluted with ethyl acetate (60 mL) and
the solution was washed with saturated aqueous sodium
hydrogen carbonate and brine, dried, and evaporated.
The residual products were purified by column chro-
matography on silica gel (27 g, EtOAc/toluene, gradient
elution 1:11!1:9) to give 14 (26 mg, 19%) as a syrup,
together with 13 (54 mg, 58%); Rf 0.18 (AcOH:toluene,
1:5);[ a]2D3 À43ꢀ (c 1.1, CHCl3);IR (neat) n 1730 (ester),
(0.93 g, 30%);[ a]D29 À78ꢀ (c 1.1, CHCl3);IR (neat)
n
1
3440 (OH), 1695 (amide) cmÀ1; H NMR [300 MHz,
(CD3)2SO, 150 ꢀC] d 7.48–7.27 (m, 5H, Ph), 5.68 (s, 1H,
CHPh), 5.38 (br s, 1H, 5a-H), 4.49–4.34 (m, 4H, 1-H, 4-
H, 6,6-H), 3.77 (br s, 1H, 2-H), 3.60 (dd, 1H, J2,3=9.5,
J3,4=7.6 Hz, 3-H), 3.50–3.05 (m, 2H, NCH2), 1.61–1.21
(m, 12H, 6 Â CH2), 0.87 (t, 3H, J=6.5 Hz, CH2CH3).
Anal. calcd for C24H32F3NO5: C, 61.13;H, 6.84; N, 2.97.
Found: C, 61.06;H, 6.83; N, 2.97.
N-Octyl-N-trifluoroacetyl-2,3-di-O-benzoyl-4,6-O-ben-
zylidene-5a-carba-ꢀ-D-xylo-hex-5(5a)-enopyranosylamine
(12). A solution of 11 (1.88 g, 3.99 mmol) in pyridine (30
mL) was treated with benzoyl chloride (2.77 mL, 23.9
mmol) for 5 h at room temperature. The mixture was
then diluted with ethyl acetate (230 mL) and the solu-
tion was thoroughly washed with water, dried, and
evaporated. The residue was purified by silica gel chro-
matography (200 g, EtOAc:hexane, gradient elution
1:9!1:6) to give 12 (2.69 g, 99%) as a white solid;mp
173–175 ꢀC;[ a]D23 À69ꢀ (c 1.1, CHCl3);IR (neat) n 3460
1695 (amide) cmÀ1 1H NMR [300 MHz, (CD3)2SO,
;
110 ꢀC] d 8.07–7.27 (m, 15H, 3ÂPh), 6.04–5.84 (m, 1H,
2-H), 5.93 (br s, 1H, 5a-H), 5.74 (dd, 1H, J2,3=8.8,
J3,4=8.1 Hz, 3-H), 5.11–4.81 (m, 8H, 1-H, 4-H, 6,6-H,
10-H, 20-H, 30-H, 40-H), 4.01–3.22 (m, 3H, 50-H, 60,60-H),
3.40–3.22 (m, 2H, NCH2), 2.00, 1.92, 1.87, and 1.85 (4 s,
each 3H, 4ÂAc), 1.60–1.03 (m, 12H, 6ÂCH2), 0.82 (t,
3H, J=6.5 Hz, CH2CH3). Anal. calcd for
C52H58F3NO17: C, 60.87;H, 5.70; N, 1.37. Found: C,
60.44;H, 5.56; N, 1.41.
(OH), 1730 (ester), 1695 (amide) cmÀ1 1H NMR
;
[300 MHz, (CD3)2SO, 150 ꢀC] d 7.95–7.26 (m, 15H,
3ÂPh), 6.00 (br s, 1H, 2-H), 5.78 (dd, 1H, J2,3=10.7,
J3,4=7.8 Hz, 3-H), 5.78 (s, 1H, CHPh), 5.70 (br s, 1H,
5a-H), 5.10 (br d, 1H, 4-H), 5.02 (br d, 1H, J1,2=7.8 Hz,
1-H), 4.58 (br s, 2H, 6,6-H), 3.52 and 3.31 (2 m, each
1H, NCH2), 1.70–1.18 (m, 12H, 6ÂCH2), 0.85 (t, 3H,
J=6.8 Hz, CH2CH3). Anal. calcd for C38H40F3NO7: C,
67.15;H, 5.93; N, 2.06. Found: C, 67.12;H, 5.93; N,
2.00.
4-O-(ꢀ-D-Galactopyranosyl)-N-octyl-5a-carba-ꢀ-D-xylo-
hex-5(5a)-enopyranosylamine (3). To a solution of 14
(26 mg, 0.025 mmol) in methanol (2 mL) was added
potassium carbonate (60 mg, 0.43 mmol), and the mix-
ture was stirred for 1h at room temperature. The mix-
ture was taken up on a column of Dowex 50WÂ2 (H+)
resin and eluted with 1% methanolic ammonia to give 3
(11 mg, 73%) as a white solid; Rf 0.34 (MeOH:
CHCl3:H2O, 35:60:8);[ a]2D3 À65ꢀ (c 0.44, MeOH);IR
(KBr) n 3440 (OH) cmÀ1; 1H NMR (270 MHz, CD3OD/
N-Octyl-N-trifluoroacetyl-2,3,6-tri-O-benzoyl-5a-carba-
ꢀ-D-xylo-hex-5(5a)-enopyranosylamine (13). A solution
of 12 (2.63 g, 3.87 mmol) and aqueous 80% acetic acid
(85 mL) was stirred for 1.5 h at 80 ꢀC, and then con-
centrated. The residue was co-evaporated with ethanol
and toluene. The product was dissolved in pyridine (45
mL), to which benzoyl chloride (0.67 mL, 5.8 mmol)
was added at À15 ꢀC, and the mixture was stirred for 2
h at À15 ꢀC. It was then diluted with ethyl acetate (300
mL), and the solution was thoroughly washed with
0
0
CDCl3, 1:2) d 5.62 (br s, 1H, 5a-H), 4.43 (d, J1 ,2 =7.3
Hz, 10-H), 4.34 and 4.02 (2 d, each 1H, Jgem=13.4 Hz,
6,6-H), 4.25 (br d, 1H, J3,4=7.7 Hz, 4-H), 3.92–3.47 (m,
5H, 30-H, 40-H, 50-H, 60,60-H), 3.69 (dd, 1H, J2,3=10.3
0
0
0
Hz, 3-H), 3.63 (dd, 1H, J2 ,3 =9.5 Hz, 2 -H), 3.51 (dd,
1H, J1,2=8.8, 2-H), 3.23 (br d, 1H, 1-H), 2.74 and 2.53
(ddd, each 1H, J=7.3, Jgem=11.4 Hz, NCH2), 1.62–
1.20 (m, 12H, 6ÂCH2), 0.89 (t, 3H, J=6.6 Hz,
CH2CH3).