5624
H. Matsuhashi, K. Shimada / Tetrahedron 58 )2002) 5619±5626
11.04. Mass -FAB): 714 -M1H). HR-MS calcd for
C41H63KNO9: 752.4140, found 752.4161.
12.0 Hz, 1H), 6.13 -t, J10.5 Hz, 1H), 6.01 -d, J9.5 Hz,
1H), 5.91 -d, J16.5 Hz, 1H), 5.87 -m, 1H), 5.75 -dd, J
16.5, 6.0 Hz, 1H), 5.49 -t, J8.5 Hz, 1H), 5.28 -t, J9.5 Hz,
1H), 5.25 -d, J16.5 Hz, 1H), 5.21 -brs, 1H), 5.15 -d, J
9.5 Hz, 1H), 4.99 -t, J3.5 Hz, 1H), 4.85 -brs, 1H), 4.71 -m,
1H), 4.51 -d, J5.0 Hz, 2H), 3.83 -d, J10.0 Hz, 1H), 3.25
-m, 2H), 2.71 -m, 1H), 2.54 -m, 1H), 2.39 -m, 1H), 2.23 -t,
J6.5 Hz, 2H), 1.90 -m, 4H), 1.78 -d, J14.0 Hz, 1H), 1.65
-dd, J15.0, 8.0 Hz, 1H), 1.60±1.18 -m, 12H), 1.10 -m,
3H), 0.98 -brq, J13.0 Hz, 1H), 0.92 -t, J8.0 Hz, 3H),
0.81 -t, J7.0 Hz, 3H), 0.80 -t, J5.0 Hz, 3H), 0.13 -s,
9H). 13C NMR -125 MHz, CDCl3) d 173.19, 163.83,
156.24, 149.80, 137.82, 135.96, 133.57, 132.90, 125.72,
123.96, 121.80, 120.72, 117.32, 80.08, 79.60, 73.26,
72.03, 65.38, 65.29, 39.31, 37.98, 37.45, 36.54, 36.04,
34.86, 34.07, 31.79, 31.22, 29.28, 26.45, 25.26, 23.56,
21.46, 19.04, 11.25, 10.98, 2.45. Mass -FAB): 746
-M1H). HR-MS calcd for C41H67KNO9Si: 784.4222,
found 784.4229. IR -CHCl3) 3454 -w), 2960 -m), 2937
-m), 1721 -s), 1514 -m), 1463 -m), 1255 -s), 1173 -m).
3.1.4. Triol /6). To a solution of ester 5 -2.25 g, 3.15 mmol)
in THF -40 ml) was added 50% aqueous tri¯uoroacetic acid
-16 ml) at room temperature, and the mixture was stirred for
1 h. The reaction mixture was quenched with aqueous satu-
rated sodium bicarbonate, and extracted with ethyl acetate
-80 ml, then 30 ml£2). Combined organic phases were
washed with H2O, brine, dried over anhydrous sodium
sulfate, ®ltrated, and concentrated in vacuo. The residue
was puri®ed by silica gel ¯ash column chromatography
-CH2Cl2±MeOH20:1, f3.0£15 cm) to afford triol 6
-1.80 g) in 85% yield as white amorphous powder.
1
Analytical data for triol 6: H NMR -500 MHz, CDCl3) d
6.96 -dd, J10.0, 6.0 Hz, 1H), 6.26 -t, J10.5 Hz, 1H), 6.16
-t, J11.0 Hz, 1H), 6.04 -d, J10.0 Hz, 1H), 5.90 -m, 1H),
5.89 -s, 2H), 5.51 -t, J10.0 Hz, 1H), 5.42 -br, 1H), 5.32 -t,
J9.5 Hz, 1H), 5.29 -d, J17.5 Hz, 1H), 5.19 -d, J
10.0 Hz, 1H), 5.05 -s, 1H), 4.88 -br, 1H), 4.74 -tt, J10.5,
4.0 Hz, 1H), 4.53 -d, J5.0 Hz, 1H), 3.81 -d, J9.5 Hz,
1H), 3.64 -brs, 1H), 3.57 -br, 1H), 3.28 -m, 1H), 3.22 -m,
1H), 3.08 -brs, 1H), 2.57 -m, 1H), 2.45 -m, 1H), 2.26 -t,
J7.5 Hz, 2H), 2.00±1.68 -m, 6H), 1.60 -m, 4H), 1.52±1.20
-m, 8H), 1.14 -m, 3H), 1.02 -m, 1H), 0.94 -t, J7.5 Hz, 3H),
0.85 -t, J7.0 Hz, 3H), 0.83 -d, J6.0 Hz, 3H). 13C NMR
-125 MHz, CDCl3) d 173.30, 164.13, 156.61, 150.19,
138.01, 135.67, 133.38, 132.86, 125.47, 124.10, 121.80,
120.63, 117.57, 80.04, 73.64, 72.10, 65.58, 65.26, 39.22,
38.03, 37.59, 36.65, 36.11, 35.28, 34.95, 34.67, 34.14,
31.85, 31.27, 29.35, 26.52, 25.31, 23.62, 21.53, 19.10,
11.31, 10.98. Mass -FAB): 674 -M1H). HR-MS calcd for
3.1.6. Chloroacetate /8). To a solution of 7 -1.53 g,
2.05 mmol) and pyridine -0.186 ml, 2.30 mmol) in dichloro-
methane -35 ml) was added chloroacetic anhydride
-351 mg, 2.05 mmol) at room temperature, and the reaction
mixture was stirred for 1 h at this temperature. It was
concentrated in vacuo, and the residue was subjected to
short silica gel column chromatography -hexane±
EtOAc1:1, f4.0£10 cm) to separate acylated products
and unreacted starting material -361 mg). The products
were further puri®ed by silica gel ¯ash column chromato-
graphy -hexane±EtOAc3:2, f3.0£40 cm) to afford
desired product 8 -527 mg) in 31% yield as colorless
viscous oil along with other isomers -623 mg). The isomers
were converted to starting material 7 by treating with pH 9.5
sodium carbonate buffer to remove all acyl group-s).
25
C38H59NNaO9: 696.4087, found 696.4080. [a]D 123.9
-c0.740, CHCl3).
3.1.5. TMS ether /7). To a solution of 6 -1.78 g, 2.64 mmol)
and imidazole -2.70 g, 39.6 mmol) in dichloromethane
-50 ml) was added dropwise chlorotrimethylsilane -3.3 ml,
26.4 mmol) for 10 min, and resulting suspension was stirred
for 12 h at room temperature. Methanol -ca. 2 ml) was
added to the reaction mixture, and it was stirred for
additional 5 min. Upon quenching with H2O -100 ml), the
product was extracted with ethyl acetate -50 ml£2).
Combined organic phases were washed with brine, dried
over anhydrous sodium sulfate, ®ltrated, and concentrated
in vacuo. The residual colorless oil was dissolved in toluene
-ca. 10 ml), and the mixture was concentrated in vacuo to
remove the volatile materials. The residue was dissolved in
THF -50 ml), and to this was added hydrogen ¯uoride
pyridine complex -0.50 ml) dropwise in an ice bath. After
stirring under ice cooling for 1 h, the reaction mixture was
quenched with H2O -150 ml), and the product was extracted
with ethyl acetate -70 ml£3). Combined organic phases
were washed with aqueous saturated sodium bicarbonate,
H2O, brine, dried over anhydrous sodium sulfate, ®ltrated,
and concentrated in vacuo. The residue was puri®ed by
silica gel ¯ash column chromatography -hexane±EtOAc
1:1, f4.0£15 cm) to afford TMS ether 7 -1.53 g) in 77%
yield as colorless viscous oil.
1
Analytical data for chloroacetate 8: H NMR -500 MHz,
CDCl3) d 6.94 -dd, J9.5, 6.0 Hz, 1H), 6.34 -t, J
11.5 Hz, 1H), 6.25 -t, J10.5 Hz, 1H), 6.04 -d, J9.5 Hz,
1H), 5.96 -td, J11.0, 3.0 Hz, 1H), 5.90 -d, J16.0 Hz, 1H),
5.89 -m, 1H), 5.79 -dd, J15.5, 5.0 Hz, 1H), 5.40 -t, J
11.0 Hz, 1H), 5.34 -t, J10.0 Hz, 1H), 5.27 -d, J16.5 Hz,
1H), 5.18 -d, J11.0 Hz, 1H), 5.06 -brs, 1H), 5.02 -t, J
5.0 Hz, 1H), 4.73 -tt, J10.5, 4.0 Hz, 1H), 4.53 -d, J
4.0 Hz, 2H), 4.05 -ABq, J14.5 Hz, 1H), 4.02 -ABq, J
14.5 Hz, 1H), 3.51 -dd, J9.5, 2.5 Hz, 1H), 3.25 -m, 2H),
2.73 -s, 1H), 2.54 -m, 1H), 2.42 -m, 1H), 2.24 -t, J7.5 Hz,
2H), 1.96±1.77 -m, 6H), 1.58 -m, 3H), 1.46 -m, 2H), 1.37
-m, 1H), 1.28 -m, 5H), 1.12 -m, 3H), 1.01 -qd, J12.5,
4.0 Hz, 1H), 0.95 -t, J7.5 Hz, 3H), 0.83 -t, J7.0 Hz,
3H), 0.82 -t, J6.0 Hz, 3H), 0.16 -s, 9H). 13C NMR
-125 MHz, CDCl3) d 173.27, 167.05, 163.70, 156.20,
149.66, 139.31, 135.28, 132.91, 127.74, 126.57, 126.28,
121.52, 120.86, 117.42, 79.84, 79.46, 72.68, 72.04, 69.92,
65.36, 40.95, 39.33, 38.00, 36.58, 36.10, 35.48, 35.07,
34.66, 34.14, 31.73, 31.26, 29.35, 26.51, 25.32, 23.58,
21.56, 19.10, 11.31, 11.04, 2.46. Mass -FAB): 822
-M1H). HR-MS calcd for C43H6835ClKNO10Si: 860.3938,
found 860.3927. IR -CHCl3) 3454 -w), 2959 -m), 2938 -m),
1722 -s), 1513 -m), 1464 -m), 1255 -s), 1174 -m).
Analytical data for TMS ether 7: 1H NMR -500 MHz,
CDCl3) d 6.92 -dd, J10.0, 6.0 Hz, 1H), 6.23 -t, J
3.1.7. Phosphate ester /9). To a solution of alcohol 8