8150 J . Org. Chem., Vol. 65, No. 24, 2000
Wang et al.
column chromatography was performed on silica gel (10-40
µm) using a mixture of petroleum ether and ethyl acetate as
the eluent. Compounds 710c and 2123 were prepared according
to published procedures.
(2S,3R,4E,8E)-N,O,O-Tr ia cet yl-9-m et h yl-4,8-sp h in ga -
d ien in e (20). To a solution of sodium (260 mg, 11 mmol) and
dibenzo-18-crown-6 (31 mg, 0.09 mmol) in liquid ammonia (10
mL) at -78 °C was added a solution of amine 19 (510 mg, 0.85
mmol) in dry THF (10 mL). After addition, the reaction
mixture was stirred at -78 °C for 40 min and was then
quenched with solid ammonium chloride to decompose the
excessive sodium. The mixture was left to rise to room
temperature during which time nitrogen was bubbled into the
solution to expel the ammonia. The residue was taken with
chloroform (3 × 20 mL), and the extracts were concentrated
under reduced pressure to give the crude sphingadienine 3.
Without further purification, the crude 3 was dissolved in
dichloromethane (10 mL) and mixed with DMAP (5 mg, 0.04
mmol), triethylamine (1 mL, 7.17 mmol), and actetic anhydride
(0.5 mL, 5.30 mmol) at 0 °C. The reaction mixture was stirred
at room temperature for 10 h and then partitioned between
water (15 mL) and dichloromethane (3 × 20 mL). The organic
extracts were dried (MgSO4) and evaporated under reduced
pressure to leave a residue that was purified by flash chro-
matography (petroleum ether/ethyl acetate, 3:2) to give the
triacetate 20 (314 mg, 84%) as a white solid: mp 62-63 °C;
[R]D -13.8 (c 1.13, CHCl3); IR (KBr) νmax 3290, 2922, 2852,
1736, 1656, 1553, 1375, 1270 cm-1; 1H NMR (300 MHz, CDCl3)
δ 5.80 (dt, J ) 15.2, 6.4 Hz, 1H), 5.65 (d, J ) 9.1 Hz, 1H), 5.42
(dd, J ) 15.2, 7.4 Hz, 1H), 5.30 (dd, J ) 7.1, 5.85 Hz, 1H),
5.08 (m, 1H), 4.45 (m, 1H), 4.30 (dd, J ) 11.6, 6.3 Hz, 1H),
4.05 (dd, J ) 11.6, 4.1 Hz, 1H), 2.10 (s, 6H), 2.0 (s, 3H), 2.15-
1.95 (m, 6H), 1.55 (s, 3H), 1.25 (m, 14H), 0.90 (t, J ) 6.9 Hz,
3H); MS (EI) m/z 438 (M+ + 1), 378 (M+ - CH3CO2), 318, 102,
84. Anal. Calcd for C25H43NO5: C, 68.61; H, 9.90; N, 3.20.
Found: C, 68.59; H, 9.96; N, 3.35.
(2R,3R,4E,8E)-1,3-Di-O-ben zyl-9-m eth yl-2-O-m eth ylsu l-
fon yl-7-(p h en ylth io)-4,8-octa d eca d ien e-1,2,3-tr iol (16). n-
Butyllithium (2.5 M in hexanes, 2.8 mL, 7 mmol) was added
dropwise to a stirred solution of phenyl sulfide 14 (2.03 g, 7
mmol) and HMPA (1.22 mL) in dry THF (20 mL) at -78 °C.
The reaction mixture was stirred at -78 °C for 2 h and gave
a deep orange colored solution, to which CuCN‚2LiCl (1 M in
THF, 8 mL, 8 mmol) was added, followed, after 10 min, by
the dropwise addition of the dimesylate 7 (2.912 g, 6 mmol) in
THF (15 mL). After addition, the reaction mixture was stirred
further for 30 min and quenched with saturated aqueous
ammonium chloride (20 mL). The mixture was extracted with
ethyl acetate (3 × 50 mL). The combined organic extracts were
washed with brine (50 mL), dried (MgSO4), and concentrated
under reduced pressure. Purification of the residue by flash
column chromatography (petroleum ether/ethyl acetate 5:1)
afforded 16 (3.62 g, 89%) as a white solid: mp 83-84 °C; [R]D
-4.6 (c 1.14, CHCl3); IR (KBr) νmax 2927, 2854, 1497, 1455,
1
1353, 1176, 929 cm-1; H NMR (300 MHz, CDCl3 ) δ 7.30 (m,
15H), 5.80 (dt, J ) 15.4, 7.1 Hz, 1H), 5.40 (dd, J ) 15.4, 8.0
Hz, 1H), 5.05 (d, J ) 10.2 Hz, 1H), 4.73 (m, 1H), 4.60-4.30
(m, 4H), 4.08 (t, J ) 7.1 Hz, 1H), 3.90 (m, 1H), 3.70 (m, 2H),
2.94 (s, 3H), 2.40 (m, 2H), 1.88 (t, J ) 7.7 Hz, 2H), 1.38 (s,
3H), 1.20 (m, 14H), 0.88 (t, J ) 6.3 Hz, 3H); MS (ESI) m/z 611
(M+ - Bn + Na), 639 (M+ - OSO2CH3 + K). Anal. Calcd for
C
40H54S2O5: C, 70.76; H, 8.01. Found: C, 70.61; H, 8.25.
(2S,3R,4E,8E)-2-Azid o-1,3-d i-O-ben zyl-9-m eth yl-7-(p h e-
n ylth io)-4,8-octa d eca d ien e-1,3-d iol (18). The mixture of
mesylate 16 (2.954 g, 3.82 mmol) and sodium azide (1.5 g, 23
mmol) in dry DMF (40 mL) was heated at 100 °C for 24 h.
Upon cooling to room temperature, the reaction mixture was
concentrated under reduced pressure and the residue was
partitioned between water (30 mL) and diethyl ether (3 × 50
mL). The combined ethereal extracts were dried (MgSO4) and
concentrated under reduced pressure. Purification by flash
column chromatography on silica gel (petroleum ether/ethyl
acetate 30:1) afforded the azide 18 (1.88 g, 78%) as a coluorless
oil: [R]D -29.1 (c 1.26, CHCl3); IR (film) νmax 2920, 2850, 2100,
(2R,3R,4E,8E)-1,3-Di-O-b en zyl-2-O-m et h ylsu lfon yl-7-
(p h en ylth io)-4,8-octa d eca d ien e-1,2,3-tr iol (23). Under the
same reaction conditions as for the preparation of compound
16, phenyl sulfide 22 (1.325 g, 4.8 mmol), n-BuLi (1.6 M in
hexanes, 3 mL, 4.8 mmol), CuCN‚2LiCl (1 M in THF, 5.5 mL,
5.5 mmol), and dimesylate 7 (1.94 g, 4.0 mmol) gave, after
purification by flash column chromatography (petroleum ether/
ethyl acetate, 5:1), the mesylate 23 (2.513 g, 94%) as a white
solid: mp 48-49 °C; [R]D -1.97 (c 3.35, CHCl3); IR (KBr) νmax
3030, 2923, 2852, 1498, 1455, 1438, 1350, 1175, 1092, 981, 930,
1
1630, 1590, 1495, 1080 cm-1
;
1H NMR (300 MHz, CDCl3) δ
748 cm-1; H NMR (600 MHz, CDCl3) δ 7.30 (m, 15H), 5.83
7.22 (m, 15H), 5.20 (dt, J ) 15.5, 7.0 Hz, 1H), 5.48 (dd, J )
15.5, 8.4 Hz, 1H), 5.05 (d, J ) 10.0 Hz, 1H), 4.60 (m, 1H), 4.51-
(d, J ) 2.1 Hz, 2H), 4.30 (m, 1H), 3.90 (m, 2H), 3.62 (m, 3H),
2.45 (m, 2H), 1.90 (dt, J ) 7.44, 7.38 Hz, 2H), 1.38 (s, 3H),
1.22 (m, 14H), 0.88 (t, J ) 7.0 Hz, 3H); MS (EI) m/z 599 (M+
- N2, 1.6), 489 (M+ - N2 - PhS, 15.7), 488 (M+ - N2 - PhSH,
15.9), 289 (32.7), 308 (0.86), 91 (100). Anal. Calcd for C39H51N3-
SO2: C, 74.84; H, 8.21; N, 6.71. Found: C, 75.02; H, 8.40; N,
6.88.
(dt, J ) 7.2, 15.6 Hz, 1H), 5.42 (dd, J ) 7.8, 15.6 Hz, 1H), 5.29
(m, 2H), 4.73 (m, 1H), 4.64-4.30 (m, 4H), 4.08 (m, 1H), 3.70
(m, 2H), 3.61 (m, 1H), 2.95 (s, 3H), 2.42 (m, 2H), 1.90 (m, 2H),
1.20 (m, 14H), 0.88 (t, J ) 6.6 Hz, 3H); MS (EI) m/z 257 (94.95),
201 (100), 77 (12.8), 91 (4.7); MS (ESI) 687.7 (M+ + Na), 665.9
(M+ + H). Anal. Calcd for C39H52S2O5: C, 70.44; H, 7.88.
Found: C, 70.50; H, 8.00.
(2S,3R,4E,8E)-2-Azid o-1,3-d i-O-ben zyl-7-(p h en ylth io)-
4,8-octa d eca d ien e-1,3-d iol (24). Under the same reaction
conditions as for compound 18, mesylate 23 (1.661 g, 2.50
mmol) and sodium azide (1.63 g, 25 mmol) gave, after purifica-
tion by flash column chromatography (petroleum ether/ethyl
acetate, 30:1), the azide 24 (1.24 g, 81%) as a colorless oil: [R]D
-29.8 (c 2.90, CHCl3); IR (film) νmax 2910, 1870, 2105, 1590,
1475, 1095, 970, 740, 700 cm-1; 1H NMR (300 MHz, CDCl3) δ
7.30 (m, 15H), 5.73 (dt, J ) 15.5, 6.6 Hz, 1H), 5.50 (dd, J )
15.5, 8.35 Hz, 1H), 5.31 (m, 2H), 4.60 (m, 1H), 4.52 (d, J ) 2.2
Hz, 2H), 4.34 (m, 1H), 3.89 (m, 1H), 3.63 (m, 4H), 2.45 (m,
2H), 1.90 (m, 2H), 1.20 (m, 14H), 0.88 t, J ) 6.6 Hz, 3H); MS
(EI) m/z 584 (M+ - N2, 0.44), 475 (M+ - N2 - SPh, 2.9), 275
(52.18), 149 (17.6), 148 (11.6), 123 (11.4), 109 (7.58), 91 (100).
Anal. Calcd for C38H49N3SO2: C, 74.59; H, 8.07. Found: C,
74.85; H, 8.22.
(2S,3R,4E,8E)-2-Am in o-1,3-di-O-ben zyl-9-m eth yl-7-(ph e-
n ylth io)-4,8-octa d eca d ien e-1,3-d iol (19). A solution of azide
18 (783 mg, 1.25 mmol) in anhydrous diethyl ether (8 mL) was
added dropwise to a slurry of lithium aluminum hydride (48
mg, 1.25 mmol) in anhydrous diethyl ether (8 mL) at 0 °C.
After being stirred at room temperature for 12 h, the reaction
was quenched with careful addition of cold water (3 mL),
diluted with ethyl acetate (20 mL), and dried (Na2SO4). The
solids were filtered off and washed with ethyl acetate (3 × 10
mL). The filtrate was evaporated under reduced pressure, and
the residue was purified by column chromatography on silica
gel (petroleum ether/ethyl acetate, 2:1) to afford the amine 19
(750 mg, 100%) as a colorless oil: [R]D -19.8 (c 1.62, CHCl3);
IR (film) νmax 2930, 2870, 1590, 1450, 1080 cm-1; 1H NMR (300
MHz, CDCl3) δ 7.30 (m, 15H), 5.72 (dt, J ) 15.5, 7.0 Hz, 1H),
5.45 (dd, J ) 15.5, 8.4 Hz, 1H), 5.08 (d, J ) 10.2 Hz, 1H), 4.57
(m, 1H), 4.49 (s, 2H), 4.30 (m, 1H), 3.95 (m, 1H), 3.75 (m, 1H),
3.62 (m, 1H), 3.49 (m, 1H), 3.10 (m, 1H), 2.45 (m, 2H), 1.90
(m, 2H), 1.75 (s, 2H), 1.38 (s, 3H), 1.25 (m, 14H), 0.90 (t, J )
7.0 Hz, 3H); MS (EI) m/z 600 (M+, 4.8), 583 (M+ - NH3, 1.0),
490 (M+ - PhSH, 5.7), 382 (12.1), 289 (11.8), 150 (100), 91
(89.2). Anal. Calcd for C39H53NSO2: C,78.08; H, 8.90; N, 2.33.
Found: C, 78.14; H, 8.95; N, 2.52.
(2S,3R,4E,8E)-2-Am in o-1,3-d i-O-ben zyl-7-(p h en ylth io)-
4,8-octa d eca d ien e-1,3-d iol (25). Under the same reaction
conditions as for compound 19, azide 24 (1.073 g, 1.75 mmol)
and lithium aluminum hydride (67 mg, 1.75 mmol) afforded,
after flash column chromatography on silica gel (petroleum
ether/ethyl acetate, 2:1), the amine 25 (1.02 g, 100%) as a
colorless oil: [R]D -17.03 (c 2.58, CHCl3); IR (film) νmax 2900,
1
2850, 1445, 1090, 740, 695 cm-1; H NMR (300 MHz, CDCl3)
δ 7.35 (m, 15H), 5.74 (apparent dt, J ) 15.5, 7.63 Hz, 1H),