Sex Pheromones of the Hair Crab Erimacrus
J ournal of Natural Products, 2001, Vol. 64, No. 9 1213
Hz), 1.94 (1H, ddt, J ) 13.5, 7.0, 7.0 Hz), 1.87 (1H, ddt, J )
13.5, 7.0, 7.0 Hz), 1.30-1.20 (16H, m), 0.86 (3H, t, J ) 7.0
Hz).
eluting with CHCl3/MeOH (95:5) gave 191 mg (0.61 mmol,
74%) of the azide 11b: 1H NMR (300 MHz, CDCl3/CD3OD, 1:1)
δ 3.90 (1H, dd, J ) 11.9 and 3.4 Hz), 3.75 (2H, m), 3.55 (2H,
m), 1.65-1.47 (4H, m), 1.40-1.20 (18H, m), 0.84 (3H, t, J )
6.9 Hz).
(2R,3R,4R)-1,3,4-Tr iben zyloxy-2-m eth a n esu lfon yloxy-
5-p en ta d ecen e (9a ). A solution of 8a (4.0 g, 7.17 mmol) in
pyridine (10.0 mL) was ice-cooled, and then MsCl (1.20 mL,
15.5 mmol) was added. The mixture was stirred for 7 h at room
temperature, then toluene was added, and the solution was
concentrated in vacuo. The resulting residue was dissolved in
ether, and the solution was washed successively with water
and brine. The organic layer was dried over Na2SO4 and
evaporated to dryness, and the residue was chromatographed
over Si gel. Elution with n-hexane/EtOAc (9:1) gave the
O-mesylate 9a (4.37 g, 6.87 mmol, 96%): 1H NMR of the 5Z-
isomer (500 MHz, CDCl3) δ 7.35-7.20 (15H, m), 5.77 (1H, dt,
J ) 11.2, 7.3 Hz), 5.46 (1H, t, J ) 11.2 Hz), 5.03 (1H, ddd, J
) 7.1, 4.0, 4.0 Hz), 4.73 (1H, d, J ) 11.0 Hz), 4.51-4.35 (6H,
m), 3.74 (1H, dd, J ) 11.0, 3.7 Hz), 2.90 (3H, s), 2.04 (1H, ddt,
J ) 14.5, 7.3, 7.3 Hz), 1.94 (1H, ddt, J ) 14.5, 7.3, 7.3 Hz),
1.35-1.20 (16H, m), 0.84 (3H, t, J ) 7.0 Hz).
(2S,3S,4R)-2-Am in o-1,3,4-p en ta d eca n etr iol (12a ). To a
solution of the azide 11a (500 mg, 1.66 mmol) in EtOH (20
mL) was added 10% palladium on carbon (500 mg). The
reaction flask was flushed with hydrogen gas and the solution
vigorously stirred for 20 h (room temperature, 1 atm). The
mixture was then filtered through a pad of Celite (with CHCl3/
MeOH rinse), the solvent concentrated, and the residue
chromatographed over Si gel under basic conditions. The
column was eluted with CHCl3/MeOH/H2O/25% NH4OH (8:2:
0.15:0.05), and the eluate was concentrated, diluted with
water, and lyophilized to afford the C15 phytosphingosine 12a
(433 mg, 1.57 mmol, 95%): 1H NMR (300 MHz, CDCl3) δ 3.72
(1H, dd, J ) 11.1, 4.3 Hz), 3.58 (1H, dd, J ) 11.1, 6.2 Hz),
3.51 (1H, m), 3.32 (1H, dd, J ) 7.7, 5.5 Hz), 2.94 (1H, dd, J )
10.1, 5.5 Hz), 1.70 (2H, m), 1.53 (2H, m), 1.40-1.20 (16H, m),
0.85 (3H, t, J ) 6.9 Hz).
(2R,3R,4R)-2-Meth a n esu lfon yloxy-1,3,4-p en ta d eca n e-
tr iol (10a ). To an ice-cooled solution of 20a (4.0 g, 7.35 mmol)
in pyridine (15.0 mL) was added MsCl (1.15 mL, 14.9 mmol).
The mixture was stirred for 15 h at room temperature, then
toluene was added, and the solution was concentrated in vacuo.
The resulting residue was dissolved in ether, and the solution
was washed successively with water and brine. The organic
layer was dried over Na2SO4 and evaporated to dryness, and
the residue was chromatographed over Si gel. Elution with
n-hexane/EtOAc (9:1, 8:2) afforded the O-mesylate 9a (4.66 g,
quant.). Then the O-mesylate 9a (2.26 g, 3.63 mmol) was
dissolved in EtOH (30 mL), and 2.30 g of 10% palladium on
carbon was added. Hydrogen gas was introduced to the
reaction flask and the solution vigorously stirred for 20 h (room
temperature, 1 atm). The reaction mixture was filtered
through a pad of Celite (with CHCl3 rinse), and the filtrate
was concentrated to give 1.24 g (3.50 mmol, 96%) of 10a as a
white powder: 1H NMR (300 MHz, CDCl3/CD3OD, 1:1) δ 4.89
(1H, ddd, J ) 6.5, 5.3, 2.1 Hz), 3.90-3.75 (2H, m), 3.53-3.48
(1H, m), 3.46 (1H, dd, J ) 8.5, 2.1 Hz), 3.14 (3H, s), 1.74 (2H,
m), 1.52 (2H, m), 1.40-1.20 (16H, m), 0.84 (3H, t, J ) 6.7 Hz).
(2S,3S,4R)-2-Am in o-1,3,4-h exa d eca n etr iol (12b). To a
solution of the azide 11b (100 mg, 0.32 mmol) in EtOH (11
mL) was added 10% palladium on carbon (110 mg). The
reaction flask was flushed with hydrogen gas and the solution
vigorously stirred for 20 h (room temperature, 1 atm). The
mixture was then filtered through a pad of Celite (with CHCl3/
MeOH rinse), the solvent concentrated, and the residue
chromatographed over Si gel. Elution with CHCl3/MeOH/H2O
(8:2:0.2, 7:3:0.5) gave the C16 phytosphingosine12b (51.0 mg,
0.18 mmol, 56%): 1H NMR (300 MHz, CDCl3/CD3OD, 1:1) δ
3.87 (1H, dd, J ) 11.8, 4.0 Hz), 3.75 (1H, dd, J ) 11.8, 7.5
Hz), 3.62 (1H, m), 3.52 (1H, dd, J ) 8.9, 4.4 Hz), 3.45 (1H, dd,
J ) 7.6, 3.7 Hz), 1.73 (2H, m), 1.49 (2H, m), 1.40-1.20 (18H,
m), 0.83 (3H, t, J ) 7.0 Hz).
9-Br om on on a n a l (14). To a stirred solution of 9-bro-
mononanol (13) (4.9 g, 22.0 mmol) in CH2Cl2 (30 mL) was
added pyridinium chlorochromate (10.0 g, 46.4 mmol). Stirring
was continued for 2 h at room temperature, and then ether
(10 mL) and Na2SO4 were added to the solution. The suspen-
sion was filtered and rinsed with ether, and the solvent
concentrated in vacuo. The residue was chromatographed over
Si gel. Elution with n-hexane/EtOAc (96:4, 9:1) gave the
aldehyde 14 (4.3 g, 19.5 mmol, 89%): 1H NMR (300 MHz,
CDCl3) δ 9.74 (1H, t, J ) 1.8 Hz), 3.38 (2H, t, J ) 7.0 Hz),
2.40 (2H, brt, J ) 7.0 Hz), 1.82 (2H, quint, J ) 7.0 Hz), 1.60
(2H, quint, J ) 7.3 Hz), 1.40 (2H, quint, J ) 7.0 Hz), 1.35-
1.25 (6H, m).
12-Br om o-2-m eth yl-3-d od ecen e (15). To an ice-cooled
suspension of isobutyltriphenylphosphonium bromide (10.0 g,
25.0 mmol) in THF (50 mL) was added 14.0 mL of n-BuLi (1.6
M solution in n-hexane). The resulting solution was stirred
for 30 min at 0 °C, and then a solution of 8-bromooctanal (4.1
g, 18.5 mmol) in THF (30 mL) was added. The mixture was
warmed to room temperature and stirring was continued for
2 h. The reaction was quenched by addition of water, and the
mixture extracted with ether. The combined ethereal fraction
was washed with brine, dried over MgSO4, and concentrated.
Chromatography on Si gel with n-hexane gave the alkene 15
as a colorless oil (3.8 g, 14.4 mmol, 78%): 1H NMR of the 3Z-
isomer (300 MHz, CDCl3) δ 5.20 (1H, dt, J ) 11.0, 6.9 Hz),
5.16 (1H, ddt, J ) 10.7, 10.7, 1.2 Hz), 3.38 (2H, t, J ) 6.7 Hz),
2.56 (1H, m), 2.00 (2H, dt, J ) 7.0, 7.0 Hz), 1.83 (2H, quint, J
) 6.9 Hz), 1.42 (2H, m), 1.40-1.20 (8H, m), 0.92 (6H, d, J )
6.7 Hz).
11-Met h yl-9-d od ecen ylt r ip h en ylp h osp h on iu m Br o-
m id e (16). The mixture of the bromide 15 (3.6 g, 16.2 mmol)
and triphenylphosphine (4.3 g, 16.4 mmol) was heated at 120
°C for 2 days to give 16. In the same manner, this reaction
was repeated twice for each of the next Wittig reactions. The
resulting viscous materials were used in the next step without
further purification.
(2R,3R,4R)-2-Met h a n esu lfon yloxy-1,3,4-h exa d eca n e-
tr iol (10b). To a solution of 9b (1.35 g, 2.12 mmol) in EtOH
(30 mL) was added 10% palladium on carbon (1.36 g). The
mixture was stirred for 22 h under a hydrogen atmosphere at
room temperature (1 atm). The Pd/C was then removed by
filtration through
a pad of Celite, and the filtrate was
concentrated to give the triol 10b as a white powder (1.24 g,
3.50 mmol, 89%): 1H NMR (300 MHz, CDCl3/CD3OD, 1:1) δ
4.90 (1H, ddd, J ) 6.6, 5.3, 2.0 Hz), 3.86 (1H, dd, J ) 12.2, 6.5
Hz), 3.80 (1H, dd, J ) 12.1, 4.9 Hz), 3.52 (1H, ddd, J ) 8.4,
8.4, 2.3 Hz), 3.46 (1H, dd, J ) 8.4, 1.9 Hz), 3.15 (3H, s), 1.75
(2H, m), 1.52 (2H, m), 1.40-1.20 (18H, m), 0.84 (3H, t, J )
6.7 Hz).
(2S,3S,4R)-2-Azid o-1,3,4-p en t a d eca n et r iol (11a ). So-
dium azide (600 mg, 9.2 mmol) was added to a solution of the
mesylate 10a (609 mg, 1.72 mmol) in DMF (20 mL) at room
temperature. The mixture was slowly heated to 100 °C over
30 min and then stirred for 3 h. The mixture was diluted with
EtOAc and washed with water and brine. The organic layer
was dried (Na2SO4) and concentrated in vacuo, and remaining
DMF was removed by lyophilization. The resulting residue was
chromatographed over Si gel with CHCl3/MeOH (97:3, 96:4)
to yield 425 mg (1.41 mmol, 82%) of the azide 11a : 1H NMR
(600 MHz, CDCl3/CD3OD, 1:1) δ 3.90 (1H, dd, J ) 12.0, 3.6
Hz), 3.74 (2H, m), 3.54 (2H, m), 1.62 (2H, m), 1.56 (2H, m),
1.40-1.20 (16H, m), 0.85 (3H, t, J ) 7.0 Hz).
(2S,3S,4R)-2-Azid o-1,3,4-h exa d eca n etr iol (11b). Sodium
azide (200 mg, 3.08 mmol) was added to a solution of the
mesylate 10b (300 mg, 0.82 mmol) in DMF (12 mL) at room
temperature. It was slowly heated to 100 °C over 30 min and
then stirred for 3 h. The reaction mixture was partitioned
between EtOAc and H2O. The organic layer was dried (Na2-
SO4) and concentrated in vacuo. Chromatography (SiO2)
1-Br om o-19-m eth yleicosa n e (18a ). To a suspension of the
phosphonium salt 16 (prepared from 3.6 g of 15) in THF (20