Synthesis of a plasmenylethanolamine
1387
(
3
24H, s), 1.97 (1H, m), 2.05 (2H, q, J = 7.1 Hz), 2.42-2.48 (1H, m),
ter stirring overnight, the reaction mixture was quenched with
sat aq. NaHCO3 and extracted 3 times with Et2O. The extract was
successively washed with water and brine, dried (Na2SO4), fil-
tered and concentrated in vacuo. The residue was purified by
SiO2 column chromatography (hexane/EtOAc = 6:1) to give 11
(16.0 mg, 61%) and acyl-migrated product S1 (2.1 mg, 8%) as a
.62-3.70 (1H, m), 3.72-3.84 (3H, m), 3.89-3.98 (1H, m), 4.41 (1H,
13
q, J = 6.8 Hz), 5.94 (1H, dd, J = 1.3, 6.2 Hz); C NMR (100 MHz,
CDCl3): δ 14.1, 22.7, 23.9, 29.3, 29.4, 29.6, 29.65, 29.67, 29.70 (4C),
2
9.72, 31.9, 63.6, 70.8, 73.0, 108.2, 144.5; HRMS (EI): m/z calcd for
+
C19H38O3, 314.2821; found, 314.2821 ([M] ).
25
pale yellow oil. [α] D −2.66 (c 1.00, CHCl3); IR: νmax 3471 (br),
1
3005 (w), 2854 (s), 1740 (m), 1668 (m), 1460 (m), 1111 (m);
H
(
R,Z)-1-((tert-Butyldimethylsilyl)oxy)-3-(hexadec-1-
NMR (400 MHz, CDCl3): δ .88 (6H, t, J = 6.8 Hz), 1.26-1.30 (44H,
m), 1.58-1.69 (2H, m), 1.89 (1H, t, J = 6.2 Hz), 1.98-2.08 (6H, m),
en-1-yloxy) propan-2-ol (9)
2
.35 (2H, t, J = 7.6 Hz), 3.75-3.86 (2H, m), 3.89 (2H, d, J = 5.2
To a stirred solution of DMAP (0.140 g, 1.14 mmol), TBSCl (0.345 g,
2
added a solution of 8 (0.300 g, 0.954 mmol) in CH2Cl2 (1.66 mL)
at 0 °C. After 5 h, the reaction mixture was quenched with water
while cooling in an ice bath and extracted 3 times with CH2Cl2.
The extract was successively washed with water and brine, dried
Hz), 4.39 (1H, q, J = 6.6 Hz), 5.04 (1H, quin, J = 5.2 Hz), 5.28-
.29 mmol) and Et3N (318 μL, 2.29 mmol) in CH2Cl2 (5.50 mL) was
13
5
.40 (2H, m), 5.91 (1H, d, J = 6.6 Hz); C NMR (100 MHz, CDCl3):
δ 14.1 (2C), 22.7 (2C), 23.9, 24.9, 27.2 (2C), 29.07, 29.10, 29.2, 29.3
3C), 29.4, 29.5, 29.6, 29.66, 29.68 (2C), 29.69 (2C), 29.71 (3C), 29.8,
1.90, 31.92, 34.3, 61.9, 70.1, 73.1, 108.2, 129.7, 130.0, 144.5, 173.6;
(
3
HRMS (FAB): m/z calcd for C37H70NaO4, 601.5166; found, 601.5170
(Na2SO4), filtered and concentrated in vacuo. The residue was
+
(
[M + Na] ).
purified by SiO2 column chromatography (hexane/EtOAc = 10:1)
2
5
25
S1: [α] D −2.98 (c 1.04, CHCl3); IR: νmax 3460 (br), 2922 (w),
to give 9 (0.323 g, 86%) as a pale yellow oil. [α] D −4.74 (c 1.00,
CHCl3); IR: νmax 3454 (br), 3030 (w), 1665 (m), 1465 (m), 1255 (m),
1
2
852 (m), 1742 (s), 1665 (s), 1465 (s), 1113 (s); H NMR (400 MHz,
105 (m); 1H NMR (400 MHz, CDCl3): δ .08 (6H, s), 0.90 (12H, m),
CDCl3): δ .88 (6H, t, J = 6.9 Hz), 1.25-1.30 (44H, m), 1.63 (2H,
quint, J = 7.0 Hz), 1.99-2.08 (6H, m), 2.35 (2H, t, J = 7.6 Hz), 2.39
1
1
3
3
.26 (24H, m), 2.05 (2H, dq, J = 1.1, 7.2 Hz), 2.41 (1H, d, J = 5.6 Hz),
.66 (1H, dd, J = 5.4, 10.1 Hz), 3.69 (1H, dd, J = 4.7, 10.1 Hz), 3.73-
.78 (2H, m), 3.80-3.87 (1H, m), 4.36 (1H, q, J = 6.9 Hz), 5.94 (1H,
(
1H, d, J = 4.9 Hz), 3.74 (1H, dd, J = 6.0, 10.5 Hz), 3.79 (1H, dd,
J = 4.6 10.5 Hz), 4.00-4.10 (1H, m), 4.11-4.23 (2H, m), 4.41 (1H, q,
13
13
J = 7.0 Hz), 5.30-5.39 (2H, m), 5.94 (1H, d, J = 6.2 Hz); C NMR
dt, J = 1.5, 6.2 Hz); C NMR (100 MHz, CDCl3): δ −5.5 (2C), 14.1,
(100 MHz, CDCl3): δ 14.1 (2C), 22.7 (2C), 23.9, 24.9, 27.2 (2C), 29.1
1
2
8.3 (3C), 22.7, 23.9, 25.8, 29.3, 29.4, 29.5, 29.65, 29.66, 29.69 (4C),
(2C), 29.2, 29.3 (3C), 29.4, 29.5, 29.6, 29.67 (2C), 29.70 (3C), 29.71
9.8, 31.9, 63.5, 70.5, 72.3, 107.7, 144.8; HRMS (EI): m/z calcd for
+
(3C), 29.8, 31.91, 31.93, 34.1, 65.1, 70.0, 72.5, 108.5, 129.7, 130.0,
C25H52O3Si, 428.3686; found, 428.3689 ([M] ).
1
44.4, 174.0; HRMS (FAB): m/z calcd for C37H70NaO4, 601.5166;
+
found, 601.5173 ([M + Na] ).
(
R)-1-((tert-Butyldimethylsilyl)oxy)-3-(((Z)-
hexadec-1-en-1-yl)oxy)propan-2-yl oleate (10)
(
2R)-1-(((2-((((9H-fluoren-9-yl)methoxy)carbonyl)
amino)ethoxy) (2-cyanoethoxy)phosphoryl)oxy)-
-(((Z)-hexadec-1-en-1-yl)oxy)propan-2-yl oleate (13)
To a stirred solution of oleic acid (1.77 ꢀ in EtOH, 1.27 mL, 2.25
mmol) and DMAP (0.276 g, 2.26 mmol) in CH2Cl2 (6.0 mL), ED-
C·HCl (0.651 g, 3.40 mmol) was added at ambient temperature.
After 30 min, 9 (0.486 g, 1.13 mmol) in CH2Cl2 (5.0 mL) was added
and resulting mixture was stirring overnight. The mixture was
quenched with water while cooling in an ice bath and extracted
3
To a stirred solution of 11 (61 mg, 0.11 mmol) in dry MeCN
5.5 mL), 1H-tetrazole (31 mg, 0.44 mmol) was added at 0 °C. Af-
(
ter 45 min, a solution of 12 (305 mg, 0.63 mmol) in dry MeCN (6.3
mL) was added at the same temperature and the resulting mix-
ture was warmed to ambient temperature. After checking the
consumption of 11 (ca. 1 h), TBHP (5.5 ꢀ in decane, 0.29 mL, 1.6
mmol) was added to the reaction mixture. After stirring for 30
min, the mixture was quenched with sat aq. NaHCO3 while cool-
ing in an ice bath and extracted 3 times with EtOAc. The extract
was successively washed with water and brine, dried (Na2SO4),
filtered and concentrated in vacuo. The residue was purified by
3
times with CH2Cl2. The extract was successively washed with
water and brine, dried (Na2SO4), filtered and concentrated in
vacuo. The residue was purified by SiO2 column chromatography
(
hexane/EtOAc = 20:1) to give 10 (0.765 g, 97%) as a pale yellow
25
oil. [α] D + 3.64 (c 1.00, CHCl3); IR: νmax 3004 (w), 2853 (s), 1741 (s),
1
1
665 (m), 1464 (m), 1253 (m), 1108 (s); H NMR (400 MHz, CDCl3):
δ .06 (6H, s), 0.86-0.90 (15H, m), 1.26-1.30 (44H, m), 1.58-1.68 (2H,
m), 1.97-2.08 (6H, m), 2.31 (2H, t, J = 7.5 Hz), 3.72 (1H, dd, J = 5.1,
1
0.8 Hz), 3.75 (1H, dd, J = 5.2, 10.8 Hz), 3.84 (1H, dd, J = 5.6, 11.3
SiO2 column chromatography (hexane/EtOAc = 1:4) to give 13
Hz), 3.89 (1H, dd, J = 4.6, 11.3 Hz), 4.34 (1H, q, J = 6.9 Hz), 5.00
1H, quin, J = 5.1 Hz), 5.29-5.39 (2H, m), 5.90 (1H, dt, J = 1.4, 6.2
24
(
77.7 mg, 75%) as a pale yellow oil. [α] D −9.33 (c 0.15, CHCl3); IR:
(
1
νmax 3013 (w), 2853 (m), 1725 (m), 1523 (m), 1451 (m), 1247 (m);
H
13
Hz); C NMR (100 MHz, CDCl3): δ −5.5 (2C), 14.1 (2C), 18.2 (3C),
NMR (600 MHz, CDCl3): δ 0.88 (6H, t, J = 7.1 Hz), 1.25-1.28 (44H,
2
2
7
2.7 (2C), 23.9, 24.9, 25.8, 27.2 (2C), 29.1 (2C), 29.2, 29.3 (2C), 29.4,
9.5, 29.6, 29.67, 29.70, 29.72 (6C), 29.8 (2C), 31.91, 31.93, 34.4, 61.3,
0.0, 72.8, 107.6, 129.7, 130.0, 144.9, 173.2; HRMS (EI): m/z calcd for
m), 1.57-1.66 (2H, m), 1.97-2.05 (6H, m), 2.32-2.35 (2H, m), 2.72-
2
.75 (2H, m), 3.50-3.53 (2H, m), 3.81-3.86 (2H, m), 4.16-4.31 (7H,
m), 4.38-4.41 (3H, m), 5.19 (1H, quin, J = 5.1 Hz), 5.30-5.37 (2H, m),
.40-5.50 (1H, m), 5.87 (1H, d, J = 4.1 Hz), 7.32 (2H, t, J = 7.4 Hz), 7.41
+
C43H84O4Si, 692.6139; found, 692.6135 ([M] ).
5
13
(
2H, t, J = 7.4 Hz), 7.61 (2H, d, J = 7.4 Hz), 7.77 (2H, d, J = 7.4 Hz);
NMR (150 MHz, CDCl3): δ 14.1 (2C), 19.7, 22.7 (2C), 23.9, 24.8, 27.2
2C), 29.08, 29.13, 29.2, 29.3 (2C), 29.35, 29.37, 29.54, 29.61, 29.67,
9.69, 29.70, 29.72, 29.73 (2C), 29.74 (2C), 29.8, 31.9 (2C), 34.2, 41.3,
C
(S)-1-(((Z)-Hexadec-1-en-1-yl)oxy)-3-hydroxypropan-
(
2
2-yl oleate (11)
To a stirred solution of TBAF (1.0 ꢀ in THF, 0.2 mL, 0.2 mmol),
was added AcOH (58.0 μL, 0.966 μmol) to adjust the pH of the
solution to 4.4-4.7. The TBAF solution prepared above (0.8 ꢀ,
47.1, 62.1 (d, J = 4.9 Hz), 66.0 (d, J = 5.8 Hz), 66.9, 67.5 (d, J = 6.3 Hz),
69.1 (d, J = 2.7 Hz), 70.2 (d, J = 5.8 Hz), 108.7, 116.3, 120.0 (2C), 125.1
(2C), 127.1 (2C), 127.7 (2C), 129.7, 130.0, 141.3 (2C), 143.8 (2C), 144.3,
156.4, 173.0; HRMS (FAB): m/z calcd for C57H89N2NaO9P, 999.6198;
0.14 mL, 0.11 mmol) was added to a solution of 10 (31.6 mg,
+
0.0456 mmol) in dry THF (0.456 mL) at ambient temperature. Af-
found, 999.6206 ([M + Na] ).