G Model
CPL 4399 No. of Pages 14
4
C. Vilchèze et al. / Chemistry and Physics of Lipids xxx (2015) xxx–xxx
ꢁ
1
(
2
2H, m, CRCCH
2
CRC); 13C NMR
d
9.5 (C-3),14.1 (C-19),18.6 (C-6),
2,5-Heneicosadiynoic acid (5e, 42%): mp 61.0–62.0 C, H NMR
0.86 (3H, t, J = 7.1 Hz, -CH ), 1.23 (24H, m, (CH 12), 1.46 (2H, m,
CH CRC), 3.30 (2H, t, J = 2.4 Hz,
C ꢀꢀ CRC), 2.12 (2H, m, CH
CRCCH CRC), 7.5 (1H, br s, CO
d
2.7 (C-18), 28.6 (C-7), 28.9 (C-8), 29.1 (C-9), 29.4 (C-16), 29.5
v
3
2
)
(
(
C-15), 29.6 (C-10–C-14), 31.9 (C-17), 68.3 (C-1), 72.9 (C-4), 78.8
C-5), 81.2 (C-2).
2
2
13
2
2
H); C NMR d 10.2 (C-4), 14.1
(C-21), 18.6 (C-7), 22.7 (C-20), 28.5 (C-8), 28.9 (C-9), 29.1 (C-10),
29.4 (C-18), 29.5 (C-17), 29.6 (C-11), 29.7 (C-12–C-16), 31.9 (C-19),
70.2 (C-2), 71.9 (C-5), 82.8 (C-6), 86.1 (C-3), 157.3 (C-1). ESI–MS
1
-CH
,4-Eicosadiyne (4e, 63%): 1H NMR
d
0.85 (3H, t, J = 7.0 Hz,
12),1.46 (2H, m, CH
C ꢀꢀ CRC), 2.03 (1H,
CRC), 3.12
9.6 (C-3),
4.1 (C-20), 18.7 (C-6), 22.7 (C-19), 28.7 (C-7), 28.9 (C-8), 29.1 (C-9),
v
3
),1.23 (24H, m, (CH
2
)
2
t, J = 2.7 Hz, CRCH), 2.13 (2H, tt, J = 2.4 Hz, J = 7.1 Hz, CH
2
ꢀ
(
2H, tt, J = 2.4 Hz, J = 2.7 Hz, CRCCH
2
CRC); 13C NMR
d
exact mass for C21
H
34
O
2
318.2559, found [M ꢀ H] 317.2481.
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1
1
2
6
2,5-Tricosadiynoic acid (5f, 30%): mp 66.0–67.0 C, H NMR
(3H, t, J = 7.0 Hz, -CH ), 1.23 (28H, m, (CH 14), 1.46 (2H, m,
CH CRC), 3.30 (2H,
C ꢀꢀ CRC), 2.13 (2H, tt, J = 2.3 Hz, J = 7.1 Hz, CH
t, J = 2.3 Hz, CRCCH
d 0.86
9.4 (C-17), 29.5 (C-16), 29.6 (C-10), 29.7 (C-11–C-15), 31.9 (C-18),
v
3
2
)
8.3 (C-1), 72.9 (C-4), 79.0 (C-5), 81.3 (C-2).
2
2
1
,4-Docosadiyne (4f, 68%): 1H NMR
d
0.86 (3H, t, J = 7.0 Hz,
2 2
CRC), 9.5 (1H, br s, CO H); C NMR d 10.2
13
v
-CH
3
); 1.23 (28H, m, (CH
2
)
14); 1.46 (2H, m, CH
2
C ꢀꢀ CRC); 2.03
(C-4), 14.1 (C-23), 18.6 (C-7), 22.7 (C-22), 28.5 (C-8), 28.9 (C-9), 29.1
(C-10), 29.4 (C-20), 29.5 (C-19), 29.6 (C-11), 29.7 (C-12 to 18), 31.9
(C-21), 70.0 (C-2), 73.3 (C-5), 82.6 (C-6), 85.91 (C-3), 157.3 (C-1).
(
1H, t, J = 2.6 Hz, CRCH); 2.13 (2H, tt, J = 2.4 Hz, J = 7.1 Hz,
1
3
CH
NMR
2
2
CRC); 3.12 (2H, tt, J = 2.4 Hz, J = 2.6 Hz, CRCCH
9.6 (C-3); 14.1 (C-22); 18.7 (C-6); 22.7 (C-21); 28.7 (C-7);
8.9 (C-8); 29.1 (C-9); 29.4 (C-19); 29.5 (C-18); 29.6 (C-10); 29.7
2
CRC);
C
d
ESI–MS exact mass for C23
H
38
O
2
346.2872, found [M ꢀ H]ꢀ
345.2729.
(
(
C-11 to 17); 31.9 (C-20); 68.3 (C-1); 72.9 (C-4); 79.0 (C-5); 81.3
C-2).
2.5. Preparation of 2,10-nonadecadiynoic acid
2
.4.3. 2,5-Alkanediynoic acids 5
To a solution of 4 (0.9 mmol) in dry THF (36 mL) at ꢀ78 C was
2.5.1. 1-Bromo-7-hexadecyne 6
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Phosphorus tribromide (170 mL, 1.79 mmol) was added drop-
added n-butyllithium (2.5 M in hexanes, 360
m
L, 0.9 mmol)
wise to a solution of 7-hexadecyn-1-ol (1.00 g, 4.19 mmol) in dry
ether (10 mL). The reaction mixture was refluxed for 2.5 h and
stirred at rt for 18 h, then poured over crushed ice and extracted
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dropwise. The mixture was stirred at ꢀ78 C for 30 min. Carbon
dioxide gas was bubbled into the reaction mixture until the
solvents had evaporated. To the residue was added diethyl ether/
2 4
with ether. The ether phases were combined, dried (Na SO ),
1
0% aqueous hydrochloric acid solution. The aqueous phase was
extracted with diethyl ether. The combined organic phases were
dried (Na SO ), filtered, and evaporated to dryness under reduced
filtered, evaporated to dryness under reduced pressure, and
purified by chromatography (elution with hexane) to give 6
1
2
4
(708 mg, 56%): H NMR
d
0.83 (3H, t, J = 6.6 Hz,
v
-CH
C-Br), 2.09 (4H, m,
Br); C NMR 13.9 (C-16),18.7
3
), 1.23 (10H,
pressure. Purification began with column chromatography (elution
with hexane/ethyl acetate/ acetic acid 4/1/0.1), followed by two
recrystallizations from hexane and lyophilization from cyclohex-
ane to afford a beige powder.
m, (CH
2
)
5
), 1.39 (8H, m, (CH
CH CRC), 3.34 (2H, t, J = 6.8 Hz, CH
2
)
4
), 1.81 (2H, m, CH
2
13
2
2
d
(C-6 and C-9), 22.6 (C-15), 27.6 (C-3), 27.8 (C-4), 28.8 (C-5 and
C-10), 29.3 (C-11 to 13), 31.7 (C-14), 32.6 (C-1), 33.3 (C-2), 79.6
(C-7), 80.3 (C-8).
ꢁ
1
2
,5-Hexadecadiynoic acid (5a, 62%): mp 42.0–42.5 C, H NMR
.86 (3H, t, J = 6.9 Hz, -CH ), 1.23 (14H, m, (CH ), 1.46 (2H, m,
CH CRC), 3.30 (2H,
C ꢀꢀ CRC), 2.13 (2H, tt, J = 2.0 Hz, J = 7.1 Hz, CH
t, J = 2.0 Hz, CRCCH CRC), 10.3 (1H, br s, CO H); C NMR
C-4), 14.1 (C-16), 18.6 (C-7), 22.7 (C-15), 28.5 (C-8), 28.8 (C-9), 29.1
C-10), 29.3 (C-13), 29.5 (C-12), 29.6 (C-11), 31.9 (C-14), 70.2 (C-2),
d
0
v
3
2 7
)
2
2
2.5.2. 1,9-Octadecadiyne 7
13
2
2
d
10.2
A suspension of lithium acetylide ethylenediamine complex
(247 mg, 2.70 mmol) in dry DMSO (4 mL) was stirred for 10 min at
room temperature under nitrogen. After the mixture was cooled to
(
(
ꢁ
72.0 (C-5), 82.8 (C-6), 86.3 (C-3),158.0 (C-1). ESI–MS exact mass for
8 C, 1-bromo-7-hexadecyne (708 mg, 2.35 mmol) was added
ꢀ
C
16
H
2
O
24 2
248.1776, found [M ꢀ H] 247.1816.
dropwise. The reaction mixture was stirred at rt overnight and
ꢁ
ꢁ
,5-Octadecadiynoic acid (5b, 42%): mp 54.0 C (lit. (Christie and
cooled to 0 C. Water (1 mL) was added very slowly. The suspension
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1
Holman, 1967) mp 53.0–54.0 C), H NMR
-CH ), 1.24 (18H, m, (CH ), 1.46 (2H, m, CH
tt, J = 2.1 Hz, J = 7.1 Hz, CH CRC), 3.30 (2H, t, J = 2.1 Hz,
CRCCH CRC), 9.7 (1H, br s, CO 10.2 (C-4), 14.1
H); 13C NMR
C-18), 18.6 (C-7), 22.7 (C-17), 28.5 (C-8), 28.8 (C-9), 29.1 (C-10),
d
0.85 (3H, t, J = 7.1 Hz,
was stirred for 10 min at rt, then poured into water (60 mL), and
extracted with hexane. The combined organic phases were dried
v
3
2
)
9
2
C ꢀꢀ CRC), 2.12 (2H,
2
2 4
(Na SO ), filtered, evaporated to dryness under reduced pressure,
2
2
d
and purified by chromatography (elution with hexane) to give 1,9-
1
(
2
octadecadiyne (423 mg, 73%): H NMR 0.82 (3H, t, J = 6.7 Hz,
-CH ), 1.21 (8H, m, (CH ), 1.35 (12H, m, (CH ), 1.86 (1H, t,
2
J = 2.6 Hz, CRCH), 2.10 (6H, m, CH CRC); C NMR d 14.0 (C-18),
d
9.4 (C-15), 29.5 (C-14); 29.6 (C-11–C-13), 31.9 (C-16), 70.1 (C-2),
v
3
2
)
4
2 6
)
13
71.9 (C-5), 82.9 (C-6), 86.3 (C-3),158.0 (C-1). ESI–MS exact mass for
ꢀ
C
18
H
2
28
O
2
276.2089, found [M ꢀH] 275.2089.
18.3 (C-3), 18.7 (C-8 and C-11), 22.6 (C-17), 28.2 (C-5 and 6), 28.4
(C-4), 28.8 and 29.0 (C-7 and C-12), 29.1 (C-13 to 15), 31.8 (C-16),
68.0 (C-1), 79.9 (C-9), 80.2 (C-10), 84.4 (C-2).
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1
,5-Nonadecadiynoic acid (5c, 60%): mp 56.0–56.5 C, H NMR
.86 (3H, t, J = 7.1 Hz, -CH ), 1.24 (20H, m, (CH 10), 1.46 (2H, m,
C ꢀꢀ CRC), 2.13 (2H, tt, J = 2.3 Hz, J = 7.1 Hz, CH CRC), 3.30 (2H,
d
0
v
3
2
)
CH
t, J = 2.3 Hz, CRCCH
2
2
13
2
CRC), 8.0 (1H, br s, CO
2
H); C NMR
d
10.2
2.5.3. 2,10-Nonadecadiynoic acid 8
(
(
(
C-4), 14.1 (C-19), 18.6 (C-7), 22.7 (C-18), 28.5 (C-8), 28.8 (C-9), 29.1
C-10), 29.4 (C-16), 29.5 (C-15), 29.6 (C-11–C-14), 31.9 (C-17), 70.2
To a solution of 7 (423 mg, 1.70 mmol) in dry THF (7 mL) at
ꢁ
ꢀ23 C was added n-butyllithium (2.5 M solution in hexanes,
C-2), 71.8 (C-5), 82.9 (C-6), 86.2 (C-3), 156.8 (C-1). ESI–MS exact
0.69 mL, 1.73 mmol) under nitrogen. The reaction mixture was
ꢀ
ꢁ
ꢁ
mass for C19
H
30
O
2
290.2246, found [M ꢀ H] 289.1693.
stirred at ꢀ23 C for 1 h and then warmed to 0 C. A stream of
carbon dioxide was bubbled into the suspension until THF was
evaporated. The residue was poured into ether/10% aqueous
hydrochloric acid solution and extracted with diethyl ether. The
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1
2
,5-Eicosadiynoic acid (5d, 43%): mp 60.0–60.5 C, H NMR
3H, t, J = 7.0 Hz, -CH ), 1.23 (22H, m, (CH 11), 1.46 (2H, m,
CH CRC), 3.30 (2H, m,
C ꢀꢀ CRC), 2.12 (2H, m, CH
CRCCH
d 0.86
(
v
3
2
)
2
2
13
2
CRC), 9.4 (1H, br s, CO
2
H); C NMR
d
10.2 (C-4), 14.1
2 4
combined organic phases were dried (Na SO ), filtered, evaporated
(
2
7
C-20), 18.6 (C-7), 22.7 (C-19), 28.5 (C-8), 28.9 (C-9), 29.1 (C-10),
9.4 (C-17), 29.5 (C-16), 29.6 (C-11), 29.7 (C-12 to 15), 31.9 (C-18),
to dryness under reduced pressure, and purified by flash
chromatography (elution with hexane/ethyl acetate/glacial acetic
acid 75/25/1) to give 2,10-nonadecadiynoic acid (416 mg, 84%): mp
0.2 (C-2), 72.0 (C-5), 82.8 (C-6), 86.1 (C-3), 157.6 (C-1). ESI–MS
304.2402, found [M ꢀ H]ꢀ 303.2347.
ꢁ
1
exact mass for C20
H
32
O
2
3
36.5–37.0 C, H NMR d 0.85 (3H, t, J = 6.6 Hz, v-CH ), 1.24 (8H, m,