Total Synthesis
FULL PAPER
(q, 3J=7.6 Hz, 2H, CH2; H(3)), 1.23 (q, 3J=7.5 Hz, 2H, CH2; H(5)),
1.14–1.09 ppm (m, 2H, CH2; H(4)); 13C NMR (75 MHz, CDCl3): d=
209.3 (Cquat), 132.2 (+), 130.7 (+), 129.3 (+), 127.1 (+), 125.6 (+), 124.4
(+), 43.7 (À), 30.6 (À), 29.9 (+), 29.4 (À), 28.8 (À), 27.0 (À), 23.7 (À),
13.3 ppm (+); IR (neat): n˜ =3014, 2932, 2856, 1716, 1358 cmÀ1; CI-MS
(NH3): m/z (%): 238 (100) [M+NH4+].
(+), 128.0 (+), 43.8 (À), 34.7 (À), 30.5 (À), 29.9 (+), 29.4 (À), 28.8 (À),
26.9 (À), 23.7 (À), 22.7 (À), 13.7 ppm (+); IR (neat): n˜ =2936, 2867,
1711, 631 cmÀ1; CI-MS (NH3): m/z (%): 240 (100) [M+NH4+].
Trimethyl((Z)-9-(2-methyl-1,3-dioxolan-2-yl)non-3-en-1-ynyl)silane (37):
To
a
dry flask 10 (0.23 g, 0.74 mmol), [PdCl2ACTHNGUTREN(NUG PPh3)2] (10 mg,
0.032 mmol), CuI (5 mg, 0.026 mmol), and NEt3 (3 mL) was added under
an inert atmosphere. To the cloudy yellow solution TMS-acetylene
(0.10 g, 1.03 mmol) was added. The reaction was stirred at RT for 4 h,
quenched with water (15 mL), extracted with ether (4ꢃ15 mL), washed
with brine and purified by flash chromatography to afford 0.15 g (71%)
of product. Rf =0.40 (petroleum ether/EtOAc 9:1); 1H NMR (300 MHz,
CDCl3): d=5.99–5.90 (m, 1H), 5.48 (dt, 4J=1.4, 3J=10.8 Hz, 1H), 3.97–
3.91 (m, 4H; OCH2), 2.37–2.27 (m, 2H; CH2), 1.68–1.61 (m, 2H; CH2),
1.47–1.35 (m, 6H; CH2), 1.32 (s, 3H; CH3), 0.20 ppm (s, 9H; SiMe3);
13C NMR (75 MHz, CDCl3): d=145.5, 110.1, 109.1, 102.8, 102.1, 64.6,
39.1, 30.2, 29.4, 28.7, 23.9, 23.7, 0 ppm; IR (neat): n˜ =2941, 2878,
2146 cmÀ1; HRMS (PI-EI): m/z: calcd for C16H28O2Si: 280.1859, found:
280.1855 [M]+.
2-Methyl-2-((6Z,9Z,11E)-trideca-6,9,11-trienyl)-1,3-dioxolane (32): The
compound was prepared following general procedure D and isolated as
colourless oil. Yield: 71 mg, 21%. Rf =0.27 (petroleum ether/EtOAc
1
24:1); H NMR (300 MHz, CDCl3): d=6.03–5.28– (m, 6H), 3.94–3.84 (m,
4H; OCH2), 2.88–2.73 (m, 2H; CH2), 2.00 (quint, 3J=6.0 Hz, 2H; CH2),
1.69 (d, 3J=6.6 Hz, 3H; CH3), 1.62–1.57 (m, 2H; CH2), 1.40–1.29 (m,
6H; CH2), 1.27 ppm (s, 3H; CH3); 13C NMR (75 MHz, CDCl3): d=131.5
(+), 130.8 (+), 130.5 (+), 129.9 (+), 127.2 (+), 127.1 (+), 110.2 (Cquat),
64.6 (À), 39.2 (À), 30.3 (À), 29.6 (À), 29.5 (À), 27.1 (À), 24.0 (À), 23.7
(+),18.0 ppm (+); CI-MS (NH3): m/z (%): 187 (100) [(C11H22O2)H+],
204 (61) [(C11H22O2)NH4+].
(8Z,11Z,13E)-Pentadeca-8,11,13-trien-2-one (5): The compound was pre-
pared following general procedure E and isolated as colourless oil in
quantitative yield (39 mg). Rf =0.47 (petroleum ether/EtOAc 4:1);
1H NMR (300 MHz, CDCl3): d=6.07–5.33 (m, 6H), 2.92–2.77 (m, 2H;
CH2), 2.41 (t, 3J=7.7 Hz, 2H; CH2), 2.13 (s, 3H; CH3), 2.04 (quint, 3J=
6.3 Hz, 2H; CH2), 1.73 (d, 3J=6.9 Hz, 3H; CH3), 1.62–1.52 (m, 2H;
CH2), 1.41–1.25 ppm (m, 4H; CH2); 13C NMR (75 MHz, CDCl3): d=
209.3 (Cquat), 131.5 (+), 130.6 (+), 130.5 (+), 129.8 (+), 127.3 (+), 127.2
(+), 43.7 (À), 30.3 (À), 29.9 (+), 29.4 (À), 28.8 (À), 26.9 (À), 23.7 (À),
18.1 ppm (+); IR (neat): n˜ =3013, 2927, 2855, 1716, 1359 cmÀ1; CI-MS
(NH3): m/z (%): 238 (100) [M+NH4+], 221 (4) [M+H+].
(Z)-Undec-8-en-10-yn-2-one (40): The compound was prepared following
general procedure E and isolated as colourless oil in 83% yield (23 mg).
1H NMR (300 MHz, CDCl3): d=6.03–5.93 (m, 1H), 5.48–5.41 (m, 1H),
4
3
3.07 (d, J=1.9 Hz, 1H), 2.43 (t, J=7.3 Hz, 2H; CH2), 2.36–2.30 (m, 2H;
CH2), 2.13 (s, 3H; CH3), 1.65–1.54 (m, 2H; CH2), 1.46–1.28 ppm (m, 4H;
CH2); 13C NMR (75 MHz, CDCl3): d=209.2, 145.8, 108.3, 81.3, 80.5, 43.7,
30.0, 29.9, 28.6, 28.5, 23.6 ppm; IR (neat): n˜ =3290, 3263, 2934, 2858,
2151, 2022, 1712 cmÀ1; HRMS (PI-EI): m/z: calcd for C11H15O: 163.1123,
found: 163.1123 [M+H+].
(Z)-11-Phenylundec-8-en-10-yn-2-one (39): The compound was prepared
following general procedure E and isolated as colourless oil in 80% yield
(30 mg). 1H NMR (300 MHz, CDCl3): d=7.45–7.41 (m, 2H), 7.34–7.28
(m, 3H), 5.71–5.65 (m, 1H), 6.10–5.91 (m, 1H), 2.46–2.38 (m, 4H; CH2),
2.11 (s, 3H; CH3), 1.67–1.30 ppm (m, 6H; CH2); 13C NMR (75 MHz,
CDCl3): d=209.2, 143.9, 131.4, 128.3, 128.1, 109.3, 86.4, 43.7, 30.2, 29.9,
28.7, 28.6, 23.7 ppm; IR (neat): n˜ =3019, 2929, 2855, 2197 cmÀ1; HRMS
(PI-EI): m/z: calcd for C17H20O: 240.1514, found: 240.1517 [M]+.
2-Methyl-2-((6Z,9Z)-pentadeca-6,9-dienyl)-1,3-dioxolane (35): The com-
pound was prepared following general procedure D and isolated as col-
ourless oil. Yield: 56 mg, 20%. Rf =0.42 (petroleum ether/EtOAc 9:1);
1H NMR (300 MHz, CDCl3): d=5.50–5.34 (m, 4H; CH), 4.00–3.90 (m,
4H; OCH2), 2.74 (t, 3J=5.5 Hz, 2H; CH2), 2.08–1.96 (m, 4H; CH2),
1.67–1.60 (m, 2H; CH2), 1.46–1.28 (m, 15H; CH2/CH3), 0.90 ppm (t, 3J=
7.0 Hz, 3H; CH3); 13C NMR (75 MHz, CDCl3): d=130.9 (+), 130.3 (+),
128.3 (+), 127.9 (+), 110.2 (Cquat), 64.6 (À), 39.2 (À), 32.6 (À), 31.4 (À),
30.5 (À), 29.6 (À), 29.5 (À), 29.2 (À), 27.1 (À), 24.0 (À), 23.7 (+), 22.6
(À), 14.1 ppm (+); IR (neat): n˜ =2925, 2855, 1376, 1067 cmÀ1; CI-MS
(NH3): m/z (%): 295 (100) [M+H+], 312 (16) [M+NH4+].
(Z)-9-Phenylnon-8-en-2-one (42): The compound was prepared following
general procedure E and isolated as colourless oil in 96% yield (23 mg).
1H NMR (300 MHz, CDCl3): d=7.32–7.13 (m, 5H), 6.36 (m, 1H), 5.59
(m, 1H), 2.36 (t, 3J=7.4 Hz, 2H; CH2), 2.34–2.22 (m, 2H; CH2), 2.07 (s,
3H; CH3), 1.46–1.16 ppm (m, 6H; CH2); 13C NMR (75 MHz, CDCl3): d=
209.2, 137.7, 132.8, 128.9, 128.7, 128.1, 126.5, 43.7, 29.9, 29.7, 28.8, 28.4,
23.7 ppm; IR (neat): n˜ =3006, 2929, 2855, 2206, 2006 cmÀ1; HRMS (PI-
EI): m/z: calcd for C15H20O: 216.1514, found: 216.1513 [M]+.
ACHTUNGTRENNUNG(8Z,11Z)-Heptadeca-8,11-dien-2-one (8): The compound was prepared
following general procedure E and isolated as colourless oil in quantita-
tive yield (36 mg). Rf =0.20 (petroleum ether/EtOAc 19:1); 1H NMR
(300 MHz, CDCl3): d=5.50–5.33 (m, 4H; CH), 2.74 (t, 3J=5.6 Hz, 2H;
3
CH2), 2.44 (t, J=7.5 Hz, 2H; CH2), 2.15 (s, 3H, CH3), 2.09–1.96 (m, 4H,
(6Z,9Z,12Z,15Z)-Henicosa-6,9,12,15-tetraen-2-one (44): Arachidonic acid
43 (0.25 g, 0.8 mmol) was dissolved in dry THF (2 mL). MeLi (1.6m in
Et2O, 2.1 mL, 3.3 mmol) was added at 08C resulting in a dark red solu-
tion. After 2 h, freshly distilled TMSCl (0.6 mL, 4.8 mmol) was added
and the mixture was allowed to warm to RT. The resulting colourless so-
lution was treated with 2m HCl (2 mL), diluted with Et2O, washed with
water and brine, dried (MgSO4) and concentrated. Purification by flash
chromatography on silica gel gave 44 as colourless oil (150 mg, 62%).
Rf =0.40 (hexane/Et2O 4:1); 1H NMR (300 MHz, CDCl3): d=5.44–5.28
(m, 8H), 2.85–2.78 (m, 6H; CH2), 2.43 (t, 3J=7.9 Hz, 2H; CH2), 2.13 (s,
3H; CH3), 2.11–2.02 (m, 4H; CH2), 1.64 (quint, 3J=7.8 Hz, 2H; CH2),
1.39–1.25 (m, 6H; CH2), 0.88 ppm (t, 3J=6.7 Hz, 3H; CH3); 13C NMR
(75 MHz, CDCl3): d=208.9, 130.5, 129.2, 128.8, 128.6, 128.2, 128.2, 127.9,
127.5, 43.0, 31.5, 29.9, 29.3, 27.2, 26.5, 25.7, 23.6, 22.6, 14.1 ppm; IR
(neat): n˜ =3011, 2925, 2857, 1715, 631 cmÀ1; CI-MS (NH3): m/z (%): 320
(100) [M+NH4+].
3
CH2), 1.65–1.55 (m, 2H, CH2), 1.44–1.26 (m, 10H, CH2), 0.90 ppm (t, J=
6.7 Hz, 3H; CH3); 13C NMR (75 MHz, CDCl3): d=209.2 (Cquat), 130.9
(+), 130.1 (+), 128.2 (+), 128.0 (+), 43.8 (À), 32.5 (À), 31.4 (À), 30.5
(À), 29.9 (+), 29.4 (À), 29.2 (À), 28.8 (À), 26.9 (À), 23.7 (À), 22.6 (À),
14.1 ppm (+); IR (neat): n˜ =3008, 2925, 2855, 1717 cmÀ1; HRMS (PI-EI):
m/z: calcd for C17H30O: 250.2297, found: 250.2295 [M]+.
2-Methyl-2-((6Z,9Z)-trideca-6,9-dienyl)-1,3-dioxolane (34): The com-
pound was prepared following general procedure D and isolated as col-
ourless oil (116 mg, 26%). Rf =0.31 (pentane/Et2O 9:1); 1H NMR
(300 MHz, CDCl3): d=5.42–5.32 (m, 4H), 3.98–3.88 (m, 4H; OCH2),
3
2.72 (t, J=5.2 Hz, 2H; CH2), 2.09–1.98 (m, 4H; CH2), 1.65–1.60 (m, 2H;
CH2), 1.42–1.25 (m, 11H), 0.88 ppm (t, 3J=8.0 Hz, 3H; CH3); 13C NMR
(75 MHz, CDCl3): d=130.6 (+), 130.3 (+), 128.5 (+), 127.9 (+), 110.2
(Cquat), 64.6 (À), 39.2 (À), 34.7 (À), 30.5 (À), 29.6 (À), 29.5 (À), 27.1 (À),
24.0 (À), 23.7 (+), 22.7 (À), 13.7 ppm (+); IR (neat): n˜ =2933, 2873,
1069, 627 cmÀ1; CI-MS (NH3): m/z (%): 267 (100) [M+H+], 284 (13)
[M+NH4+].
Pharmacological materials: GTP, ATP, adenylyl imidodiphosphate, crea-
tine kinase, creatine phosphate, bovine serum albumin and salts (highest
purity available) were purchased either from Roche (Mannheim, Germa-
ny) or Sigma (St. Louis, MO, USA). Dimethyl sulfoxide was from Merck
(Darmstadt, Germany). Tris base was purchased from USB (Cleveland,
OH, USA). The cannabinoid receptor ligands 2-arachidonyl glycerol and
anandamide were purchased from Tocris Cookson (Ballwin, MO, USA).
[g-32P]GTP was synthesized through enzymatic phosphorylation of GDP
and [32P]orthophosphoric acid (8000 CimmolÀ1, Perkin–Elmer Life Scien-
ACHTUNGTRENNUNG
E
3
3
5.39–5.29 (m, 4H), 2.68 (t, J=5.5 Hz, 2H; CH2), 2.38 (t, J=8.0 Hz, 2H;
CH2), 2.09 (s, 3H; CH3), 2.03–1.89 (m, 4H; CH2), 1.59–1.49 (m, 2H;
CH2), 1.40–1.22(m, 6H; CH2), 0.84 ppm (t, 3J=8.0 Hz, 3H; CH3);
13C NMR (75 MHz, CDCl3): d=209.3 (Cquat), 130.6 (+), 130.1 (+), 128.4
Chem. Eur. J. 2008, 14, 10978 – 10984
ꢂ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
10983