1718 s and 1643 m; dH(400 MHz; CDCl3) 6.21 (2H, dt, J 11.6, 7.3,
2 ¥ CHCHCO2Et), 5.76 (2H, dt, J 11.6, 1.5, 2 ¥ CHCHCO2Et),
5.50–5.36 (4H, m, 2 ¥ CH2CHCHCH2), 4.17 (4H, q, J 7.0, 2 ¥
CH2CH3), 2.71 (4H, qd, J 7.3, 1.5, 2 ¥ CH2CHCHCO2Et), 2.14
(4H, q, J 7.3, 2 ¥ CH2CH2CH CHCO2Et), 2.06–2.01 (4H, m, 2 ¥
CH2), 1.29 (6H, t, J 7.2, 2 ¥ CH2CH3); dC(100 MHz; CDCl3) 166.6
(C), 149.8 (CH), 131.0 (CH), 129.4 (CH), 120.0 (CH), 59.9 (CH2),
32.7 (CH2), 32.0 (CH2), 28.9 (CH2), 14.4 (CH3); LRMS (ES+) m/z
357 ([M + Na]+); HRMS (ES+) C20H31O4+ Calcd. 335.2217, found
335.2212. Data for (2Z,6E,10E,14E)-diethyl hexadeca-2,6,10,14-
tetraenedioate: nmax (neat)/cm-1 3033 w, 2982 w, 2922 w, 2846 w,
1718 s and 1646 m; dH(400 MHz; CDCl3) 6.96 (1H, dt, J 15.8,
6.8, CHCHCO2Et), 6.21 (1H, dt, J 11.5, 7.1, EtCO2CHCH), 5.82
(1H, dt, J 15.6, 1.5, CHCHCO2Et), 5.76 (1H, dt, J 11.5, 1.5,
EtCO2CHCH), 5.50–5.36 (4H, m, 2 ¥ CHCH), 4.19 (2H, q, J
6.8, CH2CH3), 4.19 (2H, q, J 7.1, CH2CH3), 2.72 (2H, qd, J 7.1,
1.4, CH2CHCHCO2Et), 2.26 (2H, br q, J 7.0, CHCH2), 2.19–
2.11 (2H, m, CH2CH), 2.06–2.01 (4H, m, CH2CH2), 1.29 (6H, t,
J 7.2, 2 ¥ CH2CH3); dC(100 MHz; CDCl3) 166.8 (C), 166.6 (C),
149.8 (CH), 148.7 (CH), 131.1 (CH), 130.8 (CH), 129.4 (CH),
128.9 (CH), 121.7 (CH), 120.0 (CH), 60.2 (CH2), 59.9 (CH2), 32.7
(CH2), 32.6 (CH2), 32.4 (CH2), 32.0 (CH2), 31.1 (CH2), 29.0 (CH2),
14.4 (CH3); LRMS (ES+) m/z 357 ([M + Na]+); HRMS (ES+)
(60% dispersion in mineral oil, 0.418 g, 10.4 mmol) [CAUTION:
evolution of H2 gas] and the mixture warmed to rt over 30 min.
The mixture was cooled to -10 ◦C and crude acid chloride (1.40 g)
in toluene (40 mL) was added dropwise. The mixture was stirred
for 45 min at -10 ◦C then warmed to rt over 45 min. The mixture
◦
was cooled to 0 C before H2O (50 mL) and Et2O (50 mL) were
added. The organic layer was separated and the aqueous layer was
extracted with Et2O (2 ¥ 50 mL). The combined organic phases
were dried (MgSO4) and concentrated in vacuo to give a yellow
oil (3.00 g). Purification on SiO2 (5 ¥ 15 cm) eluting with EtOAc–
hexane (1 : 4) afforded a white foam (2.12 g, 3.16 mmol, 68%). [a]D25
-72.1 (c 0.75 in CHCl3); nmax (neat)/cm-1 2959 m, 2915 m, 2844 w,
1680 s and 1630 m; dH(400 MHz; CDCl3) 6.45 (2H, dt, J 11.5, 1.5,
2 ¥ CHCHC(O)), 6.32 (2H, dt, J 11.5, 7.1, 2 ¥ CHCHC(O)), 5.50–
5.36 (4H, m, 2 ¥ CHCH), 3.93 (2H, dd, J 7.3, 5.3, 2 ¥ CHN), 3.50
(2H, d, J 13.8, 2 ¥ CHHSO2), 3.43 (2H, d, J 13.8, 2 ¥ CHHSO2),
2.68 (4H, qd, J 7.3, 1.5, 2 ¥ CH2CHCHC(O)), 2.20–2.06 (8H, m,
2 ¥ CHCH2 and 2 ¥ CH2CHN), 2.05–2.00 (4H, m, CH2CH2),
1.98–1.84 (6H, m, 2 ¥ CHCH2CHN and 2 ¥ CH2CHCH2CHN),
1.47–1.32 (4H, m, 2 ¥ CH2CCHN), 1.18 (6H, s, 2 ¥ CH3C), 0.98
(6H, s, 2 ¥ CCH3); dC(100 MHz; CDCl3) 164.3 (C), 151.8 (CH),
131.0 (CH), 129.2 (CH), 119.5 (CH), 65.2 (CH), 53.3 (CH2), 48.5
(C), 47.9 (C), 44.9 (CH), 38.8 (CH2), 33.0 (CH2), 32.7 (CH2), 31.9
(CH2), 29.9 (CH2), 26.7 (CH2), 21.0 (CH3), 20.0 (CH3); LRMS
(ES+) m/z 695 [M + Na]+; HRMS (ES+) C36H52N2O6S2Na+ Calcd.
695.3159, found 695.3144.
+
C20H31O4 Calcd. 335.2217, found 335.2212.
(2Z,6E,10E,14Z)-Hexadeca-2,6,10,14-tetraenedioic acid (10)
To a stirred solution of (2Z,6E,10E,14Z)-dimethyl hexadeca-
2,6,10,14-tetraenedioate (9, 1.10 g, 3.60 mmol) in MeOH (11 mL)
and H2O (33 mL) were added NaOH (1.53 g, 38.2 mmol) a◦nd
NaHCO3 (0.300 g, 3.60 mmol) and the mixture heated at 95 C
for 3 h. The mixture was cooled to rt and washed with CH2Cl2 (3 ¥
20 mL). The aqueous phase was separated, cooled to 0 ◦C and
acidified with aqueous citric acid (30 mL) and 2 M HCl (50 mL)
to pH 1. The mixture was stirred for 30 min before Et2O (100 mL)
was added. The organic layer was separated and the aqueous
layer was extracted with Et2O (2 ¥ 50 mL). The combined organic
phases were dried (MgSO4) and concentrated in vacuo to give a
pale yellow oil (0.92 g, 3.31 mmol, 92%). nmax (neat)/cm-1 2980 m,
2915 br, 2846 m, 1692 s and 1639 m; dH(400 MHz; CDCl3) 6.35
(2H, dt, J 11.6, 7.4, 2 ¥ CHCHCO2H), 5.81 (2H, dt, J 11.6, 1.8,
2 ¥ CHCHCO2H), 5.51–5.37 (4H, m, 2 ¥ CHCH), 2.73 (4H, qd, J
7.4, 1.5, 2 ¥ CH2CHCHCO2H), 2.15 (4H, q, J 7.3, 2 ¥ CHCH2),
2.09–2.03 (4H, m, CH2CH2); dC(100 MHz; CDCl3) 172.2 (C),
152.7 (CH), 131.0 (CH), 129.3 (CH), 119.5 (CH), 32.6 (CH2),
31.9 (CH2), 29.2 (CH2); LRMS (ES-) m/z 391 [M + (CF3CO2)]-;
Oxidative cyclisation products ent-4 and 13
To a stirred solution of the tetraene ent-6 (337 mg, 0.50 mmol),
AcOH (4 mL) and acetone (6 mL) at -30 ◦C was added KMnO4
(222 mg, 1.40 mmol) in one portion and the mixture warmed to
-20 ◦C over 25 min, during which time the mixture changed from
purple to dark brown. A saturated aqueous solution of Na2S2O5
(20 mL) was added to reduce the precipitated brown MnO2,
and the mixture stirred until clear. Brine (10 mL) and EtOAc
(20 mL) were added, the organic layer was separated and the
aqueous layer was extracted with EtOAc (2 ¥ 20 mL) and CH2Cl2
(20 mL). The combined organic phases were dried (MgSO4) and
concentrated in vacuo to give a yellow oil (180 mg). Purification
on SiO2 (2 ¥ 15 cm) eluting with MeOH–CH2Cl2 (1 : 49→3 : 47)
afforded an inseparable mixture of the title diastereoisomers ent-
4/13 (dr ~ 3 : 1) as a white foam (108 mg, 0.140 mmol, 28%).
Physical and spectroscopic data were recorded from the mixture
of diastereoisomers. [a]2D5 -41.0 (c 0.75 in CHCl3); nmax (neat)/cm-1
3455 w, 2961 m, 2884 m and 1690 m; dH(400 MHz; CDCl3)
4.61–4.52 (4H, m, 2 ¥ C(O)CHOH and 2 ¥ C(O)CHOHCH),
3.97 (2H, dd, J 5.2, 7.7, 2 ¥ CHN), 3.88 (2H, td, J 6.8, 4.8,
2 ¥ OCHCHOHCH2), 3.55–3.41 (6H, m, 2 ¥ CH2SO2 and 2 ¥
CHOHCH2), 2.28–2.19 (2H, m, CHHCHN), 2.14–2.01 (6H, m,
CHHCHN and CH2 THF), 1.99–1.83 (10H, m, 2 ¥ CHCH2CHN,
2 ¥ CH2CHCH2CHN and CH2 THF), 1.68 (4H, br, CH2CH2),
1.47–1.31 (4H, m, 2 ¥ CH2CCHN), 1.16 (6H, s, 2 ¥ CH3), 0.97
(6H, s, 2 ¥ CH3); dC(100 MHz; CDCl3) 172.0 (C), 83.4 (CH), 78.9
(CH), 74.0 (CH), 73.7 (CH), 66.0 (CH), 53.2 (CH2), 49.1 (C), 48.0
(C), 44.8 (CH), 38.4 (CH2), 33.1 (CH2), 28.3 (CH2), 26.5 (CH2),
21.1 (CH3), 20.0 (CH3); LRMS (ES+) m/z 795 [M + Na]+; HRMS
(ES+) C36H56N2O12S2Na+ Calcd. 795.3166, found 795.3147.
HRMS (ES-) C16H21O4 Calcd. 277.1445, found 277.1439.
-
1,16-(1S,2R)-N-[(2Z,6E,10E,14Z)-16-Oxo-2,6,10,14-
hexadecatetraenoyl]-di-camphor-10,2-sultam (5)
To a stirred solution of (2Z,6E,10E,14Z)-hexadeca-2,6,10,14-
tetraenedioic acid (10, 1.29 g, 4.64 mmol) and (COCl)2 (0.81 mL,
9.28 mmol) at 0 ◦C in CH2Cl2 (15 mL) was added DMF (0.05 mL)
and the mixture allowed to warm to rt over 3 h. The mixture was
concentrated in vacuo to give the crude acid chloride (1.40 g) as an
orange oil, which was used without further purification. Under an
atmosphere of N2, to a stirred solution of (1S,2R)-camphorsultam
(0.243 g, 1.13 mmol) in toluene (50 mL) at 0 ◦C was added NaH
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The Royal Society of Chemistry 2009
Org. Biomol. Chem., 2009, 7, 1017–1024 | 1021
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