Helvetica Chimica Acta Vol. 85 (2002)
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Data of (2Z)-Isomer: Orange oil. IR (film): 2950, 1680, 1600. 1H-NMR: 10.19 (d, J 8, HÀC(11)); 7.27
(d, J 16, HÀC(8)); 7.11 (d, J 16, HÀC(7)); 6.66 (s, HÀC(4)); 5.97 (d, J 8, HÀC(10)); 3.86 (s, MeO); 2.41, 2.30,
2.28, 2.16 (4s, 4 Me). 13C-NMR: 189.8 (C(11)); 156.8, 154.6, 135.9, 134.1, 128.3, 128.2, 122.8 (C(1), C(2), C(3), C(5),
C(6), C(9)); 136.3 (C(10)); 128.5, 128.3 (C(7), C(8)); 110.0 (C(4)); 55.3 (MeO); 21.4, 21.0, 17.4, 11.7 (4 Me).
2-[(1E,3E,5E,7E)-8-(4-Methoxy-2,3,6-trimethylphenyl)-2,6-dimethylocta-1,3,5,7-tetraenyl]malonic Acid
(9). To a mixture of 3 ((2E)/(2Z) 97:3, 9.82 g, 40.25 mmol) and dimethylisopropylidene malonate (10.6 g,
71.1 mmol) was added a soln. of Triton B (40% in MeOH, 42 ml) at 08. The soln. was stirred for 12 h at r.t. and
then hydrolyzed with a soln. of 10% HCl. The aq. layer was extracted with Et2O and the mono-ester extracted
with a soln. of 5% NaOH (2 Â 150 ml). The aq. layer was acidified with a soln. of 10% HCl and extracted with
Et2O. The org. layer was washed with H2O and brine, and dried (MgSO4). The mono-ester was saponified 2 h at
r.t. with a soln. of 0.75m NaOH (H2O/MeOH 60 :40, 200 ml). The soln. was acidified with 10% HCl and
extracted with Et2O. The org. layer was washed with H2O and brine, and dried (MgSO4) to give 9 (13 g, 93%,
(9E)/(9Z) 80 :20). The (9E)-isomer was easily separated by crystallization in Et2O (9 g, 65%). M.p. 1358. IR
(KBr): 3400, 2950, 1700. 1H-NMR (DMSO): 7.19 (dd, J 15, 11, HÀC(11)); 7.04 (d, J 15, HÀC(12)); 6.75,
6.72 (2d, J 16, HÀC(7), HÀC(8)); 6.37 (s, HÀC(4)); 6.34 (d, J 11, HÀC(10)); 3.75 (s, MeO); 2.50, 2.25,
2.18, 2.10, 2.08 (5s, 5 Me). 13C-NMR (DMSO): 167.6, 167.1 (CO2H); 156.0, 146.2, 140.5, 135.6, 133.3, 129.5, 126.8,
121.9 (C(1), C(2), C(3), C(5), C(6), C(9), C(13), C(14)); 137.9, 133.9 (C(7), C(8)); 131.1 (C(11)); 130.7, 128.9
(C(10), C(12)); 110.4 (C(5)); 55.6 (MeO); 21.5, 17.5, 16.0, 13.1, 12.1 (5 Me). Anal. calc. for C22H26O5: C 71.33,
H 7.07, O 21.59; found: C 71.30, H 7.10, O 21.60.
(3E,5E,7E,9E)-10-(4-Methoxy-2,3,6-trimethylphenyl)-4,8-dimethyldeca-3,5,7,9-tetraenoic acid (Acitretin;
1). A soln. of (9E)-9 (1.8 g, 5.2 mmol) and pyridine (0.84 g, 10.4 mmol) in CH2Cl2 (200 ml) was stirred for
24 h at r.t. The solvent was evaporated, and the residue was extracted with Et2O. The org. layer was washed with
a soln. of 10% HCl, H2O, brine, and dried (MgSO4). After evaporation 1 (1.4 g, 85%) was obtained. M.p.
(hexane) 228 2308. IR (KBr): 3400, 2950, 1700. 1H-NMR (DMSO): 7.08 (dd, J 15, 11, HÀC(11)); 6.72
(2d, J 16, HÀC(7), HÀC(8)); 6.44 (d, J 15, HÀC(10)); 6.26 (s d, J 11, HÀC(4), HÀC(12)); 5.80
(s, HÀC(14)); 3.75 (s, MeO); 2.50, 2.47, 2.20, 2.08, 2.06 (5s, 5 Me). 13C-NMR (DMSO): 168.1 (CO2H); 156.0,
152.0, 139.2, 135.5, 133.9, 129.5, 121.9 (C(1), C(2), C(3), C(5), C(6), C(9), C(13)); 138.0, 136.1 (C(7), C(8));
131.1, 130.8 (C(12), C(11)); 128.4 (C(10)); 120.0 (C(14)); 110.4 (C(5)); 55.6 (MeO), 21.5, 17.5, 13.8, 13.0, 12.1 (5
Me). Anal. calc. for C21H26O3: C 77.27, H 8.03, O 14.70; found: C 77.14, H 8.10; O 14.76.
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Acta 2001, 84, 3423.
Received March 21, 2002