114
Vol. 56, No. 1
solution was added a solution of the aldehyde 10 (90 mg, 0.40 mmol) in THF
the same manner as described for the preparation of 14 in 75% yield (16 mg)
(5 ml), the reaction mixture was stirred for an additional 2 h. The reaction as pale yellow oil. UV lmax (EtOH) nm: 254, 392. IR (CHCl3) cmꢀ1: 3013,
was quenched with saturated aqueous ammonium chloride, and then ex-
2961, 2862, 1955, 1604. 1H-NMR (C6D6): 1.02 (6H, s, Meꢂ2), 1.68 (3H, br,
tracted with ether, followed by standard workup. The residue was purified by Me), 1.71 (3H, br, Me), 1.76 (3H, s, Me), 1.98 (2H, dd, Jꢁ4.5, 2 Hz, CH2),
column chromatography on silica gel (ether : hexaneꢁ1 : 4) to afford the ni- 5.55 (1H, d, Jꢁ12 Hz, ꢁCH), 5.62—5.65 (1H, m, ꢁCH), 5.80 (1H, dt,
trile 13 (65 mg, 56%). The spectral data of this compound were identical
Jꢁ9.5, 2 Hz, ꢁCH), 6.06 (1H, d, Jꢁ8 Hz, ꢁCH–CO), 6.28 (2H, br, ꢁCH),
6.33 (1H, t, Jꢁ12 Hz, ꢁCH), 6.55 (1H, d, Jꢁ12 Hz, ꢁCH), 9.87 (1H, d,
with those of the literature.21) 1H-NMR (CDCl3) d: 1.04 (6H, s, Meꢂ2), 1.86
(3H, s, Me), 2.07 (3H, s, Me), 2.08 (2H, d, Jꢁ4.5 Hz, CH2), 2.21 (3H, s, Jꢁ8 Hz, CHO). 13C-NMR (C6D6): 12.13, 14.36, 20.31, 26.85, 31.91, 40.03,
Me), 5.18 (1H, s, ꢁCH), 5.7—5.8 (1H, m, ꢁCH), 5.85 (1H, d, Jꢁ9.5 Hz,
125.56, 126.93, 130.17, 130.54, 130.63, 131.26, 138.51, 140.71, 153.97,
ꢁCH), 6.14 (1H, d, Jꢁ11 Hz, ꢁCH), 6.27 (1H, d, Jꢁ15.5 Hz, ꢁCH), 6.29 189.73. HR-MS m/z: 282.1998 (Calcd for C20H26O: 282.1982).
(1H, d, Jꢁ15.5 Hz, ꢁCH), 6.32 (1H, d, Jꢁ15.5 Hz, ꢁCH), 6.95 (1H, dd,
Jꢁ15, 11 Hz, ꢁCH). 13C-NMR (CDCl3) d: 12.81, 16.59, 20.27, 26.71,
Acknowledgements This work was supported in part by a grant from
33.94, 39.82, 96.55, 117.96, 125.54, 127.68, 128.38, 129.26, 129.79, the Second Project for Advanced Research and Technology by Kobe Phar-
131.44, 132.37, 136.33, 138.13, 141.14, 156.85. maceutical University, a grant from the Research on Toxicogenomics, Health
(2E,4E,6E,8E)-3,7-Dimethyl-9-(2,6,6-trimethyl-1,3-cyclohexadien-1- and Labour Sciences Research Grants from the Ministry of Health, Labour
yl)-2,4,6,8-nonatetraenal (14) To a solution of the nitrile 13 (23 mg,
0.082 mmol) in dry hexane (5 ml) was added DIBAL-H (1 M solution in
hexane, 0.12 ml, 0.12 mmol) at ꢀ78 °C. The resulting mixture was stirred
1.5 h. Subsequently, homogenous silica gel (1 g, water/silica 1 : 5) was added
and stirring was continued for 30 min. The solids were filter through Celite
and washed with diethyl ether. The filtrate was dried over Na2SO4. The or-
ganic solvent was evaporated and the residue was purified by flash chro-
matography (ether : hexaneꢁ1 : 15) to give the all-E-3,4-didehydroretinal 14
(16 mg, 68%). The spectral data of this compound were identical with those
of the literature.21) 1H-NMR (CDCl3) d: 1.04 (6H, s, Meꢂ2), 1.87 (3H, s,
Me), 2.03 (3H, s, Me), 2.09 (2H, d, Jꢁ4.5 Hz, CH2), 2.32 (3H, s, Me), 5.7—
5.8 (1H, m, ꢁCH), 5.85 (1H, d, Jꢁ9.5 Hz, ꢁCH), 5.97 (1H, d, Jꢁ8 Hz,
ꢁCH), 6.21 (1H, d, Jꢁ11 Hz, ꢁCH), 6.32 (2H, br s, ꢁCHꢂ2), 6.38 (1H, d,
Jꢁ15 Hz, ꢁCH), 7.16 (1H, dd, Jꢁ15, 11 Hz, ꢁCH), 10.10 (1H, d, Jꢁ8 Hz,
CHO). 13C-NMR (CDCl3) d: 12.85, 13.06, 20.29, 26.71, 33.95, 39.03,
125.55, 127.75, 128.44, 129.03, 129.82, 129.86, 132.38, 134.71, 136.41,
138.15, 141.07, 154.67, 191.05.
(2E,4Z,6E,8E)-3,7-Dimethyl-9-(2,6,6-trimethyl-1,3-cyclohexadien-1-
yl)-2,4,6,8-nonatetraenenitrile (12) To a stirred solution of diphenyl
phosphonate (11) (46 mg, 0.15 mmol) and 18-crown-6 (37 mg, 0.14 mmol)
in THF (3 ml) was added dropwise KN(TMS)2 (0.5 M solution in toluene,
0.28 ml, 0.14 mmol) at ꢀ78 °C, and the mixture was stirred for 1 h at
ꢀ78 °C. To this solution was added a solution of the aldehyde 10 (30 mg,
0.148 mmol) in THF (4 ml). After stirring for 2 h at ꢀ78 °C, the resulting
mixture was quenched with water (5 ml) and then extracted with ether, fol-
and Welfare, Japan.
References and Notes
1) Retinoid and related compounds. Part 29. See part 28. Wada A., Ieki
Y., Nakamura S., Ito M., Synthesis, 2005, 1581—1588.
2) Sarri J. C., “The Retinoids”, 2nd ed., ed. by Sporn M. B., Roberts A.
B., Goodman D. S., Raven Press, New York, 1994, pp. 351—385.
3) Watson S., Arkinstall S., “The G-Protein Linked Receptor Facts
Book,” Academic Press, London, 1994.
4) Tang L., Ebrey T. G., Subramaniam S., Isr. J. Chem., 35, 193—209
(1995).
5) Pogozheva I. R., Lomize A. L., Mosberg H. I., Biophys. J., 1997,
1963—1985.
6) Zechmeister L., “cis–trans Isomeric Carotenoids, Vitamins A and
Arylpolyenes,” Springer Verlag, Vienna, 1962.
7) Isler O., “Carotenoids,” Birkhäuser Verlag, Basel, 1971.
8) Schwieter U., Saucy G., Montavon M., Planta C. V., Ruegg R., Isler O.,
Helv. Chim. Acta, 45, 517—528 (1962).
9) Mead D., Asato A. E., Denny M., Liu R. S. H., Hanzawa Y., Taguchi
T., Yamada A., Kobayashi N., Hosoda A., Tetrahedron Lett., 28, 259—
262 (1987).
10) Negishi E.-I., Owczarczyk Z., Tetrahedron Lett., 32, 6683—6689
(1991).
11) Borhan B., Souto M. L., Um J. M., Zhou B., Nakanishi K., Chem. Eur.
J., 1999, 1172—1175.
lowed by standard workup. The residue was purified by column chromatog- 12) Uenishi J., Kawahama R., Yonemitsu O., Wada A., Ito M., Angew.
raphy on silica gel (ether : hexaneꢁ1 : 25) to give the nitrile 12 (23 mg, 58%) Chem., Int. Ed., 37, 320—323 (1998).
and all-E-isomer 13 (12 mg, 29%). The latter is identical with the sample 13) Wada A., Fujioka N., Tanaka Y., Ito M., J. Org. Chem., 65, 2438—
obtained before.
2443 (2000).
11Z-isomer 12: UV lmax (hexane) nm: 351. IR (CHCl3) cmꢀ1: 3012, 14) Wada A., Babu G., Shimomoto S., Ito M., Synlett, 2001, 1759—1762.
2959, 2924, 2208, 1578. 1H-NMR (C6D6): 1.02 (6H, br, Meꢂ2), 1.66 (3H, s, 15) Wada A., Fukunaga K., Ito M., Mizuguchi Y., Nakagawa K., Okano T.,
Me), 1.73 (3H, s, Me), 1.77 (3H, s, Me), 1.98 (2H, d, Jꢁ4.5 Hz, CH2), 4.72
Bioorg. Med. Chem., 12, 3931—3942 (2004).
(1H, s, ꢁCH–CN), 5.33 (1H, d, Jꢁ11 Hz, ꢁCH), 5.64 (1H, dt, Jꢁ9.5, 16) Findley J. A., Mackay M. D., Can. J. Chem., 49, 2369—2371 (1971).
4.5 Hz, ꢁCH), 5.82 (1H, d, Jꢁ9.5 Hz, ꢁCH), 6.22 (1H, dd, Jꢁ12.5, 11 Hz, 17) Yamano Y., Tode C., Ito M., J. Chem. Soc., Perkin Trans. I, 1998,
ꢁCH), 6.23 (2H, s, ꢁCHꢂ2), 6.45 (1H, d, Jꢁ12.5 Hz). 13C-NMR (C6D6):
11.79, 20.03, 20.64, 26.54, 33.86, 39.72, 99.19, 117.21, 125.34, 125.90,
128.19, 129.80, 130.09, 137.07, 138.18, 140.70, 156.46. HR-MS m/z:
279.1983 (Calcd for C20H25N: 279.1985).
(2E,4Z,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethyl-1,3-cyclohexdien-1-yl)-
2,4,6,8-nonatetraenal (2) This was prepared from the nitrile 12 (21 mg,
0.0752 mmol) and DIBAL-H (1 M solution in hexane, 0.12 ml, 0.12 mmol) in
2569—2581.
18) Clark Still W., Gennari C., Tetrahedron Lett., 24, 4405—4408 (1983).
19) Ando K., J. Org. Chem., 62, 1934—1939 (1997).
20) Wang Y., Woo W. S., van der Hoef I., Lugtenburg J., Eur. J. Org.
Chem., 2004, 2166—2175.
21) van Wijk A. A. C., van de Weerd M. B., Lugtenburg J., Eur. J. Org.
Chem., 2003, 863—868.