T. Ochi et al. / Bioorg. Med. Chem. Lett. 15 (2005) 1055–1059
1059
1.53 (m, 2H, CH2), 1.63 (m, 2H, CH2), 1.76 and 2.20 (m,
2H, CH2), 2.53 (q, J = 7.0 Hz, 2H, CH2), 2.53 (m, 2H,
CH2), 2.61 (m, 4H, CH2 ), 2.83 (ddd, J = 13.3, 7.8, 3.8 Hz,
1H) and 2.66 (ddd, J = 13.3, 10.2, 3.5 Hz, 1H) (CH2), 3.58
(m, 4H, CH2), 3.58(m, 1H, CH), 6.30 (s, 1H, CH), 7.07
Acknowledgements
The authors thank Dr. Siro Kato and Dr. Hisashi Miya-
zaki for helpful discussion.
(m, 2H, CH), 7.18(m, 2H, CH) ppm;
13C NMR
References and notes
(400 MHz, CDCl3) d 11.71, 26.78, 27.68, 32.20, 36.18,
39.25, 45.05, 52.34, 52.44, 72.39, 106.01, 114.73 (d,
J = 21.5 Hz), 121.75, 129.71 (d, J = 7.5 Hz), 136.68
(d, J = 3.7 Hz), 150.30, 156.80, 158.56, 161.75 (d,
J = 245.2 Hz) ppm; MS (APCI) m/z (relative intensity):
384 ([MH+], 100).
1. Oka, M.; Hino, K. Drug. Future 1992, 17, 9–11.
2. Hino, K.; Kai, N.; Sakamoto, M.; Murata, T.; Oka, M.;
Matsumoto, J. Abstracts of Papers, MEDI 11, 200th
National Meeting of the American Chemical Society,
Washington, DC, April, 1990.
10. Optical resolution of 6 and 16 were performed at Daicel
Chemical Industries, Ltd.
3. Suzuki, K.; Hiyama, Y.; Une, T.; Fujiwara, I. Anal. Sci.
2002, 18, 1289–1290.
27
11. Spectral data, for 6a: mp 194–196 °C (EtOH); ½aꢀD
27
4. Matsuda, M.; Toda, H.; Ishiwata, A.; Mizuki, Y.; Fujii T.;
Miyazaki H. Abstracts of Papers, 140, 5th International
ISSX Meeting, Queensland, Australia, October, 1998.
5. Schreiber, S. L.; Smith, D. B. J. Org. Chem. 1989, 54,
5994–5996.
6. Ridge, D. N.; Hanifin, J. W.; Harten, L. A.; Johnson, B.
D.; Menschik, J.; Nicolau, G.; Sloboda, A. E.; Watts, D.
E. J. Med. Chem. 1979, 22, 1385–1389.
ꢁ15.1 (c 1.0, MeOH); for 6b: mp 194–196 °C (EtOH);
27
½aꢀD ꢁ28.3 (c 1.0, MeOH); for 16a: mp 170–172 °C
27
(MeOH + CH3CN); ½aꢀD +28.4 (c 1.0, MeOH); for 16b:
mp 170–172 °C (MeOH + CH3CN); ½aꢀD ꢁ28.4 (c 1.0,
MeOH); for HBr salt of 6a: mp 172–174 °C (CH3CN);
27
½aꢀD ꢁ15.1 (c 1.0, MeOH); IR (KBr) mmax 3326 cmꢁ1; H
NMR (400 MHz, CDCl3) d 1.25 (t, J = 7.3 Hz, 3H), 1.23–
1.33 (m, 1H), 1.40–1.50 (m, 1H) 1.54–1.67 (m, 3H), 1.76–
1.88 (m, 1H), 2.44–2.52 (m, 1H), 2.59 (m, 1H), 2.72–2.85
(m, 2H), 2.95–3.14 (m, 4H), 3.18(m, 2H), 3.27–3.35 (m,
1H), 3.54 (m, 2H), 4.32 (br s, 1H), 4.40 (m, 2H), 6.54 (s,
1H), 7.25–7.35 (m, 4H), 9.49 (m, 1H) ppm; MS (APCI) m/
z (relative intensity): 384 ([MH+ of free base], 100). For
1
7. Hauser, C. R.; Eby, C. J. J. Am. Chem. Soc. 1957, 79, 728–
731.
8. Spectral data for 6: 1H NMR (400 MHz, CDCl3) d 1.12 (t,
J = 7.1 Hz, 3H, CH3), 1.41 and 1.71 (m, 2H, CH2), 1.42
(br s, 1H, OH), 1.71 (m, 2H, CH2), 1.78and 1.94 (m, 2H,
CH2), 2.46 (q, J = 7.1 Hz, 2H, CH2), 2.55 (m, 4H, CH2),
2.55 (m, 1H) and 2.66 (ddd, J = 14.5, 9.9, 4.0 Hz, 1H)
(CH2), 2.85 (m, 2H, CH2), 3.53 (m, 4H, CH2), 3.56 (m, 1H,
CH), 6.29 (s, 1H, CH), 7.08(m, 2H, CH), 7.22 (m, 2H,
CH) ppm; 13C NMR (400 MHz, CDCl3) d 11.93, 23.79,
26.61, 35.58, 37.07, 40.25, 45.27, 52.33, 52.57, 72.19,
105.83, 114.77 (d, J = 21.7 Hz), 121.74, 129.72 (d,
J = 8.0 Hz), 136.66 (d, J = 3.1 Hz), 150.17, 157.09,
158.43, 161.76 (d, J = 247.1 Hz) ppm; MS (APCI) m/z
(relative intensity): 384 ([MH+], 100).
27
HBr salt of 16b: mp 271–273 °C (i-PrOH + CH3CN); ½aꢀD
+28.4 (c 1.0, MeOH); IR (KBr) mmax 3402 cmꢁ1; 1H NMR
(400 MHz, CDCl3) d 1.25 (t, J = 7.3 Hz, 3H), 1.30–
1.60 (m, 5H), 2.01 (m, 1H), 2.46–2.54 (m, 2H), 2.73
(m, 1H), 2.91 (m, 1H), 2.96–3.14 (m, 4H), 3.19 (m, 2H),
3.38(m, 1H), 3.55 (m, 2H), 4.39 (s, 1H), 4.41 (m, 2H),
6.55 (s, 1H), 7.23–7.33 (m, 4H), 9.47 (m, 1H) ppm; MS
(APCI) m/z (relative intensity): 384 ([MH+ of free base],
100).
12. Harada, N.; Watanabe, M.; Kawahara, S.; Sugio, A.;
Kasai, Y.; Ichikawa, A. Tetrahedron: Asymmetry 2000, 11,
1249–1253.
1
9. Spectral data for 16: H NMR (400 MHz, CDCl3) d 1.16
(t, J = 7.0 Hz, 3H, CH3), 1.35 (br s, 1H, OH), 1.46 and