D. Hasegawa et al. / Tetrahedron Letters 43 (2002) 7185–7187
7187
Scheme 3. Reagents and conditions: (i) LDA, methyl acetate, THF, −78°C; (ii) LDA, methyl acetate, THF, −78°C, then TBSCl,
HMPA, (iii) THF, H2O, rt; (iv) Me2SO4, tert-BuOK, HMPA, rt; (v) Et3N(HF)3, CH2Cl2, rt; (vi) PCC, NaOAc, MS3A, CH2Cl2,
rt; (vii) KHMDS, benzyltributylphosphoniumbromide, toluene, 0°C.
appropriate lactones. Further investigations on the
structure–activity relationships of b-substituted MOAs
and development of a novel pharmacologically superior
analogue are now in progress (Scheme 3).
H.; Nagasawa, K.; Aiba, Y.; Kobayashi, S. Tetrahedron
Lett. 2000, 41, 4165–4168; (b) Uchiro, H.; Nagasawa, K.;
Aiba, Y.; Kotake, T.; Hasegawa, D.; Kobayashi, S. Tet-
rahedron Lett. 2001, 42, 4531–4534; (c) Aiba, Y.;
Hasegawa, D.; Marunouchi, T.; Nagasawa, K.; Uchiro,
H.; Kobayashi, S. Bioorg. Med. Chem. Lett. 2001, 11,
2783–2786; (d) Uchiro, H.; Nagasawa, K.; Kotake, T.;
Sawa, T.; Hasegawa, D.; Kobayashi, S. Bioorg. Med.
Chem. Lett. 2002, in press.
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11. Physical data of synthesized (+)-8 and (−)-8; 1H NMR (l,
400 MHz, CDCl3) 0.89 (dt, 1H, J=3.4, 4.6 Hz) 1.28
(ddd, 1H, J=4.9, 7.6, 9.0 Hz) 2.08 (m, 1H) 2.24 (m, 1H)
4.24 (d, 1H, J=9.3 Hz) 4.36 (dd, 1H, J=4.8, 9.3 Hz) 13C
NMR (l, 100.4 MHz, CDCl3) 12.3, 17.4, 17.6, 69.5,
176.5; [h]2D4=+67.8 (+)-8 (c 1.20, CHCl3), [h]2D7=−68.0
(−)-8 (c 2.50, CHCl3); HRMS calcd for C5H6O2 (M+)
98.0368, found 98.0383.
12. Tamura, R.; Saegusa, K.; Kakihana, M.; Oda, D. J. Org.
Chem. 1988, 53, 2723–2728.
13. Physical data of synthesized (+)-7 and (−)-7; 1H NMR (l,
500 MHz, CDCl3) 1.22 (dt, 1H, J=4.9, 8.2 Hz) 1.44 (dt,
1H, J=4.9, 6.4 Hz) 2.17 (ddt, 1H, J=6.4, 8.9, 9.2 Hz)
3.40 (dt, 1H, J=6.7, 8.6 Hz) 3.65 (s, 3H) 3.67 (s, 3H) 5.13
(s, 1H) 5.95 (dd, 1H, J=9.2, 15.6 Hz) 6.53 (d, 1H,
J=15.6 Hz) 7.15–7.34 (m, 5H); 13C NMR (l, 125.6 MHz,
CDCl3) 12.6, 21.0, 25.0, 50.7, 55.2, 92.0, 125.7, 126.7,
128.5, 128.7, 130.7, 137.7, 168.4, 173.0; [h]2D4=+683 (+)-7
(c 0.040, CHCl3), [h]D24=−639 (−)-7 (c 0.548, CHCl3);
HRMS calcd for C16H18O3 (M+) 258.1256, found
258.125.
7. Uchiro, H.; Nagasawa, K.; Kotake, T.; Hasegawa, D.;
Tomita, A.; Kobayashi, S. Bioorg. Med. Chem. Lett.
2002, in press.
8. Our recent studies on the synthesis and structure–activity
relationships of 9-methoxystrobilurins, see: (a) Uchiro,