888
R. A. Tapia et al. / Tetrahedron Letters 42 (2001) 887–889
MeO
MeO
OH
OR
MeO
MeO
a, b
c
H
6a
10a
OH
O
H
H
MeO
MeO
O
3
4
R = CH2OCH3
MeO
5
9
2
10
1
3
4
8
7
O
H
11
1
6a
6
4a
MeO
OTMS
2
3
10a
12
7
12b
10
7
H
H
OMe
e
9
d
5
O
O
6
4
8
5
O
MeO
O
6
8
Scheme 2. Reagents: (a) NaH/THF −30°C, ClCH2OCH3, 95%; (b) n-BuLi/THF −78°C, citral, 78%; (c) 6N HCl/THF, 45°C, 40%;
(d) AgO/THF, 6N HNO3, 75%; (e) CH2Cl2, SiO2, 70%.
and C-3, respectively. Thus, FMO theory suggests for
quinone 8 the regiochemistry shown in Scheme 2.
3. Wessels, P.; Go¨hrt, A.; Zeeck, A.; Drautz, H.; Za¨hner, H.
J. Antibiot. 1991, 44, 1013–1018.
4. Shin-Ya, K.; Shimazu, A.; Hayakawa, Y.; Seto, H. J.
The structural assignment for compound 8 is estab-
Antibiot. 1992, 45, 124–125.
1
lished from its spectral data. First, the H NMR spec-
5. (a) Tapia, R. A.; Ga´rate, M. C.; Valderrama, J. A.;
Jenkins, P. R.; Fawcett, J.; Russell, D. R. Tetrahedron
Lett. 1997, 38, 153–154; (b) Tapia, R. A.; Ga´rate, M. C.;
Valderrama, J. A.; Jenkins, P. R. Heterocycles 1998, 48,
1365–1371; (c) Tapia, R. A.; Centella, C. R.; Valderrama,
J. A. Synth. Commun. 1999, 29, 2163–2168.
trum of 8 shows signals for three methyl groups at l
1.32, 1.54 and 1.69 ppm, an allylic proton at l 3.49
ppm and a vinylic proton at l 6.05 ppm. These signals
are similar to those of the natural product 2.3 Then,
1H-13C HMQC and HMBC correlations performed at
500 and 125 MHz allow to assign all protons and
carbons except the two gem CH3-5 and the two OCH3
at C-8 and C-10. Finally, the use of HMBC results in
combination with 13C NMR data confirms the orienta-
tion of the Diels–Alder reaction. As it is known for
analogous products, the carbonyl adjacent to the pyran
oxygen is shifted to high field.2–4,16 On this basis, the
signals at 178.0 and 184.8 ppm are assigned to CO-7
and CO-12, respectively. Then, the presence of a strong
3J HMBC correlation between H-11 and C-12 enabled
H-11 to be assigned thus providing the regiochemistry
for compound 8.
6. Tapia, R. A.; Navarro, O.; Alegr´ıa, L.; Valderrama, J. A.
Heterocycl. Commun. 1998, 4, 151–154.
7. (a) Tapia, R. A.; Valderrama, J. A.; Quintanar, C. Hete-
rocycles 1994, 38, 1797–1804; (b) Zuloaga, F.; Tapia, R.
A.; Quintanar, C. J. Chem Soc. Perkin Trans. 2 1995,
939–943.
8. Cruz-Almanza, R.; Pe´rez-Flores, F.; Lemini, C. Hetero-
cycles 1994, 37, 759–774.
9. Wriede, V.; Fernandez, M.; West, K. F.; Harcourt, D.;
Moore, H. W. J. Org. Chem. 1987, 52, 4485–4489.
10. Uliss, D. B.; Razdan, R. K.; Dalzell, H. C.; Handrick, G.
R. Tetrahedron 1977, 33, 2055–2059.
11. Mp 122–123.5°C; IR 1675 and 1640 (CꢀO) cm−1 1H
;
NMR (250 MHz, CDCl3): l 1.30 (s, 3 H, CH3-6), 1.52 (s,
3 H, CH3-6), 1.67 (s, 3 H, CH3-9), 1.2–2.1 (m, 5H, H-6a,
CH2-7, CH2-8), 3.37 (br t, 1 H, H-10a), 5.98 (m, 1 H,
H-10), 6.57 (d, 1 H, J=10.5 Hz, H-2 or H-3), 6.62 (d, 1
H, J=10.5 Hz, H-3 or H-2). 13C NMR (125.75 MHz,
Acknowledgements
We are grateful to FONDECYT (Research Grant
8980003 and 2990098) for financial support of this
work and CONICYT for a fellowship to Luz Alegr´ıa.
CDCl3): l 20.3 (C-7), 23.5 (C6 H3-9), 24.9 (C6 H3-6), 25.7
(CH3-6), 29.7 (C-8), 30.6 (C-6a), 39.7 (C-10a), 80.3 (C-6),
6
120.1 (C-10), 121.3 (C-4a), 133.3 (C-2 or C-3), 136.0
(C-9), 137.8 (C-3 or C-2), 150.9 (C-10b), 182.1 (C-4),
187.3 (C-1); Anal calcd for C16H18O3: C, 74.40, H, 7.02;
found: C, 74.20, H, 6.80.
References
12. Savard, J.; Brassard, P. Tetrahedron 1984, 40, 3455–3464.
1. (a) Berdy, J. Handbook of Antibiotic Compounds; CRC
Press: Florida, 1980; Vol. III, pp. 221–279; (b) Hayashi,
T.; Smith, F. T.; Lee, K.-H. J. Med. Chem. 1987, 30,
2005–2008; (c) Itokawa, H.; Matsumoto, K.; Morita, H.;
Takeka, K. Phytochemistry 1992, 31, 1061–1062; (d)
Sendl, A.; Chen, J. L.; Jolad, S. D.; Stoddart, C.;
Rozhon, E.; Kernan, M.; Nanakorn, W.; Balick, M. J.
Nat. Prod. 1996, 59, 808–811.
1
13. Mp 227–229°C; IR 1675 and 1645 (CꢀO) cm−1; H NMR
(500 MHz, CDCl3): l 1.32 (s, 3 H, CH3-5), 1.54 (s, 3 H,
CH3-5), 1.69 (s, 3 H, CH3-2), 1.74 (m, 1H, H-4a), 1.97
(m, 2H, CH2-4), 2.0 (m, 2 H, CH2-3), 3.49 (br t, 1 H,
H-12b), 3.91 (s, 3 H, OCH3), 3.93 (s, 3 H, OCH3), 6.05
(d, 1 H, J=5.3 Hz, H-1), 6.60 (d, 1 H, J=2.6 Hz, H-9),
7.20 (d, 1 H, J=2.6 Hz, H-11). 13C NMR (125.75 MHz,
2. Shin-Ya, K.; Imai, S.; Furihata, K.; Hayakawa, Y.;
Kato, Y.; Vanduyne, G. D.; Clardy, J.; Seto, H. J.
Antibiot. 1990, 43, 444–447.
CDCl3): l 20.7 (C-4), 24.0 (C
(CH3-5), 30.2 (C-3), 31.2 (C-12b), 40.2 (C-4a), 56.3
(OCH3-8 or OCH3-10), 56.8 (OCH3-10 or OCH3-8), 80.5
6 H3-2), 25.4 (C6 H3-5), 26.1
6
6
6
6
6