W. Li et al. / Bioorg. Med. Chem. Lett. 20 (2010) 3112–3115
3115
499.33924. Compound 11b: ½a D27
ꢁ
ꢀ16.1 (c 0.31, CHCl3); 1H NMR (400 MHz,
References and notes
CDCl3): d 4.44ꢀ4.39 (m, 1H), 4.30 (br s, 1H), 4.05 (br s, 1H), 2.44 (d, J = 14.4 Hz,
1H), 2.16ꢀ2.12 (m, 1H), 2.07ꢀ2.01 (m, 1H), 1.37 (s, 3H), 1.31 (s, 3H), 1.20 (s,
3H), 1.08 (s, 3H), 1.04 (s, 3H), 1.03 (s, 3H), 0.93 (s, 3H), 0.81ꢀ0.77 (m, 1H); 13C
NMR (100 MHz, CDCl3): d 117.4, 85.5, 82.7, 78.7, 67.7, 66.2, 66.0, 57.77, 57.75,
48.5, 46.9, 41.8, 41.5, 39.5, 35.8, 34.9, 31.9, 31.8, 31.3, 29.9, 28.2, 27.4, 27.2,
24.6, 24.3, 23.8, 23.7, 18.5, 13.7; HR-ESIMS calcd for C29H48O5Na [M+Na]+
1. (a) Higa, T.; Tanaka, J.-I.; Tsukitani, Y.; Kikuchi, H. Chem. Lett. 1981, 1647; (b)
Rao, C. B.; Ramana, K. V.; Rao, D. V.; Fahy, E.; Faulkner, D. J. J. Nat. Prod. 1988, 51,
954; (c) Gonzalez, N.; Barral, M. A.; Rodriguez, J.; Jimenez, C. Tetrahedron 2001,
57, 3487.
2. (a) Bordeleau, M.-E.; Mori, A.; Oberer, M.; Lindqvist, L.; Chard, L. S.; Higa, T.;
Wagner, G. J.; Belsham, G.; Tanaka, J.; Pelletier, J. Nat. Chem. Biol. 2006, 2, 213;
(b) Lindqvist, L.; Oberer, M.; Reibarkh, M.; Cencic, R.; Bordeleau, M.-E.; Voqt, E.;
Marintchev, A.; Tanaka, J.; Fagotto, F.; Altmann, M.; Wagner, G.; Pelletier, J. PLoS
One 2008, 3, e1583; (c) Low, W. K.; Dang, Y.; Schneider-Poetsch, T.; Shi, Z.; Choi,
N. S.; Merrick, W. C.; Romo, D.; Liu, J. O. Mol. Cell 2005, 20, 709; (d) Bordeleau,
M.-E.; Matthews, J.; Wojnar, J. M.; Lindqvist, L.; Novac, O.; Jankowsky, E.;
Sonenberg, N.; Northcote, P.; Teesdale-Spittle, P.; Pelletier, J. Proc. Natl. Acad.
Sci. U.S.A. 2005, 102, 10460; (e) Clardy, J. ACS Chem. Biol. 2006, 1, 17; (f) Pestova,
T. V.; Hellen, C. U. Nat. Chem. Biol. 2006, 2, 176.
499.33940, found 499.33975. Compound 12a: ½a D28
ꢁ
+38.0 (c 0.52, CHCl3); 1H
NMR (400 MHz, CDCl3): d 4.36ꢀ4.30 (m, 2H), 4.05 (br s, 1H), 3.08 (s, 1H),
2.23ꢀ2.19 (m, 1H), 2.08ꢀ2.01 (m, 1H), 1.42 (s, 3H), 1.31 (s, 3H), 1.04 (s, 3H),
0.89 (t, J = 7.6 Hz, 3H), 0.84 (t, J = 7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3): d
116.1, 88.5, 80.6, 78.9, 68.3, 66.6, 66.4, 58.4, 57.4, 49.9, 42.3, 40.1, 36.5, 35.5,
34.3, 33.5, 33.3, 32.7, 32.1, 31.8, 30.4, 29.8, 28.8, 28.6, 28.1, 18.5, 14.2, 8.9, 8.8;
HR-ESIMS calcd for C29H48O5Na [M+Na]+ 499.33940, found 499.34072.
Compound 12b: ½a D28
ꢁ
ꢀ17.7 (c 0.29, CHCl3); 1H NMR (400 MHz, CDCl3): d 4.42
(dd, J = 12.8, 7.2 Hz, 1H), 4.31 (br s, 1H), 4.05 (br s, 1H), 2.18ꢀ2.14 (m, 1H), 1.35
(s, 3H), 1.32 (s, 3H), 1.03 (s, 3H), 0.84 (t, J = 7.6 Hz, 6H); 13C NMR (100 MHz,
CDCl3): d 120.6, 87.9, 82.7, 78.9, 68.1, 66.4, 66.2, 58.4, 58.1, 48.9, 42.1, 39.9,
36.3, 35.3, 32.7, 32.4, 31.9, 31.8, 31.4, 30.3, 30.2, 28.7, 27.9, 26.8, 19.7, 14.2, 8.7,
8.4; HR-ESIMS calcd for C29H48O5Na [M+Na]+ 499.33940, found 499.34087.
3. Li, W.; Dang, Y.; Liu, J. O.; Yu, B. Chem. Eur. J. 2009, 15, 10356.
4. (a) Barua, N. C.; Schmidt, R. R. Synthesis 1986, 891; (b) Martin, D. D.; Marcos, I.
S.; Basabe, P.; Romero, R. E.; Moro, R. F.; Lumeras, W.; Rodríguez, L.; Urones, J.
G. Synthesis 2001, 1013; (c) Baklan, V. F.; Antipenkova, L. S.; Zakharchenko, L. I.;
Fesenko, T. E.; Kukhar, V. P. Russ. J. Org. Chem. 1984, 20, 1212; (d) Fukuzawa, S.-
I.; Sumimoto, N.; Fujinami, T.; Sakai, S. J. Org. Chem. 1990, 55, 1628.
5. (a) Botteghi, C.; Consiglio, G.; Ceccarelli, G.; Stefani, A. J. Org. Chem. 1972, 37,
1835; (b) Paquette, L. A.; Lanter, J. C.; Johnston, J. N. J. Org. Chem. 1997, 62, 1702;
(c) Hennessy, A. J.; Connolly, D. J.; Malone, Y. M.; Guiry, P. J. Tetrahedron Lett.
2000, 41, 7757.
6. (a) Akbutina, F. A.; Sadretdinov, I. F.; Vasil’eva, E. V.; Miftakhov, M. S. Russ. J.
Org. Chem. 2001, 37, 695; (b) Ueki, T.; Kinoshita, T. Org. Biomol. Chem. 2004, 2,
2777; (c) Doyle, M. P.; Dyatkin, A. B. J. Org. Chem. 1995, 60, 3035.
7. (a) Szendi, Z.; Sweet, F. Steroids 1991, 56, 458; (b) Hedtmann, U.; Klintz, R.;
Hobert, K.; Frelek, J.; Vlahov, I.; Welzel, P. Tetrahedron 1991, 47, 3753; (c)
Hobert, U.; Hedtmann, K.; Klintz, R.; Welzel, P.; Frelek, J.; Strangmann-
Diekmann, M.; Klöne, A.; Pongs, O. Angew. Chem., Int. Ed. Engl. 1989, 28, 1515.
8. Procedure for the synthesis of analogs 12a and 12b: To a solution of 2,2-
Compound 13a: ½a D27
ꢁ
+42.8 (c 0.44, CHCl3); 1H NMR (400 MHz, CDCl3): d
4.38ꢀ4.30 (m, 2H), 4.05 (br s, 1H), 3.78 (d, J = 8.0 Hz, 1H), 3.53 (d, J = 8.0 Hz,
1H), 3.10 (s, 1H), 2.22ꢀ2.18 (m, 1H), 2.07ꢀ2.01 (m, 1H), 1.38 (s, 3H), 1.30 (s,
3H), 1.21 (s, 3H), 1.07 (s, 3H), 1.03 (s, 3H), 0.80ꢀ0.76 (m, 1H); 13C NMR
(100 MHz, CDCl3): d 117.3, 80.7, 80.5, 79.8, 68.1, 66.4, 65.6, 58.3, 57.1, 49.8,
47.5, 42.1, 39.9, 37.9, 36.3, 35.2, 34.1, 32.5, 31.6, 30.1, 29.1, 28.6, 27.9, 27.1,
26.3, 18.4, 14.1; HR-ESIMS calcd for C27H44O5Na [M+Na]+ 471.30810, found
471.30893. Compound 13b: ½a D27
ꢁ
ꢀ42.0 (c 0.83, CHCl3); 1H NMR (400 MHz,
CDCl3): d 4.43ꢀ4.38 (m, 1H), 4.31 (br s, 1H), 4.05 (br s, 1H), 3.64 (d, J = 7.2 Hz,
1H), 3.51 (d, J = 8.0 Hz, 1H), 2.20ꢀ2.14 (m, 2H), 2.09ꢀ2.02 (m, 1H), 1.98ꢀ1.88
(m, 1H), 1.37 (s, 3H), 1.32 (s, 3H), 1.14 (s, 3H), 1.05 (s, 3H), 1.03 (s, 3H),
0.81ꢀ0.78 (m, 1H); 13C NMR (100 MHz, CDCl3): d 121.1, 82.7, 79.8, 79.4, 68.0,
66.6, 66.3, 58.3, 58.1, 48.7, 46.4, 42.0, 39.8, 37.9, 36.2, 35.2, 32.3, 31.76, 31.75,
30.3, 28.6, 27.8, 27.7, 26.9, 26.0, 19.0, 14.1; HR-ESIMS calcd for C27H44O5Na
[M+Na]+ 471.30810, found 471.30901. Compound 14: a 2D7
½ ꢁ ꢀ36.8 (c 0.32,
diethyl-2,3-dihydrofuran 7 (200 lL, 1.46 mmol) in anhydrous THF (3 mL) was
CHCl3); 1H NMR (400 MHz, CDCl3): d 4.60ꢀ4.55 (m, 1H), 4.42 (s, 1H), 4.31 (br s,
1H), 4.04 (br s, 1H), 2.22ꢀ2.18 (m, 1H), 2.12ꢀ2.08 (m, 1H), 1.43 (s, 3H), 1.24 (s,
3H), 1.12 (s, 3H), 1.11 (s, 3H), 1.07 (s, 3H), 1.03 (s, 3H), 0.95 (s, 3H), 0.82ꢀ0.78
(m, 1H); 13C NMR (100 MHz, CDCl3): d 114.9, 85.6, 80.1, 79.7, 69.7, 67.7, 65.9,
58.2, 57.6, 47.8, 47.6, 42.8, 39.9, 39.4, 35.8, 34.8, 31.7, 31.4, 30.2, 28.2, 27.4,
24.3, 24.0, 23.8, 23.7, 23.0, 17.8, 13.9; HR-ESIMS calcd for C29H48O5Na [M+Na]+
added t-BuLi (1.5 M in pentane, 1.3 mL, 1.95 mmol) at ꢀ68 °C. The reaction was
allowed to warm to 0 °C and the stirring continued for another 15 min at rt. The
mixture was cooled to 0 °C again and ketone
1 (91 mg, 0.16 mmol) in
anhydrous THF (1 mL) was added. After stirring for 1 h, the reaction was
quenched with H2O. The resulting mixture was diluted with EtOAc (30 mL),
and washed with brine. The organic layer was dried, filtered, and concentrated.
The residue was dissolve in THF (4 mL) and 0.1 M HCl (1 mL). After stirring for
2 h, the mixture was diluted with EtOAc (30 mL), washed with brine, dried, and
concentrated. The crude product was dissolved in anhydrous THF (2 mL), and
LiAlH4 (33 mg, 0.87 mmol) was added. After stirring for 20 min at 40 °C, the
reaction was quenched with H2O slowly. To the resulting mixture was added
EtOAc (10 mL), NaHCO3 (1 g) and Na2SO4 (1 g), and the stirring continued for
another 3 h. The mixture was then filtered and concentrated to give a residue,
which was purified by silica gel column chromatography (petroleum ether–
EtOAc, 2:1) to afford analogs 12a (34 mg, 44%) and 12b (10 mg, 13%).
499.33940, found 499.33963. Compound 19a: ½a D27
ꢁ
+11.4 (c 0.70, CHCl3); 1H
NMR (400 MHz, CDCl3): d 4.4 (dd, J = 15.2, 7.6 Hz, 1H), 4.30 (br s, 1H), 4.05 (br s,
1H), 3.98ꢀ3.92 (m, 1H), 3.76ꢀ3.72 (m, 1H), 3.29 (s, 1H), 2.22ꢀ2.18 (m, 1H),
2.09ꢀ2.03 (m, 1H), 1.32 (s, 3H), 1.25 (s, 3H), 1.03 (s, 3H), 0.80ꢀ0.77 (m, 1H);
13C NMR (100 MHz, CDCl3): d 105.0, 81.4, 81.0, 68.1, 66.5, 66.4, 61.8, 58.3, 57.1,
50.0, 42.4, 40.0, 36.3, 35.3, 33.8, 32.6, 31.6, 30.21, 30.18, 28.7, 27.9, 27.4, 24.9,
20.1, 18.5, 14.1; HR-MALDI calcd for C26H42O5Na [M+Na]+ 457.2924, found
457.2933. Compound 19b: ½a D27
ꢁ
ꢀ34.3 (c 0.94, CHCl3); 1H NMR (400 MHz,
CDCl30): d 4.38ꢀ4.33 (m, 1H), 4.30 (br s, 1H), 4.05 (br s, 1H), 3.79ꢀ3.72 (m, 1H),
3.60ꢀ3.56 (m, 1H), 2.18ꢀ2.14 (m, 1H), 2.09ꢀ2.03 (m, 1H), 1.34 (s, 3H), 1.31 (s,
3H), 1.03 (s, 3H), 0.81ꢀ0.77 (m, 1H); 13C NMR (100 MHz, CDCl3): d 110.2, 83.5,
79.2, 68.0, 66.8, 66.4, 61.1, 58.5, 58.0, 48.7, 42.0, 39.9, 36.3, 35.3, 32.3, 31.8,
31.2, 30.2, 28.6, 28.1, 27.9, 26.5, 25.1, 19.9, 19.7, 14.1; HR-MALDI calcd for
C26H42O5Na [M+Na]+ 457.2924, found 457.2928. Compound 20a: 1H NMR
(400 MHz, CDCl3): d 4.35ꢀ4.29 (m, 2H), 4.05 (br s, 1H), 3.50 (s, 1H), 2.23ꢀ2.19
(m, 1H), 1.39 (s, 3H), 1.38 (s, 3H), 1.24 (s, 3H), 1.20 (s, 3H), 1.04 (s, 3H),
0.80ꢀ0.77 (m, 1H). Compound 20b: 1H NMR (300 MHz, CDCl3): d 4.36 (dd,
J = 17.6, 10.0 Hz, 1H), 4.30 (br s, 1H), 4.05 (br s, 1H), 2.18ꢀ2.12 (m, 2H), 1.32
(s, 3H), 1.29 (s, 3H), 1.26 (s, 3H), 1.11 (s, 3H), 1.03 (s, 3H), 0.81ꢀ0.77 (m, 1H).
9. (a) Lane, K. J.; Pinder, A. R. J. Org. Chem. 1982, 47, 3171; (b) Kaneda, K.; Ueno, S.;
Imanaka, T. Chem. Commun. (Cambridge, U.K.) 1994, 797.
10. Analytical data for the analogs 11a/11b, 12a/12b, 13a/13b, 14, 19a/19b, 20a/
20b. Compound 11a: ½a D28
ꢁ
+39.9 (c 0.87, CHCl3); 1H NMR (400 MHz, CDCl3): d
4.32ꢀ4.27 (m, 2H), 4.05 (br s, 1H), 3.10 (s, 1H), 2.21ꢀ2.17 (m, 1H), 2.16ꢀ2.12
(m, 1H), 2.06ꢀ2.00 (m, 1H), 1.39 (s, 3H), 1.29 (s, 3H), 1.21 (s, 3H), 1.12 (s, 3H),
1.08 (s, 3H), 1.03(s, 3H), 0.94 (s, 3H), 0.80ꢀ0.76 (m, 1H); 13C NMR (100 MHz,
CDCl3): d 113.7, 86.2, 79.8, 78.8, 67.7, 66.0, 65.4, 57.8, 56.7, 49.3, 47.4, 41.7,
41.6, 39.5, 35.9, 34.9, 33.8, 32.1, 31.2, 29.8, 28.4, 28.2, 27.5, 25.2, 24.1, 23.9,
23.8, 18.2, 13.6; HR-ESIMS calcd for C29H48O5Na [M+Na]+ 499.33940, found