5714
X.W. Liao et al. / Tetrahedron 65 (2009) 5709–5715
1H), 4.26 (t, J¼4.8 Hz, 1H), 3.86 (br s, 1H), 3.82 (d, J¼12.6 Hz, 1H),
3.61 (s, 3H), 3.60 (s, 3H), 3.54 (dd, J¼15.6, 2.4 Hz, 1H), 3.32 (s, 1H),
3.17 (m, 2H), 2.90 (dd, J¼16.8, 6.6 Hz, 1H), 2.86 (d, J¼16.8 Hz, 1H),
2.31 (m, 1H), 2.28 (s, 3H), 2.27 (s, 3H). 13C NMR (150 MHz, DMSO-
CH2Cl2). HRMS calcd for C30H33N2O9 (MþHþ) 565.2186 Da, found
565.2161. 1H NMR (600 MHz, CD2Cl2):
d 5.90 (m, 1H), 5.40 (br s, 1H),
4.67 (dd, J¼11.4, 2.4 Hz, 1H), 4.32 (dd, J¼11.4, 2.4 Hz, 1H), 4.12 (br d,
J¼3.6 Hz, 1H), 4.01 (s, 3H), 3.98 (s, 3H), 3.85 (br d, J¼12.0 Hz, 1H),
3.67 (d, J¼6.6 Hz, 1H), 3.01 (dd, J¼16.2, 2.4 Hz, 1H), 2.87 (dd, J¼21.0,
6.6 Hz,1H), 2.64 (d, J¼21.0 Hz,1H), 2.36 (s, 3H),1.93 (s, 6H),1.68 (dq,
J¼7.2, 1.6 Hz, 3H), 1.52 (t, J¼1.6 Hz, 3H), 1.49 (ddd, J¼15.0, 12.6,
d6):
d 170.2, 146.1, 146.0, 145.1, 144.3, 133.2, 133.0, 129.6, 129.3,
122.1, 121.6, 116.0, 114.1, 62.8, 60.7, 60.4, 53.2, 50.4, 48.2, 36.0,
32.7, 16.7, 16.5.
2.4 Hz, 1H). 13C NMR (150 MHz, CD2Cl2):
d 186.6, 185.5, 182.8, 180.7,
4.8. Synthesis of compound 30
170.6, 167.2, 156.4, 155.8, 142.4, 142.0, 139.8, 136.4, 135.2, 129.6,
128.7, 127.0, 63.1, 61.3, 61.2, 59.4, 56.5, 53.4, 50.4, 40.0, 25.9, 23.8,
20.5, 15.6, 8.8, 8.7.
To a solution of compound 29 (60 mg, 0.098 mmol) in MeOH
(4 mL) at room temperature was added Pd(OH)2 (moist, Pd con-
tent 20%, 30 mg), and the mixture was hydrogenated in a Parr
apparatus (50 psi H2) for 10 h. The reaction mixture was filtered
through Celite, washed with MeOH, and concentrated under
vacuum. The residue was dissolved in EtOAc (10 mL) and was
then treated with saturated aq NaHCO3. The phases were sepa-
rated, and the aqueous phase was extracted with EtOAc
(10 mLꢂ2). The combined organic phase was washed with brine,
dried over Na2SO4, and concentrated under reduced pressure. The
pale yellow residue was purified by column chromatograph (0.2%
triethylamine in EtOAc) to afford compound 30 (39 mg, 87%) as
Acknowledgements
We thank the National Natural Sciences Foundation of China
(No. 30672518) and Specialized Research Fund for the Doctoral
Program of Higher Education (No. 20060023025) for financial
support.
Supplementary data
Experimental details and spectroscopic data for all compounds.
Supplementary data associated with this article can be found in the
a white solid. [
a
]
20: ꢀ179.4 (c 0.5, CH3OH). HRMS calcd for
D
C25H31N2O6 (MþHþ) 455.2182 Da, found 455.2295. 1H NMR
(600 MHz, DMSO-d6):
d 8.83 (s, 1H), 8.68 (s, 1H), 6.44 (s, 1H), 6.42
(s, 1H), 5.45 (dd, J¼6.0, 4.8 Hz, 1H), 4.24 (dd, J¼6.0, 4.8 Hz, 1H),
4.15 (d, J¼3.0 Hz, 1H), 3.80 (br d, J¼13.2 Hz, 1H), 3.61 (s, 3H), 3.60
(s, 3H), 3.46 (d, J¼6.6 Hz, 1H), 3.20 (m, 1H), 3.08 (dd, J¼16.8,
6.0 Hz, 1H), 2.97 (m, 1H), 2.90 (dd, J¼13.8, 2.4 Hz, 1H), 2.59 (d,
J¼16.8 Hz, 1H), 2.28 (s, 3H), 2.28 (t, J¼13.8 Hz, 1H), 2.17 (s, 3H),
References and notes
1. Davidson, B. S. Tetrahedron Lett. 1992, 33, 3721–3725.
2. For a comprehensive review of the chemistry and biology of tetrahydro-
isoquinoline alkaloid, see: Scott, J. D.; Williams, R. M. Chem. Rev. 2002, 102,
1669–1730.
3. Molinski, T. F.; Dalisay, D. S.; Lievens, S. L.; Saludes, J. P. Nat. Rev. Drug Discovery
2009, 8, 69–85.
4. (a) Magnus, P.; Matthews, K. S. J. Am. Chem. Soc. 2005, 127, 12476–12477;
(b) Lane, J. W.; Chen, Y.; Williams, R. M. J. Am. Chem. Soc. 2005, 127,
12684–12690.
2.21 (s, 3H). 13C NMR (150 MHz, DMSO-d6):
d 170.5, 147.2, 146.5,
144.5, 143.7, 132.9, 129.1, 129.3, 128.9, 128.8, 120.6, 119.9, 119.6,
79.1, 63.5, 59.87, 59.80, 59.1, 58.1, 54.5, 50.5, 31.7, 28.0, 15.57,
15.56.
5. For the biosynthesis: (a) Mikami, Y.; Takahashi, K.; Yazawa, K.; Arai, T.; Nami-
koshi, M.; Iwasaki, S.; Okuda, S. J. Biol. Chem. 1985, 260, 344–348; (b) Kerr, R. G.;
Miranda, N. F. J. Nat. Prod. 1995, 58, 1618–1621; (c) Jeedigunta, S.; Krenisky, J. M.;
Kerr, R. G. Tetrahedron 2000, 56, 3303–3307.
4.9. Synthesis of compound 31
6. (a) Kurihara, H.; Mishima, H. Tetrahedron Lett. 1982, 23, 3639–3640; (b) Jow, C.
K. Ph.D. Thesis, Rice University, Texas, 1995.
To a solution of compound 30 (35 mg, 0.077 mmol) in MeCN
(4 mL) was added salcomine (25 mg, 0.077 mmol) at room tem-
perature, and the dark suspension was stirred in air for 5 h. The
mixture was filtered through cellulose powder and the filter cake
was carefully washed with AcOEt. The combined filtrate was
washed with 0.1% aq NaHCO3 and brine, and dried over Na2SO4.
After concentration in vacuo, the residue was chromatographed on
silica gel to give compound 31 (32 mg, 86%) as an orange residue.
7. (a) Tang, Y. F.; Liu, Z. Z.; Chen, S. Z. Tetrahedron Lett. 2003, 44, 7091–7094; (b)
Wang, Y.; Liu, Z. Z.; Chen, S. Z.; Liang, X. T. Chin. Chem. Lett. 2004, 15, 505–507;
(c) Liu, Z. Z.; Wang, Y.; Tang, Y. F.; Chen, S. Z.; Chen, X. G.; Li, H. Y. Bioorg. Med.
Chem. Lett. 2006, 16, 1282–1285; (d) Wang, Y.; Zhou, Y. L.; Liu, Z. Z.; Chen, S. Z.;
Chen, X. G. Chin. Chem. Lett. 2006, 17, 1279–1282.
8. (a) Wang, Y.; Liu, Z. Z.; Chen, S. Z.; Liang, X. T. Chin. J. Org. Chem. 2003, 23, 335
(Suppl.); (b) Liu, Z. Z.; Tang, Y. F.; Wang, Y.; Chen, S. Z. Chin. J. Org. Chem. 2003,
23, 336 (Suppl.).
9. (a) Vincent, G.; Lane, J. W.; Williams, R. M. Tetrahedron Lett. 2007, 48,
3719–3722; (b) Saito, N.; Tachi, M.; Seki, R.; Kamayachi, H.; Kubo, A. Chem.
Pharm. Bull. 2000, 48, 1549–1557; (c) Endo, A.; Kann, T.; Fukuyama, T. Synlett
1999, 1103–1105; (d) Wu, Y. C.; Liron, M.; Zhu, J. J. Am. Chem. Soc. 2008, 130,
7148–7152.
10. Schmidt, E. W.; Nelson, J. T.; Fillmore, J. P. Tetrahedron Lett. 2004, 45, 3921–3924.
11. Doherty, D. G.; Vaslow, F. J. Am. Chem. Soc. 1952, 74, 931–936.
12. Arnold, Z. S. Pol. J. Chem. 1985, 59, 837–843.
[
a]
20: ꢀ266.6 (c 0.5, CHCl3). HRMS calcd for C25H27N2O8 (MþHþ)
D
483.1761 Da, found 483.1746. 1H NMR (600 MHz, CDCl3):
d 5.38 (br
s, 1H), 4.13 (d, J¼3.6 Hz, 1H), 4.01 (s, 3H), 4.00 (s, 3H), 3.87 (br d,
J¼12.6 Hz, 1H), 3.83 (br d, J¼10.8 Hz, 1H), 3.69 (d, J¼6.6 Hz, 1H),
3.49 (dd, J¼10.8, 3.0 Hz, 1H), 3.12 (dd, J¼16.8, 2.4 Hz, 1H), 2.88 (dd,
J¼20.4, 7.2 Hz, 1H), 2.71 (d, J¼20.4 Hz, 1H), 2.37 (s, 3H), 1.96 (s, 3H),
1.95 (s, 3H), 1.68 (dd, J¼16.2, 12.6 Hz, 1H). 13C NMR (150 MHz,
13. For 1,3-cis selective Pictet–Spengler reactions, see: (a) Massiot, G.; Mulamba, T.
J. Chem. Soc., Chem. Commun. 1983, 1147–1149; (b) Bailey, P. D.; Hollinshead, S. P.;
McLay, N. R.; Morgan, K.; Palmer, S. J.; Prince, S. N.; Reynolds, C. D.; Wood, S. D. J.
Chem. Soc., Perkin Trans. 1 1993, 431–439; (c) Myers, A. G.; Kung, D. W.; Zhong, B.;
Movassaghi, M.; Kwon, S. J. Am. Chem. Soc. 1999, 121, 8401–8402; (d) Myers, A. G.;
Kung, D. W. J. Am. Chem. Soc. 1999, 121, 10828–10829; (e) Chen, J.; Chen, X.; Bois-
CDCl3):
d 186.4, 185.2, 182.2, 180.7, 171.1, 155.5, 155.4, 141.9, 141.7,
136.6, 134.9, 129.0, 128.6, 65.0, 61.1, 58.8, 56.5, 53.1, 51.7, 39.8, 25.4,
24.0, 8.9, 8.8.
´
´
Choussy, M.; Zhu, J. J. Am. Chem. Soc. 2006, 128, 87–89; (f) Ortın, I.; Gonzalez, J. F.;
de la Cuesta, E.; Manguan-Garcı´a, C.; Perona, R.; Avendan˜o, C. Bioorg. Med. Chem.
2008, 16, 9065–9078.
4.10. (L)-Renieramycin G
14. (a) Kase, H.; Fujita, H.; Nakamura, J.; Hashizumi, K.; Goto, J.; Kubo, K.; Shito, K.
J. Antibiot. 1986, 39, 354–363; (b) Hirayama, N.; Iida, T.; Shirahata, K. Acta
Crystallogr., Sect. C 1990, 46, 86–88; (c) Kaufman, T. S. J. Chem. Soc., Perkin Trans.
1 1996, 2497–2505.
15. Kwon, S.; Myers, A. G. J. Am. Chem. Soc. 2005, 127, 16796–16797.
16. Hansen, D. W., Jr.; Pilipauskas, D. J. Org. Chem. 1985, 50, 945–950.
17. (a) Cabre, J.; Palomo, L. Synthesis 1984, 413–417; (b) Zheng, S.; Chan, C.; Furuuchi,
T.; Wright, B. J. D.; Zhou, B.; Guo, J.; Danishefsky, S. J. Angew. Chem., Int. Ed. 2006,
45, 1754–1759.
To a solution of compound 31 (8 mg, 0.0166 mmol) in CH2Cl2
(1 mL) was added angeloyl chloride (39.3 mg, 0.332 mmol,
20 equiv), and the solution was allowed to stand for 24 h at 25 ꢁC in
the dark. The mixture was diluted with CH2Cl2, washed with 1% aq
NaHCO3 and brine successively, dried over Na2SO4, and concen-
trated under reduced pressure. The residue was purified by pre-
parative TLC (SiO2, CHCl3:CH3OH¼100:2) to give (ꢀ)-renieramycin
18. Kende, A. S.; Liu, K.; Kaldar, I.; Dorey, G.; Koch, K. J. Am. Chem. Soc. 1995, 117,
8258–8270.
G (7 mg, 0.0142 mmol, 74%) as a yellow film. [
a]
20: ꢀ148.8 (c 0.2,
D