1555
C. N. Teijaro et al.
Feature
Synthesis
13C NMR (126 MHz, CDCl3): δ = 208.23, 167.28, 150.06, 139.25,
132.55, 129.98, 128.06, 122.79, 118.46, 109.05, 63.64, 61.27, 53.29,
51.68, 50.69, 48.32, 42.55, 37.68, 30.08, 24.89.
opinions, findings, and conclusions or recommendations expressed in
this material are those of the author(s) and do no necessarily reflect
the views of the National Science Foundation.
HRMS (FAB): m/z [M + H]+ calcd for C20H25N2O3: 341.1865; found:
341.1860.
Supporting Information
(±)-2,16-Dihydroalstolucine B (19)
Supporting information for this article is available online at
To a stirred solution of 20 (120 mg, 0.352 mmol) in THF (30 mL) at
–10 °C was added 1 M NaHMDS in THF (0.33 mL, 0.33 mmol) in THF
(2 mL) over 10 min. The resulting mixture was stirred at –10 °C for a
further 2 h. The reaction was quenched with sat. aq NH4Cl (10 mL)
and diluted with H2O (5 mL). The resulting mixture was extracted
with CH2Cl2 (2 × 10 mL). The combined organic phases were dried
(Na2SO4) and concentrated under vacuum. The residue was purified
by flash column chromatography (MeOH–CH2Cl2, 5:100) to give an in-
separable mixture of two diastereomers (30 mg, 25%) as a pale yellow
solid.
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References
(1) Sirasani, G.; Andrade, R. B. In Strategies and Tactics in Organic
Synthesis; Harmata, M., Ed.; Academic Press: Oxford, 2013.
(2) Tan, S.-J.; Low, Y.-Y.; Choo, Y.-M.; Abdullah, Z.; Etoh, T.; Hayashi,
M.; Komiyama, K.; Kam, T.-S. J. Nat. Prod. 2010, 73, 1891.
(3) Hesse, M.; Zhu, J.-P.; Hu, W. Planta Med. 1989, 55, 463.
(4) Teijaro, C. N.; Munagala, S.; Zhao, S.; Sirasani, G.; Kokkonda, P.;
Malofeeva, E. V.; Hopper-Borge, E.; Andrade, R. B. J. Med. Chem.
2014, 57, 10383.
(5) Kuehne, M. E.; Brook, C. S.; Frasier, D. A.; Xu, F. J. Org. Chem.
1994, 59, 5977.
(6) Millson, M. F.; Robinson, R.; Thomas, A. F. Experientia 1953, 9,
89.
(7) Henry, T. A. J. Chem. Soc. 1932, 2759.
(8) Shittu, H.; Gray, A.; Furman, B.; Young, L. Phytochem. Lett. 2010,
3, 53.
(9) Menzies, J. R. W.; Paterson, S. J.; Duwiejua, M.; Corbett, A. D. Eur.
J. Pharmacol. 1998, 350, 101.
IR (neat): 3381, 2949, 1723, 1706, 1482, 1170, 742 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 7.07 (td, J = 7.6, 1.2 Hz, 1 H), 6.99 (d, J =
7.4 Hz, 1 H), 6.75 (td, J = 7.4, 0.9 Hz, 1 H), 6.64 (d, J = 7.6 Hz, 1 H), 4.37
(s, 1 H), 3.75 (s, 1 H), 3.73–3.72 (m, J = 8.4 Hz, 4 H), 3.35–3.30 (m, 1 H),
3.10–2.91 (m, 3 H), 2.79 (s, 1 H), 2.73 (dd, J = 13.7, 5.0 Hz, 1 H), 2.34
(dd, J = 10.1, 3.3 Hz, 1 H), 2.22–2.18 (dd, J = 12.8, 6.0 Hz, 1 H), 2.16–
2.08 (m, 4 H), 1.69 (ddd, J = 12.8, 11.3, 8.0 Hz, 1 H), 1.41 (dt, J = 14.4,
2.3 Hz, 1 H).
13C NMR (126 MHz, CDCl3): δ = 208.30, 174.53, 149.34, 129.76,
128.35, 122.17, 118.96, 109.68, 62.14, 57.69, 53.52, 52.05, 51.35,
51.27, 47.55, 45.42, 38.88, 28.91, 26.74, 23.46.
(10) Toczko, M. A.; Heathcock, C. H. J. Org. Chem. 2000, 65, 2642.
(11) Rawal, V. H.; Michoud, C. Tetrahedron Lett. 1991, 32, 1695.
(12) Matsui, K.; Takizawa, S.; Sasai, H. J. Am. Chem. Soc. 2005, 127,
3680; and references cited therein.
(13) For a comprehensive review, see: Basavaiah, D.; Rao, A. J.;
Satyanarayana, T. Chem. Rev. 2003, 103, 811.
(14) Gonzalez-Gomez, J. C.; Medjahdi, M.; Foubelo, F.; Yus, M. J. Org.
Chem. 2010, 75, 6308.
(15) (a) Sirasani, G.; Andrade, R. B. Org. Lett. 2009, 11, 2085.
(b) Sirasani, G.; Paul, T.; Dougherty, W. Jr.; Kassel, S.; Andrade,
R. B. J. Org. Chem. 2010, 75, 3529. (c) Sirasani, G.; Andrade, R. B.
Org. Lett. 2011, 13, 4736.
HRMS (FAB): m/z [M + H]+ calcd for C20H25N2O3: 341.1865; found:
341.1862.
(±)-Alstolucine B (3)
A solution of DMSO (23.8 mg, 0.304 mmol) in CH2Cl2 (0.5 mL) was
added under argon to a solution of oxalyl chloride (14.6 mg, 0.115
mmol) in CH2Cl2 (2 mL) at –78 °C. The resulting mixture was stirred at
–78 °C for 20 min, followed by addition of a solution of 19 (26 mg, 0.1
mmol) in CH2Cl2 (0.5 mL). The stirring was continued at –78 °C for a
further 20 min, and then a solution of Et3N (38 mg, 0.4 mmol) in
CH2Cl2 (0.5 mL) was added. The mixture was allowed to warm to r.t.
over 2 h. Then the reaction was quenched with water (3 mL). The or-
ganic layer was separated and the aqueous layer was extracted with
CH2Cl2 (2 × 5 mL). The combined organic phases were dried (Na2SO4)
and concentrated under vacuum. The residue was purified by flash
column chromatography (MeOH–CH2Cl2, 1:100 to 5:100) to give an
intermediate that was dissolved in CH2Cl2 (5 mL) and subsequently
washed with 1 M aq HCl (2 mL) and 10% aq NaOH (2 mL) to give of 3
(16) Robak, M. T.; Herbage, M. A.; Ellman, J. A. Chem. Rev. 2010, 110,
3600.
(17) (a) Rawal, V. H.; Michoud, C.; Monestel, R. F. J. Am. Chem. Soc.
1993, 115, 3030. (b) Yin, W.; Kabir, S.; Wang, Z.; Rallapalli, S. K.;
Ma, J.; Cook, J. M. J. Org. Chem. 2010, 75, 3339.
(18) Garber, S. B.; Kingsbury, J. S.; Gray, B. L.; Hoveyda, A. H. J. Am.
Chem. Soc. 2000, 122, 8168.
(19) Andrews, I. P.; Kwon, O. Chem. Sci. 2012, 3, 2510.
(20) Raucher, S.; Klein, P. Tetrahedron Lett. 1984, 21, 4061.
(21) Zhao, S.; Sirasani, G.; Vaddypally, S.; Zdilla, M. J.; Andrade, R. B.
Angew. Chem. Int. Ed. 2013, 52, 8309.
1
(5 mg, 20%) as a white foam. H and 13C NMR spectra were identical
with reported literature values.2,4
(22) Brak, K.; Ellman, J. A. Org. Lett. 2010, 12, 2004.
(23) Martin, S. F.; Clark, C. W.; Corbett, J. W. J. Org. Chem. 1995, 60,
3236.
(24) (a) Yang, R.; Huang, P. Chem. Eur. J. 2010, 16, 10319. (b) Deiters,
A.; Chen, K.; Eary, C. T.; Martin, S. F. J. Am. Chem. Soc. 2003, 125,
4541.
(25) (a) Wenkert, E.; Pestchanker, M. J. J. Org. Chem. 1988, 53, 4875.
(b) Wenkert, E.; Orito, K.; Simmons, D. P. J. Org. Chem. 1983, 48,
5006.
Acknowledgment
We acknowledge the previous efforts of Dr. Gopal Sirasani and Mr.
Surendrachary Munagala on this project. We thank Dr. Richard Pederson
(Materia, Inc.) for catalyst support. This research was supported by
the National Science Foundation (CHE-1111558) and the Drug Dis-
covery Initiative (DDI) Grant from the Moulder Center for Drug Dis-
covery, Temple University (R.B.A.). This material is based upon work
supported by the National Science Foundation Graduate Research Fel-
lowship Program under Grant No. (DEG-12262) awarded to C.N.T. Any
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 1547–1556