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Date: 16-06-14 10:35:24
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Total Synthesis and Configurational Validation of (+)-Violapyrone C
[2] a) H. J. Shin, H.-S. Lee, J. S. Lee, J. Shin, M. A. Lee, H.-S. Lee,
Y.-J. Lee, J. Yun, J. S. Kang, Mar. Drugs 2014, 12, 3283–3291;
b) unpublished results.
(10S)-tert-Butyl 2,10-Dimethyl-3-oxododec-4-ynoate (17): nBuLi
(1.85 m in hexanes, 142.6 µL, 0.2638 mmol) was added to a cold
solution (–78 °C) of terminal alkyne 16 (22.8 mg, 0.16 mmol) in
THF under an atmosphere of N2. The resulting mixture was stirred
for 40 min and methyl chloroformate was added. The mixture was
allowed to warm to room temperature. The mixture was diluted
with diethyl ether and quenched with H2O. The organic layer was
dried with Na2SO4, filtered, and concentrated in vacuo. The crude
residue was purified by flash column chromatography (EtOAc/n-
hexane = 1:30) to give 16a (31.3 mg, 0.16 mmol, quantitative). tert-
Butyl propionate (59.7 µL, 0.39 mmol, 3.0 equiv.) was added drop-
wise to a stirred solution of LDA (2.0 m in THF, 1.31 mmol,
10.0 equiv.) at –78 °C. The mixture was stirred at this temperature
for 30 min before 16a (25.8 mg, 0.13 mmol) was slowly introduced;
stirring was continued at –78 °C for 2 h. The mixture was diluted
with diethyl ether and quenched with saturated aqueous solution
of NH4Cl. The organic layer was dried with Na2SO4, filtered, and
concentrated in vacuo. The crude residue was purified by flash col-
umn chromatography (EtOAc/n-hexane = 1:35) to give 17 (34.3 mg,
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1
0.12 mmol, 86% over 2 steps). H NMR (500 MHz, CDCl3): δ =
12.27 (s, 1 H), 3.40–3.44 (q, 1 H), 2.39–2.41 (t, J = 7.0 Hz, 2 H),
2.34–2.37 (t, J = 7.1 Hz, 2 H), 1.81 (s, 3 H), 1.55 (m), 1.48 (s, 9 H),
1.45 (s, 9 H), 1.25–1.32 (m), 1.07–1.12 (m), 0.82–0.85 (t, J = 7.0 Hz,
6 H), 0.82–0.84 ppm (d, J = 6.6 Hz, 6 H). 13C NMR (125 MHz,
CDCl3): δ = 183.8, 173.2, 169.0, 152.1, 104.5, 100.1, 96.8, 82.0,
81.9, 79.7, 75.3, 56.1, 49.9, 36.2, 36.1, 34.5, 34.4, 29.624, 29.617,
28.6 28.4, 28.32, 28.27, 28.22, 28.19, 28.17, 28.09, 28.0, 26.6, 26.6,
19.7, 19.4, 19.34, 19.26, 14.0, 13.6, 13.0, 11.6 ppm. HRMS (ESI):
calcd. for C18H29O3 [M – H]– 293.2117; found 293.2127.
(S)-4-Hydroxy-3-methyl-6-(5-methylheptyl)-2H-pyran-2-one (1): A
solution of gold(I) catalyst 8 (9.2 mg, 0.01 mmol, 10.0 mol-%) and
17 (34.3 mg, 0.12 mmol) in MeNO2/AcOH (4:1) was stirred for 20 h
at room temperature. The mixture was diluted with EtOAc and
quenched with a saturated aqueous solution of NaHCO3. The or-
ganic layer was washed with brine, dried with Na2SO4, filtered,
and concentrated in vacuo. The crude residue was purified by flash
column chromatography (EtOAc/n-hexane = 1:4 to 1:2) to give 1
(22.5 mg, 0.09 mmol, 81%). 1H NMR (500 MHz, CD3OD): δ =
5.99 (s, 1 H), 2.47 (t, J = 7.6 Hz, 2 H), 1.85 (s, 3 H), 1.62 (m, 2 H),
1.36 (m, 2 H), 1.33 (m, 2 H), 1.32 (m, 1 H), 1.15 (m, 2 H), 0.87 (t,
J = 7.0 Hz, 3 H), 0.87 ppm (d, J = 6.5 Hz, 3 H). 13C NMR
(125 MHz, CD3OD): δ = 169.3, 168.2, 165.0, 101.3, 99.0, 37.5, 35.7,
34.4, 30.7, 28.4, 27.6, 19.7, 11.9, 8.4 ppm. HRMS (ESI): calcd. for
C14H22O3 [M]– 238.1569; found 238.1564.
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[6] For the preparation of ynoates 5 and 6, see the Supporting
Information.
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3567.
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13123.
Supporting Information (see footnote on the first page of this arti-
cle): Experimental procedures, characterization data, and copies of
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the H NMR and 13C NMR spectra for all new compounds.
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3772; b) N. G. Angelo, P. S. Arora, J. Am. Chem. Soc. 2005,
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Acknowledgments
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51, 3225–3230; Angew. Chem. 2012, 124, 3279–3284; b) R. C.
Livingston, B. M. Trost, J. Am. Chem. Soc. 2008, 130, 11970–
11978.
This work was partially supported by the Korea Institute of Ocean
Science and Technology (grant numbers PE98986, PE99214,
PE99273) and the Ministry of Oceans and Fisheries, Republic of
Korea (grant number PM57561).
[13] For a comparison of the 1H NMR and 13C NMR spectra of
synthetic 1 and 2 and natural violapyrone C, see: Table S2 in
the Supporting Information.
[1] J. Zhang, Y. Jiang, Y. Cao, J. Liu, D. Zheng, X. Chen, L. Han,
Received: May 1, 2014
Published Online:
C. Jiang, X. Huang, J. Nat. Prod. 2013, 76, 2126–2130.
Eur. J. Org. Chem. 0000, 0–0
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