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Synlett 2010(20): 3061-3064  
DOI: 10.1055/s-0030-1259052
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

A New and Efficient Total Synthesis of (±)-Laurencenone C

Kuo-Ching Chua, Hsing-Jang Liu*a, Jia-Liang Zhu*b
a Department of Chemistry, National Tsing Hua University, Hsinchu 30043, Taiwan, Republic of China
Fax: +886(3)35665; e-Mail: hjliu@mx.nthu.edu.tw;
b Department of Chemistry, National Dong-Hwa University, Hualien 974, Taiwan, Republic of China
Fax: +886(3)8633570; e-Mail: jlzhu@mail.ndhu.edu.tw;
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Publikationsverlauf

Received 14 September 2010
Publikationsdatum:
17. November 2010 (online)

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Abstract

A novel total synthesis of laurencenone C, a chamigrene sesquitepenoid natural product, has been accomplished in 11 steps. In the synthetic sequence, the B-ring of the spirocyclic core was constructed by a one-pot operation involving a Knoevenagel condensation between ethyl cyanoacetate and paraformaldehyde combined with a Diels-Alder reaction of the resulting ethyl 2-cyanoacrylate with isoprene. Moreover, a lithium naphthalenide-induced reductive alkylation of the Diels-Alder adduct was employed to create the C-6 quaternary center and to set the stage for assembling the A-ring.

Key words

chamigrene sesquitepene - laurencenone C - Diels-­Alder reaction - natural product - total synthesis

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  • 17 The spectral data of 1 are as follows. IR (neat): 3023, 2960, 2932, 1668, 1610, 1445 cm-¹; ¹H NMR (CDCl3, 400 MHz): δ = 5.77 (s, 1 H), 5.41 (s, 1 H), 2.53 (d, J = 18.2 Hz, 1 H), 2.15 (d, J = 18.2 Hz, 1 H), 1.88 (s, 3 H), 1.98-1.91 (m, 2 H), 1.82-1.78 (m, 2 H), 1.68-1.64 (m, 2 H), 1.59 (s, 3 H), 0.94 (s, 3 H), 0.86 (s, 3 H); ¹³C NMR (CDCl3, 100 MHz): δ = 198.5 (C), 170.3 (C), 133.9 (C), 126.8 (CH), 121.4 (CH), 48.8 (CH2), 43.2 (C), 40.2 (C), 30.5 (CH2), 28.1 (CH2), 27.8 (CH2), 24.7 (CH3), 24.1 (CH3), 23.7 (CH3), 23.2 (CH3); HRMS (EI): m/z [M]+ calcd for C15H22O: 218.1671; found: 218.1669.The spectral data of the key intermediate 4 are as follows. IR (neat): 3035, 2960, 2912, 1674, 1447 cm-¹; ¹H NMR (CDCl3, 600 MHz): δ = 6.67-6.64 (m, 1 H, major), 6.63-6.61 (m, 1 H, minor), 5.87-5.82 (m, 2 H), 5.31 (d, J = 1.3 Hz, 1 H, minor), 5.26 (d, J = 1.5 Hz, 1 H, major), 2.69 (ddt, J = 17.7, 5.4, 2.7 Hz, 1 H, minor), 2.55 (ddt, J = 20, 5.5, 2.8 Hz, 1 H, major), 2.46-2.43 (m, 1 H, minor), 2.19-2.17 (m, 2 H), 2.13-2.04 (m, 4 H), 1.92-1.64 (m, 9 H), 1.59-1.57 (m, 6 H), 0.91-0.86 (m, 6 H); ¹³C NMR (CDCl3, 150 MHz): δ (major) = 204.6 (C), 145.8 (CH), 133.5 (C), 128.3 (CH), 118.2 (CH), 46.7 (C), 35.8 (CH), 37.5 (CH2), 31.2 (CH2), 26.5 (CH2), 24.3 (CH2), 23.2 (CH3), 15.5 (CH3). ¹³C NMR δ (minor) = 203.9 (C), 145.0 (CH), 132.1 (C), 127.9 (CH), 119.0 (CH), 47.5 (C), 32.4 (CH), 31.5 (CH2), 29.6 (CH2), 28.9 (CH2), 27.9 (CH2), 23.2 (CH3), 15.5 (CH3); HRMS (EI): m/z [M]+ calcd for C13H18O: 190.1358; found: 190.1362.The spectral data of the key intermediate 6 are as follows. IR (neat): 2957, 2929, 2857, 1726, 1447 cm-¹; ¹H NMR (CDCl3, 600 MHz): δ = 5.28 (br s, 2 H), 4.06-4.03 (m, 4 H), 3.61-3.59 (m, 2 H), 3.51-3.48 (m, 2 H), 2.44-2.36 (m, 2 H), 1.96-1.72 (m, 14 H), 1.60 (s, 6 H), 1.17-1.15 (m, 6 H), 1.10-1.02 (m, 2 H), 0.84-0.81 (m, 24 H), -0.02 to -0.03 (m, 12 H); ¹³C NMR (CDCl3, 150 MHz): δ = 175.8 (C), 175.7 (C), 133.0 (C), 132.9 (C), 119.8 (CH), 119.6 (CH), 61.6 (CH2), 61.5 (CH2), 59.8 (CH2), 48.3 (C), 36.3 (CH), 36.1 (CH), 29.6 (CH2), 29.4 (CH2), 28.6 (CH2), 28.5 (CH2), 28.0 (CH2), 27.9 (CH2), 25.8 (CH3), 23.1 (CH3), 18.2 (C), 14.7 (CH3), 14.1 (CH3), 13.9 (CH3), -5.35 (CH3), -5.43 (CH3); HRMS (EI): m/z [M]+ calcd for C20H38O3Si: 354.2590; found: 354.2593.The spectral data of the key intermediate 11 are as follows. IR (neat): 2920, 1651, 1614 cm-¹; mp 106.3-107.6 ˚C; ¹H NMR (CDCl3, 600 MHz): δ = 5.96 (s, 2 H), 5.46 (t, J = 1.6 Hz, 1 H), 2.13-2.11 (m, 2 H), 2.03-2.01 (m, 2 H), 1.95 (s, 6 H), 1.67-1.65 (m, 5 H); ¹³C NMR (CDCl3, 150 MHz): δ = 185.9 (C), 166.5 (C), 133.5 (C), 126.8 (2CH), 119.5 (CH), 44.1 (C), 31.9 (CH2), 29.5 (CH2), 27.3 (CH2), 23.4 (CH3), 21.4 (CH3), 21.3 (CH3); HRMS (EI): m/z [M]+ calcd for C14H18O: 202.1358; found: 202.1358cc
14

The relative stereochemistry of two diastereoisomers remains to be determined.