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

Kuo-Ching Chu; Hsing-Jang Liu; Jia-Liang Zhu

doi:10.1055/s-0030-1259052

LETTER

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

Kuo-Ching Chu^a, 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;

Abstract

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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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Referenzen

References and Notes

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The relative stereochemistry of two diastereoisomers remains to be determined.

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<A NAME="RW14610ST-17">17</A> 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: 202.1358^cc

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