The Total Synthesis of Pygmaeocin C

Chin-Long Chin; Duong Duc-Phi Tran; Kak-Shan Shia; Hsing-Jang Liu

doi:10.1055/s-2004-837222

LETTER

The Total Synthesis of Pygmaeocin C

Chin-Long Chin^a, Duong Duc-Phi Tran^b, Kak-Shan Shia^a,b, Hsing-Jang Liu*^a,b
^a Department of Chemistry, National Tsing Hua University Hsinchu, Taiwan 30013, P. R. China
^b Department of Chemistry, University of Alberta, Edmonton, Alberta, T6G 2G2, Canada
Fax: +886-3-5720711; e-Mail: hjliu@mx.nthu.edu.tw;

Abstract

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Abstract

Making use of a recently developed intramolecular Friedel-Crafts alkylation process as the key operation, the first total synthesis, in racemic form, of pygmaeocin C has been achieved.

Key words

pygmaeocin C - total synthesis - intramolecular Friedel-Crafts alkylation

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References

1a Meng Q. Hesse M. Helv. Chim. Acta 1990, 73: 455

1b

The optical rotation of pygmaeocin C has not been reported. Its diacetate shows [α]_D ²² -425.5 (c 0.235, MeOH).

2 Liu HJ. Tran DDP. Tetrahedron Lett. 1999, 40: 3827

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4 Liu HJ. Shia KS. Han Y. Wang Y. Synlett 1995, 545

5

Compound 2: IR (neat): 2973, 2847, 2746, 1729, 1705, 1465, 1384, 1300, 1253, 1205, 1185, 1144 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 9.92 (t, J = 3.2 Hz, 1 H), 2.56-2.24 (m, 2 H), 2.36 (t, J = 3.2 Hz, 2 H), 2.31 (d, J = 14.4 Hz, 1 H), 2.16 (d, J = 14.4 Hz, 1 H), 1.94-1.89 (m, 2 H), 1.28 (s, 3 H), 0.93 (s, 6 H). ¹³C NMR (100 MHz, CDCl₃): δ = 210.1 (C=O), 202.8 (CHO), 51.8 (CH₂), 48.8 (CH₂), 41.1 (C), 38.1 (C), 37.5 (CH₂), 33.7 (CH₂), 24.0 (2 × CH₃), 20.1 (CH₃). HRMS (EI): m/z (%) = 182.1305 (5) [M⁺] (calcd for C₁₁H₁₈O₂: 182.1307), 138.1036 (100, calcd for C₉H₁₄O: 138.1045), 123.0801 (69, calcd for C₈H₁₁O: 123.0810).

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9

Compound 3: IR (neat): 2963, 2936, 1588, 1574, 1481, 1464, 1429, 1411, 1334, 1294, 1219, 1172, 1058, 1008 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 6.93 (d, J = 2.2 Hz, 1 H), 6.85 (d, J = 2.2 Hz, 1 H), 3.81 (s, 3 H), 3.76 (s, 3 H), 3.29 (sep, J = 6.8 Hz, 1 H), 1.17 (d, J = 6.8 Hz, 6 H). ¹³C NMR (100 MHz, CDCl₃): δ = 153.2 (C), 145.4 (C), 144.0 (C), 121.3 (CH), 116.4 (C), 113.1 (C), 60.7 (CH₃), 55.7 (CH₃), 26.7 (CH), 23.2 (2 × CH₃). HRMS (EI): m/z (%) = 258.0245 (1) [M⁺] (calcd for C₁₁H₁₅BrO₂: 258.0255), 180.9873 (100, calcd for C₅H₁₀BrO₂: 180.9864).

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11 Liotta D. Barnum C. Puleo R. Zima G. Bayer C. Kezar HS. J. Org. Chem. 1981, 46: 2920

12

Compound 19: IR (neat): 2963, 2874, 1744, 1716, 1690, 1580, 1487, 1463, 1318, 1280, 1234, 1148, 1067, 1010 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 7.27 (s, 1 H), 6.77 (d, J = 1.6 Hz, 1 H), 6.73 (d, J = 1.6 Hz, 1 H), 6.26 (d, J = 16.4 Hz, 1 H), 6.06 (d, J = 16.4 Hz, 1 H), 3.84 (s, 3 H), 3.80 (s, 3 H), 3.77 (s, 3 H), 3.29 (sep, J = 6.8 Hz, 1 H), 2.58 (d, J = 16.0 Hz, 1 H), 2.22 (d, J = 16.0 Hz, 1 H), 1.33 (s, 3 H), 1.18 (d, J = 6.8 Hz, 6 H), 1.01 (s, 3 H), 0.99 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 194.7 (C), 164.7 (C), 161.1 (CH), 152.6 (C), 146.3 (C), 142.4 (C), 132.2 (C), 131.2 (CH), 130.3 (C), 129.4 (CH), 117.0 (CH), 107.1 (CH), 60.8 (CH₃), 55.6 (CH₃), 52.1 (CH₃), 50.0 (CH₂), 45.8 (C), 39.1 (C), 26.7 (CH), 24.7 (CH₃), 24.1 (CH₃), 23.3 (2 × CH₃), 20.3 (CH₃). HRMS (EI): m/z (%) = 400.2243 (60) [M⁺] (calcd for C₂₄H₃₂O₅: 400.2250), 369.2062 (20, calcd for C₂₃H₂₉O₄: 369.2066), 316.1677 (100, calcd for C₁₉H₂₄O₄: 316.1675), 301.1456 (34, calcd for C₁₈H₂₁O₄: 301.1440).

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15

(±)-Pygmaeocin C: IR (neat): 3369, 2966, 2934, 2873, 1627, 1574, 1440, 1337, 1307, 1292, 1264, 1131, 1037 cm^-1. ¹H NMR (600 MHz, CDCl₃): δ = 7.95 (br s, 1 H), 7.05 (s, 1 H), 6.53 (s, 1 H), 6.35 (d, J = 9.7 Hz, 1 H), 5.90 (d, J = 9.7 Hz, 1 H), 3.26 (sep, J = 6.8 Hz, 1 H), 2.66 (d, J = 17.0 Hz, 1 H), 2.14 (d, J = 17.0 Hz, 1 H), 1.24 (d, J = 6.8 Hz, 3 H), 1.22 (s, 3 H), 1.21 (d, J = 6.8 Hz, 3 H), 1.16 (s, 3 H), 0.93 (s, 3 H). ¹³C NMR (150 MHz, CDCl₃): δ = 201.0 (C), 163.0 (C), 144.5 (C), 142.1 (C), 138.5 (C), 130.5 (CH), 127.2 (C), 125.6 (CH), 124.1 (CH), 116.6 (CH), 114.8 (C), 48.3 (CH₂), 45.3 (C), 38.8 (C), 27.3 (CH), 26.1 (CH₃), 24.3 (CH₃), 22.5 (CH₃), 22.2 (CH₃), 21.3 (CH₃). HRMS (EI): m/z (%) = 312.1724 (14) [M⁺] (calcd for C₂₀H₂₄O₃: 312.1725), 294.1626 (16, calcd for C₂₀H₂₂O₂: 294.1620), 256.1094 (55, calcd for C₁₆H₁₆O₃: 256.1099), 228.1148 (100, calcd for C₁₅H₁₆O₂: 228.1150), 213.0916 (28, calcd for C₁₄H₁₃O₂: 213.0916).