Synlett 2007(19): 2983-2986  
DOI: 10.1055/s-2007-992366
LETTER
© Georg Thieme Verlag Stuttgart · New York

Synthetic Studies towards the Marine Natural Product Palmerolide A: Synthesis of the C3-C15 and C16-C23 Fragments

Guillaume Cantagrel, Christophe Meyer*, Janine Cossy*
Laboratoire de Chimie Organique, associé au CNRS, ESPCI, 10 Rue Vauquelin, 75231 Paris Cedex 05, France
Fax: +33(1)40794660; e-Mail: christophe.meyer@espci.fr; e-Mail: janine.cossy@espci.fr;
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Publikationsverlauf

Received 11 September 2007
Publikationsdatum:
08. November 2007 (online)

Abstract

The synthesis of the C3-C15 and C16-C23 fragments of the marine natural product palmerolide A has been achieved.

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The enantiomeric excess of alcohol 4 was determined by super-critical fluid (CO2) chromatography analysis of the corresponding p-nitrobenzoate derivative (4-nitrobenzoyl chloride, Et3N, CH2Cl2, r.t., 75%). Calibration was achieved with the racemic material obtained from ketone 3 by reduction (DIBAL-H, CH2Cl2, -78 °C to -30 °C, 70%) and subsequent condensation with p-nitrobenzoyl chloride.

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(3 S )-3-( tert -Butyldiphenylsilanyloxy)oct-7-en-1-yne (5) [α] d -37.5 (c 0.73, CHCl3). IR: 3305, 1640, 1589, 1427, 1105, 1086, 997, 911, 821, 739, 699 cm-1. 1H NMR (400 MHz, CDCl3): δ = 7.75-7.67 (m, 4 H), 7.45-7.34 (m, 6 H), 5.73 (ddt, J = 16.9, 10.2, 6.7 Hz, 1 H), 4.94 (dq, J = 16.9, 1.7 Hz, 1 H), 4.93-4.89 (m, 1 H), 4.34 (ddd, J = 6.6, 5.6, 2.1 Hz, 1 H), 2.30 (d, J = 2.1 Hz, 1 H), 2.01-1.95 (m, 2 H), 1.72-1.59 (m, 2 H), 1.58-1.45 (m, 2 H), 1.07 (s, 9 H). 13C NMR (100 MHz, CDCl3): δ = 138.5 (d), 136.0 (d, 2 C), 135.8 (d, 2 C), 133.6 (s), 133.5 (s), 129.7 (d), 129.6 (d), 127.6 (d, 2 C), 127.4 (d, 2 C), 114.6 (t), 85.0 (s), 72.6 (d), 63.5 (d), 37.6 (t), 33.2 (t), 26.9 (q, 3 C), 23.9 (t), 19.3 (s). MS (EI, 70 eV): m/z (%) = 305 (9)[(M - t-Bu + ], 227 (10), 207 (30), 200 (19), 199 (100), 181 (10), 147 (3), 135 (5), 123 (4), 105 (5), 77 (5). HRMS-FAB: m/z calcd for C24H30NaOSi [M + Na+]: 385.1958; found: 385.1953.

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(2 S )-(4-Methoxybenzylxoxy)-6-trimethysilanylhex-5-yn-1-ol (10)
[α] d -34.5 (c 0.50, CHCl3). IR: 3414, 2956, 2174, 1613, 1514, 1249, 1037, 842, 760 cm-1. 1H NMR (400 MHz, CDCl3): δ = 7.27 (br d, J = 8.7 Hz, 2 H), 6.88 (br d, J = 8.7 Hz, 2 H), 4.56 (d, AB syst, J = 11.2 Hz, 1 H), 4.51 (d, AB syst, J = 11.2 Hz, 1 H), 3.80 (s, 3 H), 3.75-3.69 (m, 1 H), 3.68-3.63 (m, 1 H), 3.55-3.50 (m, 1 H), 2.40-2.27 (m, 2 H), 1.86 (br s, 1 H, OH), 1.87-1.78 (m, 1 H), 1.75-1.67 (m, 1 H), 0.15 (s, 9 H). 13C NMR (100 MHz, CDCl3): δ = 159.3 (s), 130.4 (s), 129.4 (d, 2 C), 113.9 (d, 2 C), 106.6 (s), 85.0 (s), 77.9 (d), 71.6 (t), 63.9 (t), 55.2 (q), 29.9 (t), 15.9 (t), 0.00 (q, 3 C). MS (EI, 70 eV): m/z (%) = 291 (5)[M - Me+], 247 (4), 233 (8), 217 (5), 137 (9), 135 (13), 121 (100), 73 (10). HRMS-FAB: m/z calcd for C17H26NaO3Si [M + Na+]: 329.1543; found: 329.1537.

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( E )-(5 S ,6 S ,9 S )-6-( tert -Butyldimethylsilanyloxy)-9-( tert -butyldiphenylsilanyloxy)-5-(4-methoxybenzyl)tetra-deca-7,13-dien-1-yne (24)
[α] d -37.7 (c 0.79, CHCl3). IR: 3310, 1613, 1514, 1249, 1111, 1077, 1040, 836, 776, 741, 703 cm-1. 1H NMR (400 MHz, CDCl3): δ = 7.69-7.63 (m, 4 H), 7.43-7.31 (m, 6 H), 7.23 (app br d, J = 8.7 Hz, 2 H), 6.86 (app br d, J = 8.7 Hz, 2 H), 5.67 (ddt, J = 16.9, 10.2, 6.6 Hz, 1 H), 5.66 (ddd, J = 15.5, 6.7, 1.4 Hz, 1 H), 5.45 (ddd, J = 15.5, 4.9, 0.8 Hz, 1 H), 4.92-4.85 (m, 2 H), 4.58 (d, AB syst, J = 11.2 Hz, 1 H), 4.43 (d, AB syst, J = 11.2 Hz, 1 H), 4.22-4.16 (m, 2 H), 3.80 (s, 3 H), 3.42 (ddd, J = 9.7, 5.2, 2.9 Hz, 1 H), 2.24-2.15 (m, 2 H), 1.91 (t, J = 2.6 Hz, 1 H), 1.91-1.85 (m, 2 H), 1.69-1.61 (m, 1 H), 1.52-1.19 (m, 5 H), 1.05 (s, 9 H), 0.88 (s, 9 H), 0.02 (s, 3 H), -0.01 (s, 3 H). 13C NMR (75 MHz, CDCl3): δ = 159.1 (s), 138.8 (d), 136.0 (d, 2 C), 135.9 (d, 2 C), 134.5 (s), 134.3 (s), 133.8 (d), 131.0 (s), 129.5 (d), 129.4 (d), 129.3 (d, 2 C), 129.1 (d), 127.5 (d, 2 C), 127.4 (d, 2 C), 114.3 (t), 113.7 (d, 2 C), 84.5 (s), 80.7 (d), 73.8 (t), 72.7 (t), 72.6 (t), 68.3 (d), 55.3 (q), 37.3 (t), 33.6 (t), 28.7 (t), 27.1 (q, 3 C), 25.9 (q, 3 C), 23.8 (t), 19.3 (s), 18.2 (s), 15.0(t), -4.7 (q), -4.8 (q). C44H62O4Si2.