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DOI: 10.1055/s-2007-985600
Synthesis of the FG Fragment of the Pectenotoxins
Publication History
Publication Date:
22 August 2007 (online)
Abstract
The synthesis of the FG subunit of the pectenotoxins is reported herein. The synthesis hinges on the preparation of an appropriately functionalized acyclic precursor using a Z-selective Wittig reaction. Further elaboration using two sequential cyclization reactions furnished the tetrahydrofuran F ring and the tetrahydropyran G ring, respectively.
Key words
cyclization - Wittig reaction - epoxidation - shellfish toxins - pectenotoxins
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References and Notes
Selected Spectral Data
Compound 18: [α]D +7.2 (c 7.20, CHCl3). HRMS: m/z calcd for C37H57O6Si: 625.3924; found: 625.3919 [M - H]+. IR: νmax = 3433, 2929, 2856, 1613, 1514, 1463, 1249, 1083, 835, 775 cm-1. 1H NMR (300 MHz, CDCl3): δ = 0.01 (3 H, s, Me2
t-BuSi), 0.03 (3 H, s, Me2
t-BuSi), 0.85-0.94 (18 H, m, Me2
t-BuSi, CH3, H-2′′), 1.25-1.30 (1 H, m, H-2), 1.61-1.71 (5 H, m, H-1′′, H-3), 1.82-1.94 (1 H, m, H-2), 2.10-2.30 (2 H, m, H-7), 3.45-3.50 (3 H, m, H-1, H-8), 3.60-3.67 (1 H, m, H-5′), 3.80 (3 H, s, OMe), 3.94-4.00 (1 H, m, H-5′), 4.17-4.20 (2 H, m, H-4, H-4′), 4.49-4.71 (4 H, m, CH2Ar), 5.40-5.54 (2 H, m, H-5, H-6), 6.86-6.89 (2 H, m, ArH), 7.26-7.35 (7 H, m, ArH). 13C NMR (75 MHz, CDCl3): δ = -4.8 (CH3, Me2
t-BuSi), -4.2 (CH3, Me2
t-BuSi), 8.1 (CH3, C-2′′), 8.3 (CH3, C-2′′), 15.4 (CH3, Me), 18.1 (C, Me2
t-BuSi), 25.8 (CH3, Me2
t-BuSi), 29.2 (CH2, C-7), 29.6 (2 × CH2, C-1′′), 31.6 (CH2, C-2), 37.3 (CH, C-3), 55.2 (CH3, OMe), 66.4 (CH2, C-5′), 68.9 (CH2, C-1), 72.6 (CH2Ar), 72.8 (CH2Ar), 72.6 (CH, C-4), 78.5 (CH, C-4′), 79.1 (CH, C-8), 113.2 (C, C-2′), 113.7 (CH, ArH), 125.4 (CH, C5 or C6), 127.4 (CH, ArH), 127.6 (CH, ArH), 128.3 (CH, ArH), 129.4 (CH, ArH), 130.7 (C, Ar), 134.0 (CH, C5 or C6), 138.7 (C, Ar), 159.2 (C, Ar). MS-FAB: m/z (%) = 627 (0.1) [MH+], 625 (0.2), 598 (0.2), 495 (0.2), 211 (3), 137 (3), 121 (100), 91 (25) [CH2Ph], 73 (16).
Selected Spectral Data
Compound 20: [α]D -6.9 (c 1.75, CHCl3). HRMS: m/z calcd for C42H55O7Si: 699.3717; found: 699.3721 [MH+]. IR: νmax = 3469, 3069, 2930, 2856, 1612, 1513, 1247, 1110 cm-1. 1H NMR (300 MHz, CDCl3): δ = 0.99 (3 H, d, J = 6.85 Hz, CH3), 1.08 (9 H, s, Ph2
t-BuSi), 1.41-1.61 (2 H, m, H-4), 1.65-1.69 (2 H, dd, J = 11.5, 4.0 Hz, H-3′), 1.50-1.72 (1 H, m, H-3), 2.20-2.27 (1 H, br, C-1′′-OH), 2.66 (1 H, d, J = 8.0 Hz, C-1-OH), 3.15-3.34 (2 H, m, H-5), 3.34-3.42 (1 H, m, H-1), 3.56-3.72 (3 H, m, H-1′′, H-2), 3.80 (3 H, s, OMe), 3.88 (1 H, m, H-5′), 4.06-4.10 (2 H, m, H-4′, H-2′) 4.22 (1 H, d, J = 11.5 Hz, CH2Ar), 4.35-4.41 (2 H, m, CH2Ar), 4.44 (1 H, d, J = 11.5 Hz, CH2Ar), 6.85-6.88 (2 H, m, ArH), 7.16-7.37 (13 H, m, ArH), 7.66-7.69 (4 H, m, ArH). 13C NMR (75 MHz, CDCl3): δ = 15.4 (CH3, CHCH3), 19.6 (C, Ph2
t-BuSi), 27.2 (3 × CH3, Ph2
t-BuSi), 32.5 (CH2, C-4), 33.9 (CH2, C-3′), 34.7 (CH, C-3), 55.3 (CH3, OMe), 62.0 (CH2, C-1′′), 68.6 (CH2, C-5), 71.1 (CH2, CH2Ar), 72.0 (CH, C-1), 72.9 (CH2, CH2Ar), 76.5 (CH, C-2), 79.2 (CH, C-4′), 79.8 (CH, C-2′), 81.5 (CH, C-5′), 113.9 (CH, Ar), 127.5 (C, Ar), 127.5 (C, Ar), 127.6 (C, Ar), 128.3 (CH, Ar), 129.0 (CH, Ar), 129.8 (CH, Ar), 129.8 (CH, Ar), 133.6 (C, Ar), 133.7 (C, Ar), 136.0 (CH, Ar), 136.1 (CH, Ar), 138.4 (C, Ar), 159.3 (C, Ar). MS-FAB: m/z (%) = 699 (0.2) [MH+], 199 (10), 197 (8), 137 (14), 136 (13), 135 (9), 122 (10), 121 (100), 91 (27).
Selected Spectral Data
Compound 2: [α]D -6.0 (c 0.2, CHCl3). HRMS: m/z calcd for C41H55O8Si: 703.3666; found: 703.3670 [M - H]+. IR: νmax = 2932, 1729, 1613, 1514, 1428, 1248, 1170, 1093, 821, 703 cm-1. 1H NMR (300 MHz, CDCl3): δ = 1.03-1.16 (20 H, m, Ph2
t-BuSi, H-3′), 1.21 (3 H, d, J = 7.2 Hz, C-4-CH3), 1.34-1.40 (1 H, m, H-5), 1.64-1.76 (1 H, m, H-5), 1.99-2.09 (1 H, m, H-4), 3.39 (3 H, s, C-2-OMe), 3.42-3.47 (2 H, m, H-6), 3.61 (1 H, d, J = 5.0 Hz, H-3), 3.73-3.77 (1 H, m, H-4′), 3.80 (3 H, OMe, OPMB), 3.93-3.98 (1 H, m, H-5′), 4.03-4.07 (1 H, m, CH2, OPMB), 4.10-4.21 (2 H, m, H-1′′), 4.23-4.27 (1 H, m, CH2, OPMB), 4.41 (1 H, t, J = 7.5 Hz, H-2′), 6.82-6.86 (2 H, m, ArH), 7.09-7.12 (2 H, m, ArH), 7.30-7.42 (6 H, m, ArH), 7.65-7.76 (4 H, m, ArH). 13C NMR (75 MHz, CDCl3): δ = 14.1 (CHCH3), 19.7 (C, Ph2
t-BuSi), 27.1 (CH3, t-Bu), 27.1 (CH3, t-Bu), 27.2 (CH3, t-Bu), 30.4 (CH2, C-5), 31.6 (CH, C-4), 32.6 (CH2, C-3′), 50.4 (CH3, C-2-OMe), 55.3 (OCH3, OPMB), 56.4 (CH2, C-6), 63.0 (CH2, C-1′′), 70.4 (CH2, OPMB), 73.0 (CH, C-3), 78.2 (CH, C-4’), 79.8 (CH, C-5′), 80.0 (CH, C-2′), 100.6 (C, C-2), 113.8 (CH, OPMB), 127.4 (CH, Ar), 127.5 (CH, Ar), 128.8 (CH, Ar), 129.5 (CH, Ar), 129.6 (CH, Ar), 130.3 (C, Ar), 133.8 (C, Ar), 134.1 (C, Ar), 136.2 (CH, Ar), 136.2 (CH, Ar), 159.1 (C, OPMB), 178.2 (C=O). MS-FAB: m/z (%) = 703 (0.1) [M - H]+, 673 (2), 647 (0.2), 617 (2), 597 (2), 383 (18), 239 (7), 197 (7), 121 (100), 89 (18).
The stereochemistry at C2 in 2 was assumed to be that in which the OMe group adopts an axial position due to stabilization by the anomeric effect.