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DOI: 10.1055/s-2007-985585
Synthetic Studies on Azaspiracid: Synthesis of Key Intermediate for the Construction of the FGHI Ring System
Publikationsverlauf
Publikationsdatum:
14. August 2007 (online)
Abstract
A highly stereoselective and convergent approach for the key intermediate of the FGHI ring system of azaspiracid is described. The synthesis features the desymmetrization strategy for the construction of the C27-C33 fragment, Masamune-Roush coupling conditions for the C33-C34 bond formation, and Sharpless asymmetric dihydroxylation as the key steps. One more important feature of this synthetic route is that we can synthesize other enantiomers of the FGHI ring system by changing asymmetric hydroboration conditions and valerolactone.
Key words
desymmetrization - Masamune-Roush coupling conditions - Sharpless asymmetric dihydroxylation - asymmetric hydroboration
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References and Notes
Analytical Data for Compound 18: Liquid; [α]D 25 -20.18 (c = 2.0, CHCl3). IR (Neat): 2958, 2172, 1671, 1613, 1513, 1462, 1427, 1249, 1172, 1110, 1036, 843 cm-1. 1H NMR (300 MHz, CDCl3): δ = 0.13 (s, 9 H), 0.85 (d, J = 6.7 Hz, 3 H), 0.89 (m, 1 H), 0.94 (d, J = 6.6 Hz, 3 H), 0.98 (d, J = 6.2 Hz, 3 H), 1.04 (s, 9 H), 1.49-1.61 (m, 1 H), 1.64-1.78 (m, 2 H), 2.14-2.45 (m, 6 H), 2.55-2.65 (m, 1 H), 3.25-3.32 (m, 1 H), 3.37 (dd, J = 6.4, 9.8 Hz, 1 H), 3.45-3.52 (m, 1 H), 3.76 (s, 3 H), 4.33 (q, J = 11.3, 16.6 Hz, 2 H), 6.06 (d, J = 15.8 Hz, 1 H), 6.66-6.78 (m, 1 H), 6.75 (d, J = 8.6 Hz, 2 H), 7.09 (d, J = 8.6 Hz, 2 H), 7.29-7.42 (m, 6 H), 7.59-7.65 (m, 4 H). 13C NMR (100 MHz, CDCl3): δ = 0.1, 15.6, 18.1, 19.2, 19.5, 26.8, 26.9, 28.8, 33.3, 33.5, 34.5, 36.4, 45.6, 55.1, 68.7, 71.6, 81.2, 86.2, 105.2, 113.6, 127.5, 129.2, 129.5, 130.5, 132.1, 133.8, 135.5, 144.7, 159.0, 199.4. HRMS (ESI): m/z [M + NH4]+ calcd for C44H62O4Si2: 728.4530; found: 728.4501.
14Analytical Data for Compound 19: Liquid; [α]D 25 -2.584 (c = 0.6, CHCl3). IR (Neat): 2958, 2931, 2172, 1714, 1610, 1513, 1462, 1374, 1301, 1249, 1169, 1082, 1034, 844, 758, 703, cm-1. 1H NMR (300 MHz, CDCl3): δ = 0.12 (s, 9 H), 0.85 (d, J = 6.7 Hz, 3 H), 0.97 (d, J = 4.5 Hz, 6 H), 1.05 (s, 9 H), 1.30-1.39 (m, 1 H), 1.36 (s, 3 H), 1.40 (s, 3 H), 1.48-1.62 (m, 2 H), 1.68-1.90 (m, 3 H), 2.12-2.27 (m, 3 H), 2.35 (dd, J = 6.0, 18.1 Hz, 1 H), 2.74 (dd, J = 6.0, 18.1 Hz, 1 H), 3.29-3.47 (m, 2 H), 3.48-3.58 (m, 1 H), 3.76 (s, 3 H), 3.85 (d, J = 7.5 Hz, 1 H), 3.96-4.10 (m, 1 H), 4.24 (d, J = 11.3 Hz, 1 H), 4.37 (d, J = 11.3 Hz, 1 H), 6.74 (d, J = 9.0 Hz, 2 H), 7.08 (d, J = 8.3 Hz, 2 H), 7.64 (m, 6 H), 7.60-7.68 (d, J = 6.7 Hz, 4 H). 13C NMR (100 MHz, CDCl3): δ = 0.1, 15.8, 18.4, 19.2, 19.4, 26.2, 26.6, 26.8, 27.3, 33.2, 33.4, 35.3, 35.8, 44.0, 55.2, 68.7, 71.7, 75.3, 79.6, 85.5, 86.2, 105.1, 109.9, 113.6, 127.5, 129.1, 129.4, 131.0, 133.9, 135.6, 158.9, 208.9. HRMS (ESI): m/z [M + Na]+ calcd for C47H68O6Si2: 807.4452; found: 807.4474.
15Analytical Data for Compound 20: Viscous liquid; [α]D 25 -21.804 (c = 0.6, CHCl3). IR (KBr): 794, 1071, 1248, 1513, 2172, 2958 cm-1. 1H NMR (300 MHz, CDCl3): δ = 0.12 (s, 9 H), 0.78-0.86 (d, J = 6.7 Hz, 3 H), 0.87-0.93 (d, J = 6.7 Hz, 3 H), 0.94-1.00 (d, J = 6.0 Hz, 3 H), 1.04 (s, 10 H), 1.21-1.39 (m, 1 H), 1.33 (s, 3 H), 1.35 (s, 3 H), 1.40-1.88 (m, 7 H), 1.99-2.10 (dd, J = 6.7, 16.6 Hz, 1 H), 2.12-2.22 (dd, J = 5.2, 16.6 Hz, 1 H), 3.31-3.40 (dd, J = 6.7, 9.8 Hz, 1 H), 3.42-3.56 (m, 3 H), 3.58-3.65 (dd, J = 3.7, 8.3 Hz, 1 H), 3.73 (s, 3 H), 4.01-4.14 (m, 1 H), 4.24-4.32 (d, J = 10.5 Hz, 1 H), 4.34-4.42 (d, J = 11.3 Hz, 1 H), 4.48-4.56 (d, J = 12.0 Hz, 1 H), 4.58-4.65 (d, J = 11.3 Hz, 1 H), 6.64-6.71 (d, J = 8.3 Hz, 2 H), 7.03-7.10 (d, J = 8.3 Hz, 2 H), 7.17-7.27 (m, 5 H), 7.29-7.41 (m, 6 H), 7.59-7.68 (d, J = 7.5 Hz, 4 H). 13C NMR (75 MHz, CDCl3): δ = 0.1, 15.7, 18.5, 18.8, 19.2, 26.8, 27.0, 27.5, 27.7, 28.8, 33.4, 33.7, 35.8, 36.1, 37.1, 55.1, 68.7, 72.2, 72.4, 74.0, 75.9, 79.9, 80.0, 82.9, 85.7, 99.9, 105.8, 108.2, 113.5, 127.3, 127.5, 127.7, 128.2, 129.0, 129.4, 131.2, 133.9, 135.5, 138.5, 158.8. HRMS (ESI): m/z [M + Na]+ calcd for C54H76O6Si2: 899.5078; found: 899.5051.
16Analytical Data for Compound 21: Viscous liquid; [α]D 25 -15.098 (c = 0.25, CHCl3). IR (Neat): 3310, 2950, 2885, 2097, 1736, 1612, 1513, 1463, 1362, 1247, 1081, 837, 773, 632 cm-1. 1H NMR (400 MHz, CDCl3): δ = 0.01 (s, 3 H), 0.02 (s, 3 H), 0.06 (s, 3 H), 0.07 (s, 3 H), 0.74 (d, J = 6.5 Hz, 3 H), 0.88 (s, 9 H), 0.92 (s, 9 H), 0.94 (d, J = 6.5 Hz, 3 H), 0.97 (d, J = 6.5 Hz, 3 H), 0.85-1.08 (m, 3 H), 1.40-1.55 (m, 2 H), 1.66-1.91 (m, 4 H), 1.94-2.06 (m, 1 H), 2.07-2.17 (m, 2 H), 2.90 (dd, J = 7.3, 11.7 Hz, 1 H), 3.08-3.17 (m, 1 H), 3.33-3.41 (m, 1 H), 3.52-3.58 (m, 1 H), 3.67-3.75 (m, 1 H), 3.79 (s, 3 H), 3.93 (dd, J = 3.6, 10.2 Hz, 1 H), 4.25 (d, J = 10.2 Hz, 1 H), 4.51 (d, J = 10.9 Hz, 1 H), 4.62 (d, J = 11.7 Hz, 1 H), 4.69 (d, J = 12.4 Hz, 1 H), 6.79 (d, J = 8.7 Hz, 2 H), 7.17 (d, J = 8.7 Hz, 2 H), 7.23-7.31 (m, 5 H). 13C NMR (75 MHz, CDCl3): δ = -4.7, -4.5, -4.2, -3.1, 16.6, 17.9, 18.9, 19.2, 25.6, 25.9, 26.7, 28.7, 31.3, 31.4, 35.2, 38.6, 55.2, 57.4, 69.3, 70.4, 71.7, 71.9, 75.7, 77.8, 80.3, 83.0, 113.5, 120.4, 127.0, 127.3, 128.1, 128.7, 131.5, 139.5, 158.8. HRMS (ESI): m/z [M + Na]+ calcd for C44H73N3O5Si2: 802.4986; found: 802.4968.
17Analytical data for Compound 22: Liquid; [α]D 25 -47.136 (c = 1.1, CHCl3). IR (Neat): 3417, 2119, 1618, 1389, 1204, 772 cm-1. 1H NMR (400 MHz, CDCl3): δ = 0.95 (d, J = 6.5 Hz, 3 H), 1.06 (d, J = 6.5 Hz, 3 H), 1.09 (d, J = 6.5 Hz, 3 H), 1.23-1.36 (m, 2 H), 1.45-1.71 (m, 3 H), 1.74-2.05 (m, 3 H), 2.18 (dd, J = 2.1, 5.8 Hz, 2 H), 2.61 (m, 1 H), 2.68 (d, J = 5.8 Hz, 2 H), 3.07-3.21 (m, 2 H), 3.40 (m, 1 H), 3.64-3.71 (m, 1 H), 3.74 (s, 0.5 H), 3.85 (s, 0.5 H), 4.07-4.15 (m, 1 H), 4.52 (d, J = 11.7 Hz, 1 H), 4.68 (d, J = 11.7 Hz, 1 H), 7.27-7.41 (m, 5 H). 13C NMR (75 MHz, CDCl3): δ = 17.0, 17.8, 19.7, 25.9, 28.8, 31.4, 36.2, 37.0, 44.3, 44.5, 57.6, 68.3, 69.7, 71.9, 73.8, 78.6, 82.5, 127.9, 128.2, 128.5, 137.8, 213.9. HRMS (ESI): m/z [M + Na]+ calcd for C24H35N3O4: 452.2525; found: 452.2512.
18Analytical data for Compound 5 (Major Diastereomer): Liquid; [α]D 25 -18.801 (c = 0.6, CHCl3). IR (Neat): 3418, 2925, 2097, 1665, 1622, 1553, 1527, 1383, 1111, 616 cm-1. 1H NMR (400 MHz, CDCl3): δ = 0.92 (d, J = 7.1 Hz, 3 H), 0.99 (d, J = 6.2 Hz, 3 H), 1.01 (d, J = 7.1 Hz, 3 H), 1.39 (s, 1 H), 1.54-1.73 (m, 3 H), 1.77-2.05 (m, 4 H), 2.07-2.23 (m, 4 H), 2.55 (d, J = 7.1 Hz, 1 H), 3.07 (dd, J = 6.2, 11.6 Hz, 1 H), 3.18 (s, 3 H), 3.24 (dd, J = 6.2, 11.6 Hz, 1 H), 3.85-3.91 (m, 1 H), 3.95 (dd, J = 3.5, 6.2 Hz, 1 H), 4.37-4.44 (m, 1 H), 4.65 (d, J = 11.6 Hz, 1 H), 4.77 (d, J = 11.6 Hz, 1 H), 7.27-7.40 (m, 5 H). 13C NMR (100 MHz, CDCl3): δ = 16.3, 18.8, 19.2, 26.2, 28.7, 32.1, 32.4, 36.9, 37.0, 43.3, 47.7, 57.5, 69.6, 72.4, 72.5, 76.2, 82.8, 83.2, 111.2, 127.6, 127.9, 128.3, 138.5. HRMS (ESI): m/z [M + Na]+ calcd for C25H37N3O4: 466.2681; found: 466.2680.