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DOI: 10.1055/s-0029-1219557
First Total Syntheses of (+)-Garvensintriol and (+)-5-epi-Garvensintriol
Publication History
Publication Date:
26 February 2010 (online)
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Abstract
A concise and efficient carbohydrate-based approach for the total syntheses of (+)-garvensintriol and (+)-5-epi-garvensintriol is described in nine and six steps with 20% and 37% overall yield, respectively, starting from a known intermediate. A sequence of Grignard-assisted lactol opening with terminal alkyne, stereoselective keto reduction and oxidative lactonization are the key reactions.
Keywords
garvensintriol - goniotriol - cytotoxic - oxidative lactonization - Grignard-assisted lactol opening
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References and Notes
Analytical and Spectral Data of 8: white solid; mp 67 ˚C; [α]D ²5 +48.0 (c = 1.0, CHCl3). ¹H NMR (300 MHz, CDCl3): δ = 7.15-7.62 (m, 15 H), 4.60 (d, J = 6.0 Hz, 1 H), 4.46 (d, J = 13.6 Hz, 3 H), 4.29 (d, J = 11.3 Hz, 1 H), 3.96 (dd, J = 7.6, 2.7 Hz, 1 H), 3.48-3.72 (m, 4 H), 3.23 (br s, 1 H), 2.96 (br s, 1 H), 1.89 (br s, 1 H), 1.50-1.81 (m, 4 H). ¹³C NMR (75 MHz, CDCl3): δ = 137.9, 137.5, 137.5, 128.4, 128.3, 128.2, 128.0, 127.9, 127.7, 83.2, 80.3, 74.3, 71.7, 71.5, 70.7, 62.6, 28.2, 24.9. MS (ESI): m/z = 437 [M + H]+.
13Analytical and Spectral Data of 17: white solid; mp 139 ˚C; [α]D ²5 = -22.2 (c = 1.5, CHCl3). IR (neat): 3395, 3029, 2960, 2911, 2859, 1746, 1453, 1396, 1259, 1086, 1028, 761, 705 cm-¹. ¹H NMR (300 MHz, CDCl3): δ = 7.17-7.51 (m, 15 H), 4.31-4.59 (m, 5 H), 4.19 (d, J = 11.3 Hz, 1 H), 3.99-4.12 (m, 2 H), 2.56-2.79 (m, 1 H), 2.19-2.55 (m, 2 H), 1.93-2.16 (m, 2 H). ¹³C NMR (75 MHz, CDCl3): δ = 171.2, 137.7, 137.2, 128.6, 128.5, 128.4, 128.3, 128.2, 127.8, 127.7, 127.7, 81.8, 81.0, 74.4, 70.7, 70.5, 69.7, 26.0, 22.7. MS (ESI): m/z = 455 [M + Na]+.
15Analytical and Spectral Data of 2: white solid; mp 163 ˚C; [α]D ²5 -10.1 (c = 0.5, EtOH). IR (neat): 3533, 3346, 2923, 1773, 1200, 1083, 1026, 897, 850, 705, 673 cm-¹. ¹H NMR (300 MHz, CD3OD): δ = 7.07-7.51 (m, 5 H), 4.77 (m, 2 H), 4.60 (br s, 3 H), 3.65-3.78 (m, 2 H), 2.09-2.62 (m, 4 H). ¹H NMR (300 MHz, DMSO-d 6): δ = 7.12-7.53 (m, 5 H), 5.35 (dd, J = 13.8, 3.8 Hz, 2 H), 4.84 (d, J = 4.9 Hz, 1 H), 4.71 (s, 2 H), 3.44-3.66 (m, 2 H), 1.95-2.48 (m, 4 H). ¹³C NMR (75 MHz, CD3OD): δ = 180.8, 142.2, 129.9, 128.9, 128.6, 83.1, 76.4, 75.3, 73.4, 29.8, 21.8. MS (ESI): m/z = 275 [M + Na]+.
17Crystallographic data for the structure in this paper have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication number CCDC 755246 for 17. Copies of the data can be obtained free of charge on application to CCDC, 12 Union Road, Cambridge, CB2 1EZ, UK [fax: +44 (1223)336033 or e-mail: deposit@ccdc.cam.ac.uk].
18Analytical and Spectral Data of 7: white solid; mp 93 ˚C; [α]D ²5 +26.4 (c = 1.5, CHCl3). ¹H NMR (300 MHz, CDCl3): δ = 7.17-7.50 (m, 15 H), 4.40-4.64 (m, 4 H), 4.24 (d, J = 11.5 Hz, 1 H), 3.99 (t, J = 5.7 Hz, 1 H), 3.75 (t, J = 5.5 Hz, 1 H), 3.48 (t, J = 6.0 Hz, 2 H), 3.38 (d, J = 7.6 Hz, 1 H), 2.90 (br s, 3 H), 1.61-1.74 (m, 2 H), 1.38-1.52 (m, 2 H). ¹³C NMR (75 MHz, CDCl3): δ = 137.9, 137.6, 137.5, 128.4, 128.3, 128.2, 128.0, 127.8, 82.6, 78.3, 74.3, 72.3, 72.0, 70.6, 62.5, 28.5, 26.5. MS (ESI): m/z = 437 [M + H]+.
19Analytical and Spectral Data of 19: white solid; mp 127 ˚C; [α]D ²5 = +3.2 (c = 0.5, CHCl3). IR (neat): 3464, 3030, 2923, 1736, 1494, 1452, 1354, 1239, 1201, 1090, 1055, 741, 700, 579 cm-¹. ¹H NMR (300 MHz, CDCl3): δ = 7.20-7.54 (m, 15 H), 4.75 (d, J = 3.6 Hz, 1 H), 4.60 (d, J = 11.7 Hz, 1 H), 4.41-4.55 (m, 3 H), 4.31 (d, J = 11.3 Hz, 1 H), 3.95 (br s, 1 H), 3.74 (dd, J = 8.7, 1.5 Hz, 1 H), 2.58-2.76 (m, 1 H), 2.88 (br s, 1 H), 2.35-2.56 (m, 1 H), 2.78-2.15 (m, 1 H), 1.57-1.78 (m, 1 H). ¹³C NMR (75 MHz, CDCl3): δ = 169.9, 137.7, 137.5, 136.3, 128.4, 128.2, 128.1, 128.0, 127.9, 127.8, 127.7, 80.7, 80.5, 71.3, 71.1, 71.0, 68.2, 25.4, 23.0. MS (ESI): m/z = 455 [M + Na]+.
20Analytical and Spectral Data of 1: [α]D ²5 +70.3 (c = 1.5, MeOH). IR (neat): 3396, 2921, 1756, 1453, 1371, 1270, 1195, 1079, 1043, 917, 815, 705, 578 cm-¹. ¹H NMR (300 MHz, CDCl3): δ = 7.28-7.51 (m, 5 H), 4.95 (t, J = 6.2 Hz, 1 H), 4.85 (d, J = 6.6 Hz, 1 H), 3.93 (t, J = 7.6 Hz, 1 H), 3.59 (dd, J = 7.9, 1.3 Hz, 1 H), 2.58-2.75 (m, 1 H), 2.39-2.56 (m, 1 H), 2.14-2.38 (m, 2 H), 1.71 (br s, 2 H). ¹³C NMR (75 MHz, CD3OD): δ = 180.9, 142.2, 128.6, 128.9, 129.1, 81.3, 76.6, 75.6, 74.4, 29.5, 24.4. MS (ESI): m/z = 253 [M + H]+.