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DOI: 10.1055/s-2007-1000831
Syntheses of the Proposed Structures of Poison-Frog Alkaloids 179 and 207E and Their Inhibitory Effects on Neuronal Nicotinic Acetylcholine Receptors
Publication History
Publication Date:
11 December 2007 (online)
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Abstract
Syntheses of the structures postulated for 179 and 207E, members of a proposed new class of poison-frog alkaloids, 6,7-dehydro-5,8-disubstituted indolizidines, are described. The FT-IR spectrum and GC retention time of the synthetic 207E were different from those of the natural product; consequently the original structure of 207E needs to be revised. It is likely that the position of the double bond is instead at the 7,8-position.
Key words
poison-frog alkaloids 179 and 207E - inhibitory effects on neuronal nicotinic acetylcholine receptors - dehydro-5,8-disubstituted indolizidines
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References and Notes
The spectral and analytical data of synthetic 1 are as follows: IR (neat): 3025, 2957, 2871, 2781, 1456, 1377, 1326, 1287, 1179, 913, 798, 715 cm-1. 1H NMR (500 MHz, CDCl3): δ = 0.93 (3 H, t, J = 7.5 Hz), 0.94 (3 H, d, J = 6.8 Hz), 1.25-1.34 (1 H, m), 1.35-1.41 (1 H, m), 1.42-1.52 (2 H, m), 1.61-1.67 (1 H, m), 1.68-1.75 (1 H, m), 1.76-1.83 (1 H, m), 1.84 (1 H, td, J = 9.1, 6.9 Hz), 1.99-2.07 (2 H, m), 2.08-2.14 (1 H, m), 2.64 (1 H, dtd, J = 11.0, 3.6, 1.9 Hz), 3.35 (1 H, td, J = 8.4, 1.9 Hz), 5.50 (1 H, dt, J = 10.2, 1.9 Hz), 5.57 (1 H, dt, J = 10.2, 1.9 Hz). 13C NMR (75 MHz, CDCl3): δ = 14.39 (q), 18.14 (q), 18.64 (t), 20.77 (t), 29.38 (t), 36.04 (t), 37.61 (d), 52.79 (t), 63.00 (d), 67.83 (d), 128.55 (d), 131.53 (d). HRMS: m/z calcd for C12H21N: 179.1674; found: 179.1686. [α]D 26 +129.3 (c 2.74, CHCl3).
14The spectral and analytical data of synthetic 2 are as follows: IR (neat): 3030, 2957, 2929, 2871, 2781, 1458, 1378, 1329, 1260, 1177, 1105, 929, 803, 713 cm-1. 1H NMR (500 MHz, CDCl3): δ = 0.89 (3 H, t, J = 6.8 Hz), 0.91 (3 H, t, J = 7.3 Hz), 1.12-1.21 (1 H, m), 1.23-1.34 (2 H, m), 1.35-1.40 (2 H, m), 1.43-1.53 (3 H, m), 1.59-1.68 (1 H, m), 1.69-1.74 (1 H, m), 1.76-1.82 (1 H, m), 1.93 (1 H, td, J = 9.4, 6.8 Hz), 1.99-2.06 (3 H, m), 2.63 (1 H, dtd, J = 11.0, 3.4, 1.7 Hz), 3.34 (1 H, td, J = 8.5, 2.1 Hz), 5.60 (1 H, dt, J = 9.8, 1.7 Hz), 5.63 (1 H, dt, J = 9.8, 1.7 Hz). 13C NMR (75 MHz, CDCl3): δ = 14.43 (2 × q), 18.64 (t), 19.67 (t), 20.92 (t), 29.69 (t), 34.91 (t), 36.11 (t), 42.54 (d), 52.76 (t), 62.97 (d), 66.13 (d), 129.01 (d), 129.44 (d). HRMS: m/z calcd for C14H25N 207.1986; found: 207.1973. [α]D 26 +109.1 (c 0.32, CHCl3). The GC-MS instrument is a Finnigan-Thermoquest Polaris Q with a Restek-RTX-5MS column (30 m × 0.25 mm i.d.) and the program was 100-280 °C at 10 °C/min with a final hold time of 10 min; t R = 7.69 min.; natural product from Oophaga granulifera: t R = 8.41 min. MS (EI): m/z (%) = 208 (12), 207 (4), 206 (8), 164 (100), 162 (13), 136 (13), 134 (13), 132 (8), 120 (52), 106 (8), 93 (22), 92 (11), 91 (10), 79 (13), 77 (16), 70 (16), 67 (24), 65 (14). MS (EI) of natural product from Dendrobates granuliferous: m/z (%) = 207 (2), 206 (4), 17 (10), 164 (100), 162 (78), 134 (18), 120 (28), 91 (12), 79 (14), 77 (20), 65 (11).