Synthetic Approach to Sarcodictyins and Eleutherobin
1.4 Hz, 1 H), 4.66 (ddd, J = 10.5, 8.2, 3.4 Hz, 1 H), 4.15 (m, 1 H),
3.85 (dd, J = 10.5, 4.6 Hz, 1 H), 3.80 (m, 1 H), 3.70 (t, J = 10.5 Hz,
1 H), 3.24 (d, J = 10.5 Hz, 1 H, OH), 2.61 (d, J = 3.4 Hz, 1 H),
yield. Data for 19a: [α]2D0 = +140.2 (c = 1.2, CHCl3). 1H NMR
(400 MHz, CDCl3): δ = 6.06 (dq, J = 8.7, 1.4 Hz, 1 H), 4.74 (dd,
J = 8.7, 6.0 Hz, 1 H), 4.10–4.00 (m, 1 H), 3.90–3.70 (m, 1 H), 3.82
2.28 (m, 1 H), 2.04–1.94 (m, 1 H), 1.94–1.76 (m, 3 H), 1.84 (d, J (dd, J = 11.0, 8.2 Hz, 1 H), 3.71 (dd, J = 11.0, 3.4 Hz, 1 H), 2.43
= 1.4 Hz, 3 H, CH3), 1.63 (s, 3 H, CH3), 1.33–1.19 (m, 12 H, 4
CH3), 0.88 (s, 9 H, 3 CH3), 0.85 (d, J = 6.9 Hz, 3 H, CH3), 0.78
(m, 1 H), 2.15–1.80 (m, 3 H), 1.80–1.70 (m, 2 H), 1.82 (s, 3 H,
CH3), 1.64 (s, 3 H, CH3), 1.22 (m, 12 H, 4 CH3), 0.88 (2 d, J =
(d, J = 6.9 Hz, 3 H, CH3), 0.16 (s, 9 H, 3 CH3), 0.05 (s, 6 H, 2 5.5 Hz, 3 H, CH3), 0.86 (2 d, J = 5.5 Hz, 3 H, CH3), 0.18 (s, 9 H,
CH3) ppm. 13C NMR (100 MHz, CDCl3): δ = 153.9 (C), 145.7 (C), 3 CH3) ppm. 13C NMR (100 MHz, CDCl3): δ = 153.6 (C), 144.0
143.4 (CH), 119.2 (C), 117.1 (C), 108.5 (C), 90.5 (C), 67.1 (CH), (C), 140.0 (CH), 120.3 (C), 119.6 (C), 107.9 (C), 91.9 (C), 68.8
63.1 (CH2), 47.2 (CH), 47.0 (CH), 45.6 (CH), 41.7 (CH), 36.8 (CH), (CH), 64.2 (CH2), 46.6 (CH), 46.5 (CH), 45.3 (CH), 39.9 (CH),
27.0 (CH), 26.6 (CH2), 26.1 (3 CH3), 21.7 (2 CH3), 20.9 (CH3),
39.6 (CH), 27.7 (CH), 27.0 (CH2), 21.8 (2 CH3), 20.8 (CH3), 20.7
20.7 (2 CH3), 18.5 (C), 17.8 (CH3), 17.2 (CH3), 14.5 (CH3), 0.21 (3 (2 CH3), 17.9 (CH3), 17.5 (CH3), 15.6 (CH3), 0.2 (3 CH3) ppm. MS
CH ), –5.1 (CH ), –5.3 (CH ) ppm. IR (film): ν = 3442, 2955, 2146,
(GC, CI, CH4): m/z = 478 [M + H]+. C27H47NO4Si (477.76): calcd.
˜
3
3
3
1685, 1440, 1286, 1086 cm–1. MS (GC, CI, CH4): m/z = 593 [M +
H]+. C33H61NO4Si2 (592.02): calcd. C 66.95, H 10.39, N 2.37;
found C 67.05, H 10.44, N 2 45.
C 67.88, H 9.92, N 2.93; found C 67.95, H 10.12, N 2.95. Data for
1
20: [α]2D0 = +28.8 (c = 1.7, CHCl3). H NMR (400 MHz, CDCl3):
δ = 5.90 (dq, J = 9.6, 1.4 Hz, 1 H), 4.78 (t, J = 9.6 Hz, 1 H), 4.01–
3.89 (m, 2 H), 3.88–3.83 (m, 2 H), 3.01 (m, 1 H), 2.32–2.23 (m, 1
H), 2.23–2.12 (m, 1 H), 1.96–1.94 (m, 1 H), 1.90 (d, J = 1.4 Hz, 3
H, CH3), 1.84 (septd, J = 6.9, 3.7 Hz, 1 H), 1.70 (tdd, J = 11.9,
4.6, 3.7 Hz, 1 H), 1.46 (s, 3 H, CH3), 1.27 (s, 6 H, 2 CH3), 1.25 (s,
6 H, 2 CH3), 0.95 (d, J = 6.9 Hz, 3 H, CH3), 0.79 (d, J = 6.9 Hz,
3 H, CH3), 0.18 (s, 9 H, 3 CH3) ppm. 13C NMR (100 MHz,
CDCl3): δ = 153.4 (C), 144.6 (C), 136.0 (CH), 122.5 (C), 116.3 (C),
108.3 (C), 92.5 (C), 75.8 (CH), 70.6 (CH2), 48.2 (CH), 46.5 (2 CH),
40.9 (CH), 40.4 (CH), 28.6 (CH), 26.9 (CH2), 21.9 (CH3), 21.8 (2
CH3), 21.0 (2 CH3), 18.0 (CH3), 15.9 (CH3), 15.4 (CH3), 0.04 (3
CH3) ppm. MS (GC, CI, CH4): m/z = 460 [M + H]+. C27H45NO3Si
(459.74): calcd. C 70.54, H 9.87, N 3.05; found C 70.62, H 9.93, N
3.12.
(R)-Mandelate Ester of 18a: 1H NMR (400 MHz, CDCl3): δ =
7.39–7.28 (m, 5 H), 5.94 (dq, J = 9.6, 1.4 Hz, 1 H), 5.87 (dd, J =
10.1, 2.8 Hz, 1 H), 4.62 (s, 1 H), 4.1–3.75 (m, 2 H), 3.69 (dd, J =
11.0, 6.4 Hz, 1 H), 3.48 (dd, J = 11.0, 9.0 Hz, 1 H), 3.34 (s, 3 H,
CH3), 2.50 (m, 1 H), 2.05–1.80 (m, 3 H), 1.94 (d, J = 1.4 Hz, 3 H,
CH3), 1.75–1.60 (m, 2 H), 1.37 (s, 3 H, CH3), 1.25 (m, 12 H, 4
CH3), 0.81 (s, 9 H, 3 CH3), 0.79 (d, J = 6.4 Hz, 3 H, CH3), 0.76
(d, J = 6.4 Hz, 3 H, CH3), 0.17 (s, 9 H, 3 CH3), 0.02 (s, 3 H, CH3),
0.01 (s, 3 H, CH3) ppm.
(S)-Mandelate Ester of 18a: 1H NMR (400 MHz, CDCl3): δ =
7.39–7.28 (m, 5 H), 5.85 (dd, J = 9.6, 3.2 Hz, 1 H), 5.71 (dq, J =
9.6, 2.8 Hz, 1 H), 4.68 (s, 1 H), 4.1–3.8 (m, 2 H), 3.75 (dd, J =
10.6, 6.4 Hz, 1 H), 3.53 (dd, J = 10.6, 9.2 Hz, 1 H), 3.39 (s, 3 H,
CH3), 2.70 (m, 1 H), 2.05–1.90 (m, 3 H), 1.82 (d, J = 1.8 Hz, 3 H,
CH3), 1.80–1.60 (m, 2 H), 1.54 (s, 3 H, CH3), 1.25 (m, 12 H, 4
CH3), 0.84 (s, 9 H, 3 CH3), 0.81 (d, J = 5.0 Hz, 3 H, CH3), 0.80
(d, J = 5.0 Hz, 3 H, CH3), 0.15 (s, 9 H, 3 CH3), 0.02 (s, 6 H, 2
CH3) ppm.
(R)-Mandelate Ester of 18b: 1H NMR (400 MHz, CDCl3): δ =
7.45–7.28 (m, 5 H), 5.77 (d, J = 3.7 Hz, 1 H), 5.65 (dq, J = 8.7,
1.4 Hz, 1 H), 4.75 (s, 1 H), 4.1–3.80 (m, 2 H), 3.74 (dd, J = 10.6,
5.5 Hz, 1 H), 3.49 (t, J = 10.5 Hz, 1 H), 3.42 (s, 3 H, CH3), 2.69
(m, 1 H), 2.10–1.80 (m, 3 H), 1.75 (d, J = 1.4 Hz, 3 H, CH3), 1.70–
1.65 (m, 2 H), 1.65 (s, 3 H, CH3), 1.26 (m, 12 H, 4 CH3), 0.87 (s,
9 H, 3 CH3), 0.82 (d, J = 6.4 Hz, 3 H, CH3), 0.82 (d, J = 6.4 Hz,
3 H, CH3), 0.14 (s, 9 H, 3 CH3), 0.03 (s, 3 H, CH3), 0.02 (s, 3 H,
CH3) ppm.
(S)-Mandelate Ester of 18b: 1H NMR (400 MHz, CDCl3): δ =
7.45–7.25 (m, 5 H), 5.88 (dq, J = 9.1, 1.4 Hz, 1 H), 5.79 (d, J =
3.7 Hz, 1 H), 4.69 (s, 1 H), 4.1–3.80 (m, 2 H), 3.65 (dd, J = 10.5,
5.5 Hz, 1 H), 3.42 (t, J = 10.5 Hz, 1 H), 3.33 (s, 3 H, CH3), 2.61
(m, 1 H), 1.92 (d, J = 1.4 Hz, 3 H, CH3), 1.90–1.50 (m, 5 H), 1.55
(s, 3 H, CH3), 1.25 (m, 12 H, 4 CH3), 0.86 (s, 9 H, 3 CH3), 0.69
(d, J = 6.9 Hz, 3 H, CH3), 0.55 (d, J = 6.9 Hz, 3 H, CH3), 0.17 (s,
9 H, 3 CH3), 0.01 (s, 3 H, CH3), 0.00 (s, 3 H, CH3) ppm.
[3R(1S,2E),4R,5R]-3-[-1-Hydroxy-3-methyl-5-(trimethylsilyl)pent-2-
en-4-ynyl]-5-isopropyl-4-(methoxymethyl)-2-methylcyclohex-1-enyl
Diisopropylcarbamate (19b): To a solution of 18b (320 mg,
0.55 mmol) in MeOH (7 mL) was added Amberlyst 15. The reac-
tion mixture was stirred for 5.5 h at 20 °C, filtered through a pad
of celite and the solvent was removed under reduced pressure. The
crude residue was purified by chromatography on silica gel (cyclo-
hexane/AcOEt, 90:10) to furnish compound 19b (257 mg, 98%).
[α]2D0 = +13.6 (c = 0.97, CHCl3). 1H NMR (400 MHz, CDCl3): δ =
5.98 (dq, J = 8.7, 1.4 Hz, 1 H), 4.71 (d, J = 8.7 Hz, 1 H), 4.20–
4.08 (m, 1 H), 3.92 (dd, J = 10.9, 4.6 Hz, 1 H), 3.85–3.73 (m, 1 H),
3.74 (t, J = 10.9 Hz, 1 H), 2.64 (d, J = 3.6 Hz, 1 H), 2.33–2.22 (m,
1 H), 2.06–1.98 (m, 1 H), 1.96–1.76 (m, 3 H), 1.85 (d, J = 1.4 Hz,
3 H, CH3), 1.64 (s, 3 H, CH3), 1.33–1.19 (m, 12 H, 4 CH3), 0.87
(d, J = 6.9 Hz, 3 H, CH3), 0.79 (d, J = 6.9 Hz, 3 H, CH3), 0.16 (s,
9 H, 3 CH3) ppm. 13C NMR (100 MHz, CDCl3): δ = 153.9 (C),
145.7 (C), 142.6 (CH), 119.1 (C), 117.7 (C), 108.3 (C), 90.9 (C),
67.6 (CH), 62.7 (CH2), 47.2 (CH), 47.0 (CH), 45.7 (CH), 41.3 (CH),
37.2 (CH), 27.1 (CH), 26.6 (CH2), 21.7 (2 CH3), 21.0 (CH3), 20.8
(2 CH3), 17.7 (CH3), 16.9 (CH3), 14.7 (CH3), 0.2 (3 CH3) ppm. MS
(GC, CI, CH4): m/z = 478 [M + H]+. C27H47NO4Si (477.76): calcd.
C 67.88, H 9.92, N 2.93; found C 67.92, H 10.04, N 2.97.
(E)-6-(tert-Butyldimethylsilyl)-3-methylhex-2-en-4-ynal (21): To a
suspension of Pd(OAc)2 (140 mg, 0.63 mmol, 0.025 equiv.) in THF
(20 mL) at 20 °C was added tris(2,6-dimethoxyphenyl)phosphane
(275 mg,1.5 mmol, 0.25 equiv.). After stirring for 15 min ethyl bu-
tynoate (3.36 g, 30.0 mmol, 1 equiv.) was introduced. To the re-
sulting clear brown mixture obtained after 5 min was added a solu-
tion of propargyl alcohol (1.4 g, 25.0 mmol, 1 equiv.) in THF
(5 mL). The mixture turned dark brown. After 12 h at 20 °C the
mixture was concentrated under reduced pressure, and the crude
residue was purified by chromatography on silica gel (cyclohexane/
AcOEt, 80:20) to deliver ethyl (E)-6-hydroxy-3-methylhex-2-en-4-
[3R(1R,2E),4R,5R]-3-[-1-Hydroxy-3-methyl-5-(trimethylsilyl)pent-
2-en-4-ynyl]-5-isopropyl-4-(methoxymethyl)-2-methylcyclohex-1-enyl
Diisopropylcarbamate (19a) and (1R,3aR,4R,7aR)-1,3,3a,4,5,7a-
Hexahydro-4-isopropyl-7-methyl-1-[(E)-2-methyl-4-(trimethylsilyl)-
but-1-en-3-ynyl]isobenzofuran-6-yl Diisopropylcarbamate (20): To a
solution of 18a (320 mg, 0.55 mmol) in MeOH (7 mL) was added
Amberlyst 15. The reaction mixture was stirred for 5.5 h at 20 °C,
filtered through a pad of celite and the solvent was removed under
reduced pressure. The crude residue was purified by chromato-
graphy on silica gel (cyclohexane/AcOEt, 80:20) to furnish com-
pounds 19a (78 mg, 30%) and 20 (113 mg, 43%) in an overall 73%
1
ynoate (3.47 g, 83%). H NMR (400 MHz, CDCl3): δ = 6.00 (s, 1
Eur. J. Org. Chem. 2007, 5235–5243
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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