1
1110, 705 cm−1; H NMR (300 MHz, CDCl3) δ 0.85 (d, J =
washed with brine (5 mL × 2), the brine washes were extracted
with ethyl acetate (2 mL × 3) and the combined extract was
dried (MgSO4), filtered and concentrated under reduced pressure.
The crude residue was purified by flash chromatography on
silica gel (hexane–ethyl acetate 3 : 1) to give 119 (8.7 mg, 81%)
as a 3.5 : 1 (Z : E) mixture of C2 olefin isomers: 1H NMR
(400 MHz, CDCl3, major isomer) δ 7.74–7.71 (m, 2H),
7.67–7.60 (m, 7H), 7.52 (s, 1H), 7.44–7.27 (m, 12H), 6.70 (ddd,
J = 6, 8, 16 Hz, 1H), 6.28 (d, J = 16 Hz, 1H), 6.25 (s, 1H), 6.13
(dd, J = 7, 14 Hz, 1H), 6.05 (d, J = 14 Hz, 1H), 5.96 (d, J =
16 Hz, 1H), 5.90 (bs, 1H), 5.34 (d, J = 9 Hz, 1H), 5.21 (dd, J =
8, 16 Hz, 1H), 5.01 (brs, 1H), 4.89 (d, J = 12 Hz, 1H),
4.82–4.75 (m, 1H), 4.63 (s, 1H), 4.53–4.48 (m, 2H), 4.31 (s,
1H), 4.21–4.07 (m, 3H), 4.00–3.95 (m, 1H), 3.60–3.52 (m, 5H),
3.28 (s, 3H), 3.26 (s, 3H), 3.21 (s, 3H), 2.95 (d, J = 15 Hz, 1H),
2.75 (d, J = 12 Hz, 1H), 2.58–2.49 (m, 1H), 2.48–1.04 (m,
20H), 1.93 (d, J = 1 Hz, 3H), 1.18 (d, J = 1 Hz, 3H), 1.06 (s,
9H), 1.04 (s, 9H), 0.96 (d, J = 7 Hz, 3H), 0.76 (d, J = 6 Hz,
3H); HRMS (MALDI) calcd for C86H109N2O13Si279BrNa
(M + Na, 79Br)+ 1535.6549, found 1535.6544.
7 Hz, 1H), 1.10 (m, 33H), 1.93 (s, 3H), 2.00 (m, 6H), 2.28 (m,
1H), 2.45 (s, 3H), 2.55 (ddd, J = 4, 7, 8 Hz, 1H), 2.80 (m, 2H),
3.55 (m, 10H), 4.00 (t, J = 6 Hz, 1H), 4.79 (m, 1H), 6.18 (s,
1H), 6.27 (dd, J = 4, 16 Hz, 1H), 6.65 (m, 1H), 7.19 (2s, 1H),
7.50 (s, 1H), 7.55 (m, 10H); 13C NMR (75 MHz, CDCl3) δ 6.5,
13.3, 14.2, 14.4, 14.7, 18.6, 18.7, 19.7, 27.4, 35.6, 36.2, 36.8,
37.9, 39.3, 39.7, 52.1, 70.2, 78.2, 89.3, 118.4, 118.9, 128.1,
130.2, 133.9, 136.0, 136.3, 138.6, 161.0, 161.5, 172.2, 172.4,
175.4, 175.6; MS (FAB) 985 (M+), 927, 849, 729, 427, 367,
327, 239, 199, 135, 87; HRMS (FAB) m/z 985.5422, calcd for
C55H81N2O10Si2 m/z 985.5430.
(2S,4R,6R)-2-((4-((E)-2-((2R,3R,4S,5S,6R)-6-(2-(tert-Butyldi-
methylsilanyloxy)ethyl)-4-(4-methoxybenzyloxy)-3,5-dimethyl-
tetrahydro-2H-pyran-2-yl)prop-1-enyl)oxazol-2-yl)methyl)-6-((R,E)-
2,2,7,10,10,11,11-heptamethyl-3,3-diphenyl-4,9-dioxa-3,10-disila-
dodec-6-en-5-yl)-4-methoxytetrahydro-2H-pyran-2-ol (88). To a
solution of 83 (20.1 mg, 38 μmol) and diethylamine (23 μL,
226 μmol) in tetrahydrofuran (350 μL) at −78 °C was added
dropwise n-butyllithium (2.46 M solution in hexane, 20 μL,
49 μmol) during which the solution turned bright yellow. After
25 min, a solution of 84 (10.6 mg, 18.2 μmol) in tetrahydrofuran
(175 μL) at −78 °C was added via syringe over 10 min (5 μL
per 30 sec) during which the colour of the mixture faded to a
light brownish-yellow. After 40 min, the reaction was quenched
with water (1 mL) and the mixture was extracted with ether
(10 mL × 3). The combined extract was washed with brine
(10 mL), dried (Na2SO4) and concentrated under reduced
pressure, and the residual oil was purified by flash chromato-
graphy on silica gel (hexane–ethyl acetate 9 : 1) to give 88
(19.4 mg, 96%) as a colourless oil: [α]2D3 +39.7 (c 0.86, CHCl3);
IR (neat) 3372, 2955, 2928, 2856, 1613, 1576, 1513, 1462,
Acknowledgements
We are grateful to the Ministry of Science and Technology of the
Royal Thai Government for a predoctoral scholarship to P.K. and
to the Deutsche Forschungsgemeinschaft for a postdoctoral
fellowship to C.L.K. Financial support was provided by the
National Institute of General Medical Sciences (GM50574 and
GM58889).
Notes and references
1 P. A. Searle and T. F. Molinski, J. Am. Chem. Soc., 1995, 117, 8126.
2 (a) P. A. Searle, T. F. Molinski, L. J. Brzezinski and J. W. Leahy, J. Am.
Chem. Soc., 1996, 118, 9422; (b) T. F. Molinski, Tetrahedron Lett., 1996,
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J. Nat. Prod., 1993, 56, 54.
1428, 1361, 1249, 1090, 1035, 836, 776, 740, 702 cm−1
;
1H NMR (400 MHz, CDCl3) δ 7.60–7.56 (m, 4H), 7.39 (s, 1H),
7.36–7.26 (m, 8H), 6.86 (d, J = 9 Hz, 2H), 6.11 (s, 1H), 5.28 (d,
J = 8 Hz, 1H), 4.81 (s, 1H), 4.57 (d, J = 11 Hz, 1H), 4.28 (d, J =
11 Hz, 1H), 4.32–4.27 (m, 1H), 3.93–3.85 (m, 1H), 3.79 (s, 3H),
3.73–3.64 (m, 5H), 3.57–3.52 (m, 1H), 3.39 (d, J = 10 Hz, 1H)
3.32 (s, 3H), 3.18 (dd, J = 5, 10 Hz, 1H), 2.97 (d, J = 16 Hz,
1H), 2.91 (d, J = 16 Hz, 1H), 2.24–2.18 (m, 1H), 2.10–2.02 (m,
2H), 1.90–1.75 (m, 3H), 1.84 (s, 3H), 1.60–1.50 (m, 2H),
1.05–0.90 (m, 15H), 0.87 (s, 9H), 0.86 (s, 9H), 0.78 (d, J =
6 Hz, 3H), 0.01 (s, 6H), −0.02 (s, 3H), −0.02 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 160.0, 159.2, 138.6, 137.7, 136.0, 136.0,
135.5, 134.4, 134.3, 130.8, 129.4, 129.4, 129.3, 127.3, 127.2,
122.8, 118.1, 113.8, 96.5, 89.0, 83.5, 74.7, 73.5, 73.1, 71.9,
69.6, 67.6, 60.0, 55.6, 55.3, 40.6, 40.0, 36.2, 34.3, 33.3, 32.0,
30.3, 29.7, 26.9, 26.0, 25.9, 19.2, 18.4, 18.3, 14.2, 13.8, 13.6,
6.1, −5.2, −5.3; MS (ES) m/z (M+ + H) 1112; HRMS (ES) m/z
1112.6499 (calcd for C63H98NO10Si3: 1112.6461, M+ + H).
3 F. M. Uckun and C. J. Forsyth, Bioorg. Med. Chem. Lett., 2001, 11,
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R. D. Cink and C. S. Lee, J. Am. Chem. Soc., 1998, 120, 5597;
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G. Pattenden, Angew. Chem., Int. Ed., 2003, 42, 1255;
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M. A. Berliner and J. T. Reeves, Angew. Chem., Int. Ed., 2003, 42, 1258;
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T. E. Smith and V. J. Cee, J. Am. Chem. Soc., 2000, 122, 10033;
(b) D.-R. Li, D.-H. Zhang, C.-Y. Sun, J.-W. Zhang, L. Yang, J. Chen,
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Tetrahedron Lett., 1998, 39, 7185; (b) P. Wolbers, A. M. Misske and
H. M. R. Hoffmann, Tetrahedron Lett., 1999, 40, 4527; (c) P. Wolbers
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H. M. R. Hoffmann, Tetrahedron, 1999, 55, 1905; (f) A. M. Misske and
13,38-Bis(O-tert-butyldiphenylsilanyl)-33-(O-methyl)phorbox-
azole A (119). A suspension of potassium carbonate (11.7 mg,
0.085 mmol) and 18-crown-6 (104 mg, 0.393 mmol) in toluene
(6 mL) was stirred at room temperature for 3 h, then was cooled
to −78 °C and a solution of 118 (11.6 mg, 7.07 μmol) in toluene
(3 mL) was added via syringe. The mixture was slowly warmed
to room temperature and was stirred for 62 h. The mixture was
7898 | Org. Biomol. Chem., 2012, 10, 7884–7899
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