5430
A.M. Heapy, M.A. Brimble / Tetrahedron 66 (2010) 5424e5431
28 (33 mg, 0.043 mmol) in CH2Cl2 (3 mL) was added aqueous tri-
fluoroacetic acid (50% v/v, 200 L) and the resultant solution stirred
ethanol (2 mL) was added a solution of benzyl ether 30 (24 mg,
0.031 mmol) in ethanol (2 mL) and the mixture was stirred vigor-
ously for 22 h under an atmosphere of H2. The solution was filtered
through a plug of Celite that was then washed with methanol
(15 mL) and ethyl acetate (15 mL). The solvent was removed under
reduced pressure and the crude hemiacetal used without further
purification. To a stirred solution of the above crude hemiacetal in
methanol (1.0 mL) was added trimethyl orthoformate (1.0 mL,
8.39 mmol) and camphorsulphonic acid (15 mg, 0.064 mmol). The
mixture was stirred for 2 h at room temperature. The reaction was
quenched by the addition of saturated NaHCO3 (10 mL) then diluted
with water (5 mL) and ethyl acetate (5 mL). The mixture was
extracted with ethyl acetate (3ꢂ30 mL) and diethyl ether
(1ꢂ30 mL). The combined organic extracts were washed with brine
(5 mL) and dried over MgSO4. The solvent was removed under re-
duced pressure and the crude residue purified by flash column
chromatography using hexane/ethyl acetate (9:1), 0.5% triethyl-
amine as eluent to afford the title compound 4 (5 mg, 70%, two
m
vigorously at room temperature for 50 min. The reaction mixture was
quenched by the addition of saturated NaHCO3 solution (3 mL) and
diluted with H2O (2 mL) and CH2Cl2 (2 mL). The layers were sepa-
rated and the aqueous portion was extracted with CH2Cl2 (3ꢂ30 mL).
The combined organic extracts were washed with brine (10 mL) and
dried over over MgSO4. The solvent was evaporated under reduced
pressure and the crude mixture purified by flash column chroma-
tography using hexane/ethyl acetate (3:2) as eluent to afford the title
compound 29 (16 mg, 62%) as a colourless wax. Rf (40% EtOAc/hexane)
20
0.30; [
a
]
ꢀ6.9 (c 1.75, CHCl3); IR (neat) vmax (cmꢀ1): 3469 (OH),
D
3069, 2930, 2856, 1612, 1513, 1247, 1110; dH (300 MHz, CDCl3): 0.99
(3H, d, J 6.8 Hz), 1.08 (9H, s), 1.41e1.61 (2H, m), 1.65e1.69 (2H, dd, J
11.5, 4.0 Hz), 1.50e1.72 (1H, m), 2.20e2.27 (1H, br s), 2.66 (1H, d, J
8.0 Hz), 3.15e3.34 (2H, m), 3.34e3.42 (1H, m), 3.56e3.72 (3H, m),
3.80 (3H, s), 3.88 (1H, m), 4.06e4.10 (2H, m) 4.22 (1H, d, J 11.5 Hz),
4.35e4.41 (2H, m) 4.44 (1H, d, J 11.5 Hz), 6.85e6.88 (2H, m),
7.16e7.37 (13H, m), 7.66e7.69 (4H, m); dC (75 MHz, CDCl3): 15.4,19.6,
27.2, 32.5, 33.9, 34.7, 55.3, 62.0, 68.6, 71.1, 72.0, 72.9, 76.5, 79.2, 79.8,
81.5, 113.9, 127.5, 127.5, 127.6, 128.3, 129.0, 129.8, 129.8, 133.6, 133.7,
136.0, 136.1, 138.4, 159.3; ESI HRMS found: MHþ, 699.3721,
C42H55O7Si requires 699.3717.
steps) as a colourless oil. Rf (10% EtOAc/hexane) 0.30; [
a]
20 ꢀ6.0 (c
D
2.0, CHCl3); IR (neat) vmax (cmꢀ1): 2932, 1729 (C]O), 1613, 1514,
1428, 1248, 1170, 1093, 821, 703; dH (300 MHz, CDCl3): 1.05 (3H, s),
1.14 (3H, s), 1.15e1.17 (1H, m), 1.21 (3H, d, J 7.1 Hz), 1.24e1.27 (1H,
m), 1.32e1.43 (1H, m), 1.63e1.76 (1H, m), 1.99e2.09 (1H, m), 3.39
(3H, s), 3.42e3.47 (1H, m), 3.61 (1H, d, J 5.0 Hz), 3.73e3.77 (1H, m),
3.80 (3H, s), 3.93e3.98 (1H, m), 4.04 (1H, d, J 11.8 Hz), 4.11e4.17 (2H,
m), 4.23 (1H, d, J 11.8 Hz), 4.39e4.45 (1H, m), 6.82e6.86 (2H, m),
7.09e7.12 (2H, m), 7.30e7.42 (6H, m), 7.65e7.76 (4H, m); dC
(75 MHz, CDCl3): 14.1, 19.7, 27.1, 27.2, 30.4, 31.6, 32.6, 50.4, 55.3,
56.4, 63.0, 70.4, 73.0, 78.2, 79.8, 80.0,100.6,113.8,127.4,127.5,128.8,
129.5, 129.6, 130.3, 133.8, 134.1, 136.2, 136.2, 159.1, 178.2; ESI HRMS
found: [MꢀH]þ, 703.3670, C41H55O8Si requires 703.3666.
4.1.12. (2R,3R)-5-(Benzyloxy)-2-(tert-butyldiphenylsilyloxy)-1-
((20S,40R,50R)-50-(tert-butylcarbonyloxymethyl)-40-(p-methoxy-
benzyloxy)tetrahydrofuran-20-yl)-3-methylpentan-1-one (30). To a
stirred solution of diol 29 (86 mg, 0.123 mmol) in pyridine (250
m
L)
cooled to ꢀ15 ꢁC was added pivaloyl chloride (20
mL, 0.162 mmol)
and the mixture stirred for 6 h. The reaction mixture was quenched
by the addition of H2O (2 mL), cooled to 0 ꢁC, and diluted with
CH2Cl2 (5 mL). The layers were separated and the aqueous portion
was extracted with CH2Cl2 (3ꢂ30 mL). The combined organic por-
tions were washed with brine (10 mL) and dried over MgSO4. The
solvent was evaporated under reduced pressure and the crude
mixture was purified by flash column chromatography using hex-
ane/ethyl acetate (4:1) as eluent to afford the corresponding piv-
alate ester (80 mg, 83%) as a colourless liquid. A mixture of the
above secondary alcohol (77 mg, 0.098 mmol), dry pyridine
(0.210 mL, 2.70 mmol) and Dess/Martin periodinane (120 mg,
0.280 mmol) was stirred in dry CH2Cl2 (2.5 mL) at room tempera-
ture for 45 min. Saturated Na2S2O3 solution (3 mL) and saturated
NaHCO3 solution (3 mL) was added and the mixture allowed to stir
for an additional 15 min. The mixture was extracted with CH2Cl2
(3ꢂ50 mL). The organic layer was washed with brine (10 mL) and
dried over MgSO4. The solvent was evaporated under reduced
pressure and the crude mixture was purified by flash column
chromatography using hexane/ethyl acetate (4:1) as eluent to af-
Acknowledgements
We thank T.W. Wagner for conducting preliminary experiments.
A.M.H. acknowledges the award of a Bright Future Top Achiever
Doctoral Scholarship from the New Zealand Tertiary Education
Commission.
References and notes
1. Yasumoto, T.; Murata, M.; Oshima, Y.; Sano, M.; Matsumoto, G. K.; Clardy, J.
Tetrahedron 1985, 41, 1019e1025.
2. Zhou, Z.; Komiyama, M.; Terao, K.; Shimada, Y. Nat. Toxins 1994, 2, 132e135.
3. Terao, K.; Ito, E.; Yanagi, T.; Yasumoto, T. Toxicon 1986, 24, 1141e1151.
4. Allingham, J. S.; Miles, C. O.; Rayment, E. J. Mol. Biol. 2007, 371, 959e970.
5. Jung, J. H.; Sim, C. J.; Lee, C. O. J. Nat. Prod. 1995, 58, 1722e1726.
6. Chae, H. D.; Choi, T. S.; Kim, B. M.; Jung, J. H.; Bang, Y. J.; Shin, D. Y. Oncogene
2005, 24, 4813e4819.
7. Amano, S.; Fujiwara, K.; Murai, A. Synlett 1997, 1300e1302.
8. Awakura, D.; Fujiwara, K.; Murai, A. Synlett 2000, 1733e1736.
9. Fujiwara, K.; Kobayashi, M.; Yamamoto, F.; Aki, Y.; Kawamura, M.; Awakura, D.;
Amano, S.; Okano, A.; Murai, A.; Kawai, H. E.; Suzuki, T. Tetrahedron Lett. 2005,
46, 5067e5069.
10. Fujiwara, K.; Aki, Y. I.; Yamamoto, F.; Kawamura, M.; Kobayashi, M.; Okano, A.;
Awakura, D.; Shiga, S.; Murai, A.; Kawai, H.; Suzuki, T. Tetrahedron Lett. 2007, 48,
4523e4527.
11. O’Connor, P. D.; Knight, C. K.; Friedrich, D.; Peng, X. W.; Paquette, L. A. J. Org.
Chem. 2007, 72, 1747e1754.
12. Bondar, D.; Liu, J.; Muller, T.; Paquette, L. A. Org. Lett. 2005, 7, 1813e1816.
13. Paquette, L. A.; Peng, X. W.; Bondar, D. Org. Lett. 2002, 4, 937e940.
14. Peng, X. W.; Bondar, D.; Paquette, L. A. Tetrahedron 2004, 60, 9589e9598.
15. Pihko, P. M.; Aho, J. E. Org. Lett. 2004, 6, 3849e3852.
16. Helmboldt, H.; Aho, J. E.; Pihko, P. M. Org. Lett. 2008, 10, 4183e4185.
17. Aho, J. E.; Salomaki, E.; Rissanen, K.; Pihko, P. M. Org. Lett. 2008, 10, 4179e4182.
18. Lotesta, S. D.; Hou, Y. Q.; Williams, L. J. Org. Lett. 2007, 9, 869e872.
19. Kolakowski, R. V.; Williams, L. J. Tetrahedron Lett. 2007, 48, 4761e4764.
20. Vellucci, D.; Rychnovsky, S. D. Org. Lett. 2007, 9, 711e714.
21. Micalizio, G. C.; Roush, W. R. Org. Lett. 2001, 3, 1949e1952.
22. Evans, D. A.; Rajapakse, H. A.; Chiu, A.; Stenkamp, D. Angew. Chem., Int. Ed. 2002,
41, 4573e4576.
ford the title compound 30 (76 mg, 99%) as a colourless liquid. Rf
20
(20% EtOAc/hexane) 0.50; [
a]
ꢀ41.3 (c 2.0, CHCl3); IR (neat) vmax
D
(cmꢀ1): 2959, 2857, 1728 (C]O), 1613 (C]O), 1514, 1162, 1112; dH
(300 MHz, CDCl3): 1.09 (9H, s), 1.12 (3H, m), 1.17 (9H, s), 1.23e1.34
(1H, m), 1.50e1.59 (1H, m), 1.68e1.74 (1H, m), 1.91e2.00 (1H, m),
2.24e2.42 (1H, m), 3.33e3.37 (1H, m), 3.39e3.50 (2H, m),
3.62e3.63 (1H, m) 3.78 (3H, s), 4.08e4.20 (3H, m) 4.34e4.46 (3H,
m), 4.50 (1H, t, J 7.9 Hz), 4.66 (1H, d, J 2.4 Hz), 6.83e7.35 (19H, m); dC
(75 MHz, CDCl3): 18.1, 19.8, 27.1, 27.1, 30.4, 33.8, 38.6, 38.6, 55.2,
62.7, 68.2, 70.8, 72.7, 77.8, 80.0, 80.2, 80.7, 113.8, 127.3, 127.4, 127.4,
127.5, 128.3, 129.0, 129.4, 129.5, 129.8, 133.7, 133.7, 136.2, 138.6,
159.2, 178.1, 211.2; ESI HRMS found: MHþ, 781.4121, C47H61O8Si
requires 781.4136.
4.1.13. (3R,4R)-3-(tert-Butyldiphenylsilyloxy)-2-((20S,40R,50R)-40-(p-
methoxybenzyloxy)-50-(tert-butylcarbonyloxymethyl)tetrahydrofu-
ran-20-yl)-4-methyltetrahydro-2H-2-methoxypyran (4). To a stirred
slurry of freshly prepared W-5 Raney nickel (w5 mg, 0.09 mmol) in
23. Evans, D. A.; Rajapakse, H. A.; Stenkamp, D. Angew. Chem., Int. Ed. 2002, 41,
4569e4573.