Novel Tocopherol Derivatives V. The First Organometallic Derivative of Vitamin E

Synlett

Volumn 1996, Issue 5, 1996, Pages 427-429

  Rosenau, Thomas ^a   Habicher, Wolf Dieter ^a  

^a DRESDEN UNIVERSITY OF TECHNOLOGY   (Germany)

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Indexed keywords

EID: 0343887443     PISSN: 09365214     EISSN: None     Source Type: Journal    
DOI: 10.1055/s-1996-5442     Document Type: Article

References (16)

1. For examples see: Serbinova, E.; Kagan, V.; Han, D.; Packer, L. Free Radicals Biol. Med. 1991, 10, 263. Barclay, L. R. C.; Baskin, K.; Dakin, K. A.; Locke, S. J.; Vinquist, M. R. Can. J. Chem. 1990, 68, 2258.
2. For examples see: Serbinova, E.; Kagan, V.; Han, D.; Packer, L. Free Radicals Biol. Med. 1991, 10, 263. Barclay, L. R. C.; Baskin, K.; Dakin, K. A.; Locke, S. J.; Vinquist, M. R. Can. J. Chem. 1990, 68, 2258.
3. Mukai, K.; Kageyama, Y.; Ishida, T.; Fukuda, K J. Org. Chem. 1989, 54, 552; and references cited therein.
4. Halliwell, B.; Gutteridge, J. M. C. Free Radicals in Biology and Medicine; Oxford University Press: New York, 1989.
5. Rosenau, T.; Habicher, W. D.; Chen, C. L. J. Org. Chem. 1995, 60, in press. Rosenau, T.; Habicher, W. D. J. Prakt. Chem., submitted.
6. Rosenau, T.; Habicher, W. D.; Chen, C. L. J. Org. Chem. 1995, 60, in press. Rosenau, T.; Habicher, W. D. J. Prakt. Chem., submitted.
7. Rosenau, T.; Habicher, W. D. Heterocycles 1996, in press.
8. For preparation, optimized reaction conditions and possible side reactions see: Rosenau, T.; Habicher, W. D. Tetrahedron 1995, 51, 7919.
9. Kohar, I.; Suarna, C.; Southwell-Keely, P. T. Lipids 1993, 28, 1015; and references cited therein.
10. Schudel, P.; Mayer, H.; Rüegg, J.; Isler, O. Helv. Chim. Acta 1963, 46, 636. For NMR data see: Fales, H. M.; Lloyd, H. A.; Ferretti, J. A.; Silverton, J. V. J. Chem. Soc. Perkin Trans. 2, 1990, 1005.
11. Schudel, P.; Mayer, H.; Rüegg, J.; Isler, O. Helv. Chim. Acta 1963, 46, 636. For NMR data see: Fales, H. M.; Lloyd, H. A.; Ferretti, J. A.; Silverton, J. V. J. Chem. Soc. Perkin Trans. 2, 1990, 1005.
12. Nelan, D. R.; Robeson, C. D. Nature, 1962, 193, 477; J. Am. Chem. Soc. 1962, 84, 2963.(10)
13. Nelan, D. R.; Robeson, C. D. Nature, 1962, 193, 477; J. Am. Chem. Soc. 1962, 84, 2963.(10)
14. 2. The mixture was refluxed for 24 h in an inert atmosphere. After cooling to room temperature the solvent and the excess of silylating agent was removed under reduced pressure. The product, O-trimethylsilyl-5a-bromo-α-tocopherol (3) was dissolved in a mixture of 20 mL of dry (!) diethyl ether and 20 mL of dry n-hexane. 2 mL of this solution was added dropwise to magnesium filings (0.50 g, 20.56 mmol) in a mixture of 30 mL diethyl ether, 10 mL n-hexane, and 0.05 mL trimethylsilyl chloride at 10°C in a nitrogen atmosphere. When the temperature started to rise, the flask was cooled to -10°C, and the remaining solution of 3 was slowly added within 30 min. After stirring for 2 h at -10°C the mixture is warmed to room temperature, and the metallic magnesium in excess is separated by filtration under nitrogen. The solution of O-trimethylsilyl-5a-α-tocopheryl magnesium bromide (4) obtained was immediately used for subsequent reactions with carbonyl compounds. However, it can be stored for several days in the dark at -15°C.
15. 4. The solvent was evaporated. The remaining residue was recrystallized, or chromatographed on silica gel. First, the impurities were eluted with petrol ether / n-hexane (v/v = 1:1), then the products with diethyl ether / methanol (v/v = 5:1) for compounds 9a-d, diethyl ether / benzene (v/v = 1:1) for 10a-d, and n-hexane / diethyl ether (v/v = 2:1) for compounds 11a-d.
16. All compounds gave satisfactory analytical and spectral data.