Herboxidiene: Determination of absolute configuration by degradation and synthetic studies

Tetrahedron

Volumn 53, Issue 8, 1997, Pages 2785-2802

  Edmunds, A J F ^a   Trueb, W ^a   Oppolzer, W ^b   Cowley, P ^b  

^a NOVARTIS PHARMA AG   (Switzerland)

^b UNIVERSITY OF GENEVA   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

HERBICIDE; POLYKETIDE;

ARTICLE; CHIRALITY; DRUG DECOMPOSITION; DRUG STRUCTURE; DRUG SYNTHESIS; IN VITRO STUDY; INFRARED SPECTROPHOTOMETRY; MASS SPECTROMETRY; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; PRIORITY JOURNAL; STEREOCHEMISTRY;

EID: 0031584924     PISSN: 00404020     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4020(97)00021-5     Document Type: Article

References (29)

1. 1. Isaac, B. G.; Ayer, S. W.; Elliott, R.; Stonard, R.J. J. Org. Chem., 1992, 57, 7220.
2. 2. Smith, N. D.; Kocienski, P. J.; Street, S. D. A. Synthesis, 1996, 652.
3. 3. Banwell, M. G.; Bui, C. T.; Simpson G. W.; Watson, K.G. Chem. Commun., 1996, 723.
4. 4. Details of the X-ray structure will be published elsewhere; Le-Van, N.; Weber, H. P.; Trueb. W.; Sanglier, J. J., J. Antibiotics, in preparation.
5. 5. Lists of refined co-ordinates have been submitted to the editor for deposition at the Cambridge Crystallographic Data Centre, University Chemical Laboratory, Lensfield Road, Cambridge CB2 1EW. A stereoview of the molecule is shown below. (equation presented) ORTEP stereo drawing of the crystalline conformation of herboxidiene. The 50% probability ellipsoids of the anisotropic atomic thermal vibration is shown for C-and O-atoms. H-atoms have been given a constant radius of 0.10 A. Oxygen atoms are shaded.
6. 1H NMR ruling out structures A and C which contain tertiary alcohol functions. The signals for the protons adjacent to the hydroxy groups were shifted downfield to 5.09 and 4.90 ppm through acetylation. The signal at 5.05 ppm (1H) was a quintet (J = 6.6 Hz) which was assigned to the H-18 proton (herboxidiene numbering) while the signal at 4.90 ppm (1H) was a doublet (J = 7.6 Hz) which requires that D is the compound that was formed. The stereochemistry for the epoxide opening is assumed and not confirmed.
7. 7. Large scale fermentation of herboxidiene and subsequent purification also lead to isolation of the corresponding acid of 7. As we had multigram amounts of this compound (readily converted to the methyl ester using the procedure for that of herboxidiene) we were very keen to find a use for as much of the molecule as possible.
8. 8. Full details of the reactions of herboxidiene under acidic conditions will be reported shortly.
9. 1 The stereochemistry indicated for this molecule is based upon the experiment discussed in note 12.
10. 10. No evidence for oxidation at C8-C9 was observed by examination of crude NMR mixtures and analysis of the product profile after diol cleavage.
11. 11. Baskaran, S.; Chandrasekaran, S. Tetrahedron Lett. 1990, 31, 2775. The reaction presumably proceeds by elimination of water and subsequent oxidative cleavage of an intermediate enol ether, viz: (equation presented)
12. 12. It is interesting to note that this cleavage procedure would have enabled determination of the relative and absolute configuration of herboxidiene even if the crystal structure had not been available as the synthesis of the appropriate alcohol required for oxidation to 17 is reported in the literature. See; Grieco, P. A.; Hon, Y.S; Perez-Medrano, A. J. Am. Chem. Soc. 1988, 110, 1630.
13. 2,0 °C to r.t.)] of 13 in 94% yield.
14. 14. Kocienski, P. J. in Protecting Groups, Foundations of Organic Chemistry Series, Thieme, New York, 1994, pp 38-40.
15. 15. Kotsuki, H.; Ushio, Y.; Kadota, I.; Ochi, M. Chem. Lett. 1988, 927. See also Kotsuki, H. Synlett. 1992, 97.
16. 15. Kotsuki, H.; Ushio, Y.; Kadota, I.; Ochi, M. Chem. Lett. 1988, 927. See also Kotsuki, H. Synlett. 1992, 97.
17. 16. Baker, D. C.; Hawkins, L. D.; Massad, S. K. J. Org. Chem. 1983, 48, 5180.
18. 17. Walther, E. Aldolisation of Enolates Derived from Chiral N-Propionylsultams with Chiral Aldehydes and Meso Aldehydes. University of Geneva 1994.
19. 18. The syn-syn stereochemistry was unambiguously confirmed by NMR analysis of the acetonide derived from the aldol adduct as described in reference 16. The high selectivity obtained even though the substrates are "mismatched" shows that the reaction proceeds with a very high level of reagent control.
20. 4. See reference 16.
21. 20. Oppolzer, W.; Rodriguez, I.; Starkemann, C.; Walther, E. Tetrahedron Lett. 1990, 31, 5019.
22. 21. Evans, D. A.; Ratz, R. M.; Huff, B. E.; Sheppard, G. S. Tetrahedron Lett. 1994, 31, 7171.
23. 22. Arigoni, D.; Wasmuth, D.; Seebach, D. Helv. Chim. Acta. 1982, 65, 344.
24. 23. Kocienski, P. J. in Protecting Groups, Foundations of Organic Chemistry Series, Thieme, New York, 1994, p. 48. See also; Wenger, R. M. Helv. Chim. Acta. 1983, 66, 2308: Williams, D. R; Sit, S.-Y. J. Am. Chem. Soc. 1984, 106, 2949.; Meyers, A. I.; Lawson, J. P. Tetrahedron Lett. 1982, 23, 4883.
25. 23. Kocienski, P. J. in Protecting Groups, Foundations of Organic Chemistry Series, Thieme, New York, 1994, p. 48. See also; Wenger, R. M. Helv. Chim. Acta. 1983, 66, 2308: Williams, D. R; Sit, S.-Y. J. Am. Chem. Soc. 1984, 106, 2949.; Meyers, A. I.; Lawson, J. P. Tetrahedron Lett. 1982, 23, 4883.
26. 23. Kocienski, P. J. in Protecting Groups, Foundations of Organic Chemistry Series, Thieme, New York, 1994, p. 48. See also; Wenger, R. M. Helv. Chim. Acta. 1983, 66, 2308: Williams, D. R; Sit, S.-Y. J. Am. Chem. Soc. 1984, 106, 2949.; Meyers, A. I.; Lawson, J. P. Tetrahedron Lett. 1982, 23, 4883.
27. 23. Kocienski, P. J. in Protecting Groups, Foundations of Organic Chemistry Series, Thieme, New York, 1994, p. 48. See also; Wenger, R. M. Helv. Chim. Acta. 1983, 66, 2308: Williams, D. R; Sit, S.-Y. J. Am. Chem. Soc. 1984, 106, 2949.; Meyers, A. I.; Lawson, J. P. Tetrahedron Lett. 1982, 23, 4883.
28. 24. Harding, K. E.; Marman, T. H. J. Org. Chem. 1984, 49, 2834; Lavallée, P.; Ruel, R.; Grenier, L.; Bissonnette, M. Tetrahedron Lett. 1986, 27, 679.
29. 24. Harding, K. E.; Marman, T. H. J. Org. Chem. 1984, 49, 2834; Lavallée, P.; Ruel, R.; Grenier, L.; Bissonnette, M. Tetrahedron Lett. 1986, 27, 679.