Structure and mechanism in cinchona alkaloid chemistry: Overturning a 50-year-old misconception

Angewandte Chemie - International Edition

Volumn 38, Issue 17, 1999, Pages 2539-2543

  Braje, Wilfried M ^a   Wartchow, Rudolf ^b   Hoffmann, H Martin R ^a  

^a LEIBNIZ UNIVERSITY HANNOVER   (Germany)

^b Leibniz University Hannover   (Germany)

Author keywords

Alkaloids; Nitrogen heterocycles; Rearrangements; Stereoelectronic control; Structure elucidation

Indexed keywords

CINCHONA ALKALOID; HETEROCYCLIC COMPOUND; QUINIDINE; QUININE;

AQUEOUS SOLUTION; ARTICLE; CHEMICAL REACTION; CRYSTAL STRUCTURE; DRUG MECHANISM; DRUG STRUCTURE; DRUG SYNTHESIS; REACTION ANALYSIS; STEREOCHEMISTRY; X RAY CRYSTALLOGRAPHY;

EID: 0033520390     PISSN: 14337851     EISSN: None     Source Type: Journal    
DOI: 10.1002/(sici)1521-3773(19990903)38:17<2539::aid-anie2539>3.0.co;2-c     Document Type: Article

References (31)

1. H. C. Kolb, M. S. VanNieuwenhze, K. B. Sharpless, Chem. Rev. 1994, 94, 2483.
2. W. Braje, J. Frackenpohl, P. Langer, H. M. R. Hoffmann, Tetrahedron 1998, 54, 3495;
3. b) P. Langer, J. Frackenpohl, H. M. R. Hoffmann, J. Chem. Soc. Perkin Trans. 1 1998, 801;
4. c) H. M. R. Hoffmann, O. Schrake, Tetrahedron Asymmetry 1998, 9, 1051;
5. d) O. Schrake, W. Braje, H. M. R. Hoffmann, R. Wartchow, Tetrahedron Asymmetry 1998, 9, 3715;
6. e) C. von Riesen, P. G. Jones, H. M. R. Hoffmann, Chem. Eur. J. 1996, 2, 673;
7. f) C. von Riesen, H. M. R. Hoffmann, Chem. Eur. J. 1996, 2, 680;
8. g) H. M. R. Hoffmann, T. Plessner, C. von Riesen, Synlett 1996, 690.
9. Apparently, 9-chloroquinine 3 has been the only example that shows coalescence in the NMR spectrum: G. D. H. Dijkstra, R. M. Kellogg, H. Wynberg, J. Org. Chem. 1990, 55, 6121.
10. a) G. D. H. Dijkstra, R. M. Kellogg, H. Wynberg, J. S. Svendsen, I. Marko, K. B. Sharpless, J. Am. Chem. Soc. 1989, 111, 8069;
11. b) G. D. H. Dijkstra, R. M. Kellogg, H. Wynberg, J. Org. Chem. 1990, 55, 6121.
12. The close analogy between the conformation found in the solid state and in solution indicates that intramolecular forces predominate in determining the overall conformation of cinchona alkaloids, rather than solid-state or solvent interactions: F. I. Carroll, P. Abraham, K. Gaetano, S. W. Mascarella, R. A. Wohl, J. Lind, K. Petzoldt, J. Chem. Soc. Perkin Trans 1 1991, 3017.
13. P. Rabe, Justus Liebigs Ann. Chem. 1949, 561, 132.
14. a) P. Rabe, A. Hochstätter, Justus Liebigs Am. Chem. 1934, 514, 61;
15. b) P. Rabe, Chem. Ber. 1941, 74, 225.
16. R. B. Turner, R. B. Woodward in The Chemistry of Cinchona Alkaloids, Vol. III (Eds.: R. H. F. Manske, H. L. Holmes), Academic Press, New York, pp. 1-63, 1953; in particular pp. 17-18, structures 75, 76.
17. a) R. B. Woodward, W. E. Doering, J. Am. Chem. Soc. 1944, 66, 849;
18. b) R. B. Woodward, W. E. Doering, J. Am. Chem. Soc. 1945, 67, 860.
19. a) E. W. Warnhoff, Molecular Rearrangements, Vol. 2, (Ed.: P. de Mayo), Wiley, New York, 1964, pp. 877-879;
20. b) W. Solomon, Chemistry of the Alkaloids, (Ed.: S. W. Pelletier), Van Nostrand Reinhold, New York, 1970, pp. 327-330; see also:
21. c) V. Braschler, C. A. Grob, A. Kaiser, Helv. Chim. Acta 1963, 2646;
22. d) G. R. Pettit, S. K. Gupta, J. Chem. Soc. C 1968, 1208; p. 1209, footnote, structure I; F. Eiden, Pharm. Unserer Zeit 1998, 257, in particular Figure 28 on p. 269.
23. d) G. R. Pettit, S. K. Gupta, J. Chem. Soc. C 1968, 1208; p. 1209, footnote, structure I; F. Eiden, Pharm. Unserer Zeit 1998, 257, in particular Figure 28 on p. 269.
24. Structure 9 appears in electronic data bases: Beilstein Commander 4.0, search March 1999.
25. 3N; b) NaOH. J. Cossy, C. Dumas, D. G. Pardo, Synlett 1997, 905 ; further recent examples: J. Wilken, M. Kossenjans, W. Saak, D. Haase, S. Pohl, J. Martens, Liebigs Ann. 1997, 573 and references therein.
26. 3N; b) NaOH. J. Cossy, C. Dumas, D. G. Pardo, Synlett 1997, 905 ; further recent examples: J. Wilken, M. Kossenjans, W. Saak, D. Haase, S. Pohl, J. Martens, Liebigs Ann. 1997, 573 and references therein.
27. Bicyclic systems with strained bridgehead imine double bonds (E and Z isomers) have been obtained in a matrix in the dark at low temperature: a) R. S. Sheridan, G. A. Ganzer, J. Am. Chem. Soc. 1983, 105, 6158; b) J. G. Radziszewski, J. W. Downing, C. Wentrup, P. Kaszynski, M. Jawdosiuk, P. Kovacic, J. Michl, J. Am. Chem. Soc. 1985, 107, 2799.
28. Bicyclic systems with strained bridgehead imine double bonds (E and Z isomers) have been obtained in a matrix in the dark at low temperature: a) R. S. Sheridan, G. A. Ganzer, J. Am. Chem. Soc. 1983, 105, 6158; b) J. G. Radziszewski, J. W. Downing, C. Wentrup, P. Kaszynski, M. Jawdosiuk, P. Kovacic, J. Michl, J. Am. Chem. Soc. 1985, 107, 2799.
29. J. I. Seeman, Chem. Rev. 1983, 83, 83.
30. P. Rabe, Chem. Ber. 1908, 41, 62.
31. Crystallographic data (excluding structure factors) for the structures reported in this paper have been deposited with the Cambridge Crystallographic Data centre as supplementary publication nos. CCDC-115800 (7), -115801 (8), and 115802 (2c). Copies of the data can be obtained free of charge on application to CCDC, 12 Union Road, Cambridge CB21EZ, UK (fax: (+44)1223-336-033; e-mail: deposit@ccdc.cam.ac.uk).