Homeomorphic isomerism in a peptidic macrobicycle

Angewandte Chemie (International Edition in English)

Volumn 34, Issue 23, 1996, Pages 2660-2662

  Wareham, Richard S ^a   Kilburn, Jeremy D ^a   Turner, David L ^a   Rees, Nicholas H ^a   Holmes, Duncan S ^b  

^a UNIVERSITY OF SOUTHAMPTON   (United Kingdom)

^b GLAXOSMITHKLINE   (United Kingdom)

Author keywords

Atropisomerism; Isomerizations; Macrocycles

Indexed keywords

EID: 33751135463     PISSN: 05700833     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (16)

1. The in-in/out-out nomenclature is commonly used and is readily understood, but it is not strictly unambiguous; see refs. [4, 5b].
2. a) C. H. Parks, H. E. Simmons, J. Am. Chem. Soc. 1968, 90, 2431;
3. b) ibid. 1972, 94, 7184.
4. Selected references: a) J. D. Winkler, E. A. Greller, P. G. Willard, J. Org. Chem. 1993, 58, 1973, and references therein; b) R. S. Macomber, D. E. Rardon, T. J. Emge, ibid. 1992, 57, 433, and references therein; c) M. Saunders, N. Krause, J. Am. Chem. Soc. 1990, 112, 1791, and references therein.
5. Selected references: a) J. D. Winkler, E. A. Greller, P. G. Willard, J. Org. Chem. 1993, 58, 1973, and references therein; b) R. S. Macomber, D. E. Rardon, T. J. Emge, ibid. 1992, 57, 433, and references therein; c) M. Saunders, N. Krause, J. Am. Chem. Soc. 1990, 112, 1791, and references therein.
6. Selected references: a) J. D. Winkler, E. A. Greller, P. G. Willard, J. Org. Chem. 1993, 58, 1973, and references therein; b) R. S. Macomber, D. E. Rardon, T. J. Emge, ibid. 1992, 57, 433, and references therein; c) M. Saunders, N. Krause, J. Am. Chem. Soc. 1990, 112, 1791, and references therein.
7. Bicyclic systems with nitrogen bridgehead atoms can also exhibit in-in, out-out, or in-out isomers, and have been studied in detail: see R. W. Alder, E. Heilbronner, E. Honegger, A. B. McEwen, R. E. Moss, E. Olefirowicz, P. A. Petillo, R. B. Sessions, G. R. Weisman, J. M. White, Z.-Z. Yang, J. Am. Chem. Soc. 1993, 115, 6580, and references therein. However, intercoversion between the various isomeric forms can occur by inversion of the nitrogen atom, which is not homeomorphic isomerism.
8. a) B. J. Gregory, A. H. Haines, P. Karntiang, J. Chem. Soc. Chem. Commun. 1977, 918;
9. b) A. H. Haines, P. Karntiang, J. Chem. Soc. Perkin Trans. 1 1979, 2577.
10. a) G. J. Pernia, J. D. Kilburn, M. Rowley, J. Chem. Soc. Chem. Commun. 1995, 305;
11. b) R. S. Wareham, J. D. Kilburn, N. H. Rees, D. L. Turner, A. R. Leach, D. S. Holmes, Tetrahedron Lett. 1995, 36, 3047;
12. c) C. P. Waymark, J. D. Kilburn, I. Gillies, ibid. 1995, 36, 3051.
13. 1H NMR and ROESY spectra of 5, and of 10 and 11, indicate that the latter two are also out-out isomers, and also probably have the pyridine inverted as described for 5. No compounds that might correspond to the in-in isomers were isolated in these studies.
14. Amino acid analysis was performed by complete hydrolysis of 12 and 13 and conversion of the resulting amino acids into their methyl ester N-pentafluoropropionyl derivatives. The D and L isomers were separated on a Chirasil-L-Val capillary column.
15. P. Güntert, W. Braun, K. Wüthrich, J. Mol. Biol. 1991, 217, 517.
16. D. L. Turner, J. Magn. Reson. 1994, A107, 239.