Conformationally restricted TRH analogs: The compatibility of a 6,5-bicylic lactam-based mimetic with binding to TRH-R

Journal of the American Chemical Society

Volumn 118, Issue 42, 1996, Pages 10106-10112

  Li, Wenhao ^a   Moeller, Kevin D ^a  

^a WASHINGTON UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

PROTIRELIN; PROTIRELIN DERIVATIVE; PROTIRELIN RECEPTOR;

ANIMAL CELL; ARTICLE; CONTROLLED STUDY; DRUG RECEPTOR BINDING; DRUG SYNTHESIS; ENANTIOMER; HYPOPHYSIS; MOUSE; NONHUMAN; NUCLEAR MAGNETIC RESONANCE; STRUCTURE ACTIVITY RELATION;

EID: 0029855614     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja961887v     Document Type: Article

References (56)

1. For an outstanding series of reviews, see: Thyrotropin-Releasing Hormone: Biomedical Significance; Metcalf, G., Jackson, I. M. D., Eds.; Ann. N. Y. Acad. Sci. 1989, 551.
2. For an outstanding series of reviews, see: Thyrotropin-Releasing Hormone: Biomedical Significance; Metcalf, G., Jackson, I. M. D., Eds.; Ann. N. Y. Acad. Sci. 1989, 551.
3. For a summary, see: Marshall, G. R.; Gorin, F. A.; Moore, M. L. In Annual Reports in Medicinal Chemistry; Clarke, F. H., Ed.; Academic Press: New York, 1978; Vol. 13, p 227 and references therein.
4. Reference 2, p 229.
5. Font, J. Ph.D. Thesis, Washington University, St. Louis, MO, 1986, and unpublished results with Lawrence D. Rutledge.
6. For alternative approaches to understanding the conformation of TRH binding, see: (a) Hinkle, P. M.; Woroch, E. L.; Tashjian, G. H. J. Biol. Chem. 1974, 249, 3085-3090. (b) Goren, H. J.; Bauce, L. G.; Vale, W. Mol. Pharmacol. 1977, 13, 606-614. (c) Kamiya, K.; Takamoto, M.; Wada, Y.; Fujino, M.; Nishikawa, M. J. Chem. Soc., Chem. Commun. 1980, 438-439. (d) Sharif, N. A.; To, Z.; Whiting, R. L. Biochem. Biophys. Res. Commun. 1989, 161, 1306-1311. (e) Vonhof, S.; Feuerstein, G. Z.; Cohen, L. A.; Labroo, V. M. Eur. J. Pharmacol. 1990, 180, 1-12.
7. For alternative approaches to understanding the conformation of TRH binding, see: (a) Hinkle, P. M.; Woroch, E. L.; Tashjian, G. H. J. Biol. Chem. 1974, 249, 3085-3090. (b) Goren, H. J.; Bauce, L. G.; Vale, W. Mol. Pharmacol. 1977, 13, 606-614. (c) Kamiya, K.; Takamoto, M.; Wada, Y.; Fujino, M.; Nishikawa, M. J. Chem. Soc., Chem. Commun. 1980, 438-439. (d) Sharif, N. A.; To, Z.; Whiting, R. L. Biochem. Biophys. Res. Commun. 1989, 161, 1306-1311. (e) Vonhof, S.; Feuerstein, G. Z.; Cohen, L. A.; Labroo, V. M. Eur. J. Pharmacol. 1990, 180, 1-12.
8. For alternative approaches to understanding the conformation of TRH binding, see: (a) Hinkle, P. M.; Woroch, E. L.; Tashjian, G. H. J. Biol. Chem. 1974, 249, 3085-3090. (b) Goren, H. J.; Bauce, L. G.; Vale, W. Mol. Pharmacol. 1977, 13, 606-614. (c) Kamiya, K.; Takamoto, M.; Wada, Y.; Fujino, M.; Nishikawa, M. J. Chem. Soc., Chem. Commun. 1980, 438-439. (d) Sharif, N. A.; To, Z.; Whiting, R. L. Biochem. Biophys. Res. Commun. 1989, 161, 1306-1311. (e) Vonhof, S.; Feuerstein, G. Z.; Cohen, L. A.; Labroo, V. M. Eur. J. Pharmacol. 1990, 180, 1-12.
9. For alternative approaches to understanding the conformation of TRH binding, see: (a) Hinkle, P. M.; Woroch, E. L.; Tashjian, G. H. J. Biol. Chem. 1974, 249, 3085-3090. (b) Goren, H. J.; Bauce, L. G.; Vale, W. Mol. Pharmacol. 1977, 13, 606-614. (c) Kamiya, K.; Takamoto, M.; Wada, Y.; Fujino, M.; Nishikawa, M. J. Chem. Soc., Chem. Commun. 1980, 438-439. (d) Sharif, N. A.; To, Z.; Whiting, R. L. Biochem. Biophys. Res. Commun. 1989, 161, 1306-1311. (e) Vonhof, S.; Feuerstein, G. Z.; Cohen, L. A.; Labroo, V. M. Eur. J. Pharmacol. 1990, 180, 1-12.
10. For alternative approaches to understanding the conformation of TRH binding, see: (a) Hinkle, P. M.; Woroch, E. L.; Tashjian, G. H. J. Biol. Chem. 1974, 249, 3085-3090. (b) Goren, H. J.; Bauce, L. G.; Vale, W. Mol. Pharmacol. 1977, 13, 606-614. (c) Kamiya, K.; Takamoto, M.; Wada, Y.; Fujino, M.; Nishikawa, M. J. Chem. Soc., Chem. Commun. 1980, 438-439. (d) Sharif, N. A.; To, Z.; Whiting, R. L. Biochem. Biophys. Res. Commun. 1989, 161, 1306-1311. (e) Vonhof, S.; Feuerstein, G. Z.; Cohen, L. A.; Labroo, V. M. Eur. J. Pharmacol. 1990, 180, 1-12.
11. For an additional application of the models developed by Marshall and Font to the construction of TRH mimetics, see: Olson, G. L.; Cheung, H. C.; Chiang, E.; Madison, V. S.; Sepinwall, J.; Vincent, G. P.; Winokur, A.; Gary, K. A. J. Med. Chem. 1995, 38, 2866.
12. For selected examples of lactam-based peptide mimetics, see: (a) Wolf, J. P.; Rapoport, H. J. Org. Chem 1989, 54, 3164-3173, as well as refs 1-8 therein. (b) Freidinger, R. M.; Perlow, D. S.; Veber, D. F. J. Org. Chem. 1982, 47, 104-109. (c) Freidinger, R. M. J. Org. Chem. 1985, 50, 3631-3633. (d) Zydowsky, T. M.; Dellaria, J. F. Jr.; Nellans, H. N. J. Org. Chem. 1988, 53, 5607-5616. (e) Kempf, D. J.; Condon, S. L. J. Org. Chem. 1990, 55, 1390-1394. (f) Kemp, D. S.; McNamara, P. E. J. Org. Chem. 1985, 50, 5834-5838 and references therein. (g) Nagai, U.; Sato, K. Tetrahedron Lett. 1985, 26, 647-650. (h) Hinds, M. G.; Richards, N. G. J.; Robinson, J. A. J. Chem. Soc., Chem. Commun. 1988, 1447-1449. (i) Paul, P. K. C.; Burney, P. A.; Campbell, M. M.; Osguthorpe, D. J. Bioorg. Med. Chem. Lett. 1992, 2, 141-144. (j) Ward, P.; Ewan, G. B.; Jordon, C. C.; Ireland, S. J.; Hagan, R. M.; Brown, J. R. J. Med. Chem. 1990, 33, 1848-1851. (k) Deal, M. J.; Hagan, R. M.; Ireland, S. J.; Jordan, C. C.; McElroy, A. B.; Porter, B.; Ross, B. C.; Stephens-Smith, M.; Ward, P. J. Med. Chem. 1992, 35, 4195-4204. (l) Flynn, G. A.; Giroux, E. L.; Dage, R. C. J. Am. Chem. Soc. 1987, 109, 7914-7915. (m) Flynn, G. A.; Burkholder, T. P.; Huber, E. W.; Bey, P. Bioorg. Med. Chem. Lett. 1991, 1, 309-312. (n) Burkholder, T. P.; Huber, E. W.; Flynn, G. A. Bioorg. Med. Chem. Lett. 1993, 3, 231-234. (o) Robl, J. A. Tetrahedron Lett. 1994, 35, 393-396, p. Lombart, H. G.; Lubell, W. D. J. Org. Chem. 1994, 59, 6147-6149. (q) Colombo, L.; Giacomo, M. D.; Papeo, G.; Carugo, O.; Scolastico, C.; Manzoni, L. Tetrahedron Lett. 1994, 35, 4031-4034.
13. For selected examples of lactam-based peptide mimetics, see: (a) Wolf, J. P.; Rapoport, H. J. Org. Chem 1989, 54, 3164-3173, as well as refs 1-8 therein. (b) Freidinger, R. M.; Perlow, D. S.; Veber, D. F. J. Org. Chem. 1982, 47, 104-109. (c) Freidinger, R. M. J. Org. Chem. 1985, 50, 3631-3633. (d) Zydowsky, T. M.; Dellaria, J. F. Jr.; Nellans, H. N. J. Org. Chem. 1988, 53, 5607-5616. (e) Kempf, D. J.; Condon, S. L. J. Org. Chem. 1990, 55, 1390-1394. (f) Kemp, D. S.; McNamara, P. E. J. Org. Chem. 1985, 50, 5834-5838 and references therein. (g) Nagai, U.; Sato, K. Tetrahedron Lett. 1985, 26, 647-650. (h) Hinds, M. G.; Richards, N. G. J.; Robinson, J. A. J. Chem. Soc., Chem. Commun. 1988, 1447-1449. (i) Paul, P. K. C.; Burney, P. A.; Campbell, M. M.; Osguthorpe, D. J. Bioorg. Med. Chem. Lett. 1992, 2, 141-144. (j) Ward, P.; Ewan, G. B.; Jordon, C. C.; Ireland, S. J.; Hagan, R. M.; Brown, J. R. J. Med. Chem. 1990, 33, 1848-1851. (k) Deal, M. J.; Hagan, R. M.; Ireland, S. J.; Jordan, C. C.; McElroy, A. B.; Porter, B.; Ross, B. C.; Stephens-Smith, M.; Ward, P. J. Med. Chem. 1992, 35, 4195-4204. (l) Flynn, G. A.; Giroux, E. L.; Dage, R. C. J. Am. Chem. Soc. 1987, 109, 7914-7915. (m) Flynn, G. A.; Burkholder, T. P.; Huber, E. W.; Bey, P. Bioorg. Med. Chem. Lett. 1991, 1, 309-312. (n) Burkholder, T. P.; Huber, E. W.; Flynn, G. A. Bioorg. Med. Chem. Lett. 1993, 3, 231-234. (o) Robl, J. A. Tetrahedron Lett. 1994, 35, 393-396, p. Lombart, H. G.; Lubell, W. D. J. Org. Chem. 1994, 59, 6147-6149. (q) Colombo, L.; Giacomo, M. D.; Papeo, G.; Carugo, O.; Scolastico, C.; Manzoni, L. Tetrahedron Lett. 1994, 35, 4031-4034.
14. For selected examples of lactam-based peptide mimetics, see: (a) Wolf, J. P.; Rapoport, H. J. Org. Chem 1989, 54, 3164-3173, as well as refs 1-8 therein. (b) Freidinger, R. M.; Perlow, D. S.; Veber, D. F. J. Org. Chem. 1982, 47, 104-109. (c) Freidinger, R. M. J. Org. Chem. 1985, 50, 3631-3633. (d) Zydowsky, T. M.; Dellaria, J. F. Jr.; Nellans, H. N. J. Org. Chem. 1988, 53, 5607-5616. (e) Kempf, D. J.; Condon, S. L. J. Org. Chem. 1990, 55, 1390-1394. (f) Kemp, D. S.; McNamara, P. E. J. Org. Chem. 1985, 50, 5834-5838 and references therein. (g) Nagai, U.; Sato, K. Tetrahedron Lett. 1985, 26, 647-650. (h) Hinds, M. G.; Richards, N. G. J.; Robinson, J. A. J. Chem. Soc., Chem. Commun. 1988, 1447-1449. (i) Paul, P. K. C.; Burney, P. A.; Campbell, M. M.; Osguthorpe, D. J. Bioorg. Med. Chem. Lett. 1992, 2, 141-144. (j) Ward, P.; Ewan, G. B.; Jordon, C. C.; Ireland, S. J.; Hagan, R. M.; Brown, J. R. J. Med. Chem. 1990, 33, 1848-1851. (k) Deal, M. J.; Hagan, R. M.; Ireland, S. J.; Jordan, C. C.; McElroy, A. B.; Porter, B.; Ross, B. C.; Stephens-Smith, M.; Ward, P. J. Med. Chem. 1992, 35, 4195-4204. (l) Flynn, G. A.; Giroux, E. L.; Dage, R. C. J. Am. Chem. Soc. 1987, 109, 7914-7915. (m) Flynn, G. A.; Burkholder, T. P.; Huber, E. W.; Bey, P. Bioorg. Med. Chem. Lett. 1991, 1, 309-312. (n) Burkholder, T. P.; Huber, E. W.; Flynn, G. A. Bioorg. Med. Chem. Lett. 1993, 3, 231-234. (o) Robl, J. A. Tetrahedron Lett. 1994, 35, 393-396, p. Lombart, H. G.; Lubell, W. D. J. Org. Chem. 1994, 59, 6147-6149. (q) Colombo, L.; Giacomo, M. D.; Papeo, G.; Carugo, O.; Scolastico, C.; Manzoni, L. Tetrahedron Lett. 1994, 35, 4031-4034.
15. For selected examples of lactam-based peptide mimetics, see: (a) Wolf, J. P.; Rapoport, H. J. Org. Chem 1989, 54, 3164-3173, as well as refs 1-8 therein. (b) Freidinger, R. M.; Perlow, D. S.; Veber, D. F. J. Org. Chem. 1982, 47, 104-109. (c) Freidinger, R. M. J. Org. Chem. 1985, 50, 3631-3633. (d) Zydowsky, T. M.; Dellaria, J. F. Jr.; Nellans, H. N. J. Org. Chem. 1988, 53, 5607-5616. (e) Kempf, D. J.; Condon, S. L. J. Org. Chem. 1990, 55, 1390-1394. (f) Kemp, D. S.; McNamara, P. E. J. Org. Chem. 1985, 50, 5834-5838 and references therein. (g) Nagai, U.; Sato, K. Tetrahedron Lett. 1985, 26, 647-650. (h) Hinds, M. G.; Richards, N. G. J.; Robinson, J. A. J. Chem. Soc., Chem. Commun. 1988, 1447-1449. (i) Paul, P. K. C.; Burney, P. A.; Campbell, M. M.; Osguthorpe, D. J. Bioorg. Med. Chem. Lett. 1992, 2, 141-144. (j) Ward, P.; Ewan, G. B.; Jordon, C. C.; Ireland, S. J.; Hagan, R. M.; Brown, J. R. J. Med. Chem. 1990, 33, 1848-1851. (k) Deal, M. J.; Hagan, R. M.; Ireland, S. J.; Jordan, C. C.; McElroy, A. B.; Porter, B.; Ross, B. C.; Stephens-Smith, M.; Ward, P. J. Med. Chem. 1992, 35, 4195-4204. (l) Flynn, G. A.; Giroux, E. L.; Dage, R. C. J. Am. Chem. Soc. 1987, 109, 7914-7915. (m) Flynn, G. A.; Burkholder, T. P.; Huber, E. W.; Bey, P. Bioorg. Med. Chem. Lett. 1991, 1, 309-312. (n) Burkholder, T. P.; Huber, E. W.; Flynn, G. A. Bioorg. Med. Chem. Lett. 1993, 3, 231-234. (o) Robl, J. A. Tetrahedron Lett. 1994, 35, 393-396, p. Lombart, H. G.; Lubell, W. D. J. Org. Chem. 1994, 59, 6147-6149. (q) Colombo, L.; Giacomo, M. D.; Papeo, G.; Carugo, O.; Scolastico, C.; Manzoni, L. Tetrahedron Lett. 1994, 35, 4031-4034.
16. For selected examples of lactam-based peptide mimetics, see: (a) Wolf, J. P.; Rapoport, H. J. Org. Chem 1989, 54, 3164-3173, as well as refs 1-8 therein. (b) Freidinger, R. M.; Perlow, D. S.; Veber, D. F. J. Org. Chem. 1982, 47, 104-109. (c) Freidinger, R. M. J. Org. Chem. 1985, 50, 3631-3633. (d) Zydowsky, T. M.; Dellaria, J. F. Jr.; Nellans, H. N. J. Org. Chem. 1988, 53, 5607-5616. (e) Kempf, D. J.; Condon, S. L. J. Org. Chem. 1990, 55, 1390-1394. (f) Kemp, D. S.; McNamara, P. E. J. Org. Chem. 1985, 50, 5834-5838 and references therein. (g) Nagai, U.; Sato, K. Tetrahedron Lett. 1985, 26, 647-650. (h) Hinds, M. G.; Richards, N. G. J.; Robinson, J. A. J. Chem. Soc., Chem. Commun. 1988, 1447-1449. (i) Paul, P. K. C.; Burney, P. A.; Campbell, M. M.; Osguthorpe, D. J. Bioorg. Med. Chem. Lett. 1992, 2, 141-144. (j) Ward, P.; Ewan, G. B.; Jordon, C. C.; Ireland, S. J.; Hagan, R. M.; Brown, J. R. J. Med. Chem. 1990, 33, 1848-1851. (k) Deal, M. J.; Hagan, R. M.; Ireland, S. J.; Jordan, C. C.; McElroy, A. B.; Porter, B.; Ross, B. C.; Stephens-Smith, M.; Ward, P. J. Med. Chem. 1992, 35, 4195-4204. (l) Flynn, G. A.; Giroux, E. L.; Dage, R. C. J. Am. Chem. Soc. 1987, 109, 7914-7915. (m) Flynn, G. A.; Burkholder, T. P.; Huber, E. W.; Bey, P. Bioorg. Med. Chem. Lett. 1991, 1, 309-312. (n) Burkholder, T. P.; Huber, E. W.; Flynn, G. A. Bioorg. Med. Chem. Lett. 1993, 3, 231-234. (o) Robl, J. A. Tetrahedron Lett. 1994, 35, 393-396, p. Lombart, H. G.; Lubell, W. D. J. Org. Chem. 1994, 59, 6147-6149. (q) Colombo, L.; Giacomo, M. D.; Papeo, G.; Carugo, O.; Scolastico, C.; Manzoni, L. Tetrahedron Lett. 1994, 35, 4031-4034.
17. For selected examples of lactam-based peptide mimetics, see: (a) Wolf, J. P.; Rapoport, H. J. Org. Chem 1989, 54, 3164-3173, as well as refs 1-8 therein. (b) Freidinger, R. M.; Perlow, D. S.; Veber, D. F. J. Org. Chem. 1982, 47, 104-109. (c) Freidinger, R. M. J. Org. Chem. 1985, 50, 3631-3633. (d) Zydowsky, T. M.; Dellaria, J. F. Jr.; Nellans, H. N. J. Org. Chem. 1988, 53, 5607-5616. (e) Kempf, D. J.; Condon, S. L. J. Org. Chem. 1990, 55, 1390-1394. (f) Kemp, D. S.; McNamara, P. E. J. Org. Chem. 1985, 50, 5834-5838 and references therein. (g) Nagai, U.; Sato, K. Tetrahedron Lett. 1985, 26, 647-650. (h) Hinds, M. G.; Richards, N. G. J.; Robinson, J. A. J. Chem. Soc., Chem. Commun. 1988, 1447-1449. (i) Paul, P. K. C.; Burney, P. A.; Campbell, M. M.; Osguthorpe, D. J. Bioorg. Med. Chem. Lett. 1992, 2, 141-144. (j) Ward, P.; Ewan, G. B.; Jordon, C. C.; Ireland, S. J.; Hagan, R. M.; Brown, J. R. J. Med. Chem. 1990, 33, 1848-1851. (k) Deal, M. J.; Hagan, R. M.; Ireland, S. J.; Jordan, C. C.; McElroy, A. B.; Porter, B.; Ross, B. C.; Stephens-Smith, M.; Ward, P. J. Med. Chem. 1992, 35, 4195-4204. (l) Flynn, G. A.; Giroux, E. L.; Dage, R. C. J. Am. Chem. Soc. 1987, 109, 7914-7915. (m) Flynn, G. A.; Burkholder, T. P.; Huber, E. W.; Bey, P. Bioorg. Med. Chem. Lett. 1991, 1, 309-312. (n) Burkholder, T. P.; Huber, E. W.; Flynn, G. A. Bioorg. Med. Chem. Lett. 1993, 3, 231-234. (o) Robl, J. A. Tetrahedron Lett. 1994, 35, 393-396, p. Lombart, H. G.; Lubell, W. D. J. Org. Chem. 1994, 59, 6147-6149. (q) Colombo, L.; Giacomo, M. D.; Papeo, G.; Carugo, O.; Scolastico, C.; Manzoni, L. Tetrahedron Lett. 1994, 35, 4031-4034.
18. For selected examples of lactam-based peptide mimetics, see: (a) Wolf, J. P.; Rapoport, H. J. Org. Chem 1989, 54, 3164-3173, as well as refs 1-8 therein. (b) Freidinger, R. M.; Perlow, D. S.; Veber, D. F. J. Org. Chem. 1982, 47, 104-109. (c) Freidinger, R. M. J. Org. Chem. 1985, 50, 3631-3633. (d) Zydowsky, T. M.; Dellaria, J. F. Jr.; Nellans, H. N. J. Org. Chem. 1988, 53, 5607-5616. (e) Kempf, D. J.; Condon, S. L. J. Org. Chem. 1990, 55, 1390-1394. (f) Kemp, D. S.; McNamara, P. E. J. Org. Chem. 1985, 50, 5834-5838 and references therein. (g) Nagai, U.; Sato, K. Tetrahedron Lett. 1985, 26, 647-650. (h) Hinds, M. G.; Richards, N. G. J.; Robinson, J. A. J. Chem. Soc., Chem. Commun. 1988, 1447-1449. (i) Paul, P. K. C.; Burney, P. A.; Campbell, M. M.; Osguthorpe, D. J. Bioorg. Med. Chem. Lett. 1992, 2, 141-144. (j) Ward, P.; Ewan, G. B.; Jordon, C. C.; Ireland, S. J.; Hagan, R. M.; Brown, J. R. J. Med. Chem. 1990, 33, 1848-1851. (k) Deal, M. J.; Hagan, R. M.; Ireland, S. J.; Jordan, C. C.; McElroy, A. B.; Porter, B.; Ross, B. C.; Stephens-Smith, M.; Ward, P. J. Med. Chem. 1992, 35, 4195-4204. (l) Flynn, G. A.; Giroux, E. L.; Dage, R. C. J. Am. Chem. Soc. 1987, 109, 7914-7915. (m) Flynn, G. A.; Burkholder, T. P.; Huber, E. W.; Bey, P. Bioorg. Med. Chem. Lett. 1991, 1, 309-312. (n) Burkholder, T. P.; Huber, E. W.; Flynn, G. A. Bioorg. Med. Chem. Lett. 1993, 3, 231-234. (o) Robl, J. A. Tetrahedron Lett. 1994, 35, 393-396, p. Lombart, H. G.; Lubell, W. D. J. Org. Chem. 1994, 59, 6147-6149. (q) Colombo, L.; Giacomo, M. D.; Papeo, G.; Carugo, O.; Scolastico, C.; Manzoni, L. Tetrahedron Lett. 1994, 35, 4031-4034.
19. For selected examples of lactam-based peptide mimetics, see: (a) Wolf, J. P.; Rapoport, H. J. Org. Chem 1989, 54, 3164-3173, as well as refs 1-8 therein. (b) Freidinger, R. M.; Perlow, D. S.; Veber, D. F. J. Org. Chem. 1982, 47, 104-109. (c) Freidinger, R. M. J. Org. Chem. 1985, 50, 3631-3633. (d) Zydowsky, T. M.; Dellaria, J. F. Jr.; Nellans, H. N. J. Org. Chem. 1988, 53, 5607-5616. (e) Kempf, D. J.; Condon, S. L. J. Org. Chem. 1990, 55, 1390-1394. (f) Kemp, D. S.; McNamara, P. E. J. Org. Chem. 1985, 50, 5834-5838 and references therein. (g) Nagai, U.; Sato, K. Tetrahedron Lett. 1985, 26, 647-650. (h) Hinds, M. G.; Richards, N. G. J.; Robinson, J. A. J. Chem. Soc., Chem. Commun. 1988, 1447-1449. (i) Paul, P. K. C.; Burney, P. A.; Campbell, M. M.; Osguthorpe, D. J. Bioorg. Med. Chem. Lett. 1992, 2, 141-144. (j) Ward, P.; Ewan, G. B.; Jordon, C. C.; Ireland, S. J.; Hagan, R. M.; Brown, J. R. J. Med. Chem. 1990, 33, 1848-1851. (k) Deal, M. J.; Hagan, R. M.; Ireland, S. J.; Jordan, C. C.; McElroy, A. B.; Porter, B.; Ross, B. C.; Stephens-Smith, M.; Ward, P. J. Med. Chem. 1992, 35, 4195-4204. (l) Flynn, G. A.; Giroux, E. L.; Dage, R. C. J. Am. Chem. Soc. 1987, 109, 7914-7915. (m) Flynn, G. A.; Burkholder, T. P.; Huber, E. W.; Bey, P. Bioorg. Med. Chem. Lett. 1991, 1, 309-312. (n) Burkholder, T. P.; Huber, E. W.; Flynn, G. A. Bioorg. Med. Chem. Lett. 1993, 3, 231-234. (o) Robl, J. A. Tetrahedron Lett. 1994, 35, 393-396, p. Lombart, H. G.; Lubell, W. D. J. Org. Chem. 1994, 59, 6147-6149. (q) Colombo, L.; Giacomo, M. D.; Papeo, G.; Carugo, O.; Scolastico, C.; Manzoni, L. Tetrahedron Lett. 1994, 35, 4031-4034.
20. For selected examples of lactam-based peptide mimetics, see: (a) Wolf, J. P.; Rapoport, H. J. Org. Chem 1989, 54, 3164-3173, as well as refs 1-8 therein. (b) Freidinger, R. M.; Perlow, D. S.; Veber, D. F. J. Org. Chem. 1982, 47, 104-109. (c) Freidinger, R. M. J. Org. Chem. 1985, 50, 3631-3633. (d) Zydowsky, T. M.; Dellaria, J. F. Jr.; Nellans, H. N. J. Org. Chem. 1988, 53, 5607-5616. (e) Kempf, D. J.; Condon, S. L. J. Org. Chem. 1990, 55, 1390-1394. (f) Kemp, D. S.; McNamara, P. E. J. Org. Chem. 1985, 50, 5834-5838 and references therein. (g) Nagai, U.; Sato, K. Tetrahedron Lett. 1985, 26, 647-650. (h) Hinds, M. G.; Richards, N. G. J.; Robinson, J. A. J. Chem. Soc., Chem. Commun. 1988, 1447-1449. (i) Paul, P. K. C.; Burney, P. A.; Campbell, M. M.; Osguthorpe, D. J. Bioorg. Med. Chem. Lett. 1992, 2, 141-144. (j) Ward, P.; Ewan, G. B.; Jordon, C. C.; Ireland, S. J.; Hagan, R. M.; Brown, J. R. J. Med. Chem. 1990, 33, 1848-1851. (k) Deal, M. J.; Hagan, R. M.; Ireland, S. J.; Jordan, C. C.; McElroy, A. B.; Porter, B.; Ross, B. C.; Stephens-Smith, M.; Ward, P. J. Med. Chem. 1992, 35, 4195-4204. (l) Flynn, G. A.; Giroux, E. L.; Dage, R. C. J. Am. Chem. Soc. 1987, 109, 7914-7915. (m) Flynn, G. A.; Burkholder, T. P.; Huber, E. W.; Bey, P. Bioorg. Med. Chem. Lett. 1991, 1, 309-312. (n) Burkholder, T. P.; Huber, E. W.; Flynn, G. A. Bioorg. Med. Chem. Lett. 1993, 3, 231-234. (o) Robl, J. A. Tetrahedron Lett. 1994, 35, 393-396, p. Lombart, H. G.; Lubell, W. D. J. Org. Chem. 1994, 59, 6147-6149. (q) Colombo, L.; Giacomo, M. D.; Papeo, G.; Carugo, O.; Scolastico, C.; Manzoni, L. Tetrahedron Lett. 1994, 35, 4031-4034.
21. For selected examples of lactam-based peptide mimetics, see: (a) Wolf, J. P.; Rapoport, H. J. Org. Chem 1989, 54, 3164-3173, as well as refs 1-8 therein. (b) Freidinger, R. M.; Perlow, D. S.; Veber, D. F. J. Org. Chem. 1982, 47, 104-109. (c) Freidinger, R. M. J. Org. Chem. 1985, 50, 3631-3633. (d) Zydowsky, T. M.; Dellaria, J. F. Jr.; Nellans, H. N. J. Org. Chem. 1988, 53, 5607-5616. (e) Kempf, D. J.; Condon, S. L. J. Org. Chem. 1990, 55, 1390-1394. (f) Kemp, D. S.; McNamara, P. E. J. Org. Chem. 1985, 50, 5834-5838 and references therein. (g) Nagai, U.; Sato, K. Tetrahedron Lett. 1985, 26, 647-650. (h) Hinds, M. G.; Richards, N. G. J.; Robinson, J. A. J. Chem. Soc., Chem. Commun. 1988, 1447-1449. (i) Paul, P. K. C.; Burney, P. A.; Campbell, M. M.; Osguthorpe, D. J. Bioorg. Med. Chem. Lett. 1992, 2, 141-144. (j) Ward, P.; Ewan, G. B.; Jordon, C. C.; Ireland, S. J.; Hagan, R. M.; Brown, J. R. J. Med. Chem. 1990, 33, 1848-1851. (k) Deal, M. J.; Hagan, R. M.; Ireland, S. J.; Jordan, C. C.; McElroy, A. B.; Porter, B.; Ross, B. C.; Stephens-Smith, M.; Ward, P. J. Med. Chem. 1992, 35, 4195-4204. (l) Flynn, G. A.; Giroux, E. L.; Dage, R. C. J. Am. Chem. Soc. 1987, 109, 7914-7915. (m) Flynn, G. A.; Burkholder, T. P.; Huber, E. W.; Bey, P. Bioorg. Med. Chem. Lett. 1991, 1, 309-312. (n) Burkholder, T. P.; Huber, E. W.; Flynn, G. A. Bioorg. Med. Chem. Lett. 1993, 3, 231-234. (o) Robl, J. A. Tetrahedron Lett. 1994, 35, 393-396, p. Lombart, H. G.; Lubell, W. D. J. Org. Chem. 1994, 59, 6147-6149. (q) Colombo, L.; Giacomo, M. D.; Papeo, G.; Carugo, O.; Scolastico, C.; Manzoni, L. Tetrahedron Lett. 1994, 35, 4031-4034.
22. For selected examples of lactam-based peptide mimetics, see: (a) Wolf, J. P.; Rapoport, H. J. Org. Chem 1989, 54, 3164-3173, as well as refs 1-8 therein. (b) Freidinger, R. M.; Perlow, D. S.; Veber, D. F. J. Org. Chem. 1982, 47, 104-109. (c) Freidinger, R. M. J. Org. Chem. 1985, 50, 3631-3633. (d) Zydowsky, T. M.; Dellaria, J. F. Jr.; Nellans, H. N. J. Org. Chem. 1988, 53, 5607-5616. (e) Kempf, D. J.; Condon, S. L. J. Org. Chem. 1990, 55, 1390-1394. (f) Kemp, D. S.; McNamara, P. E. J. Org. Chem. 1985, 50, 5834-5838 and references therein. (g) Nagai, U.; Sato, K. Tetrahedron Lett. 1985, 26, 647-650. (h) Hinds, M. G.; Richards, N. G. J.; Robinson, J. A. J. Chem. Soc., Chem. Commun. 1988, 1447-1449. (i) Paul, P. K. C.; Burney, P. A.; Campbell, M. M.; Osguthorpe, D. J. Bioorg. Med. Chem. Lett. 1992, 2, 141-144. (j) Ward, P.; Ewan, G. B.; Jordon, C. C.; Ireland, S. J.; Hagan, R. M.; Brown, J. R. J. Med. Chem. 1990, 33, 1848-1851. (k) Deal, M. J.; Hagan, R. M.; Ireland, S. J.; Jordan, C. C.; McElroy, A. B.; Porter, B.; Ross, B. C.; Stephens-Smith, M.; Ward, P. J. Med. Chem. 1992, 35, 4195-4204. (l) Flynn, G. A.; Giroux, E. L.; Dage, R. C. J. Am. Chem. Soc. 1987, 109, 7914-7915. (m) Flynn, G. A.; Burkholder, T. P.; Huber, E. W.; Bey, P. Bioorg. Med. Chem. Lett. 1991, 1, 309-312. (n) Burkholder, T. P.; Huber, E. W.; Flynn, G. A. Bioorg. Med. Chem. Lett. 1993, 3, 231-234. (o) Robl, J. A. Tetrahedron Lett. 1994, 35, 393-396, p. Lombart, H. G.; Lubell, W. D. J. Org. Chem. 1994, 59, 6147-6149. (q) Colombo, L.; Giacomo, M. D.; Papeo, G.; Carugo, O.; Scolastico, C.; Manzoni, L. Tetrahedron Lett. 1994, 35, 4031-4034.
23. For selected examples of lactam-based peptide mimetics, see: (a) Wolf, J. P.; Rapoport, H. J. Org. Chem 1989, 54, 3164-3173, as well as refs 1-8 therein. (b) Freidinger, R. M.; Perlow, D. S.; Veber, D. F. J. Org. Chem. 1982, 47, 104-109. (c) Freidinger, R. M. J. Org. Chem. 1985, 50, 3631-3633. (d) Zydowsky, T. M.; Dellaria, J. F. Jr.; Nellans, H. N. J. Org. Chem. 1988, 53, 5607-5616. (e) Kempf, D. J.; Condon, S. L. J. Org. Chem. 1990, 55, 1390-1394. (f) Kemp, D. S.; McNamara, P. E. J. Org. Chem. 1985, 50, 5834-5838 and references therein. (g) Nagai, U.; Sato, K. Tetrahedron Lett. 1985, 26, 647-650. (h) Hinds, M. G.; Richards, N. G. J.; Robinson, J. A. J. Chem. Soc., Chem. Commun. 1988, 1447-1449. (i) Paul, P. K. C.; Burney, P. A.; Campbell, M. M.; Osguthorpe, D. J. Bioorg. Med. Chem. Lett. 1992, 2, 141-144. (j) Ward, P.; Ewan, G. B.; Jordon, C. C.; Ireland, S. J.; Hagan, R. M.; Brown, J. R. J. Med. Chem. 1990, 33, 1848-1851. (k) Deal, M. J.; Hagan, R. M.; Ireland, S. J.; Jordan, C. C.; McElroy, A. B.; Porter, B.; Ross, B. C.; Stephens-Smith, M.; Ward, P. J. Med. Chem. 1992, 35, 4195-4204. (l) Flynn, G. A.; Giroux, E. L.; Dage, R. C. J. Am. Chem. Soc. 1987, 109, 7914-7915. (m) Flynn, G. A.; Burkholder, T. P.; Huber, E. W.; Bey, P. Bioorg. Med. Chem. Lett. 1991, 1, 309-312. (n) Burkholder, T. P.; Huber, E. W.; Flynn, G. A. Bioorg. Med. Chem. Lett. 1993, 3, 231-234. (o) Robl, J. A. Tetrahedron Lett. 1994, 35, 393-396, p. Lombart, H. G.; Lubell, W. D. J. Org. Chem. 1994, 59, 6147-6149. (q) Colombo, L.; Giacomo, M. D.; Papeo, G.; Carugo, O.; Scolastico, C.; Manzoni, L. Tetrahedron Lett. 1994, 35, 4031-4034.
24. For selected examples of lactam-based peptide mimetics, see: (a) Wolf, J. P.; Rapoport, H. J. Org. Chem 1989, 54, 3164-3173, as well as refs 1-8 therein. (b) Freidinger, R. M.; Perlow, D. S.; Veber, D. F. J. Org. Chem. 1982, 47, 104-109. (c) Freidinger, R. M. J. Org. Chem. 1985, 50, 3631-3633. (d) Zydowsky, T. M.; Dellaria, J. F. Jr.; Nellans, H. N. J. Org. Chem. 1988, 53, 5607-5616. (e) Kempf, D. J.; Condon, S. L. J. Org. Chem. 1990, 55, 1390-1394. (f) Kemp, D. S.; McNamara, P. E. J. Org. Chem. 1985, 50, 5834-5838 and references therein. (g) Nagai, U.; Sato, K. Tetrahedron Lett. 1985, 26, 647-650. (h) Hinds, M. G.; Richards, N. G. J.; Robinson, J. A. J. Chem. Soc., Chem. Commun. 1988, 1447-1449. (i) Paul, P. K. C.; Burney, P. A.; Campbell, M. M.; Osguthorpe, D. J. Bioorg. Med. Chem. Lett. 1992, 2, 141-144. (j) Ward, P.; Ewan, G. B.; Jordon, C. C.; Ireland, S. J.; Hagan, R. M.; Brown, J. R. J. Med. Chem. 1990, 33, 1848-1851. (k) Deal, M. J.; Hagan, R. M.; Ireland, S. J.; Jordan, C. C.; McElroy, A. B.; Porter, B.; Ross, B. C.; Stephens-Smith, M.; Ward, P. J. Med. Chem. 1992, 35, 4195-4204. (l) Flynn, G. A.; Giroux, E. L.; Dage, R. C. J. Am. Chem. Soc. 1987, 109, 7914-7915. (m) Flynn, G. A.; Burkholder, T. P.; Huber, E. W.; Bey, P. Bioorg. Med. Chem. Lett. 1991, 1, 309-312. (n) Burkholder, T. P.; Huber, E. W.; Flynn, G. A. Bioorg. Med. Chem. Lett. 1993, 3, 231-234. (o) Robl, J. A. Tetrahedron Lett. 1994, 35, 393-396, p. Lombart, H. G.; Lubell, W. D. J. Org. Chem. 1994, 59, 6147-6149. (q) Colombo, L.; Giacomo, M. D.; Papeo, G.; Carugo, O.; Scolastico, C.; Manzoni, L. Tetrahedron Lett. 1994, 35, 4031-4034.
25. For selected examples of lactam-based peptide mimetics, see: (a) Wolf, J. P.; Rapoport, H. J. Org. Chem 1989, 54, 3164-3173, as well as refs 1-8 therein. (b) Freidinger, R. M.; Perlow, D. S.; Veber, D. F. J. Org. Chem. 1982, 47, 104-109. (c) Freidinger, R. M. J. Org. Chem. 1985, 50, 3631-3633. (d) Zydowsky, T. M.; Dellaria, J. F. Jr.; Nellans, H. N. J. Org. Chem. 1988, 53, 5607-5616. (e) Kempf, D. J.; Condon, S. L. J. Org. Chem. 1990, 55, 1390-1394. (f) Kemp, D. S.; McNamara, P. E. J. Org. Chem. 1985, 50, 5834-5838 and references therein. (g) Nagai, U.; Sato, K. Tetrahedron Lett. 1985, 26, 647-650. (h) Hinds, M. G.; Richards, N. G. J.; Robinson, J. A. J. Chem. Soc., Chem. Commun. 1988, 1447-1449. (i) Paul, P. K. C.; Burney, P. A.; Campbell, M. M.; Osguthorpe, D. J. Bioorg. Med. Chem. Lett. 1992, 2, 141-144. (j) Ward, P.; Ewan, G. B.; Jordon, C. C.; Ireland, S. J.; Hagan, R. M.; Brown, J. R. J. Med. Chem. 1990, 33, 1848-1851. (k) Deal, M. J.; Hagan, R. M.; Ireland, S. J.; Jordan, C. C.; McElroy, A. B.; Porter, B.; Ross, B. C.; Stephens-Smith, M.; Ward, P. J. Med. Chem. 1992, 35, 4195-4204. (l) Flynn, G. A.; Giroux, E. L.; Dage, R. C. J. Am. Chem. Soc. 1987, 109, 7914-7915. (m) Flynn, G. A.; Burkholder, T. P.; Huber, E. W.; Bey, P. Bioorg. Med. Chem. Lett. 1991, 1, 309-312. (n) Burkholder, T. P.; Huber, E. W.; Flynn, G. A. Bioorg. Med. Chem. Lett. 1993, 3, 231-234. (o) Robl, J. A. Tetrahedron Lett. 1994, 35, 393-396, p. Lombart, H. G.; Lubell, W. D. J. Org. Chem. 1994, 59, 6147-6149. (q) Colombo, L.; Giacomo, M. D.; Papeo, G.; Carugo, O.; Scolastico, C.; Manzoni, L. Tetrahedron Lett. 1994, 35, 4031-4034.
26. For selected examples of lactam-based peptide mimetics, see: (a) Wolf, J. P.; Rapoport, H. J. Org. Chem 1989, 54, 3164-3173, as well as refs 1-8 therein. (b) Freidinger, R. M.; Perlow, D. S.; Veber, D. F. J. Org. Chem. 1982, 47, 104-109. (c) Freidinger, R. M. J. Org. Chem. 1985, 50, 3631-3633. (d) Zydowsky, T. M.; Dellaria, J. F. Jr.; Nellans, H. N. J. Org. Chem. 1988, 53, 5607-5616. (e) Kempf, D. J.; Condon, S. L. J. Org. Chem. 1990, 55, 1390-1394. (f) Kemp, D. S.; McNamara, P. E. J. Org. Chem. 1985, 50, 5834-5838 and references therein. (g) Nagai, U.; Sato, K. Tetrahedron Lett. 1985, 26, 647-650. (h) Hinds, M. G.; Richards, N. G. J.; Robinson, J. A. J. Chem. Soc., Chem. Commun. 1988, 1447-1449. (i) Paul, P. K. C.; Burney, P. A.; Campbell, M. M.; Osguthorpe, D. J. Bioorg. Med. Chem. Lett. 1992, 2, 141-144. (j) Ward, P.; Ewan, G. B.; Jordon, C. C.; Ireland, S. J.; Hagan, R. M.; Brown, J. R. J. Med. Chem. 1990, 33, 1848-1851. (k) Deal, M. J.; Hagan, R. M.; Ireland, S. J.; Jordan, C. C.; McElroy, A. B.; Porter, B.; Ross, B. C.; Stephens-Smith, M.; Ward, P. J. Med. Chem. 1992, 35, 4195-4204. (l) Flynn, G. A.; Giroux, E. L.; Dage, R. C. J. Am. Chem. Soc. 1987, 109, 7914-7915. (m) Flynn, G. A.; Burkholder, T. P.; Huber, E. W.; Bey, P. Bioorg. Med. Chem. Lett. 1991, 1, 309-312. (n) Burkholder, T. P.; Huber, E. W.; Flynn, G. A. Bioorg. Med. Chem. Lett. 1993, 3, 231-234. (o) Robl, J. A. Tetrahedron Lett. 1994, 35, 393-396, p. Lombart, H. G.; Lubell, W. D. J. Org. Chem. 1994, 59, 6147-6149. (q) Colombo, L.; Giacomo, M. D.; Papeo, G.; Carugo, O.; Scolastico, C.; Manzoni, L. Tetrahedron Lett. 1994, 35, 4031-4034.
27. For selected examples of lactam-based peptide mimetics, see: (a) Wolf, J. P.; Rapoport, H. J. Org. Chem 1989, 54, 3164-3173, as well as refs 1-8 therein. (b) Freidinger, R. M.; Perlow, D. S.; Veber, D. F. J. Org. Chem. 1982, 47, 104-109. (c) Freidinger, R. M. J. Org. Chem. 1985, 50, 3631-3633. (d) Zydowsky, T. M.; Dellaria, J. F. Jr.; Nellans, H. N. J. Org. Chem. 1988, 53, 5607-5616. (e) Kempf, D. J.; Condon, S. L. J. Org. Chem. 1990, 55, 1390-1394. (f) Kemp, D. S.; McNamara, P. E. J. Org. Chem. 1985, 50, 5834-5838 and references therein. (g) Nagai, U.; Sato, K. Tetrahedron Lett. 1985, 26, 647-650. (h) Hinds, M. G.; Richards, N. G. J.; Robinson, J. A. J. Chem. Soc., Chem. Commun. 1988, 1447-1449. (i) Paul, P. K. C.; Burney, P. A.; Campbell, M. M.; Osguthorpe, D. J. Bioorg. Med. Chem. Lett. 1992, 2, 141-144. (j) Ward, P.; Ewan, G. B.; Jordon, C. C.; Ireland, S. J.; Hagan, R. M.; Brown, J. R. J. Med. Chem. 1990, 33, 1848-1851. (k) Deal, M. J.; Hagan, R. M.; Ireland, S. J.; Jordan, C. C.; McElroy, A. B.; Porter, B.; Ross, B. C.; Stephens-Smith, M.; Ward, P. J. Med. Chem. 1992, 35, 4195-4204. (l) Flynn, G. A.; Giroux, E. L.; Dage, R. C. J. Am. Chem. Soc. 1987, 109, 7914-7915. (m) Flynn, G. A.; Burkholder, T. P.; Huber, E. W.; Bey, P. Bioorg. Med. Chem. Lett. 1991, 1, 309-312. (n) Burkholder, T. P.; Huber, E. W.; Flynn, G. A. Bioorg. Med. Chem. Lett. 1993, 3, 231-234. (o) Robl, J. A. Tetrahedron Lett. 1994, 35, 393-396, p. Lombart, H. G.; Lubell, W. D. J. Org. Chem. 1994, 59, 6147-6149. (q) Colombo, L.; Giacomo, M. D.; Papeo, G.; Carugo, O.; Scolastico, C.; Manzoni, L. Tetrahedron Lett. 1994, 35, 4031-4034.
28. For selected examples of lactam-based peptide mimetics, see: (a) Wolf, J. P.; Rapoport, H. J. Org. Chem 1989, 54, 3164-3173, as well as refs 1-8 therein. (b) Freidinger, R. M.; Perlow, D. S.; Veber, D. F. J. Org. Chem. 1982, 47, 104-109. (c) Freidinger, R. M. J. Org. Chem. 1985, 50, 3631-3633. (d) Zydowsky, T. M.; Dellaria, J. F. Jr.; Nellans, H. N. J. Org. Chem. 1988, 53, 5607-5616. (e) Kempf, D. J.; Condon, S. L. J. Org. Chem. 1990, 55, 1390-1394. (f) Kemp, D. S.; McNamara, P. E. J. Org. Chem. 1985, 50, 5834-5838 and references therein. (g) Nagai, U.; Sato, K. Tetrahedron Lett. 1985, 26, 647-650. (h) Hinds, M. G.; Richards, N. G. J.; Robinson, J. A. J. Chem. Soc., Chem. Commun. 1988, 1447-1449. (i) Paul, P. K. C.; Burney, P. A.; Campbell, M. M.; Osguthorpe, D. J. Bioorg. Med. Chem. Lett. 1992, 2, 141-144. (j) Ward, P.; Ewan, G. B.; Jordon, C. C.; Ireland, S. J.; Hagan, R. M.; Brown, J. R. J. Med. Chem. 1990, 33, 1848-1851. (k) Deal, M. J.; Hagan, R. M.; Ireland, S. J.; Jordan, C. C.; McElroy, A. B.; Porter, B.; Ross, B. C.; Stephens-Smith, M.; Ward, P. J. Med. Chem. 1992, 35, 4195-4204. (l) Flynn, G. A.; Giroux, E. L.; Dage, R. C. J. Am. Chem. Soc. 1987, 109, 7914-7915. (m) Flynn, G. A.; Burkholder, T. P.; Huber, E. W.; Bey, P. Bioorg. Med. Chem. Lett. 1991, 1, 309-312. (n) Burkholder, T. P.; Huber, E. W.; Flynn, G. A. Bioorg. Med. Chem. Lett. 1993, 3, 231-234. (o) Robl, J. A. Tetrahedron Lett. 1994, 35, 393-396, p. Lombart, H. G.; Lubell, W. D. J. Org. Chem. 1994, 59, 6147-6149. (q) Colombo, L.; Giacomo, M. D.; Papeo, G.; Carugo, O.; Scolastico, C.; Manzoni, L. Tetrahedron Lett. 1994, 35, 4031-4034.
29. Rutledge, L. D.; Perlman, J. H.; Gershengorn, M. C.; Marshall, G. R.; Moeller, K. D. J. Med. Chem. 1996, 39, 1571.
30. (a) Li, W.; Hanau, C. E.; d'Avignon, A.; Moeller, K. D. J. Org. Chem. 1995, 60, 8155.
31. (b) Kao, J.; Li, W.; Moeller, K. D. Submitted for publication.
32. For pioneering work with anodic amide oxidations, see: (a) Ross, S. D.; Finkelstein, M.; Peterson, C. J. Am. Chem. Soc. 1964, 86, 4139. (b) Ross, S. D.; Finkelstein, M.; Peterson, C. J. Org. Chem. 1966, 31, 128. (c) Ross, S. D.; Finkelstein, M.; Peterson, C. J. Am. Chem. Soc. 1966, 88, 4657. For reviews, see: (d) Shono, T. Tetrahedron 1984, 40, 811. (e) Shono, T.; Matsumura, Y.; Tsubata, K. In Organic Synthesis, Saucy, G., Ed.; Organic Synthesis Inc., 1984; Vol. 63, p 206 and references therein. (f) Shono, T. In Topics in Current Chemistry; Steckhan, E. Ed.; Springer-Verlag: Berlin-Heidelberg-New York, 1988; Vol. 148, p 131.
33. For pioneering work with anodic amide oxidations, see: (a) Ross, S. D.; Finkelstein, M.; Peterson, C. J. Am. Chem. Soc. 1964, 86, 4139. (b) Ross, S. D.; Finkelstein, M.; Peterson, C. J. Org. Chem. 1966, 31, 128. (c) Ross, S. D.; Finkelstein, M.; Peterson, C. J. Am. Chem. Soc. 1966, 88, 4657. For reviews, see: (d) Shono, T. Tetrahedron 1984, 40, 811. (e) Shono, T.; Matsumura, Y.; Tsubata, K. In Organic Synthesis, Saucy, G., Ed.; Organic Synthesis Inc., 1984; Vol. 63, p 206 and references therein. (f) Shono, T. In Topics in Current Chemistry; Steckhan, E. Ed.; Springer-Verlag: Berlin-Heidelberg-New York, 1988; Vol. 148, p 131.
34. For pioneering work with anodic amide oxidations, see: (a) Ross, S. D.; Finkelstein, M.; Peterson, C. J. Am. Chem. Soc. 1964, 86, 4139. (b) Ross, S. D.; Finkelstein, M.; Peterson, C. J. Org. Chem. 1966, 31, 128. (c) Ross, S. D.; Finkelstein, M.; Peterson, C. J. Am. Chem. Soc. 1966, 88, 4657. For reviews, see: (d) Shono, T. Tetrahedron 1984, 40, 811. (e) Shono, T.; Matsumura, Y.; Tsubata, K. In Organic Synthesis, Saucy, G., Ed.; Organic Synthesis Inc., 1984; Vol. 63, p 206 and references therein. (f) Shono, T. In Topics in Current Chemistry; Steckhan, E. Ed.; Springer-Verlag: Berlin-Heidelberg-New York, 1988; Vol. 148, p 131.
35. For pioneering work with anodic amide oxidations, see: (a) Ross, S. D.; Finkelstein, M.; Peterson, C. J. Am. Chem. Soc. 1964, 86, 4139. (b) Ross, S. D.; Finkelstein, M.; Peterson, C. J. Org. Chem. 1966, 31, 128. (c) Ross, S. D.; Finkelstein, M.; Peterson, C. J. Am. Chem. Soc. 1966, 88, 4657. For reviews, see: (d) Shono, T. Tetrahedron 1984, 40, 811. (e) Shono, T.; Matsumura, Y.; Tsubata, K. In Organic Synthesis, Saucy, G., Ed.; Organic Synthesis Inc., 1984; Vol. 63, p 206 and references therein. (f) Shono, T. In Topics in Current Chemistry; Steckhan, E. Ed.; Springer-Verlag: Berlin-Heidelberg-New York, 1988; Vol. 148, p 131.
36. For pioneering work with anodic amide oxidations, see: (a) Ross, S. D.; Finkelstein, M.; Peterson, C. J. Am. Chem. Soc. 1964, 86, 4139. (b) Ross, S. D.; Finkelstein, M.; Peterson, C. J. Org. Chem. 1966, 31, 128. (c) Ross, S. D.; Finkelstein, M.; Peterson, C. J. Am. Chem. Soc. 1966, 88, 4657. For reviews, see: (d) Shono, T. Tetrahedron 1984, 40, 811. (e) Shono, T.; Matsumura, Y.; Tsubata, K. In Organic Synthesis, Saucy, G., Ed.; Organic Synthesis Inc., 1984; Vol. 63, p 206 and references therein. (f) Shono, T. In Topics in Current Chemistry; Steckhan, E. Ed.; Springer-Verlag: Berlin-Heidelberg-New York, 1988; Vol. 148, p 131.
37. For pioneering work with anodic amide oxidations, see: (a) Ross, S. D.; Finkelstein, M.; Peterson, C. J. Am. Chem. Soc. 1964, 86, 4139. (b) Ross, S. D.; Finkelstein, M.; Peterson, C. J. Org. Chem. 1966, 31, 128. (c) Ross, S. D.; Finkelstein, M.; Peterson, C. J. Am. Chem. Soc. 1966, 88, 4657. For reviews, see: (d) Shono, T. Tetrahedron 1984, 40, 811. (e) Shono, T.; Matsumura, Y.; Tsubata, K. In Organic Synthesis, Saucy, G., Ed.; Organic Synthesis Inc., 1984; Vol. 63, p 206 and references therein. (f) Shono, T. In Topics in Current Chemistry; Steckhan, E. Ed.; Springer-Verlag: Berlin-Heidelberg-New York, 1988; Vol. 148, p 131.
38. For examples of amide oxidations being used to functionalize peptides, see refs 8 and 10 as well as the following: (a) Shono, T.; Matsumura, Y.; Inoue, K. J. Org. Chem. 1983, 48, 1388. (b) Thaning, M.; Wistrand, L.-G. Helv. Chim. Acta 1986, 69, 1711. (c) Renaud, P.; Seebach, D. Angew. Chem., Int. Ed. Engl. 1986, 25, 843. (d) Renaud, P.; Seebach, D. Helv. Chim. Acta 1986, 69, 1704. (e) Seebach, D.; Charczuk, R.; Gerber, C.; Renaud, P.; Berner, H.; Schneider, H. Helv. Chim. Acta 1989, 72, 401. (f) Papadopoulos, A.; Heyer, J.; Ginzel K.-D.; Steckhan, E. Chem. Ber. 1989, 122, 2159. (g) Ginzel, K.-D.; Brungs, P.; Steckhan, E. Tetrahedron 1989, 45, 1691. (h) Papadopoulos, A.; Lewall, B.; Steckhan, E.; Ginzel, K.-D.; Knoch, F.; Nieger, M. Tetrahedron 1991, 47, 563. (i) Barrett, A. G. M.; Pilipauskas, D. J. Org. Chem. 1991, 56, 2787. (j) Moeller, K. D.; Rutledge, L. D. J. Org. Chem. 1992, 57, 6360. (k) Cornille, F.; Fobian, Y. M.; Slomczynska, U.; Beusen D. D.; Marshall, G. R.; Moeller, K. D. Tetrahedron Lett. 1994, 35, 6989-6992. (l) Cornille, F.; Slomczynska, U.; Smythe, M. L.; Beusen, D. D.; Moeller, K. D.; Marshall, G. R. J. Am. Chem. Soc. 1995, 117, 909. (m) Slomczynska, U.; Chalmers, D. K.; Cornille, F.; Smythe, M. L.; Beusen, D. D.; Moeller, K. D.; Marshall, G. R. J. Org. Chem. 1996, 61, 1198-1204. (n) Fobian, Y. M.; d'Avignon, D. A.; Moeller, K. D. Bioorg. Med. Chem. Lett. 1996, 6, 315-318.
39. For examples of amide oxidations being used to functionalize peptides, see refs 8 and 10 as well as the following: (a) Shono, T.; Matsumura, Y.; Inoue, K. J. Org. Chem. 1983, 48, 1388. (b) Thaning, M.; Wistrand, L.-G. Helv. Chim. Acta 1986, 69, 1711. (c) Renaud, P.; Seebach, D. Angew. Chem., Int. Ed. Engl. 1986, 25, 843. (d) Renaud, P.; Seebach, D. Helv. Chim. Acta 1986, 69, 1704. (e) Seebach, D.; Charczuk, R.; Gerber, C.; Renaud, P.; Berner, H.; Schneider, H. Helv. Chim. Acta 1989, 72, 401. (f) Papadopoulos, A.; Heyer, J.; Ginzel K.-D.; Steckhan, E. Chem. Ber. 1989, 122, 2159. (g) Ginzel, K.-D.; Brungs, P.; Steckhan, E. Tetrahedron 1989, 45, 1691. (h) Papadopoulos, A.; Lewall, B.; Steckhan, E.; Ginzel, K.-D.; Knoch, F.; Nieger, M. Tetrahedron 1991, 47, 563. (i) Barrett, A. G. M.; Pilipauskas, D. J. Org. Chem. 1991, 56, 2787. (j) Moeller, K. D.; Rutledge, L. D. J. Org. Chem. 1992, 57, 6360. (k) Cornille, F.; Fobian, Y. M.; Slomczynska, U.; Beusen D. D.; Marshall, G. R.; Moeller, K. D. Tetrahedron Lett. 1994, 35, 6989-6992. (l) Cornille, F.; Slomczynska, U.; Smythe, M. L.; Beusen, D. D.; Moeller, K. D.; Marshall, G. R. J. Am. Chem. Soc. 1995, 117, 909. (m) Slomczynska, U.; Chalmers, D. K.; Cornille, F.; Smythe, M. L.; Beusen, D. D.; Moeller, K. D.; Marshall, G. R. J. Org. Chem. 1996, 61, 1198-1204. (n) Fobian, Y. M.; d'Avignon, D. A.; Moeller, K. D. Bioorg. Med. Chem. Lett. 1996, 6, 315-318.
40. For examples of amide oxidations being used to functionalize peptides, see refs 8 and 10 as well as the following: (a) Shono, T.; Matsumura, Y.; Inoue, K. J. Org. Chem. 1983, 48, 1388. (b) Thaning, M.; Wistrand, L.-G. Helv. Chim. Acta 1986, 69, 1711. (c) Renaud, P.; Seebach, D. Angew. Chem., Int. Ed. Engl. 1986, 25, 843. (d) Renaud, P.; Seebach, D. Helv. Chim. Acta 1986, 69, 1704. (e) Seebach, D.; Charczuk, R.; Gerber, C.; Renaud, P.; Berner, H.; Schneider, H. Helv. Chim. Acta 1989, 72, 401. (f) Papadopoulos, A.; Heyer, J.; Ginzel K.-D.; Steckhan, E. Chem. Ber. 1989, 122, 2159. (g) Ginzel, K.-D.; Brungs, P.; Steckhan, E. Tetrahedron 1989, 45, 1691. (h) Papadopoulos, A.; Lewall, B.; Steckhan, E.; Ginzel, K.-D.; Knoch, F.; Nieger, M. Tetrahedron 1991, 47, 563. (i) Barrett, A. G. M.; Pilipauskas, D. J. Org. Chem. 1991, 56, 2787. (j) Moeller, K. D.; Rutledge, L. D. J. Org. Chem. 1992, 57, 6360. (k) Cornille, F.; Fobian, Y. M.; Slomczynska, U.; Beusen D. D.; Marshall, G. R.; Moeller, K. D. Tetrahedron Lett. 1994, 35, 6989-6992. (l) Cornille, F.; Slomczynska, U.; Smythe, M. L.; Beusen, D. D.; Moeller, K. D.; Marshall, G. R. J. Am. Chem. Soc. 1995, 117, 909. (m) Slomczynska, U.; Chalmers, D. K.; Cornille, F.; Smythe, M. L.; Beusen, D. D.; Moeller, K. D.; Marshall, G. R. J. Org. Chem. 1996, 61, 1198-1204. (n) Fobian, Y. M.; d'Avignon, D. A.; Moeller, K. D. Bioorg. Med. Chem. Lett. 1996, 6, 315-318.
41. For examples of amide oxidations being used to functionalize peptides, see refs 8 and 10 as well as the following: (a) Shono, T.; Matsumura, Y.; Inoue, K. J. Org. Chem. 1983, 48, 1388. (b) Thaning, M.; Wistrand, L.-G. Helv. Chim. Acta 1986, 69, 1711. (c) Renaud, P.; Seebach, D. Angew. Chem., Int. Ed. Engl. 1986, 25, 843. (d) Renaud, P.; Seebach, D. Helv. Chim. Acta 1986, 69, 1704. (e) Seebach, D.; Charczuk, R.; Gerber, C.; Renaud, P.; Berner, H.; Schneider, H. Helv. Chim. Acta 1989, 72, 401. (f) Papadopoulos, A.; Heyer, J.; Ginzel K.-D.; Steckhan, E. Chem. Ber. 1989, 122, 2159. (g) Ginzel, K.-D.; Brungs, P.; Steckhan, E. Tetrahedron 1989, 45, 1691. (h) Papadopoulos, A.; Lewall, B.; Steckhan, E.; Ginzel, K.-D.; Knoch, F.; Nieger, M. Tetrahedron 1991, 47, 563. (i) Barrett, A. G. M.; Pilipauskas, D. J. Org. Chem. 1991, 56, 2787. (j) Moeller, K. D.; Rutledge, L. D. J. Org. Chem. 1992, 57, 6360. (k) Cornille, F.; Fobian, Y. M.; Slomczynska, U.; Beusen D. D.; Marshall, G. R.; Moeller, K. D. Tetrahedron Lett. 1994, 35, 6989-6992. (l) Cornille, F.; Slomczynska, U.; Smythe, M. L.; Beusen, D. D.; Moeller, K. D.; Marshall, G. R. J. Am. Chem. Soc. 1995, 117, 909. (m) Slomczynska, U.; Chalmers, D. K.; Cornille, F.; Smythe, M. L.; Beusen, D. D.; Moeller, K. D.; Marshall, G. R. J. Org. Chem. 1996, 61, 1198-1204. (n) Fobian, Y. M.; d'Avignon, D. A.; Moeller, K. D. Bioorg. Med. Chem. Lett. 1996, 6, 315-318.
42. For examples of amide oxidations being used to functionalize peptides, see refs 8 and 10 as well as the following: (a) Shono, T.; Matsumura, Y.; Inoue, K. J. Org. Chem. 1983, 48, 1388. (b) Thaning, M.; Wistrand, L.-G. Helv. Chim. Acta 1986, 69, 1711. (c) Renaud, P.; Seebach, D. Angew. Chem., Int. Ed. Engl. 1986, 25, 843. (d) Renaud, P.; Seebach, D. Helv. Chim. Acta 1986, 69, 1704. (e) Seebach, D.; Charczuk, R.; Gerber, C.; Renaud, P.; Berner, H.; Schneider, H. Helv. Chim. Acta 1989, 72, 401. (f) Papadopoulos, A.; Heyer, J.; Ginzel K.-D.; Steckhan, E. Chem. Ber. 1989, 122, 2159. (g) Ginzel, K.-D.; Brungs, P.; Steckhan, E. Tetrahedron 1989, 45, 1691. (h) Papadopoulos, A.; Lewall, B.; Steckhan, E.; Ginzel, K.-D.; Knoch, F.; Nieger, M. Tetrahedron 1991, 47, 563. (i) Barrett, A. G. M.; Pilipauskas, D. J. Org. Chem. 1991, 56, 2787. (j) Moeller, K. D.; Rutledge, L. D. J. Org. Chem. 1992, 57, 6360. (k) Cornille, F.; Fobian, Y. M.; Slomczynska, U.; Beusen D. D.; Marshall, G. R.; Moeller, K. D. Tetrahedron Lett. 1994, 35, 6989-6992. (l) Cornille, F.; Slomczynska, U.; Smythe, M. L.; Beusen, D. D.; Moeller, K. D.; Marshall, G. R. J. Am. Chem. Soc. 1995, 117, 909. (m) Slomczynska, U.; Chalmers, D. K.; Cornille, F.; Smythe, M. L.; Beusen, D. D.; Moeller, K. D.; Marshall, G. R. J. Org. Chem. 1996, 61, 1198-1204. (n) Fobian, Y. M.; d'Avignon, D. A.; Moeller, K. D. Bioorg. Med. Chem. Lett. 1996, 6, 315-318.
43. For examples of amide oxidations being used to functionalize peptides, see refs 8 and 10 as well as the following: (a) Shono, T.; Matsumura, Y.; Inoue, K. J. Org. Chem. 1983, 48, 1388. (b) Thaning, M.; Wistrand, L.-G. Helv. Chim. Acta 1986, 69, 1711. (c) Renaud, P.; Seebach, D. Angew. Chem., Int. Ed. Engl. 1986, 25, 843. (d) Renaud, P.; Seebach, D. Helv. Chim. Acta 1986, 69, 1704. (e) Seebach, D.; Charczuk, R.; Gerber, C.; Renaud, P.; Berner, H.; Schneider, H. Helv. Chim. Acta 1989, 72, 401. (f) Papadopoulos, A.; Heyer, J.; Ginzel K.-D.; Steckhan, E. Chem. Ber. 1989, 122, 2159. (g) Ginzel, K.-D.; Brungs, P.; Steckhan, E. Tetrahedron 1989, 45, 1691. (h) Papadopoulos, A.; Lewall, B.; Steckhan, E.; Ginzel, K.-D.; Knoch, F.; Nieger, M. Tetrahedron 1991, 47, 563. (i) Barrett, A. G. M.; Pilipauskas, D. J. Org. Chem. 1991, 56, 2787. (j) Moeller, K. D.; Rutledge, L. D. J. Org. Chem. 1992, 57, 6360. (k) Cornille, F.; Fobian, Y. M.; Slomczynska, U.; Beusen D. D.; Marshall, G. R.; Moeller, K. D. Tetrahedron Lett. 1994, 35, 6989-6992. (l) Cornille, F.; Slomczynska, U.; Smythe, M. L.; Beusen, D. D.; Moeller, K. D.; Marshall, G. R. J. Am. Chem. Soc. 1995, 117, 909. (m) Slomczynska, U.; Chalmers, D. K.; Cornille, F.; Smythe, M. L.; Beusen, D. D.; Moeller, K. D.; Marshall, G. R. J. Org. Chem. 1996, 61, 1198-1204. (n) Fobian, Y. M.; d'Avignon, D. A.; Moeller, K. D. Bioorg. Med. Chem. Lett. 1996, 6, 315-318.
44. For examples of amide oxidations being used to functionalize peptides, see refs 8 and 10 as well as the following: (a) Shono, T.; Matsumura, Y.; Inoue, K. J. Org. Chem. 1983, 48, 1388. (b) Thaning, M.; Wistrand, L.-G. Helv. Chim. Acta 1986, 69, 1711. (c) Renaud, P.; Seebach, D. Angew. Chem., Int. Ed. Engl. 1986, 25, 843. (d) Renaud, P.; Seebach, D. Helv. Chim. Acta 1986, 69, 1704. (e) Seebach, D.; Charczuk, R.; Gerber, C.; Renaud, P.; Berner, H.; Schneider, H. Helv. Chim. Acta 1989, 72, 401. (f) Papadopoulos, A.; Heyer, J.; Ginzel K.-D.; Steckhan, E. Chem. Ber. 1989, 122, 2159. (g) Ginzel, K.-D.; Brungs, P.; Steckhan, E. Tetrahedron 1989, 45, 1691. (h) Papadopoulos, A.; Lewall, B.; Steckhan, E.; Ginzel, K.-D.; Knoch, F.; Nieger, M. Tetrahedron 1991, 47, 563. (i) Barrett, A. G. M.; Pilipauskas, D. J. Org. Chem. 1991, 56, 2787. (j) Moeller, K. D.; Rutledge, L. D. J. Org. Chem. 1992, 57, 6360. (k) Cornille, F.; Fobian, Y. M.; Slomczynska, U.; Beusen D. D.; Marshall, G. R.; Moeller, K. D. Tetrahedron Lett. 1994, 35, 6989-6992. (l) Cornille, F.; Slomczynska, U.; Smythe, M. L.; Beusen, D. D.; Moeller, K. D.; Marshall, G. R. J. Am. Chem. Soc. 1995, 117, 909. (m) Slomczynska, U.; Chalmers, D. K.; Cornille, F.; Smythe, M. L.; Beusen, D. D.; Moeller, K. D.; Marshall, G. R. J. Org. Chem. 1996, 61, 1198-1204. (n) Fobian, Y. M.; d'Avignon, D. A.; Moeller, K. D. Bioorg. Med. Chem. Lett. 1996, 6, 315-318.
45. For examples of amide oxidations being used to functionalize peptides, see refs 8 and 10 as well as the following: (a) Shono, T.; Matsumura, Y.; Inoue, K. J. Org. Chem. 1983, 48, 1388. (b) Thaning, M.; Wistrand, L.-G. Helv. Chim. Acta 1986, 69, 1711. (c) Renaud, P.; Seebach, D. Angew. Chem., Int. Ed. Engl. 1986, 25, 843. (d) Renaud, P.; Seebach, D. Helv. Chim. Acta 1986, 69, 1704. (e) Seebach, D.; Charczuk, R.; Gerber, C.; Renaud, P.; Berner, H.; Schneider, H. Helv. Chim. Acta 1989, 72, 401. (f) Papadopoulos, A.; Heyer, J.; Ginzel K.-D.; Steckhan, E. Chem. Ber. 1989, 122, 2159. (g) Ginzel, K.-D.; Brungs, P.; Steckhan, E. Tetrahedron 1989, 45, 1691. (h) Papadopoulos, A.; Lewall, B.; Steckhan, E.; Ginzel, K.-D.; Knoch, F.; Nieger, M. Tetrahedron 1991, 47, 563. (i) Barrett, A. G. M.; Pilipauskas, D. J. Org. Chem. 1991, 56, 2787. (j) Moeller, K. D.; Rutledge, L. D. J. Org. Chem. 1992, 57, 6360. (k) Cornille, F.; Fobian, Y. M.; Slomczynska, U.; Beusen D. D.; Marshall, G. R.; Moeller, K. D. Tetrahedron Lett. 1994, 35, 6989-6992. (l) Cornille, F.; Slomczynska, U.; Smythe, M. L.; Beusen, D. D.; Moeller, K. D.; Marshall, G. R. J. Am. Chem. Soc. 1995, 117, 909. (m) Slomczynska, U.; Chalmers, D. K.; Cornille, F.; Smythe, M. L.; Beusen, D. D.; Moeller, K. D.; Marshall, G. R. J. Org. Chem. 1996, 61, 1198-1204. (n) Fobian, Y. M.; d'Avignon, D. A.; Moeller, K. D. Bioorg. Med. Chem. Lett. 1996, 6, 315-318.
46. For examples of amide oxidations being used to functionalize peptides, see refs 8 and 10 as well as the following: (a) Shono, T.; Matsumura, Y.; Inoue, K. J. Org. Chem. 1983, 48, 1388. (b) Thaning, M.; Wistrand, L.-G. Helv. Chim. Acta 1986, 69, 1711. (c) Renaud, P.; Seebach, D. Angew. Chem., Int. Ed. Engl. 1986, 25, 843. (d) Renaud, P.; Seebach, D. Helv. Chim. Acta 1986, 69, 1704. (e) Seebach, D.; Charczuk, R.; Gerber, C.; Renaud, P.; Berner, H.; Schneider, H. Helv. Chim. Acta 1989, 72, 401. (f) Papadopoulos, A.; Heyer, J.; Ginzel K.-D.; Steckhan, E. Chem. Ber. 1989, 122, 2159. (g) Ginzel, K.-D.; Brungs, P.; Steckhan, E. Tetrahedron 1989, 45, 1691. (h) Papadopoulos, A.; Lewall, B.; Steckhan, E.; Ginzel, K.-D.; Knoch, F.; Nieger, M. Tetrahedron 1991, 47, 563. (i) Barrett, A. G. M.; Pilipauskas, D. J. Org. Chem. 1991, 56, 2787. (j) Moeller, K. D.; Rutledge, L. D. J. Org. Chem. 1992, 57, 6360. (k) Cornille, F.; Fobian, Y. M.; Slomczynska, U.; Beusen D. D.; Marshall, G. R.; Moeller, K. D. Tetrahedron Lett. 1994, 35, 6989-6992. (l) Cornille, F.; Slomczynska, U.; Smythe, M. L.; Beusen, D. D.; Moeller, K. D.; Marshall, G. R. J. Am. Chem. Soc. 1995, 117, 909. (m) Slomczynska, U.; Chalmers, D. K.; Cornille, F.; Smythe, M. L.; Beusen, D. D.; Moeller, K. D.; Marshall, G. R. J. Org. Chem. 1996, 61, 1198-1204. (n) Fobian, Y. M.; d'Avignon, D. A.; Moeller, K. D. Bioorg. Med. Chem. Lett. 1996, 6, 315-318.
47. For examples of amide oxidations being used to functionalize peptides, see refs 8 and 10 as well as the following: (a) Shono, T.; Matsumura, Y.; Inoue, K. J. Org. Chem. 1983, 48, 1388. (b) Thaning, M.; Wistrand, L.-G. Helv. Chim. Acta 1986, 69, 1711. (c) Renaud, P.; Seebach, D. Angew. Chem., Int. Ed. Engl. 1986, 25, 843. (d) Renaud, P.; Seebach, D. Helv. Chim. Acta 1986, 69, 1704. (e) Seebach, D.; Charczuk, R.; Gerber, C.; Renaud, P.; Berner, H.; Schneider, H. Helv. Chim. Acta 1989, 72, 401. (f) Papadopoulos, A.; Heyer, J.; Ginzel K.-D.; Steckhan, E. Chem. Ber. 1989, 122, 2159. (g) Ginzel, K.-D.; Brungs, P.; Steckhan, E. Tetrahedron 1989, 45, 1691. (h) Papadopoulos, A.; Lewall, B.; Steckhan, E.; Ginzel, K.-D.; Knoch, F.; Nieger, M. Tetrahedron 1991, 47, 563. (i) Barrett, A. G. M.; Pilipauskas, D. J. Org. Chem. 1991, 56, 2787. (j) Moeller, K. D.; Rutledge, L. D. J. Org. Chem. 1992, 57, 6360. (k) Cornille, F.; Fobian, Y. M.; Slomczynska, U.; Beusen D. D.; Marshall, G. R.; Moeller, K. D. Tetrahedron Lett. 1994, 35, 6989-6992. (l) Cornille, F.; Slomczynska, U.; Smythe, M. L.; Beusen, D. D.; Moeller, K. D.; Marshall, G. R. J. Am. Chem. Soc. 1995, 117, 909. (m) Slomczynska, U.; Chalmers, D. K.; Cornille, F.; Smythe, M. L.; Beusen, D. D.; Moeller, K. D.; Marshall, G. R. J. Org. Chem. 1996, 61, 1198-1204. (n) Fobian, Y. M.; d'Avignon, D. A.; Moeller, K. D. Bioorg. Med. Chem. Lett. 1996, 6, 315-318.
48. For examples of amide oxidations being used to functionalize peptides, see refs 8 and 10 as well as the following: (a) Shono, T.; Matsumura, Y.; Inoue, K. J. Org. Chem. 1983, 48, 1388. (b) Thaning, M.; Wistrand, L.-G. Helv. Chim. Acta 1986, 69, 1711. (c) Renaud, P.; Seebach, D. Angew. Chem., Int. Ed. Engl. 1986, 25, 843. (d) Renaud, P.; Seebach, D. Helv. Chim. Acta 1986, 69, 1704. (e) Seebach, D.; Charczuk, R.; Gerber, C.; Renaud, P.; Berner, H.; Schneider, H. Helv. Chim. Acta 1989, 72, 401. (f) Papadopoulos, A.; Heyer, J.; Ginzel K.-D.; Steckhan, E. Chem. Ber. 1989, 122, 2159. (g) Ginzel, K.-D.; Brungs, P.; Steckhan, E. Tetrahedron 1989, 45, 1691. (h) Papadopoulos, A.; Lewall, B.; Steckhan, E.; Ginzel, K.-D.; Knoch, F.; Nieger, M. Tetrahedron 1991, 47, 563. (i) Barrett, A. G. M.; Pilipauskas, D. J. Org. Chem. 1991, 56, 2787. (j) Moeller, K. D.; Rutledge, L. D. J. Org. Chem. 1992, 57, 6360. (k) Cornille, F.; Fobian, Y. M.; Slomczynska, U.; Beusen D. D.; Marshall, G. R.; Moeller, K. D. Tetrahedron Lett. 1994, 35, 6989-6992. (l) Cornille, F.; Slomczynska, U.; Smythe, M. L.; Beusen, D. D.; Moeller, K. D.; Marshall, G. R. J. Am. Chem. Soc. 1995, 117, 909. (m) Slomczynska, U.; Chalmers, D. K.; Cornille, F.; Smythe, M. L.; Beusen, D. D.; Moeller, K. D.; Marshall, G. R. J. Org. Chem. 1996, 61, 1198-1204. (n) Fobian, Y. M.; d'Avignon, D. A.; Moeller, K. D. Bioorg. Med. Chem. Lett. 1996, 6, 315-318.
49. For examples of amide oxidations being used to functionalize peptides, see refs 8 and 10 as well as the following: (a) Shono, T.; Matsumura, Y.; Inoue, K. J. Org. Chem. 1983, 48, 1388. (b) Thaning, M.; Wistrand, L.-G. Helv. Chim. Acta 1986, 69, 1711. (c) Renaud, P.; Seebach, D. Angew. Chem., Int. Ed. Engl. 1986, 25, 843. (d) Renaud, P.; Seebach, D. Helv. Chim. Acta 1986, 69, 1704. (e) Seebach, D.; Charczuk, R.; Gerber, C.; Renaud, P.; Berner, H.; Schneider, H. Helv. Chim. Acta 1989, 72, 401. (f) Papadopoulos, A.; Heyer, J.; Ginzel K.-D.; Steckhan, E. Chem. Ber. 1989, 122, 2159. (g) Ginzel, K.-D.; Brungs, P.; Steckhan, E. Tetrahedron 1989, 45, 1691. (h) Papadopoulos, A.; Lewall, B.; Steckhan, E.; Ginzel, K.-D.; Knoch, F.; Nieger, M. Tetrahedron 1991, 47, 563. (i) Barrett, A. G. M.; Pilipauskas, D. J. Org. Chem. 1991, 56, 2787. (j) Moeller, K. D.; Rutledge, L. D. J. Org. Chem. 1992, 57, 6360. (k) Cornille, F.; Fobian, Y. M.; Slomczynska, U.; Beusen D. D.; Marshall, G. R.; Moeller, K. D. Tetrahedron Lett. 1994, 35, 6989-6992. (l) Cornille, F.; Slomczynska, U.; Smythe, M. L.; Beusen, D. D.; Moeller, K. D.; Marshall, G. R. J. Am. Chem. Soc. 1995, 117, 909. (m) Slomczynska, U.; Chalmers, D. K.; Cornille, F.; Smythe, M. L.; Beusen, D. D.; Moeller, K. D.; Marshall, G. R. J. Org. Chem. 1996, 61, 1198-1204. (n) Fobian, Y. M.; d'Avignon, D. A.; Moeller, K. D. Bioorg. Med. Chem. Lett. 1996, 6, 315-318.
50. For examples of amide oxidations being used to functionalize peptides, see refs 8 and 10 as well as the following: (a) Shono, T.; Matsumura, Y.; Inoue, K. J. Org. Chem. 1983, 48, 1388. (b) Thaning, M.; Wistrand, L.-G. Helv. Chim. Acta 1986, 69, 1711. (c) Renaud, P.; Seebach, D. Angew. Chem., Int. Ed. Engl. 1986, 25, 843. (d) Renaud, P.; Seebach, D. Helv. Chim. Acta 1986, 69, 1704. (e) Seebach, D.; Charczuk, R.; Gerber, C.; Renaud, P.; Berner, H.; Schneider, H. Helv. Chim. Acta 1989, 72, 401. (f) Papadopoulos, A.; Heyer, J.; Ginzel K.-D.; Steckhan, E. Chem. Ber. 1989, 122, 2159. (g) Ginzel, K.-D.; Brungs, P.; Steckhan, E. Tetrahedron 1989, 45, 1691. (h) Papadopoulos, A.; Lewall, B.; Steckhan, E.; Ginzel, K.-D.; Knoch, F.; Nieger, M. Tetrahedron 1991, 47, 563. (i) Barrett, A. G. M.; Pilipauskas, D. J. Org. Chem. 1991, 56, 2787. (j) Moeller, K. D.; Rutledge, L. D. J. Org. Chem. 1992, 57, 6360. (k) Cornille, F.; Fobian, Y. M.; Slomczynska, U.; Beusen D. D.; Marshall, G. R.; Moeller, K. D. Tetrahedron Lett. 1994, 35, 6989-6992. (l) Cornille, F.; Slomczynska, U.; Smythe, M. L.; Beusen, D. D.; Moeller, K. D.; Marshall, G. R. J. Am. Chem. Soc. 1995, 117, 909. (m) Slomczynska, U.; Chalmers, D. K.; Cornille, F.; Smythe, M. L.; Beusen, D. D.; Moeller, K. D.; Marshall, G. R. J. Org. Chem. 1996, 61, 1198-1204. (n) Fobian, Y. M.; d'Avignon, D. A.; Moeller, K. D. Bioorg. Med. Chem. Lett. 1996, 6, 315-318.
51. For examples of amide oxidations being used to functionalize peptides, see refs 8 and 10 as well as the following: (a) Shono, T.; Matsumura, Y.; Inoue, K. J. Org. Chem. 1983, 48, 1388. (b) Thaning, M.; Wistrand, L.-G. Helv. Chim. Acta 1986, 69, 1711. (c) Renaud, P.; Seebach, D. Angew. Chem., Int. Ed. Engl. 1986, 25, 843. (d) Renaud, P.; Seebach, D. Helv. Chim. Acta 1986, 69, 1704. (e) Seebach, D.; Charczuk, R.; Gerber, C.; Renaud, P.; Berner, H.; Schneider, H. Helv. Chim. Acta 1989, 72, 401. (f) Papadopoulos, A.; Heyer, J.; Ginzel K.-D.; Steckhan, E. Chem. Ber. 1989, 122, 2159. (g) Ginzel, K.-D.; Brungs, P.; Steckhan, E. Tetrahedron 1989, 45, 1691. (h) Papadopoulos, A.; Lewall, B.; Steckhan, E.; Ginzel, K.-D.; Knoch, F.; Nieger, M. Tetrahedron 1991, 47, 563. (i) Barrett, A. G. M.; Pilipauskas, D. J. Org. Chem. 1991, 56, 2787. (j) Moeller, K. D.; Rutledge, L. D. J. Org. Chem. 1992, 57, 6360. (k) Cornille, F.; Fobian, Y. M.; Slomczynska, U.; Beusen D. D.; Marshall, G. R.; Moeller, K. D. Tetrahedron Lett. 1994, 35, 6989-6992. (l) Cornille, F.; Slomczynska, U.; Smythe, M. L.; Beusen, D. D.; Moeller, K. D.; Marshall, G. R. J. Am. Chem. Soc. 1995, 117, 909. (m) Slomczynska, U.; Chalmers, D. K.; Cornille, F.; Smythe, M. L.; Beusen, D. D.; Moeller, K. D.; Marshall, G. R. J. Org. Chem. 1996, 61, 1198-1204. (n) Fobian, Y. M.; d'Avignon, D. A.; Moeller, K. D. Bioorg. Med. Chem. Lett. 1996, 6, 315-318.
52. The unrestricted analog was synthesized from proline amide using standard peptide coupling conditions.
53. Perlman, J. H.; Thaw, C. N.; Laakkonen, L.; Bowers, C. Y.; Osman, R.; Gershengorn, M. C. J. Biol. Chem. 1994, 269, 1610. Straub, R. E.; Frech, G. C.; Joho, R. H.; Gershengorn, M. C. Proc. Natl. Acad. Sci. U.S.A. 1990, 87, 9514.
54. Perlman, J. H.; Thaw, C. N.; Laakkonen, L.; Bowers, C. Y.; Osman, R.; Gershengorn, M. C. J. Biol. Chem. 1994, 269, 1610. Straub, R. E.; Frech, G. C.; Joho, R. H.; Gershengorn, M. C. Proc. Natl. Acad. Sci. U.S.A. 1990, 87, 9514.
55. For a detailed experimental discussion concerning biological data and an interpetation of the data with respect to a second model for the binding of TRH to TRH-R based on receptor mutants, see: Laakkonen, L.; Li, W.; Perlman, J. H.; Guarnieri, F.; Osman, R.; Moeller, K. D. and Gershengorn, M. C. Mol. Pharmacol. 1996, 49, 1092.
56. For a general experimental section, see: Wong, P. L.; Moeller, K. D. J. Am. Chem. Soc. 1993, 115, 11434.