Solid-phase synthesis of constrained terminal and internal lactam peptidomimetics

Organic Letters

Volumn 6, Issue 10, 2004, Pages 1629-1632

  Scott, William L ^a   Alsina, Jordi ^a   Kennedy, Joseph H ^b   O'Donnell, Martin J ^a  

^a INDIANA UNIVERSITY   (United States)

^b ELI LILLY AND COMPANY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO ACID; HYDROGEN; LACTAM DERIVATIVE; PEPTIDE DERIVATIVE;

ARTICLE; CHEMICAL STRUCTURE; PRECURSOR; RACEMIZATION; SYNTHESIS;

CYCLIZATION; LACTAMS; MOLECULAR MIMICRY; MOLECULAR STRUCTURE; PEPTIDES, CYCLIC;

EID: 2542638050     PISSN: 15237060     EISSN: None     Source Type: Journal    
DOI: 10.1021/ol049547z     Document Type: Article

References (33)

1. For excellent reviews on peptidomimetic chemistry, see: (a) Giannis, A.; Kolter, T. Angew. Chem., Int. Ed. Engl. 1993, 32, 1244-1267. (b) Gante, J. Angew. Chem., Int. Ed. Engl. 1994, 33, 1699-1720. (c) Hanessian, S.; McNaughton-Smith, G.; Lombart, H.-G.; Lubell, W. D. Tetrahedron 1997, 53, 12789-12854. (d) Gillespie, P.; Cicariello, J.; Olson, G. L. Biopolym. (Peptide Sci.) 1997, 43, 191-217. (e) Synthesis of Peptides and Peptidomimetics. In Houben-Weyl, Methods in Organic Chemistry; Goodman, M., Felix, A., Moroder, L., Toniolo, C., Eds.; Thieme: Stuttgart, New York, 2003; Vol. E22c.
2. For excellent reviews on peptidomimetic chemistry, see: (a) Giannis, A.; Kolter, T. Angew. Chem., Int. Ed. Engl. 1993, 32, 1244-1267. (b) Gante, J. Angew. Chem., Int. Ed. Engl. 1994, 33, 1699-1720. (c) Hanessian, S.; McNaughton-Smith, G.; Lombart, H.-G.; Lubell, W. D. Tetrahedron 1997, 53, 12789-12854. (d) Gillespie, P.; Cicariello, J.; Olson, G. L. Biopolym. (Peptide Sci.) 1997, 43, 191-217. (e) Synthesis of Peptides and Peptidomimetics. In Houben-Weyl, Methods in Organic Chemistry; Goodman, M., Felix, A., Moroder, L., Toniolo, C., Eds.; Thieme: Stuttgart, New York, 2003; Vol. E22c.
3. For excellent reviews on peptidomimetic chemistry, see: (a) Giannis, A.; Kolter, T. Angew. Chem., Int. Ed. Engl. 1993, 32, 1244-1267. (b) Gante, J. Angew. Chem., Int. Ed. Engl. 1994, 33, 1699-1720. (c) Hanessian, S.; McNaughton-Smith, G.; Lombart, H.-G.; Lubell, W. D. Tetrahedron 1997, 53, 12789-12854. (d) Gillespie, P.; Cicariello, J.; Olson, G. L. Biopolym. (Peptide Sci.) 1997, 43, 191-217. (e) Synthesis of Peptides and Peptidomimetics. In Houben-Weyl, Methods in Organic Chemistry; Goodman, M., Felix, A., Moroder, L., Toniolo, C., Eds.; Thieme: Stuttgart, New York, 2003; Vol. E22c.
4. For excellent reviews on peptidomimetic chemistry, see: (a) Giannis, A.; Kolter, T. Angew. Chem., Int. Ed. Engl. 1993, 32, 1244-1267. (b) Gante, J. Angew. Chem., Int. Ed. Engl. 1994, 33, 1699-1720. (c) Hanessian, S.; McNaughton-Smith, G.; Lombart, H.-G.; Lubell, W. D. Tetrahedron 1997, 53, 12789-12854. (d) Gillespie, P.; Cicariello, J.; Olson, G. L. Biopolym. (Peptide Sci.) 1997, 43, 191-217. (e) Synthesis of Peptides and Peptidomimetics. In Houben-Weyl, Methods in Organic Chemistry; Goodman, M., Felix, A., Moroder, L., Toniolo, C., Eds.; Thieme: Stuttgart, New York, 2003; Vol. E22c.
5. For excellent reviews on peptidomimetic chemistry, see: (a) Giannis, A.; Kolter, T. Angew. Chem., Int. Ed. Engl. 1993, 32, 1244-1267. (b) Gante, J. Angew. Chem., Int. Ed. Engl. 1994, 33, 1699-1720. (c) Hanessian, S.; McNaughton-Smith, G.; Lombart, H.-G.; Lubell, W. D. Tetrahedron 1997, 53, 12789-12854. (d) Gillespie, P.; Cicariello, J.; Olson, G. L. Biopolym. (Peptide Sci.) 1997, 43, 191-217. (e) Synthesis of Peptides and Peptidomimetics. In Houben-Weyl, Methods in Organic Chemistry; Goodman, M., Felix, A., Moroder, L., Toniolo, C., Eds.; Thieme: Stuttgart, New York, 2003; Vol. E22c.
6. (a) O'Donnell, M. J.; Zhou, C.; Scott, W. L. J. Am. Chem. Soc. 1996, 118, 6070-6071.
7. (b) Scott, W. L.; Zhou, C.; Fang, Z.; O'Donnell, M. J. Tetrahedron Lett. 1997, 38, 3695-3698.
8. For a recent short review about UPS chemistry, see: (c) O'Donnell, M. J.; Scott, W. L. Unnatural Amino Acid and Peptide Synthesis (UPS). In Peptides 2000: Proceedings of the Twenty-Sixth European Peptide Symposium; Martinez, J., Fehrentz, J.-A., Eds.; EDK: Paris, 2001; pp 31-36.
9. (a) Scott, W. L.; O'Donnell, M. J.; Delgado, F.; Alsina, J. J. Org. Chem. 2002, 67, 2960-2969.
10. (b) O'Donnell, M. J.; Alsina, J.; Scott, W. L. Tetrahedron Lett. 2003, 44, 8403-8406.
11. Scott, W. L.; Alsina, J.; O'Donnell, M. J. J. Comb. Chem. 2003, 5, 684-692.
12. (a) Freidinger, R. M.; Veber, D. F.; Perlow, D. S.; Brooks, J. R.; Saperstein, R. Science 1980, 210, 656-658.
13. (b) Freidinger, R. M.; Perlow, D. S.; Veber, D. F. J. Org. Chem. 1982, 47, 104-109.
14. (c) Aubé, J. Synthetic Routes to Lactam Peptidomimetics. In Advances in Amino Acid Mimetics and Peptidomimetics; JAI Press, Inc.: Greenwich, CT, 1997; Vol. 1, pp 193-232.
15. (d) Freidinger, R. M. J. Med. Chem. 2003, 46, 5553-5566.
16. (e) Dolbeare, K.; Pontoriero, G. F.; Gupta, S. K.; Mishra, R. K.; Johnson, R. L. J. Med. Chem. 2003, 46, 727-733.
17. For selected recent references concerning the solution- and solid-phase synthesis of the related β-lactam systems, see: (a) Palomo, C.; Aizpurua, J. M.; Benito, A.; Miranda, J. I.; Fratila, R. M.; Matute, C.; Domercq, M.; Gago, F.; Martin-Santamaria, S.; Linden, A. J. Am. Chem. Soc. 2003, 125, 16243-16260. (b) Shunk, S.; Enders, D. Org. Lett. 2000, 2, 907-910. (c) Meloni, M. M.; Taddei, M. Org. Lett. 2001, 3, 337-340.
18. For selected recent references concerning the solution- and solid-phase synthesis of the related β-lactam systems, see: (a) Palomo, C.; Aizpurua, J. M.; Benito, A.; Miranda, J. I.; Fratila, R. M.; Matute, C.; Domercq, M.; Gago, F.; Martin-Santamaria, S.; Linden, A. J. Am. Chem. Soc. 2003, 125, 16243-16260. (b) Shunk, S.; Enders, D. Org. Lett. 2000, 2, 907-910. (c) Meloni, M. M.; Taddei, M. Org. Lett. 2001, 3, 337-340.
19. For selected recent references concerning the solution- and solid-phase synthesis of the related β-lactam systems, see: (a) Palomo, C.; Aizpurua, J. M.; Benito, A.; Miranda, J. I.; Fratila, R. M.; Matute, C.; Domercq, M.; Gago, F.; Martin-Santamaria, S.; Linden, A. J. Am. Chem. Soc. 2003, 125, 16243-16260. (b) Shunk, S.; Enders, D. Org. Lett. 2000, 2, 907-910. (c) Meloni, M. M.; Taddei, M. Org. Lett. 2001, 3, 337-340.
20. For reports of the solid-phase synthesis of seven-membered dehydro-Freidinger lactams by a ring-closing metathesis strategy, see: (a) Piscopio, A. D.; Miller, J. F.; Koch, K. Tetrahedron Lett. 1997, 38, 7143-7146. (b) Piscopio, A. D.; Miller, J. F.; Koch, K. Tetrahedron Lett. 1998, 39, 2667-2670. (c) Piscopio, A. D.; Miller, J. F.; Koch, K. Tetrahedron 1999, 55, 8189-8198.
21. For reports of the solid-phase synthesis of seven-membered dehydro-Freidinger lactams by a ring-closing metathesis strategy, see: (a) Piscopio, A. D.; Miller, J. F.; Koch, K. Tetrahedron Lett. 1997, 38, 7143-7146. (b) Piscopio, A. D.; Miller, J. F.; Koch, K. Tetrahedron Lett. 1998, 39, 2667-2670. (c) Piscopio, A. D.; Miller, J. F.; Koch, K. Tetrahedron 1999, 55, 8189-8198.
22. For reports of the solid-phase synthesis of seven-membered dehydro-Freidinger lactams by a ring-closing metathesis strategy, see: (a) Piscopio, A. D.; Miller, J. F.; Koch, K. Tetrahedron Lett. 1997, 38, 7143-7146. (b) Piscopio, A. D.; Miller, J. F.; Koch, K. Tetrahedron Lett. 1998, 39, 2667-2670. (c) Piscopio, A. D.; Miller, J. F.; Koch, K. Tetrahedron 1999, 55, 8189-8198.
23. Holladay, M. W.; Nadzan, A. M. J. Org. Chem. 1991, 56, 3900-3905.
24. The following abbreviations are used: BEMP, 2-tert-butylimino-2- diethylamino-1,3-dimethylperhydro-1,3,2-diazaphosphorine; BTPP, tert-butylimino-tri(pyrrolidino)phosphorane; DIEA, N,N-diisopropylethylamine; Fmoc, 9-fluorenylmethoxycarbonyl; HOAc, acetic acid; LC/MS, liquid chromatography/mass spectrometry; 2-Npth, 2-naphthoyl; UPS, unnatural peptide synthesis.
25. For a comparison of the basicities of BTPP and BEMP, see footnote 12 in: O'Donnell, M. J.; Delgado, F.; Hostettler, C.; Schwesinger, R. Tetrahedron Lett. 1998, 39, 8775-8778.
26. Crude HPLC purity of the six-membered ring lactam product 1c (Figure 3) was lower because the ω-chloro compound 5 partially cyclized on the relatively unreactive imine nitrogen to form the five-membered ring α-substituted proline (17% by HPLC).
27. Cleaved product 2b contained 28% (by HPLC) of the five-membered ring dipeptide Fmoc-Pro-Gly-OH.
28. Clayden, J.; Greeves, N.; Warren, S.; Wothers, P. Organic Chemistry; Oxford University Press: Oxford, 2001; pp 1138-40.
29. For solution-phase routes to compounds related to 21, see: (a) de Laszlo, S. E.; Bush, B. L.; Doyle, J. J.; Greenlee, W. J.; Hangauer, D. G.; Halgren, T. A.; Lynch, R. J.; Schorn, T. W.; Siegl, P. K. S. J. Med. Chem. 1992, 35, 833-846. (b) Casimir, J. R.; Tourwé, D.; Iterbeke, K.; Guichard, G.; Briand, J.-P. J. Org. Chem. 2000, 65, 6487-6492. (c) Van Rompaey, K.; Van den Eynde, I.; De Kimpe, N.; Tourwé, D. Tetrahedron 2003, 59, 4421-4432.
30. For solution-phase routes to compounds related to 21, see: (a) de Laszlo, S. E.; Bush, B. L.; Doyle, J. J.; Greenlee, W. J.; Hangauer, D. G.; Halgren, T. A.; Lynch, R. J.; Schorn, T. W.; Siegl, P. K. S. J. Med. Chem. 1992, 35, 833-846. (b) Casimir, J. R.; Tourwé, D.; Iterbeke, K.; Guichard, G.; Briand, J.-P. J. Org. Chem. 2000, 65, 6487-6492. (c) Van Rompaey, K.; Van den Eynde, I.; De Kimpe, N.; Tourwé, D. Tetrahedron 2003, 59, 4421-4432.
31. For solution-phase routes to compounds related to 21, see: (a) de Laszlo, S. E.; Bush, B. L.; Doyle, J. J.; Greenlee, W. J.; Hangauer, D. G.; Halgren, T. A.; Lynch, R. J.; Schorn, T. W.; Siegl, P. K. S. J. Med. Chem. 1992, 35, 833-846. (b) Casimir, J. R.; Tourwé, D.; Iterbeke, K.; Guichard, G.; Briand, J.-P. J. Org. Chem. 2000, 65, 6487-6492. (c) Van Rompaey, K.; Van den Eynde, I.; De Kimpe, N.; Tourwé, D. Tetrahedron 2003, 59, 4421-4432.
32. 3-THF (60:40, or similar solvent composition) and CHCl3-THF-HOAc (80:20:2, or similar solvent composition), respectively, to provide the desired products, generally as amorphous solids. See Supporting Information for specific information for each compound.
33. Yields of the final compounds, after chromatographic purification (as described above), were calculated on the basis of the initial loading of the starting resins given by the manufacturer and are the overall yields for all reaction steps starting from these resins. Only fractions with excellent HPLC purity were considered in the calculation of the purified yield.