The synthesis of thrombin inhibitor L-370,518 via an α-hydroxy-β- lactam

Tetrahedron Letters

Volumn 37, Issue 29, 1996, Pages 5045-5048

  Cutrona, Kellie J ^a   Sanderson, Philip E J ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

L 370518; THROMBIN INHIBITOR; UNCLASSIFIED DRUG;

AMINO ACID SUBSTITUTION; ARTICLE; CARBOXY TERMINAL SEQUENCE; DRUG POTENCY; DRUG SELECTIVITY; DRUG SYNTHESIS; ENZYME BINDING; STEREOCHEMISTRY; THERMODYNAMICS;

EID: 0030586144     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/0040-4039(96)01013-1     Document Type: Article

References (20)

1. 1. Brady, S. F.; Lewis, S. D.; Colton, C. D.; Stauffer, K. J.; Sisko, J. T.; Ng, A. S.; Homnick, C. F; Bogusky, M. J.; Shafer, J. A.; Veber, D. F.; Nutt, R. F. Proceedings of the Fourteenth American Peptide Symposium, Kaumaya, P. T. P. (Ed.), Escom, Leiden, The Netherlands, 1995, in press.
2. 2. (a) Buckhart, J. P.; Peet, N. P.; Bey, P. Tetrahedron Lett. 1990, 31, 1385-1388;
3. (b) Iwanowicz, E. J.; Lin, J.; Roberts, D. G. M.; Michel, I. M.; Seiler, S. M. BioMed. Chem. Lett. 1992, 2, 1607-1612;
4. (c) Wipf, P.; Kim, H-Y. Tetrahedron Lett. 1992, 33, 4275-4278;
5. (d) Hagihara, M.; Schreiber, S. L. J. Am. Chem. Soc. 1992, 114, 6570-6571.
6. 1 used an unselective hydrogenation of α-BOC-4-aminophenylglycine to make the cyclohexane and required a difficult chromatographic separation of the two isomers.
7. 4. (a) Kobayashi, Y.; Takemoto, Y.; Kamijo, T.; Harada, H.; Ito, Y.; Terashima, S. Tetrahedron 1992, 48, 1853-1868;
8. (b) Georg, G. I.; Akgun, E.; Mashava, P. M.; Milstead, M.; Ping, H.; Wu, Z.; Velde D. V. Tetrahedron Lett. 1992, 33, 2111-2114;
9. (c) Farina, V.; Hauck, S. I.; Walker, D. G. Synlett 1992, 761-763;
10. (d) Bourzat, J. D.; Commercon, A. Tetrahedron Lett. 1993, 34, 6049-6052.
11. 5. Pearlman, W. M. Org. Synth. Coll. Vol. V , 1973, 670-672.
12. 6. Nahm, S.; Weinreb, S. M. Tetrahedron Lett. 1981, 22, 3815-3818.
13. 2) and 7.72 (d, CHNHBn) and the relative integrals show a 12:1 mixture.
14. 8. Palomo, C.; Arrieta, A.; Cossio, F. P.; Aizpurua, J. M.; Mielgo, A.; Aurrekoetxea, N. Tetrahedron Lett. 1990, 37, 6429-6432.
15. 3): δ 1.01-1.10 (4 H, m, cyclohexyl H's), 1.43 (9 H, s, t-Bu), 1.70-2.05 (5 H, m, cyclohexyl H's), 3.27 (1 H, t, J = 5.2 Hz, CHCHOBn), 3.30 (1 H, br s, CHNHBOC), 4.02 (1 H, d, J = 14.9 Hz, benzylic H), 4.34 (1 H, br s, NH), 4.59 (1 H, d, J = 5.2 Hz, CHCHOBn), 4.71 (1 H, d, J = 11.9 Hz, benzylic H), 4.84 (1 H, d, J = 14.9 Hz, benzylic H), 4.93 (1 H, d, J = 11.9 Hz, benzylic H), 7.17-7.37 (10 H, m, Ph's).
16. 10. Lynch, J. E.; Riseman, S. M.; Laswell, W. L.; Tschaen, D. M.; Volante, R. P.; Smith, G. B.; Shinkai, I. J. Org. Chem. 1989, 54, 3792-3796.
17. 11. Evans, D. A.; Sjogren, E. B. Tetrahedron Lett. 1985, 26, 3783-3786.
18. 12. Ojima, I.; Habus, I.; Zhao, M.; Zucco, M.; Park, Y. H.; Sun, C. M.; Brigaud, T. Tetrahedron 1992, 48, 6985-7012.
19. 13. Prepared by a standard coupling and hydrolysis from BOC-N-methyl-D-Phe (BACHEM).
20. B).