Cyclizations of α-keto ester modified aspartic acids in peptides

Synlett

Volumn , Issue 11, 2006, Pages 1774-1776

  Seufert, Wolfgang ^a   Fleury, Antoine ^a   Giese, Bernd ^a  

^a UNIVERSITY OF BASEL   (Switzerland)

Author keywords

keto ester; lactams; Cyclizations; Diastereoselectivity; Peptidomimetics

Indexed keywords

ASPARTIC ACID; BETA LACTAM DERIVATIVE; ESTER; PEPTIDE;

ARTICLE; CHEMICAL STRUCTURE; CONFORMATION; CYCLIZATION;

EID: 33746309418     PISSN: 09365214     EISSN: None     Source Type: Journal    
DOI: 10.1055/s-2006-944203     Document Type: Article

References (12)

1. Obkircher, M.; Seufert, W.; Giese, B. Synlett 2005, 1182.
2. During this reaction at least four different products were formed, with 5 only as a minor component.
3. 9: C, 57.57; H, 6.76; N, 8.06. Found: C, 57.62; H, 6.75; N, 8.01.
4. To our knowledge, such a cyclization of an amide group into an a-keto ester under basic conditions has been described only with β-lactams leading to six-membered rings: (a) Bryan, D. B.; Hall, R. F.; Holden, K. G.; Huffman, W. F.; Gleason, J. G. J. Am. Chem. Soc. 1977, 99, 2353.
5. (b) Aszodi, J.; Chantot, J.-F.; Collard, J.; Teutsch, G. Heterocycles 1989, 28, 1061.
6. (c) Arnoldi, A.; Merlini, L.; Scaglioni, L. J. Heterocycl. Chem. 1987, 24, 75.
7. The cis and trans refer to the relative configuration of the amine and the hydroxy substituent. Assignment of the diastereomers was made on the basis of NOESY experiments.
8. DFT calculations (B3LYP) indicate that the cis diastereomer A is thermodynamically slightly more stable than the trans diastereomer B. Only in the cis isomer A does an H bond (1.9 Å) between the OH and the benzyl ester exist.
9. A similar cyclization under acidic conditions has been described recently: Takeuchi, Y.; Nagao, Y.; Toma, K.; Yoshikawa, Y.; Akiyama, T.; Nishioka, H.; Abe, H.; Harayama, T.; Yamamoto, S. Chem. Pharm. Bull. 1999, 47, 1284.
10. The preferred formation of trans products under slightly acidic conditions was also observed with peptides 6 and 9. Not only acidic silica gel but also acetic acid could be used.
11. (a) Freidinger, R. M.; Veber, D. F.; Perlow, D. S.; Brooks, J. R.; Saperstein, R. Science 1980, 210, 656.
12. (b) Freidinger, R. M. J. Med. Chem. 2003, 46, 5553.