A novel kinetically-controlled peptide synthesis - Dramatic increase of chemical yield with retention of chiral integrity

Tetrahedron Letters

Volumn 40, Issue 40, 1999, Pages 7167-7170

  Shieh, Wen Chung ^a   Carlson, John A ^a   Shore, Michael E ^a,b  

^a NOVARTIS PHARMA AG   (Switzerland)

^b AGOURON PHARMACEUTICALS INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO ACID; CARBON; CARBOXYL GROUP; FORMIC ACID DERIVATIVE; NITROGEN;

ARTICLE; CHEMICAL MODIFICATION; CHEMICAL REACTION KINETICS; CHIRALITY; PEPTIDE SYNTHESIS; STRUCTURE ACTIVITY RELATION;

EID: 0033214271     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(99)01493-8     Document Type: Article

References (17)

1. (a) Bodanszky, M. In Principle of Peptide Synthesis; Springer-Verlay: Berlin, Heidelberg, New York and Tokyo, 1984; pp 36-44.
2. (b) The Peptides; Gross, E.; Meienhofer, J., Eds.; Academic Press: New York, 1979; Vol. 1.
3. (c) Saha, A. K.; Schultz, P.; Rapoport, H. J. Am. Chem. Soc. 1989, 111, 4856-4859.
4. Vaughan, J. R. J. Am. Chem. Soc. 1951, 73, 3547.
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6. (b) Dudash, J.; Jiang, J.; Mayer, S. C.; Joullié, M. M. Synth. Commun. 1993, 23(3), 349-356.
7. Racemization occurs through either mixed anhydride or oxazolone intermediate, see: Kemp, D. S. in Ref. 1b, Chapter 7.
8. For symmetric anhydride formation, see: Bailey, P. D. In An Introduction to Peptide Chemistry; John Wiley & Sons: Chichester, New York, Brisbane, Toronto and Singapore, 1992; pp 131-132.
9. (a) De Lombaert, S.; Erion, M. D.; Tan, J.; Blanchard, L.; El-Chehabi, L.; Ghai, R. D.; Sakane, Y.; Berry, C.; Trapani, A. J. Med. Chem. 1994, 37, 498-511.
10. (b) De Lombaert, S.; Singh, K.; Blanchard, L.; Soliman, V. F. Bioorg. Med. Chem. Lett. 1994, 4, 899-902.
11. (c) Trapani, A. J.; Beil, M. E.; De Lombaert, S.; Erion, M. D.; Ghai, R. D.; Peppard, J. V.; Lappe, R. W.; Worcel, M. J. Hypertens. 1993, 11 (suppl 5): s222-s223.
12. Shieh, W.-C; Carlson, J. A. J. Org. Chem. 1992, 57, 379-381.
13. 5: C, 71.69; H, 6.82; N, 5.57. Found: C, 71.59; H, 6.80; N, 5.52. The enantiomeric purity was established by chiral HPLC analysis, see Table 1, footnote c. The chemical purity was determined by achiral HPLC using a Waters μBondapak C-18 column (methanol:aqueous PIC B5 buffer 4:1).
14. (a) Carpino, L. A. J. Am. Chem. Soc. 1993, 115, 4397-4398.
15. (b) Miyazawa, T.; Otomatsu, T.; Yamada, T.; Kuwata, S. Chem. Express 1991, 6, 61-64.
16. 8 was successfully achieved employing this strategy.
17. 13: C, 59.57; H, 7.30; N, 12.50. Found: C, 59.30; H, 7.16; N, 12.75.