Solid phase synthesis of azapeptides using an automatic synthesizer

Molecular Diversity

Volumn 4, Issue 1, 1998, Pages 23-24

  Ahn, In Ae ^a   Kim, Sang Woong ^a   Ro, Seonggu ^a  

^a LG Chemical Ltd   (South Korea)

Author keywords

Automatic synthesizer; Azaamino acid; Azaglycine; Azapeptide; Peptidomimetics; Solid phase synthesis

Indexed keywords

GLYCINE; HETEROCYCLIC COMPOUND;

ARTICLE; CHEMISTRY; DRUG DESIGN; PEPTIDE SYNTHESIS; SYNTHESIS;

AZA COMPOUNDS; DRUG DESIGN; GLYCINE; PEPTIDE BIOSYNTHESIS;

EID: 0032234555     PISSN: 13811991     EISSN: None     Source Type: Journal    
DOI: 10.1023/A:1009651612974     Document Type: Article

References (14)

1. Goodman, M. and Ro, S., Peptidomimetics for Drug Design, in Wolff, M. E. (Ed.), Burger's Medicinal Chemistry and Drug Discovery (5th ed.), Vol. I: Principles and Practice, Wiley, New York, NY, 1995, pp. 803-861.
2. Gante, J., Azapeptides, Synthesis (1989) 405-413.
3. Gray, C. J., Quibell, M., Bagett, N. and Hammerle, T., Incorporation of azaglutamine residues into peptides synthesised by the ultra-high load solid(gel)-phase technique, Int. J. Pept. Protein Res., 40 (1992) 351-362.
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6. Greenlee, W.J., Thorsett, E.D., Springer, J.P. and Patchett, A.A., Azapeptides: a new class of angiotensin-converting enzyme inhibitors, Biochem. Biophys. Res. Commun., 122 (1984) 791-797.
7. Fassler, A., Bold, G., Capro, H., Cozens, R., Meastan, J., Poncioni, B., Rosel, J., Tintelon-Blomley, M. and Lang, M., Aza-peptide analogs as potent human immunodeficiency virus type-1 protease inhibitors with oral bioavailability, J. Med. Chem., 39 (1996) 3203-3216.
8. Magrath, J. and Abeles, R. H., Cysteine protease inhibition by azapeptide esters, J. Med. Chem., 53 (1992) 4279-4283.
9. 10 equiv of protected amino acid, 20 equiv of HOBT and 20 equiv of DCC to resin were mixed for preactivation. After 25 min this preactivated protected amino acid was added to the resin.
10. Treated with 25% of TFA/DCM for 3 min then 50% TFA/DCM for 15 min and finally neutralized with DIEA.
11. 1.5 mL of thioanisole/EDT to the resin 1g was stirred fir 10 min and then treated with 10 mL of TFA for 7 min. Finally 1 mL of TFMSA was added and stirred for 2 h.
12. A treatment of 20% piperidine/NMP for 1 min was performed for deprotection followed by treatment with 20% piperidine for 20 min.
13. 10 equiv of Fmoc amino acid to the resin and 0.9 equiv of 0.45 M HBTU/HOBT/DMF of Fmoc amino acid were mixed for 6 min. 2 equiv of DIEA to Fmoc amino acid was then added.
14. Treated with 2.5% water in TFA for 1 h.