Segment coupling to a highly hindered N-terminal, alamethicin-related α-aminoisobutyric acid (Aib) residue

Tetrahedron Letters

Volumn 48, Issue 41, 2007, Pages 7404-7407

  Carpino, Louis A ^a   Abdel Maksoud, Adel Ali ^b   Mansour, E M E ^c   Zewail, Mohamed A ^d  

^a UNIVERSITY OF MASSACHUSETTS   (United States)

^b Universities and Research centers District   (Egypt)

^c Alexandria University Faculty Of Science   (Egypt)

^d NATIONAL RESEARCH CENTRE   (Egypt)

Author keywords

[No Author keywords available]

Indexed keywords

2 AMINO 2 METHYLPROPIONIC ACID; ALAMETHICIN; AMIDE; RESIN; VALINE;

ARTICLE; CHEMICAL REACTION; DRUG SYNTHESIS;

EID: 34548596987     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.tetlet.2007.07.215     Document Type: Article

References (20)

1. Goodman M., and McGahren W.J. Tetrahedron 23 (1967) 2031
2. Carpino L.A. J. Am. Chem. Soc. 115 (1993) 4397
3. Carpino L.A., and El-Faham A. J. Org. Chem. 59 (1994) 695
4. Carpino L.A., El-Faham A., and Albericio F. J. Org. Chem. 60 (1995) 3561
5. For a recent review on the synthesis of peptides containing α,α-dialkyl amino acid including those incorporating these amino acids in consecutive positions see: Formaggio, F.; Broxterman, Q. B.; Toniolo, C. In Houben-Weyl, Methods in Organic Chemistry, Goodman, M.; Felix, A.; Moroder, L.; Toniolo, C., Eds.; Thieme: Stuttgart, Germany, 2003; Vol. E22c, pp 292-310.
6. Wenschuh H., Beyermann M., Krause E., Brudel M., Winter R., Schümann M., Carpino L.A., and Bienert M. J. Org. Chem. 59 (1994) 3275
7. Wenschuh H., Beyermann M., Haber H., Seydel J.K., Krause E., Bienert M., Carpino L.A., El-Faham A., and Albericio F. J. Org. Chem. 60 (1995) 405
8. Balasubramanian T.M., Kendrick N.C.E., Taylor M., Marshall G.R., Hall J.E., Vodyanoy F., and Reusser F. J. Am. Chem. Soc. 103 (1981) 6127
9. Schmitt H., and Jung G. Liebigs Ann. Chem. (1985) 321
10. Gisin B.F., Davis D.G., Borowska Z.K., Hall J.E., and Kobayashi S. J. Am. Chem. Soc. 103 (1981) 6373
11. Although couplings of peptide segments C-terminating in proline have long been considered safe, this is not the case for coupling to an Aib residue, especially if the proline residue is attached to an Aib unit or some other sterically hindered residue, for example, the pivaloyl group. Loss of configuration in such systems is believed to proceed via a positively charged oxazolonium intermediate. See:. Nagaraj R., and Balaram P. Tetrahedron 37 (1981) 2001
12. Peggion C., Coin I., and Toniolo C. Pept. Sci. 76 (2004) 485
13. Davies J.S., and Thomas R.J. J. Chem. Soc., Perkin Trans. 1 (1981) 1639
14. Benoiton N.L., Young C.L., and Chen F.M.F. Int. J. Pept. Protein Res. 38 (1991) 574
15. Carpino L.A., Ionescu D., and El-Faham A. J. Org. Chem. 61 (1996) 2460
16. Carpino L.A., Henklein P., Foxman B.M., Abdelmoty I., Costisella B., Wray V., Domke J., El-Faham A., and Mügge C. J. Org. Chem. 66 (2001) 5245
17. Carpino L.A., and El-Faham A. Tetrahedron 55 (1999) 6813
18. 2O 0.1% TFA for 15 min.
19. Carpino L.A., Ismail M., Truran G.A., Mansour E.M.E., Iguchi S., Ionescu D., El-Faham A., Riemer C., and Warrass R. J. Org. Chem. 64 (1999) 4324
20. 2O, 5% phenol and 2% triisopropylsilane for 2 h. All reactions involving DMF alone were carried out in plastic syringes as described in the general procedure whereas those involving mixtures of DMF/DCM or DCM alone were carried out in capped vials with stirring only in the case of DCM. HPLC analyses were carried out as described above. Data from the various runs are collected in Table 1. The species formed during the coupling processes were identified in each case by the retention times of the l- or d-epimers of the undecapeptide amide 4 or the residual unreacted pentapeptide amide 5 as determined by the analysis of the authentically synthesized model compounds. The completeness of the coupling process could be judged qualitatively by the absence of significant absorption in the HPLC trace near the retention time (9.36 min) of the recovered amide 5. Integration of the peaks at 15.19 and 16.14 min due to the d-Val epimer and the all l-epimer, respectively, of the undecapeptide amide 4 gave the extent of the loss of configuration as noted in Table 1. Details for representative runs are given in the Supplementary data.