| Title | Synthesis of cis-4-hydroxy-L-proline and its incorporation into biologically important peptides | |
| Authors | George Stavropoulos, Vassiliki Magafa, Kostas Karagiannis and Dionissios Papaioannou
Department of Chemistry, University of Patras, Patra 260 10, Greece |
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| Citation | Stavropoulos, G., Magafa, V., Karagiannis, K. and Papaioannou, D.: Synthesis of cis-4-Hydroxy-L-proline and its incorporation into biologically important peptides, Epitheorese Klin. Farmakol. Farmakokinet. 9(2-3): 103-106 (1995) | |
| Publication Date | 1995 | |
| Full Text Language | English | |
| Order – Buy | Ηλεκτρονική Μορφή: pdf (10 €) – Digital Type: pdf (10 €)
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| Keywords | Peptide synthesis, cis-4-hydroxy-L-proline. | |
| Other Terms | review article | |
| Summary | An efficient intramolecular Mitsunobu reaction resulted in the conversion of trans-4-hydroxy-N-trityl-L-proline (Trt-Hyp) to 5-trityl-2-oxa-5-aza-bicyclo[2.2.1]heptane-3-one. This lactone is a key intermediate in the synthesis of cis-4- hydroxy-L-proline (CHyp) and derivatives suitable for use in peptide synthesis. Methanolysis catalysed by triphenyiphosphine (TPP)-diethyl azodicarboxylate (DEAD) transformed the lactone into the methyl ester of cis-4-hydroxy-N-trityl-L-proline, while ammoniolysis in isopropyl alcohol gave the corresponding amide. Detritylation of lactone, ester and amide was affected by treatment with p-toluenesulfonic acid. On the other hand saponification of the lactone provided cis-4-hydroxy-N-trityl-L-proline which after O-benzyiation and carboxy activation allowed the incorporation of cHyp into model peptides such as Trt-Cys(Trt)-cHyp(Bzl)-Lys(Trt)-Gly-NH2 and Trt-cHyp(Bzl)-Leu-Gly-NH2. Similar methodology was applied to the TRH analogue Glp-His(Nm-Trt)- Hyp-OH, prepared by SPPS on the bulky and mild acid sensitive solid support 2-chlorotrltyl resin, to convert it to Glp-His(Nm– Trt)-cHyp lactone with inversion of configuration at C-4 of the Hyp residue. Trans-esterification of this lactone with MeOH/TPP-DEAD, followed by detritylation, provided the tripeptide ester GIp-His-cHyp-OMe which gave the corresponding amide and acid on ammoniolysis and saponification, white x-ray crystallography, FT-IR and ¹H NMR techniques were used for structure identification of the thus prepared compounds. | |
| References | 1. Fischer, E.: Ber. 35: 2660 (1902)2. Inoye, K., Sakakibara, S., Prockop, D.: Biochem. Biophys. Acta 420: 133 (1976)
3. Mauger, A.B., Witkop, B.: Chem. Rev. 66: 47 and references therein (1966) 4. Buku, A., Schwartz, I., Yamin, N., Wyssbod, H., Gazis, J. Med. Chem. 30: 1509 (1987) 5. Uitto, J., Prockop, D.: Arch. Biochem. Biophys. 181: 293 (1977) 6. Mitsunobu, O. (1983) Synthesis 1 7. Zervas, L., Theodoropoulos, D.: J. Am. Chem. Soc. 78: 1359 (1956) 8. Barlos, K., Papaioannou, D., Patrianakou, S., Tsegenidis, T.: Liebigs Ann. Chem.: 1950 (1986) 9. Papaioannou, D., Stavropoulos, G., Nastopoulos, V., Voliotis, S.: Acta Cryst. C45:1651 (1989) 10. Barlos, K., Papaioannou, D., Theodoropoulos, D.: Int. J. Peptide Protein Res. 23: 300 (1984) 11. Enzmann, E., Boler, J., Folker, K., Bowers, C., Schally, A.: J. Med. Chem. 14: 469 (1971) 12. Barlos K., Chatzi, O., Gatos, D., Stavropoulos, G.: ht. J. Peptide Protein Res. 37: 513 (1991) 13. Barlos, K., Mamos, P., Papaioannou, D., Sanida, C., Antonopoulos, C.: J. Chem. Soc. Chem. Commun.: 1258 (1986) 14. Papaioannou, D., Stavropoulos, G., Karagiannis, K., Francis, G.W., Brekke, T.t Aksnes, D.W.: Acta Chem. Scand. 44: 243 (1990) 15. Stavropoulos, G., Karagiannis, K., Vynios, D., Papaioannou, D., Aksnes, D.W., Froystein, N.A., Francis G.W.: Ada Chem. Scand. 45: 1047 (1991) |
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Online ISSN 1011-6575
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| ΕΤΗΣΙΑ ΣΥΝΔΡΟΜΗ 1995 – ANNUAL SUBSCRIPTION 1995 | |
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