Solid-phase synthesis of a putative heptapeptide intermediate in vancomycin biosynthesis

Abstract

The solid-phase synthesis was completed of the heptapeptide D-Leu-D-Tyr-L-Asn-Hpg-Hpg-L-Tyr-Dhpg, a putative intermediate in vancomycin biosynthesis, where Dhpg = (S)-3,5-dihydroxyphenylglycine and Hpg = (R)-4-hydroxyphenylglycine, using 2-chlorotrityl resin, benzyl side-chain protecting groups for the aromatic residues, and Alloc chemistry for chain elongation; the heptapeptide was obtained in 16% yield with the correct relative and absolute configuration.

References

1. A. M. A. vanWageningen, P. N. Kirkpatrick, D. H. Williams, B. R. Harris, J. K. Kershaw, N. J. Lennard, M. Jones, S. J. M. Jones and P. J. Solenberg, Chem. Biol., 1998, 5, 155.
2. P. J. Solenberg, P. Matsushima, D. R. Stack, S. C. Wilkie, R. C. Thompson and R. H. Baltz, Chem. Biol., 1997, 4, 195.
3. S. Pelzer, R. Sussmuth, D. Heckmann, J. Recktenwald, P. Huber, G. Jung and W. Wohlleben, Antimicrob. Agents Chemother., 1999, 43, 1565.
4. R. D. Sussmuth, S. Pelzer, G. Nicholson, T. Walk, W. Wohlleben and G. Jung, Angew. Chem., Int. Ed., 1999, 38, 1976.
5. K. C. Nicolaou, C. N. C. Boddy, S. Bräse and N. Winssinger, Angew. Chem., Int. Ed., 1999, 38, 2096.
6. For a review, see F. Guibé, Tetrahedron, 1998, 54, 2967.
7. K. Barlos, O. Chatzi, D. Gatos and G. Stavropoulos, Int. J. Pept. Protein Res., 1991, 37, 513.
8. N. Thieriet, J. Alsina, E. Giralt, F. Guibé and F. Albericio, Tetrahedron Lett., 1997, 38, 7275.
9. H. Brückner and C. Keller-Hoehl, Chromatographia, 1990, 30, 621.