Efficient synthesis of O-(2-acetamido-2-deoxy-β-D- glucopyranosyl)-serine and -threonine building blocks for glycopeptide formation 

Abstract

Glucosamine donors 1–3 having N-TCP, N,N-diacetyl and N-Teoc protection, respectively, give with N^α-Boc-protected serine and threonine benzyl esters 4a,b as acceptors exclusively the β-glycosides; they can be transformed into O-GlcNAc serine and threonine derivatives 8a,b. The high yielding O-glycosylation of compounds 4a,b with trichloroacetimidate 3 and the ease of replacement of the N-Teoc group by the N-acetyl group prompted the use of N ^α-Fmoc-protected serine and threonine allyl (9a,b) and Pfp active esters (12a,b) as acceptors, thus very efficiently yielding the corresponding O-(N,O-acetylglucosamino) serine and threonine derivatives 11a,b and 14a,b as active esters.

References

1. C. R. Torres and G. W. Hart, J. Biol. Chem., 1984, 259, 3308; G. W. Hart, R. S. Haltiwanger, G. D. Holz and W. G. Kelly, Annu. Rev. Biochem., 1989, 58, 841.
2. L. S. Griffith, M. Mathes and B. Schmitz, J. Neurosci. Res., 1995, 41, 270 and references therein.
3. R. S. Haltiwanger, W. G. Kelly, E. P. Roquemore, M. A. Blomberg, L.-Y. Dong, L. Kreppel, T.-Y. Chou and G. W. Hart, Biochem. Soc. Trans., 1992, 20, 264.
4. A. Vargas-Berenguel, M. Meldal, H. Paulsen and K. Bock, J. Chem. Soc., Perkin Trans. 1, 1994, 2615; E. Meinjohanns, M. Meldal, H. Paulsen and K. Bock, J. Chem. Soc., Perkin Trans. 1, 1995, 405; E. Meinjohanns, A. Vargas-Berenguel, M. Meldal, H. Paulsen and K. Bock, J. Chem. Soc., Perkin Trans. 1, 1995, 2165.
5. K. J. Jensen, P. R. Hansen, D. Venugopal and G. Barany, J. Am. Chem. Soc., 1996, 118, 3148.
6. U. Ellervik and G. Magnusson, Carbohydr. Res., 1996, 280, 251; L. Szabo, J. Ramza, C. Langdon and R. Polt, Carbohydr. Res., 1995, 274, 11.
7. H. Paulsen, Angew. Chem., 1990, 102, 851; Angew. Chem., Int. Ed. Engl., 1990, 29, 823.
8. H. G. Garg, K. von dem Bruch and H. Kunz, Adv. Carbohydr. Chem. Biochem., 1994, 50, 277; H. Kunz, Angew. Chem., 1987, 99, 297; Angew. Chem., Int. Ed. Engl., 1987, 26, 294.
9. M. Meldal and K. J. Jensen, J. Chem. Soc., Chem. Commun., 1990, 483; M. Meldal and K. Bock, Tetrahedron Lett., 1990, 31, 6987; A. M. Jansson, M. Meldal and K. Bock, Tetrahedron Lett., 1990, 31, 6991; S. Peters, T. Bielfeldt, M. Meldal, K. Bock and H. Paulsen, Tetrahedron Lett., 1992, 33, 6445; K. J. Jensen, M. Meldal and K. Bock, J. Chem. Soc., Perkin Trans. 1, 1993, 2119.
10. J. Banoub, P. Boullanger and D. Lafont, Chem. Soc. Rev., 1992, 92, 1167.
11. M. Schultz and H. Kunz, Tetrahedron Lett., 1992, 33, 5319; Tetrahedron: Asymmetry, 1993, 4, 1205.
12. H. Paulsen and J.-P. Hölck, Liebigs Ann. Chem., 1982, 1121; H. Paulsen, M. Paal and M. Schultz, Tetrahedron Lett., 1983, 24, 1759.
13. For the synthesis of compound 1, see J. C. Castro-Palomino and R. R. Schmidt, (a)Tetrahedron Lett., 1995, 36, 5343; (b)Liebigs Ann. Chem., 1996, 1623; (c) the N-TCP group was independently investigated for glucosamine with the pent-4-en-1-yl group at the anomeric oxygen as leaving group; see ref. 17.
14. For the synthesis of compound 2, see J. C. Castro-Palomino and R. R. Schmidt, Tetrahedron Lett., 1995, 36, 6871.
15. For the synthesis of compound 3, see (a) H. Paulsen and B. Helpap, Carbohydr. Res., 1991, 216, 289; (b) W. Dullenkopf, J. C. Castro-Palomino, L. Manzoni and R. R. Schmidt, Carbohydr. Res., 1996, 296, 135.
16. Compounds 4a,b are commercially available.
17. J. S. Debenham, R. Madsen, C. Roberts and B. Fraser-Reid, J. Am. Chem. Soc., 1995, 117, 3302.
18. Instead of Teoc the abbreviation Troc has also been used; see: T. B. Windholz and D. B. R. Johnston, Tetrahedron Lett., 1967, 2555 and references therein.
19. For the use of N-Teoc in a glycosyl donor, see: S. Kusumoto, H. Yoshimura, M. Imoto, T. Shimamoto and T. Shiba, Tetrahedron Lett., 1985, 26, 909.
20. M. Ciommer and H. Kunz, Synlett, 1991, 593.
21. I. Schön and L. Kisfaludy, Synthesis, 1986, 303.
22. U. K. Saha and R. R. Schmidt, unpublished work.