Synthesis of oligomers of tetrahydrofuran amino acids: furanose carbopeptoids

Abstract

An acid catalysed ring rearrangement of a triflate derivative of D-mannono-?-lactone 6 is the key step in the synthesis of the C-glycosyl sugar amino acid derivatives 3 and 4, examples of carbohydrate amino acid building blocks with specific conformational preferences suitable for incorporation into combinatorial amide libraries; homo-oligomerisation via solution phase coupling procedures affords furanose carbopeptoids 1 which adopt novel solution state secondary structures.

References

1. J. P. McDevitt and P. T. Lansbury, J. Am. Chem. Soc., 1996, 118, 3818; P. S. Ramamoorthy and J. Gervay, J. Org. Chem., 1997, 62, 7801; M. J. Sofia, R. Hunter, T. Y. Chan, A. Vaughan, R. Dulina, H. Wang and D. Gange, J. Org. Chem., 1998, 63, 2802.
2. E. G. von Roedern, E. Lohof, G. Hessler, M. Hoffmann and H. Kessler, J. Am Chem. Soc., 1996, 118, 10 156.
3. K. C. Nicolaou, H. Florke, M. G. Egan, T. Barth and V. A. Estevez, Tetrahedron Lett., 1995, 36, 1775.
4. J. Gervay, T. M. Flaherty and C. Nguyen, Tetrahedron Lett., 1997, 38, 1493 and references cited therein.
5. C. Muller, E. Kitas and H. P. Wessel, J. Chem. Soc. Chem. Commun., 1995, 2425; B. Drouillat, B. Kellam, G. Dekany, M. S. Starr and I. Toth, Bioorg. Med. Chem. Lett., 1997, 7, 2247.
6. L. Poitout, Y. le Merrer and J.-C. Depazay, Tetrahedron Lett., 1995, 36, 6887.
7. S. S. Choi, P. M. Myerscough, A. J. Fairbanks, B. M. Skead, C. J. F. Bichard, S. J. Mantell, J. C. Son, G. W. J. Fleet, J. Saunders and D. Brown, J. Chem. Soc., Chem. Commun., 1992, 1605.
8. J. R. Wheatley, C. J. F. Bichard, S. J. Mantell, J. C. Son, D. J. Hughes, G. W. J. Fleet and D. Brown, J. Chem. Soc., Chem. Commun., 1993, 1065.
9. C. J. F. Bichard, T. W. Brandstetter, J. C. Estevez, G. W. J. Fleet, D. J. Hughes and J. R. Wheatley, J. Chem. Soc., Perkin Trans. 1, 1996, 2151.
10. O. T. Schmidt, Methods Carbohydr. Chem., 1963, 2, 319; A. R. Beacham, I. Bruce, S. Choi, O. Doherty, A. J. Fairbanks, G. W. J. Fleet, B. M. Skead, J. M. Peach, J. Saunders and D. J. Watkin, Tetrahedron: Asymmetry, 1991, 2, 883; S. Morgenlie, Acta Chem. Scand., 1972, 26, 2518; D. Horton and J. S. Jewel, Carbohydr. Res., 1966, 2, 251; J. A. J. M. Vekemans, J. Boerekamp, E. F. Godefroi and G. J. F. Chittenden, Recl. Trav. Chim. Pays-Bas, 1985, 104, 266.
11. I. Kalwinsh, K.-H. Metten and R. Brückner, Heterocycles, 1995, 409, 939.
12. J. C. Estevez, A. J. Fairbanks, K. Y. Hsia, P. Ward and G. W. J. Fleet, Tetrahedron Lett., 1994, 35, 3361.
13. Selected data for 2: δ_H(500 MHz, CD₃CN) 3.58 (1H, d, J 3.7, OH-4), 3.64–3.74 (3H, m, H-6, H-6′, OH-6), 3.70 (3H, s, CO₂Me), 3.88 (1H, q, J 3.2, H-5), 4.03–4.05 (1H, m, H-4), 4.12 (1H, ddd, J 4.3, 1.9, 8.4, H-3), 4.33 (1H, d, J 8.4, OH-3), 4.59 (1H, d, J 4.3, H-2).
14. Selected data for 11: δ_H(500 MHz, CD₃OD) 1.27 (6H, t, J 6.2, Me₂CH), 3.38 (1H, dd, J 4.7, 12.7, H-6′), 3.62, (1H, dd, J 7.5, 12.7, H-6′), 3.91–3.94 (1H, m, H-5), 3.95 (1H, dd, J 2.8, 5.7, H-4), 4.26 (1H, dd, J 2.8, 5.1, H-3), 4.61 (1H, d, J 5.1, H-2), 5.07 (1H, septet, J 6.2, Me₂CH).
15. Selected data for 16(500 MHz, CDCl₃, 298 K):
    Table 1

    	Ring A	Ring B	Ring C	Ring D
    δC(C^1)	167.81	168.11	167.68	167.15
    δH(C^2)	4.669	4.692	4.708	4.687
    δC(C^2)	81.02	81.74	81.38	78.93
    δH(C^3)	5.646	5.559	5.495	5.475
    δC(C^3)	76.08	75.57	76.01	76.66
    δH(C^4)	4.904	4.837	5.003	5.250
    δC(C^4)	78.40	78.06	77.68	77.57
    δH(C^5)	4.153	4.027	4.123	4.055
    δC(C^5)	85.00	85.18	85.00	83.19
    δH(C^6)	3.708/3.461	4.027/3.224	3.861/3.228	3.781/3.481
    δC(C^6)	51.43	41.28	41.28	40.48
    δH(NH)	–	6.910	8.025	8.191

    ---

    
    

    Carbopeptoids are identified alphabetically from the N- to the C-terminus; protons on each ring are numbered according to IUPAC recommendations on carbohydrate nomenclature

    .
16. M. D. Smith, T. D. W. Claridge, G. E. Tranter, M. S. P. Sansom and G. W. J. Fleet, Chem. Commun., 1998, 2041 .