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Volumn 74, Issue 2, 2009, Pages 660-668

Synthesis of conformationally constrained peptidomimetics using multicomponent reactions

Author keywords

[No Author keywords available]

Indexed keywords

MODELING STUDIES; MULTI-COMPONENT REACTIONS; NMR STUDIES; PEPTIDE MOIETIES; PEPTIDOMIMETIC; PEPTIDOMIMETICS; STEP SEQUENCES; SYNTHETIC APPROACHES; TURN STRUCTURES; X-RAY CRYSTAL STRUCTURES; X-RAY CRYSTALLOGRAPHIES;

EID: 60849087692     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo802052j     Document Type: Article
Times cited : (34)

References (54)
  • 7
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    • For reviews on peptidomimetics, see: (a) Ball, J. B.; Alewood, P. F. J Mol. Recoenit. 1990, 3, 55-64.
    • For reviews on peptidomimetics, see: (a) Ball, J. B.; Alewood, P. F. J Mol. Recoenit. 1990, 3, 55-64.
  • 11
    • 0030845948 scopus 로고    scopus 로고
    • Test, B, Ed, Academic Press: London
    • (e) Giannis, A.; RUbsam, F. Advances in Drug Research; Test, B., Ed.; Academic Press: London, 1997; Vol. 29, pp 1-78.
    • (1997) Advances in Drug Research , vol.29 , pp. 1-78
    • Giannis, A.1    RUbsam, F.2
  • 12
    • 64549109665 scopus 로고    scopus 로고
    • Synthesis of Peptides and Peptidomimetics. In Houben- Weyl, Methods of Organic Chemistry; Felix, A., Moroder, L., Toniolo, C., Eds.; Thieme: Stuttgart, New York, 2003; E22c.
    • (f) Synthesis of Peptides and Peptidomimetics. In Houben- Weyl, Methods of Organic Chemistry; Felix, A., Moroder, L., Toniolo, C., Eds.; Thieme: Stuttgart, New York, 2003; Vol. E22c.
  • 15
    • 0019163001 scopus 로고    scopus 로고
    • A good illustration of this concept is the constrained analogue of LHRH (see ref 7) by Freidinger: Freidinger, R. M, Veber, D. F, Perlow, D. S, Brooke, J. R, Saperstein, R. Science 1980, 210, 656-658
    • A good illustration of this concept is the constrained analogue of LHRH (see ref 7) by Freidinger: Freidinger, R. M.; Veber, D. F.; Perlow, D. S.; Brooke, J. R.; Saperstein, R. Science 1980, 210, 656-658.
  • 16
    • 9144267831 scopus 로고    scopus 로고
    • See also ref 4. For recent examples, see: (a) Palomo, C.; Aizpurua, J. M.; Benito, A.; Miranda, J. I.; Fratila, R. M.; Matute, C.; Domercq, M.; Gago, F.; Martin-Santamaria, S.; Linden, A. J. Am. Chem. Soc. 2003, 125, 16243-16260.
    • See also ref 4. For recent examples, see: (a) Palomo, C.; Aizpurua, J. M.; Benito, A.; Miranda, J. I.; Fratila, R. M.; Matute, C.; Domercq, M.; Gago, F.; Martin-Santamaria, S.; Linden, A. J. Am. Chem. Soc. 2003, 125, 16243-16260.
  • 21
    • 64549112943 scopus 로고    scopus 로고
    • LHRH: luteinizing hormone-releasing hormone
    • LHRH: luteinizing hormone-releasing hormone.
  • 34
    • 0035959447 scopus 로고    scopus 로고
    • For a review on β-turn mimetic library synthesis, see
    • For a review on β-turn mimetic library synthesis, see: Souers, A. J.; Ellman, J. A. Tetrahedron 2001, 57, 7431-7448.
    • (2001) Tetrahedron , vol.57 , pp. 7431-7448
    • Souers, A.J.1    Ellman, J.A.2
  • 41
    • 0034191466 scopus 로고    scopus 로고
    • The rather high stability of the carbinolamine and therefore slow formation of the imine most likely explains the long reaction time of this particular Ugi reaction and the formation of side products such as the iminoimidazolidine
    • (b) Atherton, J. H.; Brown, K. H.; Crampton, M. R. J. Chem. Soc., Perkin Trans. 2 2000, 941-946. The rather high stability of the carbinolamine and therefore slow formation of the imine most likely explains the long reaction time of this particular Ugi reaction and the formation of side products such as the iminoimidazolidine.
    • (2000) J. Chem. Soc., Perkin Trans. 2 , pp. 941-946
    • Atherton, J.H.1    Brown, K.H.2    Crampton, M.R.3
  • 42
    • 0000887411 scopus 로고    scopus 로고
    • There is evidence that pure N-methyleneaniline occurs as a cyclic trimer. However, since nucleophilic species are present the formation of this trimer is not likely. See: Miller, J. G.; Wagner, E. C. J. Am. Chem. Soc. 1932, 54, 3698-3706.
    • There is evidence that pure N-methyleneaniline occurs as a cyclic trimer. However, since nucleophilic species are present the formation of this trimer is not likely. See: Miller, J. G.; Wagner, E. C. J. Am. Chem. Soc. 1932, 54, 3698-3706.
  • 43
    • 64549123843 scopus 로고    scopus 로고
    • 3N · HCl was added, the amidine was not present after 77 h and the yield of 15 is 73%. During the reaction, however, 13 was observed onTLC, supporting its involvementas an intermediate.
    • 3N · HCl was added, the amidine was not present after 77 h and the yield of 15 is 73%. During the reaction, however, 13 was observed onTLC, supporting its involvementas an intermediate.
  • 46
    • 64549100625 scopus 로고    scopus 로고
    • See ref 6a and references therein
    • See ref 6a and references therein.
  • 49
    • 64549155591 scopus 로고    scopus 로고
    • For all data, see Supporting Information
    • For all data, see Supporting Information.
  • 50
    • 64549116226 scopus 로고    scopus 로고
    • 1H NMR signals (especially for 10). These values are therefore not reliable and were excluded from the table.
    • 1H NMR signals (especially for 10). These values are therefore not reliable and were excluded from the table.
  • 51
    • 64549118574 scopus 로고    scopus 로고
    • Although the signals for H2 and H3 overlap in the 233-283 K range, it is clear from Figure 5B that the temperature coefficients for both protons are significantly larger than in the 294-330 K range. However, it must be noted that high temperature coefficients are especially observed in the low temperature range, where line broadening (possibly due to aggregation) is observed
    • Although the signals for H2 and H3 overlap in the 233-283 K range, it is clear from Figure 5B that the temperature coefficients for both protons are significantly larger than in the 294-330 K range. However, it must be noted that high temperature coefficients are especially observed in the low temperature range, where line broadening (possibly due to aggregation) is observed.
  • 53
    • 64549104536 scopus 로고    scopus 로고
    • Partial cleavage of the DMB group took place under acidic conditions, and therefore 1 equiv of acid was used in the reactions using 2,4-dimethoxy- benzylamine.
    • Partial cleavage of the DMB group took place under acidic conditions, and therefore 1 equiv of acid was used in the reactions using 2,4-dimethoxy- benzylamine.
  • 54
    • 64549127272 scopus 로고    scopus 로고
    • 2 was added to increase the solubility of the dihydropyridone starting material, since it is very poorly soluble in MeOH.
    • 2 was added to increase the solubility of the dihydropyridone starting material, since it is very poorly soluble in MeOH.


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