New macrobicyclic receptors for amino acids

Tetrahedron Letters

Volumn 41, Issue 20, 2000, Pages 3963-3966

  Jullian, Valerie ^a   Shepherd, Emma ^a   Gelbrich, Thomas ^a   Hursthouse, Michael B ^a   Kilburn, Jeremy D ^a  

^a UNIVERSITY OF SOUTHAMPTON   (United Kingdom)

Author keywords

Amino acid; Host guest; Receptor

Indexed keywords

AMINO ACID RECEPTOR; METHYL CHLORIDE;

ARTICLE; CHEMICAL REACTION; CONFORMATIONAL TRANSITION; CRYSTAL STRUCTURE; HYDROGEN BOND; REACTION ANALYSIS; SYNTHESIS;

EID: 0034697561     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(00)00488-3     Document Type: Article

References (16)

1. For recent examples, see: (a) Henley, P. D.; Kilburn, J. D. Chem. Commun. 1999, 1335;
2. (b) Fessmann, T.; Kilburn, J. D. Angew. Chem., Int. Ed. Engl. 1999, 38, 1993;
3. (c) Xu, R.; Greiveldinger, G.; Marenus, L. E.; Cooper, A.; Ellman, J. A. J. Am. Chem. Soc. 1999, 121, 4898;
4. (d) Sirish, M.; Schneider, H.-J. Chem. Commun. 1999, 907 and references cited therein.
5. (a) Pernia, G. J.; Kilburn, J. D.; Essex, J. W.; Mortishire-Smith, R. J.; Rowley, M. J. Am. Chem. Soc. 1996, 118, 10220;
6. (b) Pernia, G. J.; Kilburn, J. D.; Rowley, M. Chem. Commun. 1995, 305.
7. For other examples of macrobicyclic peptide receptors of this type, see: (a) Henley, P. D.; Waymark, C. P.; Kilburn, J. D.; Gillies, I. J. Chem. Soc., Perkin Trans. 1 2000, in press;
8. (b) Waymark, C. P.; Kilburn, J. D.; Gillies, I. Tetrahedron Lett. 1995, 36, 3051.
9. For the preparation of related pyridyl aryl ethers, see: Markley, L. D.; Tong, Y. C.; Dulworth, J. K.; Steward, D. L.; Goralski, C. T.; Johnston, H.; Wood, S. G.; Vinagradoff, A. P.; Bargar, T. M. J. Med. Chem. 1986, 29, 427.
10. Attempted reduction of nitrile 5 using borane, as successfully employed in the preparation of the original biarylmethane spacer used in macrobicycles 1 and 2, led to cleavage of the pyridylaryl ether to give back the hydroxy benzoate.
11. 2 was essential in the Boc deprotection step to avoid partial conversion of the thiourea moiety to the corresponding urea.
12. 2)]=0.061, wR2(all data)=0.133, Flack parameter=0.11(8).
13. Binding constants were calculated by fitting the titration data to a 1:1 binding isotherm using NMRTit HG software, kindly provided by Prof. C. A. Hunter, University of Sheffield. See: A. P. Bisson, C. A. Hunter, J. C. Morales, K. Young, Chem. Eur. J. 1998, 4, 845-851.
14. (a) Connors, K. A. Binding Constants, The Measurement of Molecular Complex Stability; Wiley: 1987; pp. 24-28.
15. (b) Job, A. Annales de Chimie 1928, 9, 113.
16. With receptor 2, N-acetyl L-alanine carboxylate salt (and the corresponding phenylalanine carboxylate salt) was bound predominantly within the bowl shaped cavity, utilising a carboxylate-thiourea interaction, but with the acetyl amide in the cis configuration (with the cis amide stabilised by two hydrogen bonds from the rim of the macrobicycle to the acetyl amide carbonyl). However detailed NMR studies (see Ref. 2a) revealed that there were additional modes of binding for these substrates, involving the trans configuration of the acetyl amide.