Journal of Computer-Aided Molecular Design

, Volume 21, Issue 6, pp 351–357 | Cite as

Computational assessment of synthetic procedures

Original Article

Abstract

Synthetic chemistry is hard because some reasonable looking molecules cannot be made, because there are errors in the chemical literature, because it is easy to miss reaction possibilities and because even the shape of molecules is very difficult to determine. We propose an approach to the computational analysis of reactions that tries to circumvent these difficulties, by restricting the analysis to simple rules for reactivity that can generate a large number of competing pathways. This huge ensemble is filtered using computational methods to pick out the most likely pathways, and to suggest possible products.

Keywords

Computer-aided synthesis Conformation analysis Chemical informatics Data analysis 

Notes

Acknowledgments

We thank Elsevier MDL and Unilever for financial support.

References

  1. 1.
    Paterson I, Anderson EA (2005) Science 310:451CrossRefGoogle Scholar
  2. 2.
    Yoon TP, Jacobsen EN (2003) Science 299:1691CrossRefGoogle Scholar
  3. 3.
    de Silva KM, Goodman JM (2005) J Chem Inf Model 45:81CrossRefGoogle Scholar
  4. 4.
    Lipinski CA, Lombardo F, Dominy BW, Feeney PJ (1997) Adv Drug Del Rev 23:3CrossRefGoogle Scholar
  5. 5.
    Adams SE, Goodman JM, Kidd RJ, McNaught AD, Murray-Rust P, Norton FR, Townsend JA, Waudby CA (2004) Org Biomol Chem 2:3067CrossRefGoogle Scholar
  6. 6.
    Russell B, Goodman JM University of Cambridge, manuscript in preparationGoogle Scholar
  7. 7.
    Lee C, Yang W, Parr RG (1988) Phys Rev B 37:785Google Scholar
  8. 8.
    Harding WW, Lewis PA, Jacobs HM, McLean S, Reynolds W, Tay L, Yang J-P (1995) Tetrahedron Lett 36:8137CrossRefGoogle Scholar
  9. 9.
    (a) Xiong ZM, Corey EJ, (2000) J Am Chem Soc 122:4831. (b) Xiong ZM, Corey, EJ (2000) J Am Chem Soc 122:9328. (c) Morimoto Y, Iwai T, Kinoshita T (2000) J Am Chem Soc 122:7124Google Scholar
  10. 10.
    Bellenie BR, Goodman JM (2001) Tetrahedron Lett 42:7477CrossRefGoogle Scholar
  11. 11.
    Bauer I, Maranda L, Young KA, Shimizu Y (1995) Tetrahedron Lett 36:991CrossRefGoogle Scholar
  12. 12.
    Walsh LM, Goodman JM (2003) Chem Comm 20:2616Google Scholar
  13. 13.
    Fleming I, Woodward RB (1973) J Chem Soc, Perkin Trans I, 1653Google Scholar
  14. 14.
    Davies JE, Fleming I, Goodman JM (2003) Org Biomol Chem 1:3570CrossRefGoogle Scholar
  15. 15.
    Dominey AP, Goodman JM (1999) Org Lett 1:473CrossRefGoogle Scholar
  16. 16.
    Nadin A, Nicolaou KC (1996) Angew Chem, Int Ed Engl 35:1622CrossRefGoogle Scholar
  17. 17.
    Goodman JM (1997) J Chem Inf Comput Sci 37:876CrossRefGoogle Scholar
  18. 18.
    Nair N, Goodman JM (1998) J Chem Inf Comput Sci 38:317CrossRefGoogle Scholar
  19. 19.
    Hayakawa H, Ohmori M, Takamichi K, Matsuda F, Miyashita M (1997) Chem Commun 1219Google Scholar
  20. 20.
    Jorgensen WL, Laird ER (1990) Pure Appl Chem 62:1921Google Scholar
  21. 21.
    Höllering R, Gasteiger J, Steinhauer L, Schulz K, Herwig A. (2000) J Chem Inf ComputSci 40:482CrossRefGoogle Scholar
  22. 22.
    Satoh H, Funatsu K (1996) J Chem Inf Comput Sci 36:173CrossRefGoogle Scholar
  23. 23.
    Sello G (1992) J Chem Inf Comput Sci 32:713CrossRefGoogle Scholar
  24. 24.
    Agarwal KK, Larsen DL, Gelernter HL (1978) Comput Chem 2:75CrossRefGoogle Scholar
  25. 25.
    Ugi I, Bauer J, Blomberger C, Brandt J, Dietz A, Fontain E, Gruber B, vScholley-Pfab A, Senff A, Stein NJ (1994) Chem Inf Comput Sci 34:3Google Scholar
  26. 26.
    Hendrickson JB, Parks CA (1992) J Chem Inf Comput Sci 32:209Google Scholar
  27. 27.
    Zefirov NS, Baskin II, Palyulin VA (1994) J Chem Inf Comput Sci 34:994CrossRefGoogle Scholar
  28. 28.
    Socorro IM, Taylor K, Goodman JM (2005) Org Lett 7:3541CrossRefGoogle Scholar
  29. 29.
    Socorro IM, Goodman JM (2006) J Chem Inf Model 46:606CrossRefGoogle Scholar
  30. 30.
    Java Version 1.4.1. http://java.sun.com/ (accessed Sep 2005)Google Scholar
  31. 31.
    Cheshire Studio, version 3.0.0.54.; Elsevier MDL: San Leandro, CAGoogle Scholar
  32. 32.
    Maestro, version 5.0.019; Schrodinger Inc.: Portland, Oregon, 2000Google Scholar
  33. 33.
    MDL CTfile Formats http://www.mdl.com/solutions/white_papers/ctfile_formats.jsp (accessed March 2007)Google Scholar
  34. 34.
    Ciavatta ML, Gavagnin M, Puliti R, Cimino G (1996) Tetrahedron 52:12831CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2007

Authors and Affiliations

  1. 1.Unilever Centre for Molecular Science Informatics, Department of ChemistryUniversity of CambridgeCambridgeUK

Personalised recommendations