On the structure of total synthesis of complex natural products

Journal of Organic Chemistry

Volumn 63, Issue 22, 1998, Pages 7982-7989

  Whitlock, H W ^a  

^a UNIVERSITY OF WISCONSIN MADISON   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 0001166252     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo9814546     Document Type: Article

References (28)

1. Woodward, R. B.; Bader, F. E.; Bickel, H.; Frey, A. J.; Kierstead, R. Tetrahedron 1958, 2, 1-57.
2. Corey, E. J.; Long, a. K.; Rubenstein, D. Science 1985,228,408-418.
3. Acher, T. D.; Buszek, K. R.; Fang, F. G.; Forsyth, C. J.; Jung, S. H.; Kishi, Y.; Matelich, M. J.; Scola, P. M.; Spero, D. M.; Yoon, S. K. J. Am. Chem. Soc. 1992, 114, 3162.
4. (a) Bertz, S. H. J. Am. Chem. Soc. 1981,103, 3599-3601.
5. Bertz, S. H. J. Am. Chem. Soc. 1982,104, 5801-5803.
6. Bertz, S. H. J. Chem. Soc., Chem. Commun. 1986, 1627-1628
7. Bertz, S. H. Abstracts of Papers, National Meeting of the American Chemical Society; American Chemical Society: Washington, DC, 1996, ORGN, 282.
8. Available on request as source and executable from the author.
9. A similar procedure has been used by Corey in evaluating synthetic transforms. Corey, E. J., Long,. A. K.; Lotto, I.; Rubenstein, S. D. Red. Trav. Chim. Pay. 1992, 111, 304.
10. Pseudo-atoms currently incorporated into fm.cpp are "Et" for ethyl group, "Pr" for propyl, "R" for generic alkyl, "Cx" for carboxyl, "E" for methyl or other simple ester, "Bn" for benzyl, "Ph" for phenyl or simply substituted phenyl, "Ac" for acetyl, "Q" for generic trisubstituted silyl protecting group, and "Bz" for benzoyl or simply substituted benzoyl group.
11. The molecular formula calculation uses characteristic valency information. Fm.exe "understands the following elements: "X" (monovalent), "I", "Li", "Se", "Bz", "R", "O", "Cl", "Br", "N", "P", "S", "S(O2)", "N(+)" (quadravalent ammonium ion), "Si", and "Sn". These are present as a data array and are readily modified and added to.
12. Landes, D. S. The Wealth and Poverty of Nations; W. W. Norton, 1998; p 416.
13. (a) McCabe, T. IEEE Trans. Software Eng., SE-2 1976,4, 308.
14. (b) McCabe, T. IEEE Software 1996, May.
15. (c) Feghali, I.; Watson, A. Communications of the ACM, April 1994.
16. (d) McConnell, S. Code Complete; Microsoft Press: Redmond, CA, 1993.
17. Bertz (see ref 3) has observed a similar phenomenon using a graph-theoretic measure of complexity.
18. Denmark, S. E.; Thorarenscn, A.; Middleton, D. S. J. Am. Chem. Soc. 1996, 118, 8266.
19. Velluz, L.; Vails, J.; Mathieu, J. Angew Chem., Int. Ed. Engl. 1967, 6, 778.
20. The structure numbering used in this Scheme is that contained in the Supporting Information. This is also on the author's web site http://organic.chein.wisc.edu.
21. m| is the sum of the absolute values of the individual steps divided by the number of steps.
22. We thank Ms. Karin Maxson for this test case.
23. Corey, E. J.; Liu, K. J. Am. Chem. Soc. 1997, 119, 9929.
24. Corey, E. J.; Luo, G.; Lin, L. S. J. Am. Chem. Soc. 1997, 119, 9927.
25. A particularly thorough consideration of the formal properties of synthesis trees may be found in Hendrickson, J. Topics Current Chem. 1976, 62, 49-172.
26. Luzanov, A. V.; Babich, E. N. J. AM. Struct. (THEOCHEM) 1995, 333, 279.
27. We rely heavily on the fact that two syntheses of the same target differ.
28. m| is 1.