From synthesis planning to combinatorial chemistry: Applications of the LHASA suite


Alan Long1, Rong Chen2, Craig A. Marby2, Alexander P. Sukharevsky3, and Keith Ohm2. (1) Harvard University, 1414 Massachusetts Ave., Room 430, Cambridge, MA 02138, (2) Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford St., Cambridge, MA 02138, (3) Aventis Pharmaceuticals, Cambridge, MA
The LHASA (Logic and Heuristics Applied to Synthetic Analysis) program for target-oriented retrosynthetic analysis has evolved since the early 1970ís into a suite of programs that includes DEREK (for toxicology prediction), PROTECT (for protective-group analysis), APSO (for teaching organic synthesis), and, most recently, LCOLI (for diversity-oriented generation of compound libraries). Improvements in hardware and software have shifted the emphasis in synthetic analysis from interactive, user-driven strategy and tactic selection to non-interactive processing requiring intelligent screening of results. One approach to optimal route selection using analysis of synthetic accessibility and complexity will be discussed. The availability of multiple tools in the suite also allows a more comprehensive approach to synthesis planning. For example, the virtual libraries generated by LCOLI using its knowledge-based diversity-oriented synthesis (DOS) approach can be screened automatically and ranked according to synthetic accessibility and potential toxicity of the products. Applications to drug design will be discussed.

Herman Skolnik Award Symposium
8:15 AM-11:45 AM, Tuesday, August 24, 2004 Pennsylvania Convention Center -- 110A&B, Oral

Division of Chemical Information

The 228th ACS National Meeting, in Philadelphia, PA, August 22-26, 2004