Computer-assisted synthetic analysis: Stereochemical processing and knowledge-base extensions to the LHASA program

The LHASA computer program is a tool designed to aid chemists with the retrosynthetic analysis of complex organic molecules. This dissertation describes the author's contributions to the development of the LHASA program at the Harvard University Chemistry Department.;The research described in this thesis is mainly concerned with the addition of new stereochemical capabilities to the LHASA program. This effort was initially focused on developing a low-level support structure of basic stereochemical perception and evaluation tools. The graphical perception and assignment of stereochemical nomenclature by computer is discussed and algorithms that were developed to implement these facilities are described. Extensions to the CHMTRN computer language were then developed to facilitate the addition of stereoselective chemistry to the LHASA knowledge-base. These language enhancements are documented in the categories of stereochemical evaluation, mechanism, and cross-referencing.;Strategies developed for stereochemical antithetic analysis by the LHASA program are discussed next. The concept of "strategic stereocenters" in LHASA is first introduced and a set of tactics based on the selection of strategic stereocenters are defined. A control module written to emulate these tactics and implement additional options for retrosynthetic stereochemical control is described in detail at the end of this section.;A comprehensive survey of up-to-date stereoselective methods that have been added to LHASA from the chemical literature is presented in the next chapter. An overview of the scope and limitations of the relevant methodology is given for each class of stereoselective chemistry followed by a retrosynthetic perspective on the corresponding transforms. Recent developments in the area of stereoselective chemical methodology are outlined in a discussion of future program maintenance and extensions to the chemical knowledge-base. Two sample retrosynthetic analyses using stereochemical tactics are described at the end of this section and a summary of the resulting sequences generated by the LHASA program is presented and discussed.;The last chapter contains a description of research that was not directly related to the stereochemical processing capabilities in LHASA. This section is subdivided by area and represents a sampling of additional LHASA projects that were completed by the author.