In search of simplification:: the use of topological complexity indices to guide retrosynthetic analysis

Topological complexity indices N-S, N-T, N-S(lpe), N-T(lpe), twc and wcx are used to rank the one-bond disconnections of bicyclo[2.2.1]heptane, spiro[3.3]heptane and their aza derivatives with respect to the degree of simplification they afford. Selected two-bond disconnections of bicyclo[2.2.1]heptane and its aza derivatives are also evaluated. Simplification principles are derived which are useful for guiding the retrosynthetic analysis of complex target molecules. Comparison with the LHASA rules for strategic bonds reveals a great deal of similarity and some important differences.